An overview of Coordination Chemistry with Metals, Ligands, Complexes and Applications

AN OVERVIEW OF COORDINATION CHEMISTRY WITH METALS, LIGANDS, COMPLEXES AND APPLICATIONS In Honor of Hacali Necefoğlu’s 70th Birthday Editor Füreya Elif ÖZTÜRKKAN Lyon 2025 AN OVERVIEW OF COORDINATION CHEMISTRY WITH METALS, LIGANDS, COMPLEXES AND APPLICATIONS In Honor of Hacali Necefoğlu’s 70th Birthday Editor Füreya Elif ÖZTÜRKKAN Lyon 2025 An overview of Coordination Chemistry with Metals, Ligands, Complexes and Applications: In Honor of Hacali Necefoğlu’s 70th Birthday Editor • Assoc. Prof. Dr. Füreya Elif ÖZTÜRKKAN • Orcid: 0000-0001-6376-4161 Cover Design • Motion Graphics Book Layout • Motion Graphics First Published • December 2025, Lyon e-ISBN: 978-2-38236-965-4 DOI: 10.5281/zenodo.17848648 copyright © 2025 by Livre de Lyon All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without prior written permission from the Publisher. The author or authors of the relevant section are responsible for any copyright infringement that may occur due to the images and graphics used in the book. The editor or publisher does not assume responsibility in this regard. Publisher • Livre de Lyon Address • 37 rue marietton, 69009, Lyon France website • http://www.livredelyon.com e-mail • [email protected] I FOREWORD This book has been prepared as a tribute to our esteemed professor, Prof. Dr. Hacali Necefoğlu, on the occasion of his 70th birthday. Throughout nearly fifty years of his academic life, his students, colleagues, and the many people he has inspired have all witnessed his devotion to science, hard work, and humanity. With his pioneering contributions to the field of coordination chemistry and his scientific vision, our professor continues to shed light on the development of this discipline. As one of his students who has had the privilege of knowing him for almost a quarter of a century, I learned immensely from his profound knowledge, meticulousness, and guidance during my master’s and doctoral studies. Yet what I learned from him was not limited to scientific knowledge alone; he also taught me that learning is an attitude, sharing is a responsibility, and mentorship is an act of the heart. Our professor has continued to offer his guidance not only during our years as students but also long afterward. At every stage, he has been there for his students and colleagues alike—with his honest words, thoughtful advice, and constructive support. Always remembering his own late mentor, Prof. Dr. Khudu Memmedov, with great affection and respect, our professor inherited not only his teacher’s knowledge but also his kindness and loyalty toward his students. His enduring connection with his former students, and the love and respect he receives from colleagues both in our country and abroad, stand as the most beautiful testament to this legacy. This book, entitled “An Overview of Coordination Chemistry with Metals, Ligands, Complexes and Applications,” brings together diverse perspectives and original contributions in the field of coordination compounds. Each chapter focuses on a different aspect of the field and has been written by experts who have significantly contributed to its advancement. During the preparation process, his students, collaborators, and friends also shared their knowledge, experience, and support. Thus, this work stands not only as a product of individual effort but also as one of collective collaboration and shared purpose. For me, preparing this volume has been both an expression of gratitude and an opportunity to make a small contribution to the journey shaped under the guidance of our professor. I sincerely hope that this tribute finds a place, with the same warmth, in the hearts of his students, friends, and colleagues who continue to be inspired by his light. II   AN OVERVIEW OF COORDINATION CHEMISTRY WITH METALS . . . The authors contributing to this book have enriched the volume with comprehensive chapters focused on contemporary areas of coordination chemistry. Elman M. Movsumov authored the chapter “Coordination Chemistry of Benzoic Acid Derivatives”; Famil Musa Chyragov and Esmira Jalil Eyyubova contributed the chapter “Synthesis, Structure and Application of Azocompound-β-Diketone Based Metal Complexes: A Comprehensive Review”; Maia Tsintsadze prepared the chapter “Coordination Chemistry in the Republic of Georgia”; Batirbay Torambetov and Shakhnoza Kadirova authored “Recent Advances in 1,3,4-Thiadiazole-Based Metal Complexes: Coordination Chemistry, Crystal Structures, and Biological Activities”; and A.Z. Zalov, G.M. Talybov, Z.Z. Yakhshieva, H.I. Ibrahimov, and U.B. Abasguliyeva contributed the chapter “Complexes of Nickel with Monoallyl Ethers α-Glycols, Biological Properties and Their Application.” Additionally, Melda Bolat and Dursun Ali Köse authored “Boron and Boron Esters: From Chemical Fundamentals to Biological Applications”; Ömer Yurdakul and Dursun Ali Köse prepared “Metal(Mⁿ⁺)– Carboxylate(COO⁻) Complexes: Bonding Properties, Applications and Structural Characterization Methods”; Tuğrul Yıldırım and Dursun Ali Köse contributed “N-Donor Ligands: Structural Features, Chemical Properties and Application Fields”; Mehmet Sait İzgi, Ömer Şahin, and Erhan Onat authored “Green Synthesis of Nickel Nanoparticles from Caffeine and Their Catalytic Activity in Ammonia Borane”; Giray Buğra Akbaba prepared “Biological Applications of Caffeine’s Metal Complexes”; Ömer Aydoğdu and Azer Özen contributed the chapters “Crystal Structures of Metal(II) Methoxybenzoato Complexes” and “Crystal Structures of Metal Cyanobenzoate Complexes”; Güventürk Uğurlu authored “Structural and Electronic Properties of Aromatic N-Acylhydrazones and Their Complexes”; and Füreya Elif Öztürkkkan contributed the chapter “Structural Aspects of Naproxen Complexes of Transition Metals.” Through these diverse and original contributions, the authors collectively expanded the scientific scope of the book. Assoc. Prof. Füreya Elif ÖZTÜRKKAN Editor III CONTENTS Foreword I CHAPTER I. COORDINATION CHEMISTRY OF BENZOIC ACID DERIVATIVES 1 Elman Mahammad oglu Movsumov CHAPTER II. BORON AND BORON ESTERS: FROM CHEMICAL FUNDAMENTALS TO BIOLOGICAL APPLICATIONS 17 Melda BOLAT & Dursun Ali KÖSE CHAPTER III. SYNTHESIS, STRUCTURE AND APPLICATION OF AZOCOMPOUND-β-DIKETONE BASED METAL COMPLEXES: A COMPREHENSIVE REVIEW 37 Famil Musa CHYRAGOV & Esmira Jalil EYYUBOVA CHAPTER IV. BIOLOGICAL APPLICATIONS OF CAFFEINE’S METAL COMPLEXES 53 Giray Buğra AKBABA 75 87 AROMATIC N-ACYLHYDRAZONES AND THEIR COMPLEXES Güventürk UĞURLU CHAPTER VII. RECENT ADVANCES IN 1,3,4-THIADIAZOLE-BASED METAL COMPLEXES: COORDINATION CHEMISTRY, CRYSTAL STRUCTURES, AND BIOLOGICAL ACTIVITIES 101 Batirbay TORAMBETOV & Shakhnoza KADİROVA CHAPTER VIII. METAL(Mn+) – CARBOXYLATE(COO-) COMPLEXES: BONDING PROPERTIES, APPLICATIONS AND STRUCTURAL CHARACTERIZATION METHODS 131 Ömer YURDAKUL & Dursun Ali KÖSE CHAPTER IX. CRYSTAL STRUCTURES OF METAL CYANOBENZOATE COMPLEXES 153 Azer ÖZEN & Ömer AYDOĞDU CHAPTER V. COORDINATION CHEMISTRY IN THE REPUBLIC OF GEORGIA CHAPTER VI. STRUCTURAL AND ELECTRONIC PROPERTIES OF Maia TSINTSADZE IV   AN OVERVIEW OF COORDINATION CHEMISTRY WITH METALS . . . CHAPTER X. COMPLEXES OF NICKEL WITH MONOALLYL ETHERS Α-GLYCOLS, BIOLOGICAL PROPERTIES AND THEIR APPLICATION 167 Ali Zal Zalov, G.M.Talybov, Zuhra Ziyatovna Yakhshieva, Husu Isa Ibrahimov, Ulviya Balabey Abasguliyeva CHAPTER XI. GREEN SYNTHESIS OF NICKEL NANOPARTICLES FROM CAFFEINE AND THEIR CATALYTIC ACTIVITY IN AMMONIA BORANE 191 Mehmet Sait İZGİ & Ömer ŞAHİN & Erhan ONAT METHOXYBENZOATO COMPLEXES 245 Ömer AYDOĞDU & Azer ÖZEN CHAPTER XIV. STRUCTURAL ASPECTS OF NAPROXEN COMPLEXES OF TRANSITION METALS 261 Füreya Elif ÖZTÜRKKAN CHAPTER XII. N-DONOR LIGANDS: STRUCTURAL FEATURES, CHEMICAL PROPERTIES AND APPLICATION FIELDS 203 Tuğrul YILDIRIM & Dursun Ali KÖSE CHAPTER XIII. CRYSTAL STRUCTURES OF METAL(II) COORDINATION CHEMISTRY OF BENZOIC ACID DERIVATIVES   7 Crystal structure of bis(μ2-4-aminobenzoato-κ2 O:O′)bis[bis(4-aminobenzoato-κ2 O,O′)diaquathulium(III)] dihydrate, [Tm2(C7H6NO2)6(H2O)4]·2H2O, is in the form of a dimer [11] (Ali vd., 2022). Fig. 11. Crystal structure of p-aminobenzoato Tm(III) (Ali vd., 2022). Crystal structure of pyrazine (Pyr) adduct of nickel phtalate, [Ni(Pyr) (H2O)4]Phth, has ionic nature and exists as a one-dimensional polymeric structure [12] (Aliyeva vd., 2023). Fig. 12 Crystal structure of [Ni(Pyr)(H2O)4]Phth (Aliyeva vd., 2023). Moleculyar structure of neodymium(III) p-aminobenzoate (crystallographic parameters: a=9,882, b=22,810, c=9,851 Å, β = 10,8, 02, Z =4, V=2186, 6 Å3, R= 0,046) is dimer (Fig. 13) [13] (Khiyalov vd., 1981). 8   AN OVERVIEW OF COORDINATION CHEMISTRY WITH METALS . . . Fig. 13 Crystal structure of Nd(III) p-aminobenzoate (Khiyalov vd., 1981). Bis(p-aminobenzoato)tetraaquo manganese(II), [Mn(H2NC6H4COO)2(H2O)4] (crystallographic parameters: a= 8,671, b=9,212, c=20,645 Å, β= 97, 68º, Z=4, V=1685, 45 Å3, R= 0,056) has amonomeric structure (Fig. 14) [14] (Amiraslanov vd., 1978). Fig. 14. Molecular structure of [Mn(H2NC6H4COO)2(H2O)4] (Amiraslanov vd., 1978). As seen from Fig. 15, the central atom Cu coordinates with the donor nitrogen atom of the pyridine molecule, the oxygen atom of the hydroxyl group of the ligand, and one oxygen atom of the carboxyl group, forming a distorted quadratic-pyramidal geometric polyhedron in the dimeric molecular structure of bis-(3,5-dinitrosalicylate)-di-pyridine copper(II) (Fig. 15). Crystallographic parameters: a=9,286Å, b=5,054Å, c=26,881Å, β=109,94º, P21/c , Z=2, V=1369,25 Å3 , R=0,058 [15] (Alieva vd., 2024). COORDINATION CHEMISTRY OF BENZOIC ACID DERIVATIVES   9 Fig. 15. Molecular structure of bis-(3,5-dinitrosalicylate)-di-pyridine copper(II) (Alieva vd., 2024). catenaPoly[[diaquabis(4-nitrobenzoato-κO1)cobalt(II)]-µ-pyrazineκ2N:Nʹ] (crystalloqraphic parameters: a=22,1289Å, b=7,099Å, c=12,316 Å, β=408,69º, Z=4, V=1468,5 Å3 , R=0,085) has a polymeric structure (Fig. 16) [16] (Hesenova vd. 2022). Fig. 16. Molecular structure of the Co(II) complex (Hesenova vd. 2022). catenaPoly[[diaquabis(4-nitrobenzoato-κO1)manganese(II)]-µ-pyrazine– κ2N:Nʹ] (crystallographic parameters: a=22,702Å, b=7,811Å, c=41,589 Å, β=105,45º, Z=4, V=1268,5 Å3, R=0,029) is isostructural with the above 10   AN OVERVIEW OF COORDINATION CHEMISTRY WITH METALS . . . mentioned Co-complexs . As seen from Fig. 17, the carboxyl group of the ligand forms a monodentate bond with the Mn(II) cation, forming an ionic bond structure (Mn(1)-O(1)=2.216Å. The other oxygen of the carboxyl group does not form a bond with the central atom, but forms hydrogen bonds with the water molecules that enter the structure and are coordinated to the metal [16] (Hesenova vd. 2022). Fig. 17 Molecular structure of the Mn(II) complex (Hesenova vd. 2022). Bis-(p-nitrobenzoato)-di-(pyrazine) nickel(II) has also polimeric structure (Fig. 18). Crystallographic parameters: a=22,092, b=13,979, c=12,378 Å, β=113,67º, Z=4, V=1906,15 Å3 , R=0,0259 [17] (Hesenova, 2022a). Fig. 18 Molecular structure of bis-(p-nitrobenzoate)-di-(pyrazine) Ni(II) (Hesenova, 2022a). COORDINATION CHEMISTRY OF BENZOIC ACID DERIVATIVES   11 Molecular structure of the complex compound Bis-(3,5-dinitrobenzoatoO,O) Zn(II) is dimer. Fig. 19 shows that the central atom Zn(II) forms a monodentate bond with the carboxyl groups of the ligand. The water molecule entering the structure forms a donor-acceptor bond with the Zn(II) cation through the donor oxygen atom, completing its coordination number to three. Crystallographic parameters: a=11,109, b=11,109, c=11,602 Å, β=106,95º, Z=4, V=1240,5 Å3 , R=0,028 [18] (Hesenova, 2017). Fig. 19 Molecular structure of the complex compound Bis(3,5-dinitrobenzoatoO,O) Zn(II) (Hesenova, 2017). Bis-(3,5-dinitrobenzoato) U(VI) tetrahydrate (crystallographic parameters: a=6,601, b=14,418, c=20,081 Å, α=β=g=90º, Z=4, V=1308,87 Å3, R=0,033) has monomeric structure (Fig. 20) [19] (Hesenova, 2022b). Fig. 20 Crystal structure of the complex compound bis-(3,5-dinitrobenzoate) Uranium(VI) (Hesenova, 2022b). 12   AN OVERVIEW OF COORDINATION CHEMISTRY WITH METALS . . . In molecular complex tris(pyridine)bis(2-acetamido-5-nitrobenzoate) copper(II) (crystallographic parameters: a=8,237, b=20,610, c=10,156Å, β=103,3º, Z=2, V=1678,7 Å3 , R=0,028) the Cu atom has the characteristic tetragonal-bipyramidal coordination 4 + 1 + 1 (Fig. 21) [20] (Mamedova vd., 2011). Fig. 21 Molecular structure tris(pyridine)bis(2-acetamido-5-nitrobenzoate) copper(II) (Mamedova vd., 2011). Bis(p-nitrosalycilato) zinc(II) tetrahydrate has a centrocsymmetric monomeric structure. Crystallographic parameters: a=5,140Å, b=14,784Å, c=11,941Å, β=97,540, Z=2, V=897,7Å3 , R=0,027 [21] (Navaz T. M. Vd., 1997). Fig. 22 Crystal structure p-nitrosalycilato zinc(II) (Navaz T. M. Vd., 1997). COORDINATION CHEMISTRY OF BENZOIC ACID DERIVATIVES   13 REFERENCES Ali, K. S., Ashfaq, M., Tahir, M. N., Movsumov, E. M., & Munawar, K. S. (2022). Synthesis, crystal structure, Hirshfeld surface and void analysis of bis(μ2-4-aminobenzoato-κ2 O:O′)bis[bis(4-aminobenzoato-κ2 O,O′) diaquathulium(III)] dihydrate. Acta Cryst. E78(3), 282–286. https://doi. org/10.1107/s2056989022001116 Alieva Q. M., Navaz T. M., Khurram, Sh. M., Mehran, F.-D., , Muhammad, A., Hasanova, S. S., Hasanova, U. M., Kerimova, T. Q., , Iskenderova, S. A., Alieva, Sh. C. & Movsumov, E. M. (2024). One-dimensional polymer of copper with salicylic acid and pyridine linkers: Synthesis, characterizations, solid state assembly investigation by hirshfeld surface analysis, and computational studies. Journal of Molecular Structure. 1297(2), 136956. https://doi.org/10.1016/j. molstruc.2023.136956 Aliyeva , Q. M., Tahir, M .N., Ashfaq, M., Munawar, K. S., Rahmanova, S. Y., Hasanova, U. M., Rustamova A. A., Mammadova, H. F. & Movsumov E. M. (2023). Nickel(II) Coordination Polymer Using Pyrazine Linkers And Phthalate Counter-Anion: Synthesis, Crystal Structure, Hirshfeld Surface And Voids Analysis. Journal of Structural Chemistry. 64(6), 111684. https://doi. org/10.1134/S0022476623060045 Amiraslanov, I. R., Dzhafarov, N. K., Nadzhafov G. N., Mamedov, Kh. S., Movsumov, E. M. & Usubaliev, B. T. (1980). An X-ray structural study of complexes of p-aminobenzoic acid with metals V. Crystal and molecular structure of Bis(p-aminobenzoato)lead(II). Zh. Strukt. Khim. 21(1), 104-108. Amiraslanov, I. R., Mamedov, Kh. S., Movsumov, E.M., Musaev, F. N. & Nadzhafov G. N. (1979c). An X-ray structural study of complexes of p-aminobenzoic acid with metals. IV. Crystal and molecular structure of di(paminobenzoato)tetraaquacobalt(II). Zh. Strukt. Khim. 20(6), 917-922. Amiraslanov, I. R., Mamedov, Kh.S., Movsumov, E. M., Musaev, F. N, Shnulin, A. N. & Nadzhafov G. N. (1979b). X-ray structural study of complexes of p-aminobenzoic acid with metals. II. Crystal and molecular structure of bis(paminobenzoato)diaquonickel (II). Journal of Structural Chemistry. 19(6) 962966. Amiraslanov, I. R., Movsumov E. M. & Mamedov Kh.S. (1979a). Crystalline and molecular structure of zinc(II) bis-aminobenzoate hydrate. DAN Azerb. SSR, 35(1), 50-51. Amiraslanov, I. R., Movsumov, E. M., Mamedov, Kh. S. & Nadzhafov G. N. (1978). An X-ray structural study of complexes of p-aminobenzoic acid with 14   AN OVERVIEW OF COORDINATION CHEMISTRY WITH METALS . . . metals. I. Crystal and molecular structure of bis-(p-aminobenzoato)tetraaqua manganese(II). Journal of Structural Chemistry. p. 1120-1128. Dzhafarov, N. K., Amiraslanov, I. R., Nadzhafov, G. N., Movsumov, E.M., Kerimova, F. R. & Mamedov, Kh. S. (1981). Crystal and molecular structure of monoaquo-bis-(p-hydroxybenzoato) lead (II) monohydrate. J. Struct. Chem. 22, 245–248 https://doi.org/10.1007/BF00745201 Hesenova, S. S. (2022a). Syntezis, physicochemical study and crystal structure of bis-(pnitrobenzoate)-di-(pyrazine) nickel(II) dihidrate. Chemical problems, 20(1), 95-101. Hesenova, S. S. (2022b). Synthesis, physico-chemocal analysis and cristal structure of 3,5dinitrobenzoate of uranium U(VI). Advanced physical research. 4(2), 100-105. Hesenova, S. S., Maharramov, A. M., Asgarov, R. K., Safarova, L. N. & Movsumov, E. M. (2017). Synthesis of molecular and crystalline structure of the 3,5-dinitrobenzoata Zn(II). 3rd International Turkic World Conference on Chemical Sciences and Technologies. Baku Azerbaijan, September 10-13, 175. Hesenova, S. S., Mamedova, L. N., Ashfaq, M., Khurram, S. M., Movsumov, E. M., Muhammad, Kh., Tahir, M. N. & Imran, M. (2022). Synthesis, crystal structure, Hirshfeld surface analysis and theoretical investigation of polynuclear coordination polymers of cobalt and manganese complexes with nitrobenzene and pyrazine. Journal of Molecular Structure. 1250(2), 131851. Khilayov M. S., Amiraslanov I. R., Mamedov Kh. S. & Movsumov, E. M. (1981). Crystal and molecular structure of neodymium(III) p-aminobenzoate. Journal of Structural Chemistry. 22(3) 400-405. Mamedova, A. T., Ilyuhin, A. B., Sergeyenko V. S. & Movsumov E. M. (2011). Crystal Structure of [CuL2Py3] (HL is 2-(Acetylamino)-5-Nitrobenzoic Acid). Journal Inorganic Chemistry (Russian). 56(7), 1107-1109. Movsumov, E. M., Antsyshkina, A. S., Ostrikova, V. N., Karaeva, K.T. (1990). Crystal and molecular-structure of disilver (I) disalicylate. Koord. Khim. 16 (4), 517-520. Musaev, F. N., Movsumov, E.M., Mamedov, Kh.S. & Amiraslanov, I. R. (1978). Crystal and molecular structure of di(monothiobenzoato)di(pyridine) zinc(II). Koord. Khim. 4, 1420-1426. Nadzhafov, G. N., Usubaliev, B. T., Amiraslanov, I. R., Movsumov, E. M., & Mamedov, Kh. S. (1981). Crystal Structure of bis-pyridine-bis-(phydroxybenzoato) zinc (II) Koord. Khim, 7(5), 770. COORDINATION CHEMISTRY OF BENZOIC ACID DERIVATIVES   15 Navaz T. M., Ülkü, D. & Movsumov E. M. (1997). Tetraaquabis(pnitrosalicylato) Complexes of Zinc(II) and Cobalt(II). Acta Cryst. C53, 176179. Ülkü, D., Tahir, M. N. & Movsumov, E. M. (1996). Poly[bis (3, 5-dinitrobenzoato-O1: O2) disilver (I)-O2: Ag; Ag’: O2’]. Acta Cryst. C52 (11) 2678-2680 Usubaliev B. T., Amiraslanov I. R., Nadzhafov G. N., Movsumov E. M.. Musaev F.N. & Mamedov Kh.S. (1981.) Crystalline and molecular self-structure of bis-pyridine-bisnitrobenzoate copper (II). Koord. Khim, 7(3), 440-444. BORON AND BORON ESTERS: FROM CHEMICAL FUNDAMENTALS . . .   23 3.1. Boron Derivatives Obtained From Natural Sources Boron derivatives obtained from natural sources include aplasmomycin, boromycin, borophysin, and tartrolon. Boron forms stable complexes using the tetrahedral borate anion. It is known that this type of chelates is found in the structure of natural biomolecules. Figure 7 shows the molecular structures of Boromycin, Aplasmomycin, Tartrolon B, and Borofisin compounds, respectively (Dibek et al., 2020; Hemscheidt et al., 1994; Mulzer & Berger, 2004; Nakamura et al., 1977; Yünlü, 2016). 3.2. Synthetically Obtained Boron Derivatives Tavaborol, vaborbaktam, vabomeri, benzoxaborol, akoziborol, and ixazomib are other synthetically derived boron derivatives. The molecular structures of these synthetic boron compounds are shown in Figure 8 (Dibek et al., 2020). OO O B O O O O O H C CH 3 CH 3 C O H 3 CCH 3 HO H 3 C H 3 C CH 3 O O CH 3 O O NH 3 CH 3 H 3 C H OH (a) B OO O O O O OH O Me H H O Me Me O Me H O Me Me O H H Me Ag O O HHH Me H OH (b) O O HO O OO O O B O O OO O Na OH (c) (d) O O O O B O O O O O O O O OH OH Na Figure 7. (a) Boromycin (b) Aplasmomycin (c) Tartrolon B (d) Boroficin compounds 24   AN OVERVIEW OF COORDINATION CHEMISTRY WITH METALS . . . O B OH F (a) SNH O B OH OH O O (b) N H N O S N HO O O S H N O B O HO OH O (c) O BOH Cl (d) N O FF F F O BOH (e) (f) Cl Cl NH O OB HO OH CH 3 CH 3 O O B OH N (g) N N N H H N OH B O OH O (h) Figure 8. a) Tavaborol, b) Vaborbactam, c) Vabomeri, d) Benzoxaborole, e) Akoziborole, f) Ixazomib, g) Crisaborole, h) Bortezomib compounds The chemical form of boron in nutrition is one of the key factors determining its bioavailability and physiological effects. Therefore, studying the chemical forms of boron in plant sources and how these forms are transformed in biosystems is of great importance (Brown & Hu, 1996; Hunt, 2012; Nielsen, 2014; Pizzorno, 2015). BORON AND BORON ESTERS: FROM CHEMICAL FUNDAMENTALS . . .   25 4. The Function of Boron Compounds in Plants Boron is an element necessary for the normal growth and development of plants (Warington, 1923). Until now, it has been accepted that one of the main functions of boron in vascular plants is closely related to the structure and function of the cell wall. It has been proven that boron plays a direct role in the formation of cross-bridges that connect rhamnogalacturonan II (RG-II) (Figure 9) and pectin structures found in the cell wall, thus demonstrating that boron is indispensable for cell wall integrity and strength (O’Neill et al., 2004). O O O O O OO O O B O O Figure 9. Plant cell wall boron-rhamnogalacturonan II (RG-II) complex Therefore, boron is considered a critical element in the growth and development of plant tissues. Indeed, boron deficiency can seriously slow down or completely stop the growth of both vegetative and reproductive organs (Dell & Huang, 1997). This structural importance of boron, combined with its limited mobility in many crop plants, necessitates a continuous external supply of boron throughout the plant’s life cycle. (Brown & Shelp, 1997). Therefore, monitoring and maintaining the boron level in the soil is of great agricultural importance for healthy plant development and achieving high yields (Herrera-Rodríguez et al., 2010). In plants, boron is found in the form of sugar esters (Brown & Hu, 1996) There are studies showing that its assimilation is closely related to the chemistry of sugar esters (Brown & Hu, 1996; Brown & Shelp, 1997; Scorei & Cimpoiaşu, 2006). Boron sugar esters are the best chemical form for assimilation by cells (Hu et al., 1997). While researching various boron compounds, scientists discovered a boron plant form known as calcium fructoborate diester (CF), a boron complex naturally found in fruits, vegetables, and other foods (HerreraRodríguez et al., 2010). This boron form is not only safe but also significant for its bioavailability compared to other commercial boron forms (Hunter et al., 2019; Miljkovic, 1999). 26   AN OVERVIEW OF COORDINATION CHEMISTRY WITH METALS . . . (C6H10O6)-B-(C6H10O6) \ (fructose-B-fructose), fructose borate (FB), a complex anion of this composition, is a naturally occurring boron compound identified in plants (Scorei & Rotaru, 2011; Wagner & Baran, 2008; Wagner et al., 2008). The structure of the fructoborate anion is shown in Figure 10 (Hunter et al., 2019). It has been determined that boron forms fructose borate ester complexes in the extracellular nectar of peach plants. (Brown & Shelp, 1997; Hu et al., 1997). It has been reported that these fructose borate esters are also found in various vegetables and fruits consumed by humans and animals (Scorei & Popa, 2013). Plant-based foods are important as the main natural source of organic boron compounds. Calcium fructoborate, the most common form of these compounds, is naturally found in fresh fruits, vegetables, honey, and especially in dried fruits such as plums, raisins, and apricots (Xia et al., 2017). O O O O H O H OH B O O OOH OH O H Figure 10. Fructoborate anion structure Some researchers have studied CF in aqueous solutions and found that CF exists as three different molecules in an aqueous solution environment. The species detected as free boric acid, diester, and monoester complexes (speciation of fructoborates) are shown in Figure 11. Figure 11. The classification of fructoborates (Hunter et al., 2019) BORON AND BORON ESTERS: FROM CHEMICAL FUNDAMENTALS . . .   27 Fructoborate derivatives, an intriguing concept that could be the focus of future research, are suggested to have a biological role, such as functioning as a coenzyme or cofactor. The proposed mechanism for the use of boron derivatives as coenzymes or cofactors is shown in Figure 12 (Hunter et al., 2019). Figure 12. Proposed mechanism for the use of boron derivatives as coenzymes or cofactors (Hunter et al., 2019). Studies have shown that dietary intake of boron and magnesium significantly affects calcium metabolism and, consequently, bone health. In animal studies, it has been found that boron requirements increase, especially under nutritional stresses that disrupt calcium metabolism, such as magnesium deficiency, and that the combined deficiency of boron and magnesium leads to significant negative changes in bone structure. Similarly in human studies, it has been observed that boron deficiency lowers plasma ionized calcium and calcitonin levels, while increasing plasma total calcium and urinary calcium excretion. It has been reported that these effects become even more pronounced with low magnesium intake. It has also been determined that magnesium deficiency reduces plasma ionized calcium and cholesterol. These findings reveal that boron and magnesium deficiencies show similarities to the metabolic changes observed in postmenopausal women with osteoporosis, suggesting that both elements are necessary for optimal calcium metabolism and the prevention of bone loss (Nielsen, 1990, 2010). 5. Boron and Human Health: From Arthritis to Cancer 5.1. The Effects of Boron on Arthritis and Osteoarthritis Arthritis is the most common cause of disability in adults and is particularly prevalent in those with heart disease, diabetes, and obesity. A significant portion 28   AN OVERVIEW OF COORDINATION CHEMISTRY WITH METALS . . . of patients experience limitations in their daily activities. Self-management training and regular physical activity are recommended to improve quality of life. Although treatment for inflammatory rheumatic diseases has advanced, osteoarthritis, the most common joint disorder, increases with aging and obesity. Non-pharmacological, pharmacological, and surgical methods are used together in the management of the disease, and research on new biomarkers and cellbased therapies is ongoing. (Barbour et al., 2013; Buttgereit et al., 2015). Boron is recognized as an efficacious adjunct in the management of arthritis. Enhancing the biological integration of calcium in bone, joint, and cartilage tissues facilitates recovery in 95% of instances. Moreover, it indirectly modulates bone metabolism by influencing the concentrations of critical hormones, including boron, testosterone, and estrogen (Devirian & Volpe, 2003). Extensive studies investigating the correlation between soil and dietary boron concentrations and the prevalence of arthritis revealed that the incidence of arthritis varied from 20% to 70% in regions with a daily boron intake of 1 mg or less, whereas this rate diminished to 0% to 10% in areas with an intake of 3–10 mg. Research in the Middle East indicates that serum boron levels in persons with rheumatoid arthritis are 50% lower than those in healthy individuals. The data indicate that boron may have a preventive function in the pathophysiology of osteoarthritis and rheumatoid arthritis. A daily consumption of no less than 3 mg of boron is especially crucial for those with arthritis or those predisposed to the condition (Racu et al., 2021). 5.2. The Effects of Boron on Bone Health Boron is a trace element that is crucial for various biological activities, including calcium metabolism and the development and preservation of bone structure. Boron supplementation has demonstrated considerable beneficial effects on human bone health via modulating the metabolism of calcium, vitamin D, and sex hormones. A daily consumption of 3 mg of boron, whether administered independently or in conjunction with other micronutrients, is recognized as an effective and safe dosage for preserving bone mineral density, averting bone loss, and diminishing the risk of osteoporosis (Rondanelli et al., 2020). The regulatory influence of boron on leptin concentrations has been linked to a notable enhancement in bone strength (Khaliq et al., 2018). Additionally, boron supports bone tissue regeneration by stimulating the expression of genes that control osteoblast activity (e.g., genes related to 17β-estradiol, testosterone, and vitamin D) (Pizzorno, 2015). Clinical studies indicate that CF supplementation is useful for knee joint problems. Following 7, 14, and 90 days of treatment, an BORON AND BORON ESTERS: FROM CHEMICAL FUNDAMENTALS . . .   29 enhancement in knee flexibility and a notable decrease in pain intensity were recorded. The National Health and Nutrition Examination Survey (NHANES) in the United States offers the most extensive national statistics regarding the health and nutritional status of the populace. Recent studies reveal that older adults have increasingly utilized (CF) supplementation to mitigate joint pain (Hunter et al., 2019). 5.3. The Effects Of Boron On Cancer Boron compounds have acquired considerable significance in current chemotherapeutic and drug development research. They are highly significant for their chemopreventive potential, particularly for prostate, breast, and cervical malignancies. Studies indicate a negative correlation between daily boron consumption and prostate cancer risk, suggesting that boron compounds may serve as potential agents for cancer prevention and treatment (Scorei et al., 2008; Scorei & Popa, 2013; Soriano-Ursua et al., 2014). Sugar borate esters (SBEs), organic boron compounds that combine with natural sugars such as fructose and ribose, have demonstrated enduring protective benefits against prostate cancer (Militaru et al., 2013). The anticancer properties of boron are linked to its regulatory function on NAD and calcium channels. Interruption of NAD synthesis impairs cellular energy metabolism, whereas boron chemicals regulate this process, safeguarding cellular metabolism. Research indicates that borates inhibit the multiplication of cancer cells by 30-97%. (Barranco et al., 2009). In an epidemiological investigation in Turkey, no cervical cancer instances were identified in women residing in boron-rich areas, whereas cytopathological abnormalities were observed in districts with low boron concentrations (Korkmaz et al., 2007). 5.4. Neurological, Antioxidant, and Cardiovascular Effects of Boron The impact of boron on cognitive performance is also significant. Research indicates that elderly adults with a boron-deficient diet demonstrate considerable deficits in cognitive functions, including hand-eye coordination, attention span, perception, and short-term memory (Penland, 1998). This impact is believed to be associated with alterations in ion conductivity across neuronal membranes (Bhasker et al., 2016; Nielsen, 2000; Nielsen & Stoecker, 2006). The administration of calcium fructoborate and resveratrol for 60 days dramatically lowered CRP levels, hence reducing inflammation and the risk of coronary artery disease (Militaru et al., 2013). 30   AN OVERVIEW OF COORDINATION CHEMISTRY WITH METALS . . . Boron is also efficacious in wound healing and cellular regeneration processes. Enhancing the synthesis of extracellular matrix proteins, including type I collagen, osteopontin, osteocalcin, and bone sialoprotein, facilitates osteoblast proliferation and bone mineralization (Pizzorno, 2015). In conclusion, the anti-inflammatory, antioxidant, and chemopreventive attributes of boron elevate it from a mere trace element to a bioregulatory element that enhances human health in various aspects (Donoiu et al., 2018; I Scorei & Popa, 2010). 5.5. Biochemical Significance of Natural Boron-Oxygen Complexes Boron-oxygen coordination is recognized as a phenomena present in inorganic compounds and as a dynamic, functional connection that occurs spontaneously in biological systems. This bond type specifically originates from the interactions between boric acid and aromatic metabolites that possess phenolic or cis-diol groups, including catechol, pyrogallol, gallic acid, chlorogenic acid, quercetin, myricetin, curcumin, pyridoxine (Vitamin B₆), riboflavin (Vitamin B₂), and dopamine. These ligands establish transient yet functional B–O–C coordination interactions in plants, microorganisms, and human tissues through enol-diol groups attached to the boron atom via cis-diol or β-diketone configurations. Consequently, in nature, they serve as inorganic-organic intermediaries, creating boron-based organic complexes akin to traditional metal complexes, which play a crucial role in cellular communication (e.g., quorum sensing), antioxidant equilibrium, and enzymatic control mechanisms (Dembitsky et al., 2025). 6. Conclusion Boron and boron esters represent a unique group of elements in both their chemical and biological aspects. Boron is not just a laboratory component; it is a building block found within living systems, protecting and balancing them. Its flexible bonding structure and strong interactions with oxygen make boron esters both stable and biologically active. Today, borate esters are no longer just substances studied in chemistry laboratories; they have become compounds with real application potential in fields such as health, materials science, and biotechnology. Thanks to the natural-like complexes they form with fructose, ribose, or vitamins, boron compounds support cell renewal, reduce oxidative stress, and balance metabolic processes. With these properties, boron plays a role in many biological processes, from protecting bone and cartilage tissue to BORON AND BORON ESTERS: FROM CHEMICAL FUNDAMENTALS . . .   31 strengthening the immune system. It also stands out as a promising supportive component in complex health issues such as cancer, cardiovascular, and neurodegenerative diseases. In short, boron and boron esters are no longer just a “chemical curiosity,” but versatile compounds that support biological balance, promote healing, and shed light on future therapeutic approaches. In this respect, boron is truly a key element in a long journey that extends from chemical foundations to biological applications. References Ali, H. A., Dembitsky, V. M., & Srebnik, M. (2005). Contemporary aspects of boron: chemistry and biological applications. (Studies in Inorganic Chemistry). Anderson, J., Eyring, E., & Whittaker, M. (1964). Temperature Jump rate studies of polyborate formation in Aqueous Boric Acid. The Journal of Physical Chemistry, 68(5), 1128-1132. Barbour, K. E., Helmick, C. G., Theis, K. A., Murphy, L. B., Hootman, J. M., Brady, T. J., & Cheng, Y. J. (2013). Prevalence of doctor-diagnosed arthritis and arthritis-attributable activity limitation—United States, 2010–2012. Morbidity and mortality weekly report, 62(44), 869. Barranco, W. T., Kim, D. H., Stella Jr, S. L., & Eckhert, C. D. (2009). Boric acid inhibits stored Ca 2+ release in DU-145 prostate cancer cells. Cell biology and toxicology, 25, 309-320. https://doi.org/10.1007/s10565-008-9085-7 Bhasker, T. V., Gowda, N., Mondal, S., Krishnamoorthy, P., Pal, D., Mor, A., Bhat, S. K., & Pattanaik, A. (2016). Boron influences immune and antioxidant responses by modulating hepatic superoxide dismutase activity under calcium deficit abiotic stress in Wistar rats. Journal of Trace Elements in Medicine and Biology, 36, 73-79. https://doi.org/10.1016/j.jtemb.2016.04.007 Bolat, M., Köse, D. A., & Akbaba, S. (2025). Boron Salicylate Ester Compounds as Boron Therapeutics. Their Synthesis, Structural Characterizations and Anticancer Effects against MDA-MB-231: Biological trace element research, 203(6), 3031-3044. https://doi.org/10.1007/s12011-024-04394-z Brown, P. H., & Hu, H. (1996). Phloem mobility of boron is species dependent: evidence for phloem mobility in sorbitol-rich species. Annals of Botany, 77(5), 497-506. 32   AN OVERVIEW OF COORDINATION CHEMISTRY WITH METALS . . . https://doi.org/10.1006/anbo.1996.0060 Brown, P. H., & Shelp, B. J. (1997). Boron mobility in plants. Plant and soil, 193(1), 85-101. https://doi.org/10.1023/A:1004211925160 Buttgereit, F., Burmester, G.-R., & Bijlsma, J. W. (2015). Non-surgical management of knee osteoarthritis: where are we now and where do we need to go? RMD open, 1(1), e000027. http://dx.doi.org/10.1136/rmdopen-2014-000027 Bülter, M. B., & Köse, D. A. (2023). Boron citrate esters as boron daily food supplementing agents. Synthesis and structural characterizations. Journal of Trace Elements and Minerals, 5, 100089. https://doi.org/10.1016/j. jtemin.2023.100089 Dell, B., & Huang, L. (1997). Physiological response of plants to low boron. Plant and soil, 193(1), 103-120. https://doi.org/10.1023/A:1004264009230 Dembitsky, V. M., Terent’ev, A. O., Baranin, S. V., & Gursky, M. E. (2025). Aromatic compounds and their fascinating boron complexes as potential quorum sensing molecules. Vietnam Journal of Chemistry. https://doi.org/10.1002/ vjch.70013 Devirian, T. A., & Volpe, S. L. (2003). The physiological effects of dietary boron. Critical Reviews in Food Science and Nutrition, 43(2), 219–231. https:// doi.org/10.1080/10408690390826491 Dibek, E., Babayeva, A., Kürkçü, M. S., Çöl, N. A., & Çöl, B. (2020). Bor içeren bazı biyoaktif bileşikler. Journal of Boron, 5(1), 29-39. https://doi. org/10.30728/boron.604069 Donoiu, I., Militaru, C., Obleagă, O., Hunter, J. M., Neamţu, J., Biţă, A., Scorei, I. R., & Rogoveanu, O. C. (2018). Effects of boron-containing compounds on cardiovascular disease risk factors–a review. Journal of Trace Elements in Medicine and Biology, 50, 47-56. https://doi.org/10.1016/j.jtemb.2018.06.003 Edwards, J. O. (1953). Detection of anionic complexes by pH measurements. I. Polymeric borates. Journal of the American Chemical Society, 75(24), 61516154. Greenwood, N. N., & Earnshaw, A. (2012). Chemistry of the Elements. Elsevier. Hemscheidt, T., Puglisi, M. P., Larsen, L. K., Patterson, G. M., Moore, R. E., Rios, J. L., & Clardy, J. (1994). Structure and biosynthesis of borophycin, a new boeseken complex of boric acid from a marine strain of the blue-green alga Nostoc linckia. The Journal of Organic Chemistry, 59(12), 3467-3471. https:// doi.org/10.1021/jo00091a042 SYNTHESIS, STRUCTURE AND APPLICATION OF AZOCOMPOUND-β-DIKETONE . . .   39 the complexation of 1,3-diphenylpropane-1,3-dione with Ni (II) has led to a diverse array of Ni²⁺ bischelate-based host systems with tunable properties (Hansen, 2023). On a parallel front, uranyl β-diketonates have been extensively studied for their structural diversity and practical applications, particularly in ion extraction and environmental remediation. However, despite the wide array of structurally characterized uranyl complexes, mixed-ligand systems involving 1,3-diphenylpropane-1,3-dione and nitrogen containing ligands such as N,N-diethylnicotinamide remain unexplored. This gap presents a compelling opportunity for future research, especially toward the development of novel uranyl coordination complexes with tailored electronic and supramolecular features for potential use in sensing, separation, or catalysis (Akhmadiev vd., 2024; Nieto vd., 2018). The integration of azocompounds and β-diketones brought to the advancement of novel hybrid particles with tailored properties. For example, the preparation of novel bis(arylsulfanyl diketones) has shown promising antifungal activity, highlighting their potential in agricultural applications (Aromi vd., 2008; Axelrod vd., 2022; Vigato vd., 2009). Additionally, they`re explored as multifunctional compounds in organic synthesis, facilitating the development of various compounds with potential biological activities. These advancements underscore the synergistic potential of azocompounds and β-diketones in the creation of advanced functional materials. This article delves into the structural characteristics, synthesis strategies, and emerging applications of azocompounds and β-diketones, with an emphasis on their synergistic potential in advanced functional materials. 2. MATERIALS AND METHODS 2.1. Synthesis of the reagent The reagent was synthesized according to a known procedure (Eyyubova vd., 2024). An appropriate amount of amine and 1 g of KOH in 20 ml of water were introduced to a three-neck flask with a capacity of 0.5 l, since the reaction mixture should have an alkaline environment. The resulting mixture was stirred with a mechanical stirrer in an ice bath at 0 ℃. NaNO2 solution in 8 ml of pure water is dispenced drop by drop to the cooled solution with continuous stirring. In any case, the temperature is controlled so that it does not exceed 0-3 ℃. The diazotization reaction is carried out for 30 minutes. To remove excess NaNO2 from the solution, add a little urea to the solution. Then a solution of 40   AN OVERVIEW OF COORDINATION CHEMISTRY WITH METALS . . . acetylacetone, sodium acetate and alcohol is added to a 0.5 liter three-neck flask. The resulting mixture is cooled to 0 ℃, stirred with a mechanical stirrer, and diazonium salt is continuously added little by little. The synthesis reaction of an azo compound is carried out within an hour. Finally, the resulting precipitate is passed through filter paper and crystallized again, washing with distilled water. Final product was recrystallized in ethanol several times to get single crystals. For this process, the reagent was fully dissolved by heating and then left at room temperature for three days. After this period, yellow needle-shaped crystals began to form. The single crystals were then filtered and washed with distilled water. 2.2. Equipment The reagent’s structure was analyzed using an XtaLAB Synergy, Dualflex, HyPix, and “BRUKER D8 ADVANCE” X-ray diffractometer (λ = 1.54184 Å, T = 100 K). During the titration, pH value was controlled by glass electrode supplied PHS 25 ionomer. 3. Results and discussions A synthesized azo compound derived from 4-aminoantipyrine and its nickel(II) complexes, both in solution and solid states, have been investigated (Tahirli vd., 2025). Scheme 1. Mechanism of Ni(II)-complex synthesis. The structure and properties were validated using elemental analysis, IR, and NMR spectroscopy. The 1H NMR (ppm) spectra displayed the following signals (Tahirli vd., 2025). A combination of experimental techniques and theoretical modeling was employed to examine the compound’s structural and chemical properties, along with its complexation behavior with Ni(II). SYNTHESIS, STRUCTURE AND APPLICATION OF AZOCOMPOUND-β-DIKETONE . . .   41 Figure 1. Optimization of the C16H18N4O3 monomer by the HF/6-31G method. The calculated geometric, energetic, and electronic properties were thoroughly analyzed. The HOMO-LUMO energy gap was also calculated to evaluate chemical reactivity. Both metal complexes demonstrated significant inhibitory activity against butyrylcholinesterase (BChE) and acetylcholinesterase (AChE). In cancer-fighting assessments, compound E1 reduced cell viability by approximately 40–45% at high concentrations, whereas compound E2 achieved a higher inhibition rate of about 65–70% at equivalent doses. Both compounds showed strong binding affinity to VEGFR1 (Tahirli vd., 2025). A series of new metal complexes were synthesized (Zhen vd., 2015). 42   AN OVERVIEW OF COORDINATION CHEMISTRY WITH METALS . . . Figure 2. Crystal structures of 1–4. For complex 1, N,N-diethylnicotinamide (R) was used as an additional ligand. These complexes (1–4) were characterized using modern analysis methods. The main crystalline parameters are given. Empirical formula of complex 1 is C40H36N2O7U with molecular weight equal to 894.74. The main cell parameters: a (Å)= 10.1236(3), b (Å)= 13.8673(4), c (Å)= 14.4569(4), α(°)=8.774(1), β(°)=70.477(1), γ(°)=82.230(1), V (Å3)= 1782.87(9), Dcalc (g cm-3)= 1.667, (GOF) on F2=1.000, R1 a (1≥ 2σ)= 0.0274, wR2 b (1≥ 2σ)= 0.0557. Empirical formula of complex 2 is C34H34NiO6S2 with molecular weight equal to 661.44, crystal system is monoclinic, space group is P21/c. The main cell parameters: a (Å)= 11.3074(5), b (Å)= 14.5489(7), c (Å)= 9.7457(5), α (°)=90, β (°)=98.0000(10), γ (°)=90, V (Å3)= 1587.66(13), Dcalc (g cm-3)= 1.384, (GOF) on F2=1.000, R1 a (1≥ 2σ)= 0.0289, wR2 b (1≥ 2σ)= 0.0752. Empirical formula of complex 3 is C24H34CoN4O14 with molecular weight equal to 661.48, crystal SYNTHESIS, STRUCTURE AND APPLICATION OF AZOCOMPOUND-β-DIKETONE . . .   43 system is triclinic, space group is P1. The main cell parameters: a (Å)= 7.2585(5), b (Å)= 7.7735(5), c (Å)= 13.9705(9), α (°)=79.6720(10), β (°)=77.0370(10), γ (°)=69.3200(10), V (Å3)= 714.34(8), Dcalc (g cm-3)= 538, (GOF) on F2=1.000, R1 a (1≥ 2σ)= 0.0343, wR2 b (1≥ 2σ)= 0.1025. Empirical formula of complex 4 is C24H26N4O14U with molecular weight equal to 832.52, crystal system is triclinic, space group is P1¯. The main cell parameters: a (Å)= 7.9248(15), b(Å)= 8.1139(16), c(Å)= 12.228(2), α(Å)=88.646(3), β(Å)=87.261(3), γ (Å)=74.721(3), V (Å3)= 1587.66(13), Dcalc (g cm-3)= 1.825, (GOF) on F2=1.077, R1 a (1≥ 2σ)= 0.0441, wR2 b (1≥ 2σ)= 0.1102. Complex 1 features a uranyl ion (UO₂²⁺), while in complex 2, the Ni²⁺ center adopts a distorted octahedral configuration. Complexes 3 and 4 incorporate the HL2 ligand, which contains a hydrazone group stabilized by intramolecular hydrogen bond assisted by resonance, with N···HO distances of 2.5469(18) Å and 2.549(7) Å, correspondingly. The crystal packing in all four complexes is stabilized through a variety of non-covalent interactions, including ormation of hydrogen, CH–π, and π–π bonds, contributing to the formation of supramolecular networks. A new coordination complex of copper (II) with 4,4′-(ethane-1,2-diylbis(azomethine))bis(3-(2-(4-chlorophenyl)vinylidene)flavone) ligands (1) was synthesized and characterized (Bakhmanova vd., 2020). Figure 3. The structure of C24H24CuF2N6O2 (CuL) molecule 44   AN OVERVIEW OF COORDINATION CHEMISTRY WITH METALS . . . X-ray diffraction (XRD) analysis determined that the system is monoclinic, with the space group P2₁/n and the cell parameters: empirical formula C24H24CuF2N6O2, a = 11.1340(9) Å, b = 11.6716(10) Å, c = 18.7797(16) Å, β = 94.792(2)°, cell volume V = 2431.9(4) ų, Z = 4, density Dₓ = 1.713 g/cm³, agreement coefficient R = 0.0695. In this case, the N6 atom deviates significantly from the equatorial plane, which indicates asymmetry in the metal environment. The structural data are registered in the Cambridge Crystallographic Database (CCDC) under number 1907359. An X-ray diffraction new nickel (II) complex featuring an azomethine ligand was carried out. The complex cell parameters are learned. The complex has a spatially developed structure with a pronounced directionality of bonds, which indicates the participation of the molecule in the formation of a stable crystal lattice (Magherramov vd., 2017). Figure 4. Crystalline structure of Ni(II) complex The complex of uranyl ion is synthesized and studied (Solhnejad vd., 2013). Scheme 2. Synthesis of the complex SYNTHESIS, STRUCTURE AND APPLICATION OF AZOCOMPOUND-β-DIKETONE . . .   45 Figure 5. Crystalline structure of C24H31N7O16SU complex An ethanol–water (1:1 v/v) solution containing H₃L was reacted with UO₂(NO₃)₂·6H₂O and bpm under stirring, followed by slow evaporation at room temperature. After five days, red crystals of the uranium complex (1) were obtained in 42% yield based on UO₂(NO₃)₂·6H₂O. Elemental analysis matched the expected composition for C₂₄H₃₁N₇O₁₆SU. The ESI-MS spectrum showed a molecular ion peak at m/z 890.14, consistent with [M–3H₂O + H]⁺. IR spectroscopy revealed characteristic bands corresponding to O–H, N–H, C=O, and C=N vibrations. Single-crystal X-ray diffraction confirmed that compound 1 crystallizes in a triclinic system with two formula units per unit cell. The uranium atom exhibits a distorted pentagonal bipyramidal coordination geometry, with HL²⁻ and bpm ligands occupying the equatorial positions. Intramolecular hydrogen bonding and uranyl coordination promote tautomerization of bpm, resulting in the formation of a zwitterionic complex. Complex of Fe(III) was synthesized (Mahmudov vd., 2013). Various methodswere used to characterize the synthesized product. Then main cell parameters are given: crystal system is triclinic, space group P 1, a=11.0372(19) Å, b =11.2243(19) Å, c=11.2715(17) 46   AN OVERVIEW OF COORDINATION CHEMISTRY WITH METALS . . . Å, α= 67.357(7)°, β =78.198(7)°, γ =89.434(7)°, V = 1257.8(4) Å3, T =100(2) K, ρcalcd = 1.510 M gm−3, μ = 5.067 mm−1. The central Fe(III) ion exhibits a distorted octahedral geometry, coordinated by the trianionic ligand L³⁻ in a tridentate O,N,O binding mode, along with three water molecules occupying the remaining coordination sites. The crystal structure shows that extra water molecules are located within the channels of the 3D supramolecular framework, where they are stabilized through interactions with the carbonyl and sulfonyl groups of the L³⁻ ligand, as well as the coordinated water molecules. Figure 6. Crystalline structure of C14H28ClFeN2O14S complex A nickel(II) complex was synthesized and characterized through X-ray diffraction analysis (Magerramov vd., 2011). Scheme 3. Formation of Ni(C8H4F3O2S)2(C2H6OS)2 complex. SYNTHESIS, STRUCTURE AND APPLICATION OF AZOCOMPOUND-β-DIKETONE . . .   47 The nickel complex crystallizes in a monoclinic system (space group P2₁) and consists of discrete mononuclear units of [Ni(C₈H₄F₃O₂S)₂(C₂H₆OS)₂]. The nickel center exhibits a distorted octahedral geometry, coordinated by four equatorial oxygen atoms from two β-diketonate ligands and two axial oxygen atoms from DMSO molecules. The Ni–O bond lengths indicate slightly longer axial bonds compared to equatorial ones. The crystal packing is stabilized solely through van der Waals interactions, with no significant intermolecular hydrogen bonding or coordination extensions. In the complex [Cu(C₈H₄F₃O₂S)₂(C₁₀H₁₄N₂O)], the Cu²⁺ center exhibits a distorted square-pyramidal geometry. The metal ion lies slightly above the basal plane formed by four oxygen atoms from two β-diketonate ligands and is displaced toward the axial nitrogen atom of the coordinated pyridine ligand. The crystal structure is stabilized by weak intermolecular C—H⋯O and C—H⋯F hydrogen bonds. One of the thienyl rings is disordered over two orientations with an occupancy ratio of approximately 0.69:0.31. The main cell parameters are given (Maharramov vd., 2011). Figure 7. Structure of the Cu(C8H4F3O2S)2(C10H14N2O) complex. 4. APPLICATION The structures may be of interest for further research in the fields of materials science, molecular architecture and coordination chemistry. The iron(III) complex also demonstrated catalytic efficiency and was stabilized through a combination of chelation and intermolecular halogen bonding. The integration of chromophoric and heteroaromatic β-diketone ligands offers prospects for further development of photoactive and electrochemical materials, while the structural insights from crystallographic studies underscore the design principles guiding the formation of stable and functional metal-organic frameworks. All four complexes exhibited catalytic activity. Among these, complex 3 demonstrated the best performance in aqueous conditions. Molecular 48   AN OVERVIEW OF COORDINATION CHEMISTRY WITH METALS . . . dynamics (MD) simulations indicated that E2 forms more stable complexes with hAChE and hBChE compared to E1, positioning E2 as a promising candidate for future anticancer and anticholinesterase drug development. 5. CONCLUSION This study gives information about the synthesis, structure establishment, and functional evaluation of new transition metal complexes, with a primary focus on nickel(II), uranyl, cobalt(II), and iron(III) coordination compounds. Using a combination of experimental techniques—including IR and NMR spectroscopy, elemental analysis, ESI-MS, and single-crystal X-ray diffraction the geometries, electronic properties, and potential reactivities of the synthesized compounds were thoroughly investigated. Among the synthesized complexes, the azo-based Ni(II) complexes (E1 and E2) derived from 4-amino antipyrine exhibited promising biological activity. Additionally, E2 demonstrated higher anticancer efficacy, inhibiting cell viability up to 70%, supporting its potential as a multifunctional therapeutic agent. Several structurally characterized metal complexes (including those of UO₂²⁺, Ni²⁺, Co²⁺, and Fe³⁺) exhibited diverse coordination geometries—ranging from distorted octahedral to pentagonal bipyramidal—and intricate supramolecular architectures involving hydrogen bond, π–π and CH–π formation. Particularly, the uranyl and cobalt complexes displayed efficient catalytic performance in the Henry (nitroaldol) reaction, with complex 3 in aqueous medium yielding high product selectivity and conversion rates (68–91%, syn/anti 77:23–73:27). Synthesized metal complexes have been applied in different fields showing promising results. REFERENCES Akhmadiev, N. L., Galimzyanova, N. F., & Akhmetova, V. R. (2024). Synthesis of New Bis(arylsulfanyl Diketones) as Promising Building Blocks with Fungicidal Activity. Russian Journal of Applied Chemistry, 96, 594–601. doi:10.1134/S1070427223050129. Aromi, G., Gamez, P., & Reedijk, J. (2008). Poly beta-diketones: Prime ligands to generate supramolecular metalloclusters. Coord. Chem. Rev., 252(89), 964-989. https://doi.org/10.1016/j.ccr.2007.07.008.18 Axelrod, S., Shakhnovich, E., & Gomez-Bombarelli, R. (2022). Thermal half-lives of azobenzene derivatives: virtual screening based on intersystem crossing using a machine learning potential. ACS Cent. Sci., 9(2), 166–176. https://doi.org/10.1021/acscentsci.2c00897. BIOLOGICAL APPLICATIONS OF CAFFEINE’S METAL COMPLEXES   55 in the treatment of infections. In contrast, among the synthesized complexes, [CdL(S)(Caf)], in particular, was reported to exhibit significant antibacterial activity against all bacterial strains tested, while the [ZnL(S)(Caf)] compound was effective only against some bacteria. The findings indicate that significant growth inhibition was achieved against both Gram-negative (Escherichia coli, Pseudomonas aeruginosa) and Gram-positive (Staphylococcus aureus) bacteria. Furthermore, the generally higher antibacterial activity of the metal(II) complexes compared to free ligands suggests that metal ions play a decisive role in enhancing the biological activity of the ligands. Tweedy’s chelation theory and Overtone’s membrane permeability principle account for this enhanced antibacterial activity. According to Overtone’s method, the lipid layer in the cell membrane allows fat-soluble substances to permeate more easily into the cell, and therefore, the lipophilic nature of the compounds directly affects antibacterial activity. In chelation, the sharing of the metal cation’s charge with the donor atoms on the ligand and the π-electron delocalization decrease the polarity of the complex, increasing its lipophilicity. Thus, the complexes can more easily cross the bacterial cell membrane and target and destroy the cell more effectively (Bouhdada et al., 2019). Hamdani and colleagues (2016) synthesized complexes with the general formula [M(phen)(caf)2X2] (X=CN-, SCN-, M= Co(II), Fe(II), Mn(II), Cu(II), caf: caffeine; phen: phenanthroline). In this study, it was determined that the caffeine ligand alone did not exhibit any antibacterial activity against E. coli, S. aureus, K. pneumonia, P. putida, and K. oxytoca bacteria. However, it was found that antibacterial activity increased significantly in complexes formed by caffeine with the 1,10-phenanthroline ligand and various metals. Particularly, Cu(II)-containing caffeine complexes ([Cu(phen)(caf)2(SCN)2] and [Cu(phen) (caf)2(CN)2]) showed the highest activity on S. aureus, with inhibition zones reaching 28 mm, and these values are comparable to the activity of gentamicin. Fe(II)- and Co(II)-centered caffeine complexes were shown to have minimal antibacterial action against the studied microorganisms, but Mn(II)-centered caffeine complexes showed moderate activity. In addition, the resistance of Pseudomonas putida to all caffeinated complexes suggests that the natural outer membrane barrier of this bacterium limits complex permeation. These results suggest that although caffeine alone does not have antibacterial activity, its biological activity can be significantly enhanced by coordination with appropriate metal ions and auxiliary ligands (H. E. L. Hamdani et al., 2016). Inhibition zones are given in Figure 2. 56   AN OVERVIEW OF COORDINATION CHEMISTRY WITH METALS . . . Figure 2. Zone diameters indicating antibacterial activity (H. E. L. Hamdani et al., 2016). Altun and Şuözer (2019) evaluates the antibacterial properties of free caffeine and gold(III)-caffeine complex (Figure 3) against various bacterial and fungal strains such as E. coli, Salmonella typhimirium, Staphylococcus aureus, Listeria monocytogenes, Bacillus cereus, and Candida albicans. Free caffeine has slight antibacterial action against S. typhimurium, S. aureus, L. monocytogenes, B. cereus, and C. albicans at 200 μg/mL. The gold(III) compound was efficient against S. aureus and L. monocytogenes at concentrations of 50 and 100 μg/ mL, and moderately active against C. albicans at 200 μg/mL. As a result, the obtained complex has higher antibacterial activity than free caffeine. The increased activity of the complex can be due to the change in the complex’s structure and the polarity of the metal, which can be explained by the partial sharing of the positive charge of the gold(III) cation with the donor groups on CA (Altun & Şuözer, 2019). Figure 3. Gold(III) caffeine complex (Altun & Şuözer, 2019). The antibacterial activities of the Cu(II)–2,2’-bipyridine–caffeine– thiocyanate complex (Figure 4) and its ligands, caffeine and 2,2’-bipyridine, BIOLOGICAL APPLICATIONS OF CAFFEINE’S METAL COMPLEXES   57 were evaluated on the pathogenic bacteria E. coli, B. cereus, S. aureus, B. subtilis, S. typhimurium, and L. monocytogenes. It was determined that the complex showed inhibitory activity against all tested species. According to MIC results, E. coli, Bacillus cereus, and Staphylococcus aureus species were inhibited at a concentration of 25 µg/mL, while inhibition for B. subtilis, S. typhimurium, and L. monocytogenes species was determined at a concentration of 50 µg/mL. The complex exhibited generally higher antibacterial activity compared to the free ligands. The effect observed especially on B. cereus is remarkable; The MIC value for this species was 100 µg/mL for caffeine and 200 µg/mL for bipyridine, while it decreased to 25 µg/mL for the complex. Coordination of the Cu(II) ion with ligands may increase the lipophilicity of the complex, facilitating its passage through the bacterial cell membrane and thus enhancing its biological activity (Kisku et al., 2022). Figure 4. Cu(II)–2,2’-bipyridine–caffeine–thiocyanate complex (Kisku et al., 2022). The caffeine complex of copper(II) trimethylacetate was prepared by Yambulatov and colleagues, and its structure was characterized by various methods. The structure is shown in Figure 5. The antibacterial activity of the complex was also evaluated. The tested copper complex (I) exhibited significant antibacterial activity against M. smegmatis. The MIC value 58   AN OVERVIEW OF COORDINATION CHEMISTRY WITH METALS . . . of the complex was 250 μg/disc, while the MIC value of free caffeine was 2000 μg/disc. This indicates that copper complexation increased antibacterial activity approximately eightfold. Furthermore, a 6.5 mm inhibition zone was observed after 24 hours, while the effect disappeared after 120 hours (0 mm), suggesting that the complex lost its activity over time, i.e., exhibited a transient antibacterial effect. Overall, these results demonstrate that the biological activity is significantly enhanced by the complexation of copper ions with caffeine (Yambulatov et al., 2020). Figure 5. Copper(II) trimethylacetate caffeine complex (Yambulatov et al., 2020) In antibacterial tests performed by Borówka et al. (2024), the Ag-IBUCAF complex showed significant antimicrobial activity against a wide range of bacteria. MIC values were generally found to be in the range of 5–20 µg/mL for all Gram-positive and Gram-negative strains tested, and it was determined that Ag-IBU-CAF showed stronger inhibition compared to Ag-IBU complex, especially against E. coli, E. faecalis, and S. aureus strains. Kirby–Bauer diffusion test results also supported these findings; inhibition zones of the Ag-IBU-CAF complex were reported to be wider than those of Ag-IBU in most cases (e.g., 17 mm and 9 mm for Ag-IBU for E. coli). This suggests that the presence of CAF may enhance the antibacterial activity of the Ag complex by enhancing cell wall interaction, membrane permeability, or ion release dynamics. In contrast, the Cu-IBU-CAF complex did not exhibit any inhibitory effect on any bacterial species at concentrations tested up to 160 µg/mL. Therefore, in BIOLOGICAL APPLICATIONS OF CAFFEINE’S METAL COMPLEXES   59 terms of antibacterial activity, the presence of CAF appears to have protectively reduced toxicity in the copper complex, while enhancing antibacterial activity in the silver complex. Furthermore, the lower MIC values of Ag-IBU-CAF than the IC₅₀ values of normal fibroblasts indicate that this complex may have a relatively favorable therapeutic window and represents a significant advantage for its future evaluation as an antibacterial agent (Borówka et al., 2024). Schiff base complexes of Cu(II), Ni(II), Cd(II), and Zn(II) containing caffeine with the formula [M(L)2(caf)2] (Figure 6) were synthesized by Bouhdada et al. (2023). In the study, the antimicrobial effects of the ligands (salicylidene-aniline and caffeine) and the synthesized metal(II) complexes against eight bacteria (S. aureus, S. pneumoniae, E. coli, Bacillus spp., S. saprophyticus, A. boumannii, K. pneumoniae, and P. putida) and four fungal strains (A. niger, Aspergillus spp., A. nidulans, and C. albicans) were evaluated by disk diffusion method (Figure 7). The results showed that the salicylidene-aniline and caffeine ligands did not exhibit significant biological activity against all bacterial and fungal species. The Cu(II) compound exhibited only weak antibacterial effectagainst Staphylococcus saprophyticus and was inactive against other bacteria, while it exhibited good antifungal activity against Aspergillus spp. and Aspergillus nidulans. The Cd(II) complex exhibited high activity against both bacteria and fungi, the Zn(II) complex had moderate activity, and the Ni(II) complex was limited (especially against Streptococcus pneumoniae and Bacillus spp.). In general, the stronger antimicrobial action of the metal(II) complexes compared to starting ligands was attributed to the chelation of the metal cations with the ligands, increasing their lipophilicity (Bouhdada et al., 2023). Figure 6. Predicted structure of [M(L)2(caf)2] complexes (Bouhdada et al., 2023). 60   AN OVERVIEW OF COORDINATION CHEMISTRY WITH METALS . . . Figure 7. Histogram of inhibition zones of [M(L)2(caf)2] complexes against various bacterial and fungal species. (S1 : Staphylococcus aureus, S2 : Streptococcus pneumoniae, S3 : E. coli, S4 : Bacillus spp, S5 : Staphylococcus saprophyticus, S6 : Acinetobacter Bounannue, S7 : Klebsiella pneumonia, S8 : Pseudomonas putida, and M1 : Aspergillus niger, M2 : Aspergillus spp, M3 : Aspergillus nidulans, and M4 : Candida albicans) (Bouhdada et al., 2023). Di-cationic compounds with the formula [M(C8H10N4O2)4](PF6)2, (M= Fe(II), Co(II), Mn(II), Cd(II), Zn(II), Cu(II), Ni(II)) (Figure 8) were synthesized BIOLOGICAL APPLICATIONS OF CAFFEINE’S METAL COMPLEXES   61 by Hamdani and Amane (2019). In addition, the synthesized comppounds were tested for in vitro antibacterial activities against Escherichia coli, Staphylococcus aureus, Klebsiella pneumonia, Klebsiella oxytoca, and Pseudomonas putida using the diffusion method (H. El. Hamdani & Amane, 2019) Figure 8. Proposed structure of [M(C8H10N4O2)4](PF6)2 complexes (H. El. Hamdani & Amane, 2019). The histogram of the inhibition zones of [M(C8H10N4O2)4](PF6)2 complexes against various bacterial species is given in Figure 9. According to the results obtained, the starting compounds, caffeine and KPF6, did not exhibit any inhibitory property on bacterial growth and were therefore reported to be microbiologically inactive. The [Cd(caf)4](PF6)2 complex was reported to show inhibition against Staphylococcus aureus, Klebsiella pneumonia, Klebsiella oxytoca and Pseudomonas putida, the [Ni(caf)4] (PF6)2 complex exhibited activity only against Staphylococcus aureus, and [M(caf)4](PF6)2, with M=Mn(II), Cu(II), Co(II) and Fe(II), had negligible antibacterial activity on all species. In general, these metal (II) complexes containing caffeine have been reported to cause greater antibacterial effects than starting ligands due to chelation, which increases the lipophilic property 62   AN OVERVIEW OF COORDINATION CHEMISTRY WITH METALS . . . and facilitates passage through the lipid walls of the bacterial membrane (H. El. Hamdani & Amane, 2019). Figure 9. Histogram of inhibition zones of [M(C8H10N4O2)4](PF6)2 complexes against various bacterial species (H. El. Hamdani & Amane, 2019). Al-Saif et al. (2020) synthesized palladium-caffeine complexes with the general formula [Pd(nta)(caf)(Cl)2] (1), [Pd(pia)(caf)(Cl)] (2), and [Pd(ina)(caf) (Cl)] (3) (Figure 10). The antibacterial activities of the synthesized palladium(II) complex were tested on four different bacterial species: K. pneumoniae, E. coli, S. aureus and S. epidermidis by the disk diffusion method. However, none of the complexes exhibited significant antibacterial action against the tested microorganisms. This can be explained by the inability of the metal center or ligand structure to effectively interact with the target sites on the bacterial cell wall or membrane. In particular, the coordination of caffeine and similar nitrogenous ligands in the complexes with the metal may have left some of the molecule’s active sites unoccupied, reducing its binding capacity with bacterial cells. Consequently, the antibacterial activity of these complexes was found to be limited. (Al-Saif et al., 2020) BIOLOGICAL APPLICATIONS OF CAFFEINE’S METAL COMPLEXES   63 Figure 10. Proposed structure of the complexes [Pd(nta)(caf)(Cl)2] (1), [Pd(pia) (caf)(Cl)] (2), and [Pd(ina)(caf)(Cl)] (3). (Al-Saif et al., 2020) 1.2. Anticarcinogenic and Cytotoxic Effects of Caffeine’s Metal Complexes In the study conducted by Altun and Şuözer (2019), the cytotoxic and anticarcinogenic effects of caffeine and Au(III)-caffeine complex were evaluated using the MTT assay on MEF (healthy human fibroblast) cells and Du145 (prostate), HeLa (cervix), HT29 (colon), and MCF7 (breast) cancer cells. As a result of the study, IC₅₀ values, corresponding to 50% suppression of cell proliferation, were calculated from the dose-response curves and were determined as >1000 µM, 58.87 µM, 164 µM, 252 µM, and 328 µM for MEF, Du145, HeLa, HT29, and MCF7 cells, respectively. Compared to similar studies reported in the literature, the prepared gold(III)-caffeine complex was observed to exhibit lower levels of activity against HeLa, HT29, and MCF7 cell lines. When the overall effect profile was examined, it was determined that the complex application significantly reduced cell viability, particularly in Du145 and HeLa cells; however, it induced moderate cytotoxicity compared to the control in HT29 and MCF7 cells after 24 hours of incubation. In cytotoxicity assessments, no cell death was observed in healthy MEF cells at any concentration, indicating the complex’s selective effect potential. In contrast, the gold(III)-caffeine complex caused significant cell death in all cancer cell lines examined at concentrations of 400 and 800 µM. In conclusion, the study demonstrates that caffeine and the gold(III)- caffeine complex can exhibit anticarcinogenic activity on cancer cells at certain concentrations without harming healthy cells, supporting the potential 64   AN OVERVIEW OF COORDINATION CHEMISTRY WITH METALS . . . of these complexes as potential candidates for targeted anticancer drug design (Altun & Şuözer, 2019). Using MTT and Trypan blue techniques, Kisku et al. (2022) assessed the anticarcinogenic potential of Cu(II)–2,2’-bipyridine–caffeine–thiocyanate complex (Figure 3) on colorectal adenocarcinoma (Caco-2) and breast cancer (MCF-7) cell lines. MTT results showed that After 24 hours of treatment, the complex (Cu(II)–2,2’-bipyridine–caffeine–thiocyanate) significantly reduced the viability of MCF-7 cells. It’s interesting to note that Complex exhibited a larger death percentage than caffeine alone in both MCF-7 and their drugresistant cousins, according to Trypan blue assay data. It showed that 40% of the cells died after 6 h of treatment with Complex (50 μg/ml). In contrast, caffeine was able to cause only 24% cell death during treatment. Complex caused 25% cell death after 6 hours of treatment, while caffeine caused 14%. Significantly better results were obtained when the treatment duration reached 12 hours. Continuing the treatment for 24 hours or longer, particularly with the complex, has been shown to cause significant cell death. (Kisku et al., 2022). The cytotoxic effects of [Zn(caf)(H2O)X2] (X=Cl, Br, I) and [Cu(caf)2Br2] complexes were evaluated by MTT assay using postnatal human dental pulp stem cells (DPSC) and breast cancer (MCF-7) cells. The highest cytotoxic effect was determined at concentrations of 5x10–5 and 1x10–4 mol L–1 in the MCF-7 cell line. At these concentrations, the complexes were found to be more cytotoxic than their starting components. At a concentration of 1x10–4 mol L–1, the [Cu(caf)2Br2] complex was more cytotoxic to the MCF-7 cell line than the [Zn(caf)(H2O)X2] (X = Cl, Br, I) complexes. This was explained by the [Cu(caf)2Br2] complex’s planar structure, which makes it easier for it to integrate into DNA and damages it. Because of the nearly equal distance between the ligands in the complexes’ cis positions, which is comparable to the distance between neighboring base pairs along the DNA helix, it was observed that the cytotoxic effects of zinc and copper bromide complexes were extremely similar at the concentrations examined (Rukk et al., 2020). Borówka and colleagues (2024) reported that the toxicity levels of Ag(I), Cu(II) complexes containing ibuprofen (IBU), and caffeine (CAF) varied significantly depending on the metal type. They reported that silver-containing complexes exhibited significantly stronger cytotoxic effects in healthy fibroblasts compared to copper-based complexes. The IC₅₀ value of the Ag-IBU complex was 25.10 µg/mL, while that of the Ag-IBU-CAF complex containing CAF was BIOLOGICAL APPLICATIONS OF CAFFEINE’S METAL COMPLEXES   71 areas will be crucial for advancing the safe and effective utilization of caffeine– metal complexes in biomedical and pharmaceutical contexts. 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A., Lutsenko, I. A., Kiskin, M. A., Shmelev, M. A., Bekker, O. B., Efimov, N. N., Ugolkova, E. A., Minin, V. V., Sidorov, A. A., & Eremenko, I. L. (2020). Copper(II) Trimethylacetate Complex with Caffeine: Synthesis, Structure, and Biological Activity. Russian Journal of Coordination Chemistry, 46(11), 772-778. https://doi.org/10.1134/ S1070328420110093 75 CHAPTER V COORDINATION CHEMISTRY IN THE REPUBLIC OF GEORGIA Maia TSINTSADZE (Prof. Dr.) Georgian Technical University, Tbilisi, Republic of Georgia. E-mail: [email protected] ORCID: 00009-0004-3345-9667 1. INTRODUCTION It has been more than 100 years since Alfred Werner created the theory of coordination chemistry. Since then, significant research has been carried out in the field of coordination chemistry in Germany (P. Pfeiffer), Great Britain (J. Chat), the USA (J. Baylar), Sweden (L. Silen), and many others. After World War II, along with the increase in the production of rare metals, interest in the chemistry of coordination compounds has greatly increased worldwide. It is worth noting the invaluable contribution of scientists from the former Soviet countries to the development of this field. The history of the development of coordination compound chemistry in Georgia is interesting and unique. In the 1930s, along with the formation of the direction of chemistry by L.A. Pisatzhevsky (Georgian Polytechnic Institute, Acad. I.V. Tananaev, and Prof. O.E. Zviagentsev), coordination compound chemistry gradually gained a foothold. At the head of the school stood Academicians P. Gogorishvili, G. Tsintsadze, A. Tsivadze, Professors A. Shvelashvili, R. Machkhoshvili, and others, who were joined by a whole number of scientists and who are now continuing their work in this field in scientific centers in different countries of the world. Coordination compounds, or higher-order compounds, as Berzelius (1779– 1848) called them, are complex multicomponent chemical compounds. Modern coordination chemistry addresses challenges across inorganic, organic, analytical, supramolecular and organoelement chemistry. Its foundational principles support the design of supramolecular structures and the 76   AN OVERVIEW OF COORDINATION CHEMISTRY WITH METALS . . . synthesis of multifunctional materials, which are increasingly in demand and widely applied in contemporary chemical and biological technologies, industrial processes, pharmaceutical production, and beyond. Among the fields of coordination chemistry, bioinorganic (biocoordination) chemistry is rapidly developing, which studies inorganic substances contained in living organisms and their functioning in the body. This allows us to identify and correctly manage the numerous biochemical processes that occur in the bodies of plants, animals, and humans. In this regard, bioinorganic chemistry is closely related to ecology, agriculture, pharmacology, pharmacotherapy, toxicology, hygiene, virology, and other fields of medicine. It has been shown that the primary cause of the harmful side effects of drug ligands is their ability to form endogenous complexes within the body. Many biologically active substances act on the body as complex-forming agents. Most of them exhibit pharmacological activity only when interacting with metal ions. Over the past few decades, complexation has been explored and applied as an effective method for removing toxic metals and radionuclides from the body. Therefore, it is advisable to increase the pharmacological effect of biologically active and medicinal substances and minimize side effects and toxicity by their functional modification. The latter involves the synthesis of new organic molecules – ligands and then obtaining metal coordination compounds on their basis and a wide study of their properties. The bioactive properties of metal coordination compounds are higher than the bioactive properties of free (uncoordinated) ligands and significantly reduce their toxicity, expand the spectrum of pharmacological action. 1.1. Goal In this direction, for many years now, a cycle of research has been underway in the Chemistry Department of the Faculty of Chemical Technology and Metallurgy of GTU and the Physical Chemistry Laboratory of the R. Agladze Institute of Inorganic and Electrochemistry of I. Javakhishvili Tbilisi State University, under my direct leadership, by a group of employees, in the following main directions: · Preparative coordination chemistry - search and development of sophisticated methods for the targeted synthesis of new coordination compounds; · Theoretical structural coordination chemistry; COORDINATION CHEMISTRY IN THE REPUBLIC OF GEORGIA   77 · Research of synthesized coordination compounds using complex research with modern chemical, physicochemical, and physical methods. That is: · Synthesis and research of compounds obtained as a result of the interaction of monoligand mononuclear hydrazone complexes and amines; as well as synthesis and research of compounds obtained as a result of the interaction of mononuclear amino complexes and hydrazones; development of a new technology for the synthesis of coordination compounds of amides, amines, hydrazides, bicyclic bisureas, as well as mixed-ligand and mixedmetal: hydrazino-amino, hydrazino-amido, amido-amino complexes with trace elements and alkali metals and their isolation in the solid state; · Chemical research of synthesized compounds; · Mathematical modeling of ligands, as well as complex compounds using modern computer programs, identification of coordination capabilities of ligands, and planning of targeted synthesis, selection of optimal conditions, etc.; · Isolation of representatives of individual classes of the obtained coordination compounds in a single-crystal state and their study by the X-ray structural method, scanning electron microscopic (SEM) method; · Thermal analysis of the obtained compounds; · Study of the obtained compounds by the spectroscopic method, determination of spectral criteria for identifying their structure; · Tracing of structural regularities using spectral criteria, taking into account the type and nature of metals and ligands, the composition of the compounds, and the interdependence of other factors; · Investigation of the bioactivity (antituberculosis, antibacterial, and other biological properties) of the obtained compounds and determination of the regularities of the relationship between their structure and bioactive properties; · Modeling of biochemical processes and prediction of drugs for various purposes based on the traced regularities. The relevance of these tasks and problems was determined by the special role of amido and amino complexes in the development of theoretical structural coordination chemistry, in explaining and modeling vital processes at the molecular level, and their prospects in medicine, which have a potential therapeutic effect - they are used as psychotropic, antitumor, tuberculosis, antiinflammatory drugs, antidepressants, and analgesics. 78   AN OVERVIEW OF COORDINATION CHEMISTRY WITH METALS . . . 1.2. Research A range of new hydrazones has been synthesized in this area, including benzaldehyde dibenzoylhydrazone, isonicotinoyl-, nicotinoyl-, and picolinoylhydrazones, para-dimethylaminobenzaldehydedibenzoyl hydrazone, acetone isonicotinoyl hydrazone, meta-bromobenzoyl hydrazone, para-dimethylamino benzaldehyde hydrazone, meta-nitrobenzoyl hydrazone, and others. Their chemical composition, color, solubility in various solvents, and melting points have been characterized. On the basis of synthesized organic molecules, technological methods for the synthesis of metal hydrazonocomplexes using aqueous solutions, alcohol-aqueous solutions, and alcohol solutions have been developed for the first time, and many coordination compounds unknown in the literature have been obtained. Their composition has been established; their chemical composition, color, and solubility in various organic solvents have been studied, and melting temperatures have been determined. The mass change and the rate of mass change were also determined using dynamic thermogravimetric analysis. The role of molecular modeling in chemistry is significant, despite the obvious priority of experimental research in this area of natural science. The most important theoretical results are those that are impossible to obtain by experimental means, extremely difficult, or very expensive. A quantum-chemical semi-empirical AM1, MP3, MNDO-d, DFT, and density functional theory study of both ligands and complex compounds has been conducted for each molecule; the energetic, electronic, and structural characteristics of each molecule have been determined both in gas and in various organic solvents. In order to pre-plan and select optimal conditions for the synthesis of complex compounds, it has been established that, in the simplest case, these ligands have two donor-active centers - the nitrogen atom of the azomethine group and the oxygen atom of the carbonyl group - through which a coordination bond can be formed. Bidentate, tridentate, polydentate, and bridge bonds can also be formed. Coordination of the hydrazone molecule with a metal complexing agent is possible in both the ketonic and enolic forms, forming stable five-membered metallocycles. This makes them interesting for the preparation of homoand heterometallic complex compounds. The energy-dispersive X-ray spectra (EDX) and corresponding scanning electron microscope (SEM) images of the synthesized complex compounds have been analyzed. Using them, the qualitative and quantitative composition of COORDINATION CHEMISTRY IN THE REPUBLIC OF GEORGIA   79 various elements has been calculated - for example, in the presented samples of various metals, as well as carbon, nitrogen, oxygen, various halogens, etc. The synthesized coordination compounds were analyzed using thermogravimetric methods. Temperature changes (T), mass loss (TG), and dynamic differential curves - differential thermal analysis (DTA) and derivative thermogravimetry (DTG) - were recorded. Thermal effects and mass loss occurring during heating of the samples up to 600 °C were also observed. The mentioned hydrazone molecules and the synthesized coordination compounds have been studied by the method of infrared absorption spectroscopy, on the basis of which the coordination rule of the organic ligand, water molecules, and acid ligands in the synthesized compounds has been established. The results of the absorption spectra are in full agreement with the results of quantumchemical calculations. The proposed molecular structures of the synthesized complex compounds are presented. The biological properties of the synthesized coordination compounds have been investigated, with particular focus on their physiological activity against pathogenic microorganisms. The study showed that the majority of the studied compounds are biologically active and have an inhibitory (suppressing) effect on the growth and development of microorganisms (test cultures). The selective biocidal properties of some of them presumably depend on the change in the structure of the test substance and the change in the active functional groups or metals in them. Physiological activity should be due not only to the presence of microelements (bioliths) in them but also to the nature and structure of ligands and substituted groups. The effects of the synthesized coordination compounds on the growth and development of test chicks have also been examined. It has been established that the coordination compounds - biostimulants developed by us in various ratios - represent a chemical additive to the premix of poultry feed. This is accompanied by an increase in live weight and a reduction in feed consumption. In addition, physiological and biochemical indicators are within the normal range. This cycle of work has established a number of important regularities: the influence of the nature of the organic radical of hydrazoligands on the composition, properties, and structure of coordination compounds; the influence of the nature of the complex-forming metal and acid groups. The cycle of conducted studies has created the foundations of the chemistry of metal hydrazide complexes. Over the past 30 years, the synthesis of mixed-ligand coordination compounds has been actively underway. Such studies are particularly interesting 80   AN OVERVIEW OF COORDINATION CHEMISTRY WITH METALS . . . in that two biologically active molecules are selected as ligands, which potentiates the special pharmacological effect of the synthesized compounds; the joint inclusion of two different active molecules in the complex gives the compounds unique structural and functional properties, which may become the basis of their pharmacological activity. There has been growing interest in the study of double and bimetallic complex compounds, particularly regarding their structures and properties. This interest is driven by the potential for the existence of coordination isomers and coordination polymers. Studies of this type of compound are conducted in two main directions: some scientists study the structure and magnetic properties of the compounds, and some research is conducted to develop a synthesis methodology. Several works have been performed in this direction; synthesized mono-, bi-, and double (mixed metal) mixed-ligand complex solutions. Hydrazides, dihydrazides, and their derivatives are promising nitrogencontaining polydentate ligands that coordinate even in the neutral form. Hydrazides and dihydrazides of alkyl and aromatic carboxylic acids contain one or more CONHNH2 or CONHNH groups, with the O=C–NHfragment exhibiting notable biological and physiological activity. The hydrazide moiety possesses potential therapeutic properties and is utilized in the development of psychotropic, anticancer, antitubercular, anti-inflammatory, antidepressant, and analgesic agents. A number of mixed-ligand coordination compounds of transition metals with hydrazides such as 1-[2-(benzylcarbamoyl)-ethyl]-2-isonicotinoyl hydrazide (nialamide), meta-bromobenzoyl hydrazide, para-nitrophenyl hydrazine, caproic acid hydrazide, azelaic acid dihydrazide, 2-amino-6-methylpyridine, malonic acid dihydrazide, etc., have been synthesized. Quantum-chemical studies of organic ligand molecules have been carried out to determine the conformation, structure, and electronic characteristics of polyfunctional ligands, as well as to study complex formation with metals. Double and bimetallic (cationic-anionic) coordination compounds with metals have been synthesized with isonicotinamide, picolinamide, N,N-dimethylformamide, 4.4′-dipyridine, acidoligands - thiocyanate ion, nitroprusside ion, hexacyanoferrate (II, III) ions. The ability of the synthesized compounds to form complexes with organic molecules in various solvents has been investigated, and their donor properties have been identified. The compounds were characterized using a range of physicochemical techniques, including IR spectroscopy and thermogravimetric analysis. 87 CHAPTER VI STRUCTURAL AND ELECTRONIC PROPERTIES OF AROMATIC N-ACYLHYDRAZONES AND THEIR COMPLEXES Güventürk UĞURLU Department of Physics, Kafkas University, 36100, Kars, Türkiye E-mail: [email protected], ORCID: 0000-0003-4171-7879 1. Introduction The some chemical and physical properties of hydrazones, hydrazinehydrazines containing the -NH-N=CHformation and hydrazidehydrazines carrying the -CONH-N=CHmoiety, were investigated. Acylhydrazones, characterized by the –CONH–N=CH– functional moiety, represent a critically important class of Schiff bases. These compounds are synthesized via the condensation of acylhydrazides with aldehydes or ketones, resulting in a molecular framework that integrates an amide bond (–CONH–) with an imine group (–CH=N–). This unique architecture confers significant chemical versatility and a wide array of applications. The delocalized π-electron system across the hydrazone bridge, coupled with the capacity to exhibit tautomerism, underpins their diverse reactivity and ability to interact with biological targets and metal ions. The pharmacological relevance of hydrazones is particularly notable. They serve as key scaffolds in medicinal chemistry due to their structural flexibility, which can be tailored to enhance bioavailability, metabolic stability, and target specificity. Their biological profile encompasses antimicrobial, antiinflammatory, antitubercular, and anticancer activities, among others (Popiołek, 2017; Wahbeh & Milkowski, 2019). The presence of the imine nitrogen and carbonyl oxygen provides multiple coordination sites, enabling the formation of stable chelates with transition metals. Beyond biomedicine, hydrazones and their metal complexes find utility in analytical chemistry as sensors (Chen et 88   AN OVERVIEW OF COORDINATION CHEMISTRY WITH METALS . . . al., 2019), in industrial chemistry as corrosion inhibitors (Singh et al., 2018), in catalysis (Tsai et al., 2019) and and especially pharmacology (Ebrahimipour et al., 2015; Mathew et al., 2011). The application of these compounds in the pharmaceutical field is highlighted because these ligands exhibit a wide range of biological activities in the treatment of tuberculosis (Clark et al., 1952; Patole et al., 2003), intestinal antiseptics (Begovic et al., 2016), antifungal agents (Secci et al., 2012) or antidepressants (Hojati, 2019) and others. The use of hydrazones in medicine may potentially exhibit properties such as anti-microbial (Popiołek, 2017), anti-inflammatory (Wahbeh & Milkowski, 2019), antihypertensive (Sikder et al., 1993), anti-infectious (Sharma et al., 2020), anti-malarial (Kumar et al., 2017), and anti-leishmanial (Ali et al., 2012). The electronic properties of these molecules, dictated by substituents on the aromatic rings, also make them promising candidates for materials science applications, including nonlinear optics (NLO) and molecular electronics.This review consolidates recent advances in the study of hydrazone ligands and their metal complexes, with a focus on spectroscopic characterization (FT-IR, NMR, UV-Vis), structural insights from X-ray crystallography, and computational explorations of their electronic properties. We examine molecular electrostatic potential (MEP) maps, frontier molecular orbitals (HOMO-LUMO), and associated quantum chemical descriptors to establish a coherent structure-property relationship. The compounds studied are listed below. N-acylhydrazones (HL) (Polo-Cerón et al., 2021). Benzoic acid (2-hydroxy-3-methoxy-benzylidene)-hydrazide (HL1). Benzoic acid (2,3-dihydroxy-benzylidene)-hydrazide (HL2). Benzoic acid (2-hydroxy-benzylidene)-hydrazide (HL3). Benzoic acid (5-bromo-2-hydroxy-benzylidene)-hydrazide (HL4). Benzoic acid pyridine-2-yl methylene-hydrazide (HL5) (Pouralimardan et al., 2007). Copper Complex of Salicylaldehyde Benzoyl Hydrazone (HL6) (Shrestha & Maharjan, 2012). Salicylaldehyde benzoyl hydrazone (HL7) (Cordier et al., 2004) (Cordier et al., 2004). 2-hydrxyibenzohydrazide (HL8). N’-benzylidene-2-hydroxybenzohydra zide (HL9). N’-(2-chlorobenzylidene)-2-hydroxy benzohydrazide (HL10). N’-(2,4-dichlorobenzylidene)-2-hydroxy benzohydrazide (HL11). N’-(4-hydroxy-3-methoxybenzylidene)- 2-hydroxybenzohydrazide (HL12). STRUCTURAL AND ELECTRONIC PROPERTIES OF AROMATIC . . .   89 N’-(3,4-dimethoxybenzylidene)-2hydroxybenzohydrazide (HL13). N’-(3,4-methylendioxybenzylidene)-2hydroxybenzohydrazide (HL14). N’-(4-methybenzylidene)-2-hydroxy benzohydrazide (HL15). N’-(4-methoxybenzylidene)-2-hydroxy benzohydrazide (HL16) (Budiati et al., 2012). (1Z,2Z)-1,2-bis (3-Chlorophenyl Hydrazino) Benzil (HL17) (Tabbiche et al., 2022). [(N’-benzylidene-4-oxo-2-thioxo-1,2,3,4tetrahydropyrimidine5-carbohydrazide (HL18)(BTC). N’ (4-chlorobenzylidene)-4-oxo-2-thioxo-1,2,3,4tetrahydropyrimidine-5carbohydrazide (HL19) (CBTC). N’-(4-methoxybenzylidene)-4-oxo-2-thioxo-1,2,3,4-tetrahydropyrimidine-5carbohydrazide (HL20)(MOBTC). N’-(4-bromobenzylidene)-4-oxo-2-thioxo-1,2,3,4tetrahydropyrimidine-5carbohydrazide (HL21)(BBTC). N’-[(furan-2-yl)methylene]-4-oxo-2-thioxo-1,2,3,4tetrahydropyrimidine-5carbohydrazide (HL22). N’- (4-methylbenzylidene)-4-oxo-2-thioxo-1,2,3,4tetrahydropyrimidine-5carbohydrazide (HL23) (MBTC) (Sakr et al., 2022). 4-[(Pyridine 3-carbonyl)-hydrazonomethyl]-benzoic acid(HL24) (Özbek et al., 2020). N’-(pyridine-4-ylmethylene)nicotic acid hydrazide (HL25) N’-(pyridine-3-ylmethylene)nicotic acid hydrazide (HL26) (Özbek et al., 2021),. N′-[(E)-3-pyridinylmethylene] nicotinohydrazide trihydrate (HL27) (Uğurlu, 2025). (E)-N’-benzylidenebenzohydrazide (HL28). (E)-N’-(3,4-methoxybenzylidene)benzohydrazide (HL29). (E)-N’-(4-chlorobenzylidene)benzohydrazide (HL30). (E)-N’-(4-(dimethylamino)benzylidene)benzohydrazide (HL31). (E)-4-methoxy-N’-(4-methylbenzylidene) benzohydrazide (HL32). 2. Spectroscopic Characterization The structural elucidation of synthesized hydrazone derivatives routinely employs techniques such as X-ray crystallography, NMR, FT-IR, and UV-Vis spectroscopy. The acylhydrazone motif presents several characteristic vibrational bands, most notably Amide I, II, and III, alongside ν(N–N) and ν(C=N) stretches. The Amide I band, primarily arising from C=O stretching vibrations (70-85%), is typically observed between 1600 and 1700 cm⁻¹. The Amide II band, found between 1550 and 1600 cm⁻¹, results from a combination of N–H bending (4060%) and C–N stretching (18-40%). The Amide III region is more complex, 90   AN OVERVIEW OF COORDINATION CHEMISTRY WITH METALS . . . originating from mixed C–N stretching and N–H deformation modes, and usually appears around 1230-1240 cm⁻¹.A survey of the literature reveals the characteristic vibrational frequencies for a series of N-acylhydrazone ligands (HL1-HL16) and a copper complex (Polo-Cerón et al., 2021; Pouralimardan et al., 2007; Shrestha & Maharjan, 2012; Budiati et al., 2012). As summarized in Table 1and 2, the C=O stretching vibration (Amide I) occurs between 1557 and 1730 cm⁻¹. The N–H stretch is observed in the 3180.6–3395.7 cm⁻¹ range, while the C=N stretch appears between 1600 and 1665 cm⁻¹. Among the surveyed compounds, the theoretical (DFT/B3LYP) structure of HL exhibits the highest N–H stretching frequency, whereas its experimental counterpart shows the lowest. The ligand HL5 displays the highest C=N stretching frequency, and the copper complex Cu-HL6 shows the lowest, indicative of coordination-induced electron density shifts. Table 1. Characteristic Vibration Bands of Selected Hydrazone Ligands Compound N-H C=N Ref. HL Exper. 3180.6 1622.1 17 HL B3LYP 3395.7 1626.1 17 HL1 Exper. 3378 1650 18 HL2 Exper. 3231 1649 18 HL3 Exper. 3262 1673 18 HL4 Exper. 3386 1659 18 HL5 Exper. 3393 1665 18 HL6 Exper. 3280 1630 19 CuHL6 Exper. -- 1600 19 HL7 Exper. -- 20 HL8 Exper. -- 21 HL9 Exper. -- 1612 21 HL10 Exper. -- 1605 21 HL11 Exper. -- 1606 21 HL12 Exper. -- 1594 21 HL13 Exper. -- 1605 21 HL14 Exper. -- 1605 21 HL15 Exper. -- 1610 21 HL16 Exper. -- 1607 21 STRUCTURAL AND ELECTRONIC PROPERTIES OF AROMATIC . . .   91 Table 2. Characteristic Vibration Bands of Selected Hydrazone Ligands Compound/Ref A m i d e - I Amide-II Amide-III ν ( C = O ) ν (CN+ NNδ(NH δ(NH δ(NH) ( νC N +δ N H) (δ(NH)+… HL/17 Exper. Exper. Exper. Exper. Exper.tal 1656.9 -- -- HL/17 B3LYP 1730. -- -- HL1/18 Exper. 1573 -- -- HL2/18 Exper. 1557 -- -- HL3/18 Exper. 1612 -- -- HL4/18 Exper. 1574 -- -- HL5/18 Exper. 1557 -- -- HL6/19 Exper. 1675 1535 1275 CuHL6/19 Exper. 1500 1030 HL7/20 Exper. 1673 1553 1282 HL8/21 Exper. 1647 1531 -- HL9/21 Exper. 1630 1564 -- HL10/21 Exper. 1637 1548 -- HL11/21 Exper. 1631 1545 -- HL12/21 Exper. 1638 1562 -- HL13/21 Exper. 1632 1512 -- HL14/21 Exper. 1632 1567 -- HL15/21 Exper. 1627 1555 -- HL16/21 Exper. 1627 1556 -- 3. Molecular electrostatic potential and HOMO–LUMO Analysis Frontier molecular orbital analysis is a cornerstone of computational chemistry for predicting reactivity. The energy difference between the Highest Occupied Molecular Orbital (HOMO) and the Lowest Unoccupied Molecular Orbital (LUMO) defines the energy gap (ΔE), a key indicator of chemical stability and polarizability. A smaller HOMO-LUMO gap generally signifies a softer molecule with higher chemical reactivity and kinetic instability. Molecular Electrostatic Potential (MEP) mapping provides a visual representation of the charge distribution across a molecule’s van der Waals 92   AN OVERVIEW OF COORDINATION CHEMISTRY WITH METALS . . . surface, highlighting regions susceptible to nucleophilic (negative, red) and electrophilic (positive, blue) attack. For N-acylhydrazone derivatives (HL, HL17-HL27), MEP analyses consistently reveal strongly negative electrostatic potential regions localized around the carbonyl oxygen and imine nitrogen atoms (Polo-Cerón et al., 2021; Tabbiche et al., 2022; Sakr et al., 2022; Özbek et al., 2020, 2021; Uğurlu, 2025). This confirms these sites as primary donors for metal coordination. Positive potential regions are typically associated with hydrogen atoms of the aromatic rings and the N-H group. The electron-withdrawing or -donating nature of substituents on the aromatic rings significantly modulates this electrostatic landscape, thereby influencing both reactivity and intermolecular interactions. STRUCTURAL AND ELECTRONIC PROPERTIES OF AROMATIC . . .   93 MEP Ref. MEP Ref. 21 18 19 19 19 19 19 19 20 17 21 6 Figure 1. Molecular Electrostatic Potential Maps of Representative Hydrazone Derivatives 94   AN OVERVIEW OF COORDINATION CHEMISTRY WITH METALS . . . Molecular Electrostatic Potential Maps of studied compounds are given Figure 1. 4. The energy gap (∆E) and dipole moment (μ) Quantum chemical calculations provide crucial insights into the electronic properties of hydrazones. The HOMO-LUMO energy gap (ΔE) and dipole moment (μ) are summarized in Table 3 for a series of derivatives (HL17-HL32) (Alam & Lee, 2015; Maheswari & Manjula, 2016; Tabbiche et al., 2022; Sakr et al., 2022; Özbek et al., 2020, 2021). The dipole moment, a measure of molecular polarity, influences solubility, intermolecular interactions, and behavior in biological systems. The computed dipole moments for these compounds vary significantly, with HL25 exhibiting the largest value (11.65 D) and HL26 the smallest (4.13 D). This variation is directly attributable to differences in molecular symmetry and the polarity of constituent substituents. The HOMOLUMO energy gap also shows considerable variation, reflecting differences in electronic conjugation and stability. For instance, the energy gap for compound HL24 was calculated as 2.77 eV (LSDA), 4.15 eV (DFT), and 9.81 eV (HF), demonstrating the dependence of this parameter on the chosen computational method. The experimental value for HL24 (2.83 eV) aligns closely with the LSDA calculation. Compound HL21, computed at the CAM-B3LYP/631G++(2d,2p) level, exhibits a larger gap of 6.890 eV, suggesting higher kinetic stability. STRUCTURAL AND ELECTRONIC PROPERTIES OF AROMATIC . . .   95 Table 3. Computed Energy Gaps and Dipole Moments of Selected Hydrazone Derivatives. Compound/ Ref. method DEeV() ()Debye m HL27/27 DFT/B3LYP/6-31G(d,p) 6.198 -- HL28/27 DFT/B3LYP/6-31G(d,p) 5.32 -- HL29/27 DFT/B3LYP/6-31G(d,p) 5.218 -- HL30/27 DFT/B3LYP/6-31G(d,p) 3.808 -- HL31/28 DFT/B3LYP/6-31G(d,p) 4.9372 -- HL31/28 DFT/B3LYP/6-31G(d,p) 5.7605 -- HL17/22 DFT/B3LYP/6–31 G (d, p) 3.5873 -- HL18/23 CAM-B3LYP/6–31 G (d,p) 7.007 10.40 HL19/23 CAM-B3LYP/6–31 G (d,p) 6.896 6.301 HL21/23 CAM-B3LYP/6-31G + + (2d, 2p) 6.890 6.301 HL23/23 CAM-B3LYP/6-31G + + (2d, 2p) 6.847 7.182 HL20/23 CAM-B3LYP/6-31G + + (2d, 2p) 6.593 8.489 HL22/23 CAM-B3LYP/6-31G + + (2d, 2p) 3.982 8.016 HL24/24 DFT/6-311++G(d,p) 4.15 4.60 HL24 HF/6-311++G(d,p) 9.81 5.05 HL24 LSDA/6-311++G(d,p) 2.77 -- HL24 EXP. 2.827 -- HL25 DFT/6-311++G(d,p) 3.51 11.65 HL26 DFT/6-311++G(d,p) 4.42 4.13 Also, the energy band gap (Eg=ELUMO-EHOMO) values have been obtained by using ELUMO and EHOMO at the level of both theories. The equilibrium state (ground state) energy band gap of the studied compounds were calculated as 2.77 LSDA/6-311++G(d,p) for HL24, as 6.890 CAM-B3LYP/6-31G + + (2d, 2p) for HL21, respectively. 5. Conclusion This review underscores the significance of aromatic N-acylhydrazones as a versatile class of compounds with applications spanning pharmacology, catalysis, and materials science. The integration of experimental spectroscopic techniques with advanced computational methods provides a profound understanding of their structure-property relationships. Spectroscopic analysis confirms the characteristic vibrational signatures of the hydrazone motif, with 96   AN OVERVIEW OF COORDINATION CHEMISTRY WITH METALS . . . frequencies sensitive to molecular substitution and metal coordination. MEP calculations successfully visualize the nucleophilic character of the carbonyl and imine groups, rationalizing their role as primary metal-binding sites. Furthermore, the analysis of frontier molecular orbitals and associated quantum chemical descriptors, such as the HOMO-LUMO gap and dipole moment, offers predictive power regarding the compounds’ chemical reactivity, stability, and overall functional potential. The systematic variation in these electronic parameters across different derivatives highlights how subtle structural modifications can be harnessed to fine-tune molecular properties for targeted applications. The consistent correlation between computational predictions and experimental observations validates the use of theoretical models like DFT as indispensable tools for the rational design of new hydrazone-based molecules with tailored characteristics. References Alam, M. S., & Lee, D. (2015). Quantum‐Chemical Studies to Approach the Antioxidant Mechanism of Nonphenolic Hydrazone Schiff Base Analogs: Synthesis, Molecular Structure, Hirshfeld and Density Functional Theory Analyses. Bulletin of the Korean Chemical Society, 36(2), 682–691. https://doi. org/10.1002/bkcs.10132 Ali, M. R., Marella, A., Alam, M. T., Naz, R., Akhter, M., Shaquiquzzaman, M., Saha, R., Tanwar, O., Alam, M. M., & Hooda, J. (2012). Review of biological activities of hydrazones. Indonesian Journal of Pharmacy, 23(4), 193–202. Begovic, B., Ahmetagic, S., Calkic, L., Vehabovic, M., Kovacevic, S., Catic, T., & Mehic, M. (2016). Open Clinical Trial on Using Nifuroxazide Compared to Probiotics in Treating Acute Diarrhoeas in Adults. Materia Socio Medica, 28(6), 454. https://doi.org/10.5455/msm.2016.28.454-458 Budiati, T., Stephanie, D. A., & Widjajakusuma, E. C. (2012). Rapid solvent-free microwave assisted synthesis of some n’-benzylidene salicylic acid hydrazides. Indonesian Journal of Chemistry, 12(2), 163–166. Chen, G., Lan, H.-H., Cai, S.-L., Sun, B., Li, X.-L., He, Z.-H., Zheng, S.-R., Fan, J., Liu, Y., & Zhang, W.-G. (2019). Stable Hydrazone-Linked Covalent Organic Frameworks Containing O,N,O′-Chelating Sites for Fe(III) Detection in Water. ACS Applied Materials & Interfaces, 11(13), 12830–12837. https://doi.org/10.1021/acsami.9b02640 Clark, C. M., Elmendorf Jr, D. F., Cawthon, W. U., Muschenheim, C., & McDermott, W. (1952). Isoniazid (isonicotinic acid hydrazide) in the treatment RECENT ADVANCES IN 1,3,4-THIADIAZOLE-BASED METAL . . .   103 1,3,4-Thiadiazole derivatives have been studied for their versatility as ligands, capable of coordinating to metal centers either through a single donor site or through two, and also of linking two metal ions, leading to the formation of dior trinuclear complexes. In the first section of this review article, we summarize metal complexes based on 1,3,4-thiadiazole derivatives. Hu et al. reported a copper complex in which the 1,3,4-thiadiazole ligand coordinates to the metal center through its endocyclic nitrogen atoms, acting as a bridging unit between two ligands(metals) and resulting in the formation of a polymeric coordination complex (Hu vd., 2008). Song et al. also reported a copper complex of 2-methyl-1,3,4-thiadiazole, which exhibits a coordination mode similar to that observed in previously described complex involving endocyclic nitrogen atoms. A notable structural feature of this compound is the formation of one-dimensional copper chains, facilitated by the bridging of dinitrogen (N–N) units. This structural arrangement is likely, is the result of in situ desulfurization of the original 2-methyl-1,3,4thiadiazole ligand, leading to the formation of 5-methyl-1,3,4-thiadiazole as the actual coordinating species (Song vd., 2003). Liu et al. reported a series of seven metal complexes based on 2,5-dimethyl1,3,4-thiadiazole, incorporating silver (Ag), copper (Cu), and nickel (Ni) as central metal ions. In these complexes, the thiadiazole ligand typically coordinates through its endocyclic nitrogen atoms, either in a monodentate fashion or as a bridging ligand between adjacent metal centers. This bridging coordination commonly results in polynuclear architectures, particularly in complexes 1–4, 6, and 7. Interestingly, complex 5 with cupper metal center, deviates from this trend, as the thiadiazole ligand binds to the copper ion through only one nitrogen atom and does not function as a bridge, highlighting the flexible coordination behavior of thiadiazole-based ligands depending on the metal center and surrounding ligands (Liu vd., 2013). Similarly, ten structures have been reported based on 2-amino-1,3,4thiadiazole, where coordination occurs through the endocyclic nitrogen atoms, either in a monodentate manner or as bridging ligands. Among these, two copper, one cobalt, and one zinc complexes are mixed-ligand systems that incorporate tridentate ligands along with 2-amino-1,3,4-thiadiazole (Suen vd., 2011, Ishankhodzhaeva vd., 1998, Khusenov vd., 1998, Maekawa vd., 1999, Gurbanov vd., 2023, Gurbanov vd., 2018, Nuralieva vd., 2025). The 5-substituted 2-amino-1,3,4-thiadiazole derivatives form the second most commonly reported class of metal complexes, with 39 known structures involving metals such as Cu, Zn, Cd, Hg, Ni, Fe, Co, Ag, Mo, and Pt (Gurbanov 104   AN OVERVIEW OF COORDINATION CHEMISTRY WITH METALS . . . vd., 2023, Zahoor vd., 2021, Besleaga vd., 2021, Fei vd., 2019, Wang vd., 2009, Zhu vd., 2017, Tunsrichon vd., 2022, Huxel vd., 2015, Song vd., 2012, Fu vd., 2017, Kadirova vd., 2007, Zheng vd., 2007, Lynch & Ewington 2001, Lynch & Duckhouse 2001, Ishankhodzhaeva vd., 2000, Wang vd., 2008, Ishankhodzhaeva vd., 2001, Slyvka 2014, Lynch 2002, Antolini vd., 1988). Coordination typically occurs through the endocyclic nitrogen atoms, either binding a single metal ion or bridging multiple metal atom, and many complexes also contain co-ligands that result in the formation of mixed-ligand complexes (Lynch 2002). Thanks to their adaptable coordination modes, 1,3,4-thiadiazole derivatives have been widely studied as ligands capable of binding metal ions through one or two donor sites and bridging metal centres to form di and trinuclear complexes. In contrast, the 2,5-diamino-1,3,4-thiadiazole derivative is less explored, with only five reported structures involving Ni, Co, Cu, Mn, and Dy. Coordination in these cases occurs via the endocyclic nitrogen atoms, either acting as single-point donors or bridging ligands (Gurbanov vd., 2023, Fabretti vd., 1991, Fabretti vd., 1993, Li vd., 2022). The 1,3,4-thiadiazole-2-thiol scaffold is notable for its strong sulfur donor site, which enhances its ability to stabilize a variety of metal centers and facilitates diverse coordination architectures. A total of 32 structures involving 5-amino-1,3,4-thiadiazole-2-thiol have been reported with metals such as Pd, Cd, Ni, Au, Ag, Co, Pt, Re, Zn, Sn, and Cu. In these complexes, the ligand coordinates primarily through the nitrogen or thiolate sulfur, often leading to the formation of polynuclear and polymeric assemblies (Weng vd., 1990, Varna vd., 2018, Chontal-Vidal vd., 2012, Varna vd., 2022, Kao vd., 2019). Nineteen structures of 5-substituted thio-1,3,4-thiadiazol-2-amine have been reported involving metals such as Ag, Cd, Co, Fe, Hg, Ir, Pd, and Zn. These ligands typically coordinate through the endocyclic nitrogen atom at the 3rd position or serve as bridging ligands between metal centers. Notably, one complex featuring iridium exhibits coordination through the nitrogen atom at the 4th position. This variability in binding sites highlights the ligand’s flexible coordination behavior, enabling diverse structural motifs (Gurbanov vd., 2023, Heidari vd., 2020, Slyvka vd., 2021, Ardan vd., 2017, Torambetov vd., 2019, Kadirova vd., 2022, Soudani vd., 2014, Pan vd., 2017, Slyvka vd., 2022, Hu vd., 2013, Atashov vd., 2024). Similarly, nine structures of 1,3,4-thiadiazol-2-thiol complexes have been reported with metals including Co, Sn, Pb, Ag, and Hg. In these compounds, the ligand binds through its nitrogen or thiolate sulfur or both, often leading to the formation of polynuclear assemblies. The presence of the thiolate group RECENT ADVANCES IN 1,3,4-THIADIAZOLE-BASED METAL . . .   105 allows for strong metal–sulfur interactions, which play a key role in stabilizing extended metal clusters and networks (Mu vd., 2016, Guo vd., 2010, Hu vd., 2010, Wang vd., 2009). When the thiol proton in 1,3,4-thiadiazol-2-thiol is replaced by an alkyl group, the resulting thioether ligands exhibit altered coordination behavior. The loss of the acidic proton shifts the coordination preference toward the endocyclic nitrogen atoms. These ligands have been reported in 16 structures with metals such as Ag, Cu, Co, and Ni, where they typically bind through nitrogen either monodentately, bidentately, or as bridging ligands. This structural variation supports the formation of a wide range of coordination geometries and complex architectures (Li vd., 2012, Qin vd., 2009, Qin vd., 2010, Wang vd., 2008, Yu vd., 2010, Huang vd., 2009, Qin vd., 2011, Li vd., 2011, Hu vd., 2009, Hu vd., 2008). The dual donor nature of 2,5(dithiol)-1,3,4-thiadiazole plays a key role in forming structurally diverse metal complexes. To date, 24 structures featuring this ligand have been reported with metals including Cu, Sn, Os, Ni, Pd, Pt, Re, Hg, Au, Sb, and Ru. Coordination occurs either through the sulfur atom usually as a deprotonated thiolate or through the nitrogen atoms, with the ligand binding in monodentate or bidentate modes. This versatility in coordination promotes the assembly of polynuclear complexes and a wide variety of coordination geometries (Tannai vd., 2006, Li vd., 2008, Li & Leong 2008, Ma vd., 2004, Lo & Ng 2004, Tannai vd., 2003, Castaño vd., 1989, Wilton-Ely vd., 2001, Ma vd., 2004, Tannai vd., 2005, Ma vd., 2003). 5-Methyl-1,3,4-thiadiazole-2-thiol is the derivative with the greatest number of reported metal complexes, totalling 41 structures involving metals such as Co, Zn, Cu, and Pt. In these complexes, the ligand binds through the sulfur atom in its thiolate form or through nitrogen atoms, facilitating the formation of polynuclear assemblies. The prevalence of this derivative highlights the strong coordinating ability of the thiol and nitrogen donor sites, which contribute to a variety of stable and structurally diverse metal complexes (Varna vd., 2018, Tannai vd., 2003, Luqman vd., 2016, Luqman vd., 2014, Al-Mouqdady vd., 2022, Wang vd., 2012, Dong vd., 2009, Kajitani vd., 2012, Zheng vd., 2019, Liu & Zhao vd., 2018, Liu & Tanski vd., 2022, Ma vd., 2006, Dong vd., 2013, Bharati vd., 2013, Kumar vd., 2010, Chen vd., 2021, Ameen vd., 2024). The structural database survey was conducted using ConQuest software (CSD, Version 5.46, November 2024) within the Cambridge Structural Database (Groom vd., 2016). 106   AN OVERVIEW OF COORDINATION CHEMISTRY WITH METALS . . . Table 1. Representative structures of 1,3,4-thiadiazole derivatives and their examples. Sl. No. Represntative Structure Example structures Ref. 1 NN S Cu O NN S Cu O NO 2 N N - ONO 2 + (Hu vd., 2008) 2 NN S Cu NN S NN S Cu NN S Cu NN S Cu Cu Cu Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl (Song vd., 2003) 3 NN S Co O ON O O N S N N O O NN S NN S NN S NN S N N S N NS Ag Ag Ag Ag O O OH 2 H 2 O Cl Cl O O O O O O (Liu vd., 2013) 4 N N S H2N NN SNH2 N N S H2N NN S NH2 N N S H2N N NS NH2 Cu Cu Cu Cu OH ClO4N NS H 2 N Cu N O O S N HN Ph MeOC O O (Suen vd., 2011, Ishankhodzhaeva vd., 1998, Khusenov vd., 1998, Maekawa vd., 1999, Gurbanov vd., 2023, Gurbanov vd., 2018, Nuralieva vd., 2025) 5 N N S H 2 NR R=Me, Et, Ph, n-heptyl, o,p-pyridine, o-chlorobenzyl, p-nitrobenzyl, o-fenyl, 2-hydroxyphenyl, m-Tol, 2-furanyl NN S m-Tol NH 2 Co Cl N Cl N S m-Tol NH 2 NN S H 2 N Cu Cl NN SNH 2 Cu Cl (Gurbanov vd., 2023, Zahoor vd., 2021, Besleaga vd., 2021, Fei vd., 2019, Wang vd., 2009, Zhu vd., 2017, Tunsrichon vd., 2022, Huxel vd., 2015, Song vd., 2012, Fu vd., 2017, Kadirova vd., 2007, Zheng vd., 2007, Lynch & Ewington 2001, Lynch & Duckhouse 2001, Ishankhodzhaeva vd., 2000, Wang vd., 2008, Ishankhodzhaeva vd., 2001, Slyvka 2014, Lynch 2002, Antolini vd., 1988, Lynch 2002) 6 NN S H 2 NNH 2 H O NN S H 2 NNH 2 Co Cl NN S H 2 NNH 2 Co Cl NN S H 2 NNH 2 H O Co N NS NH 2 NH 2 N N S H 2 N H 2 N OH 2 H 2 O Cl - H 2 O + + Gurbanov vd., 2023, Fabretti vd., 1991, Fabretti vd., 1993, Li vd., 2022 RECENT ADVANCES IN 1,3,4-THIADIAZOLE-BASED METAL . . .   107 7 N N S S NH 2 N N S H 2 N S Zn Zn Zn N N S N N S S N N S Pd NN tBu tBu H 2 NNH 2 Weng vd., 1990, Varna vd., 2018, Chontal-Vidal vd., 2012, Varna vd., 2022, Kao vd., 2019 8 N N S H 2 NS R N N S H2N S N N S NH2 S Cu Cu O O O O OO O O Gurbanov vd., 2023, Heidari vd., 2020, Slyvka vd., 2021, Ardan vd., 2017, Torambetov vd., 2019, Kadirova vd., 2022, Soudani vd., 2014, Pan vd., 2017, Slyvka vd., 2022, Hu vd., 2013, Atashov vd., 2024 9 N N S HS S N N S Ag Ag Ag Ag Ag Cl N Ag N Ag S S Mu vd., 2016, Guo vd., 2010, Hu vd., 2010, Wang vd., 2009 10 N N S S R S S N N N N S S S N NS SN N S Ag O O2N Ag Ag ONO2 N Li vd., 2012, Qin vd., 2009, Qin vd., 2010, Wang vd., 2008, Yu vd., 2010, Huang vd., 2009, Qin vd., 2011, Li vd., 2011, Hu vd., 2009, Hu vd., 2008 11 N N S HS SH N N S SS N NS S S NN S S S NN S S S N N S S S Sn Sn Sn Sn Sn Tannai vd., 2006, Li vd., 2008, Li & Leong 2008, Ma vd., 2004, Lo & Ng 2004, Tannai vd., 2003, Castaño vd., 1989, Wilton-Ely vd., 2001, Ma vd., 2004, Tannai vd., 2005, Ma vd., 2003 12 N N S H 3 CSH N N S S N N S S NN S S NN SS Pt Pt Ni NH 2 NH 2 N H 2 N H 2 N N S S N N S S Varna vd., 2018, Tannai vd., 2003, Luqman vd., 2016, Luqman vd., 2014, Al-Mouqdady vd., 2022, Wang vd., 2012, Dong vd., 2009, Kajitani vd., 2012, Zheng vd., 2019, Liu & Zhao vd., 2018, Liu & Tanski vd., 2022, Ma vd., 2006, Dong vd., 2013, Bharati vd., 2013, Kumar vd., 2010, Chen vd., 2021, Ameen vd., 2024 108   AN OVERVIEW OF COORDINATION CHEMISTRY WITH METALS . . . 3. BIOLOGICAL PROPERTIES Metal complexes of 1,3,4-thiadiazole derivatives frequently exhibit enhanced biological activity compared to their uncoordinated ligands. This improvement is attributed to several factors, such as greater stability and improved bioavailability, which enable the complexes to remain active longer within biological systems. Metal coordination also tends to increase cellular uptake and promote selective interactions with biological targets. Furthermore, the combined effect of the metal ion and the thiadiazole ligand often results in stronger binding and heightened activity, highlighting the potential of these complexes in pharmaceutical and therapeutic applications. 3.1. Antimicrobial activity Among heavy metals, bismuth is unique due to its potent antibacterial activity, ecological compatibility, and low toxicity to humans. Luqman et al. synthesized five mixed-ligand thiolatobismuth(III) complexes using thione derivatives from nitrogen-based heterocycles and tested for antimicrobial activity. The results indicate that complexes 1–4 exhibited strong antimicrobial activity against all tested Gram-positive bacterial strains. In contrast, their efficacy against Gram-negative bacteria was more limited, with only complexes 1, 2, and 3 showing significant inhibitory effects (Luqman vd., 2016). Bi S NNNN N S N N H 1 S N S N S S Bi N N S S 2 S N S N S S Bi NN S S N S Br Br Br 3 NN SN H R Fe R = CH 3 (4); C 2 H 5 (5); C 6 H 5 (6). NN SN H R Re CO OC CO R = CH3 (7); C2H5 (8); C6H5 (9). Quintana et al. synthesized six derivatives of organometallic complexes based on 1,3,4-thiadiazoles containing cyrhetrenyl and ferrocenyl fragments with metals like Iron and rhenium. These derivatives were evaluated for their activity against Mycobacterium tuberculosis using the mc27000 strain. Biological evaluation revealed that inserting organometallic fragment into the thiadiazole RECENT ADVANCES IN 1,3,4-THIADIAZOLE-BASED METAL . . .   109 framework resulted in a comparable antitubercular activity, but lower than, that of isoniazid, which served as the control drug (Quintana vd., 2015). Chen et al. has synthesized thirteen ferrocene-based 1,3,4-thiadiazolylpyrazoline derivatives and tested for antifungal activity. The findings revealed that all the tested compounds demonstrated notable antifungal activity. Among the three fungal strains tested, Gibberella sanbinetti was the most susceptible, showing greater sensitivity compared to Pythium solani and Gibberella nicotiancola. Notably, compounds 10 and 11 showed strong and consistent antifungal effects across all three species (Chen vd., 2018). N N Fe N N S Cl Cl 10 N N Fe N N S O 11 Five silver(I) complexes, containing heterocyclic thioamides and phosphine ligands, were synthesized by Varna et al. and assessed for their antibacterial properties. Among them, four complexes (12-15) exhibit a distorted tetrahedral coordination geometry, while complex 16 adopts a trigonal planar structure. In vitro testing demonstrated that these complexes exhibited significant antibacterial activity against Gram-positive bacteria, but showed no effect against the Gramnegative bacterium. Notably, complex 16, featuring trigonal planar geometry, showed the strongest antibacterial activity among the series, outperforming the tetrahedral complexes (Varna vd., 2018). N HN S S Ag Cl Ph 3 P Ph 3 P 12 S Ag PPh 3 Ph 3 P Ph 3 P HN H NO 13 N H N S S Ag PPh3 Ph3P Ph3P 14 N H N S S NH 2 Ag PPh 3 Ph 3 P Ph 3 P 15 N N S S NH 2 Ag Ph 3 P Ph 3 P 16 A novel copper(II) coordination polymer (17), using 2,5-bis(pyridine-2yl)-1,3,4-thiadiazole was synthesized and tested for its antifungal activity against Verticillium dahliae and Fusarium oxysporum fsp. melonis, both of which cause wilt diseases in key crops. The complex showed moderate inhibition of V. dahliae strains SH and SE, and F. oxysporum fsp. melonis at 50 μg·mL−1, while 110   AN OVERVIEW OF COORDINATION CHEMISTRY WITH METALS . . . it inhibited strain SJ of V. dahliae by over 60%, indicating greater sensitivity. At higher concentrations (100 and 200 μg·mL−1), inhibition increased to about 90% for strains SJ, SE, and F. oxysporum fsp. melonis, and 75% for strain SH (Laachir vd., 2020). N N S NN N N S N N N N SN NCuCu Cl Cl Cl Cl Cu Cu Cl Cl Cl Cl N NNN 17 Two copper coordination complexes, 18 and 19, were synthesized by Kumara et al. and assessed for their antibacterial and antifungal activities. Antibacterial studies indicated that 18 exhibited superior activity compared to 19, as evidenced by its larger inhibition zones. In contrast, 19 showed stronger antifungal activity than 18, also supported by larger inhibition zones against the tested fungal strains. The free ligand displayed only slight activity in both cases (Kumari & Ahmad 2024). N NNNNN Cu Cu Cu NO O O NO O O NO O O NN SNH 2 NN SNH 2 NN SNH 2 OH 2 OH 2 OH 2 OCu 18 Cu H2O N N S H2N N N S H2N N N S NH2 N NS NH2 OH2 (NO 3 ) 2 19 Varna et al. synthesized five Ag(I) complexes (20-24) containing phosphines and heterocyclic thioamide ligands with either NH₂ or CF₃ substituents, and evaluated their antibacterial and anticancer properties against Gram-positive and Gram-negative strains. Among them, complex 21 showed the highest potency against all the Gram-positive bacteria. In contrast, complex 20, 22 and 23 were activite against E. coli, while complex 24, bearing a CF₃substituted thioamidate, exhibited weak antibacterial activity against both Grampositive and Gram-negative strains. Its NH₂-substituted analogue, complex 23, demonstrated significantly higher efficacy against both (Varna vd., 2022). A Zn(II) complex (25) incorporating 5-ethyl-2-amino-1,3,4-thiadiazole was synthesized by Shen et al. and tested for antimicrobial testing against Staphylococcus aureus revealed distinct inhibition zones of above 20 mm for both free ligand and the complex. These findings demonstrate that both ligand and its complex exhibit strong antibacterial activity, showing similar inhibition zones with only minimal differences in efficacy. This suggests that the RECENT ADVANCES IN 1,3,4-THIADIAZOLE-BASED METAL . . .   111 antimicrobial activity is mainly attributed to the 1,3,4-thiadiazole moiety, with metal coordination having little impact on overall efficacy (Shen vd., 2004). N HN S S NH 2 Ag Cl O PPh 2 PPh 2 20 N NH S S H 2 N Ag O PPh 2 PPh 2 O Ph 2 P Ph 2 P Ag N HN S S NH 2 21 N N S S NH 2 Ag PPh 3 Ph 3 P Ph 3 P 22 N N S SH H 2 N Ag O PPh 2 PPh 2 O Ph 2 P Ph 2 P Ag N NS HS NH 2 23 N N N S F 3 C Ag O PPh 2 PPh 2 O Ph 2 P Ph 2 P Ag N NN S CF 3 24 NN S NN S NH 2 H 2 N Zn O O O O 25 Rogolino et al. introduced a thio group into vanillin and its derivatives to enhance their potential biological activity, and their corresponding copper complexes were subsequently synthesized. The antifungal activity of the complexes against Aspergillus flavus was then evaluated. Among all the complexes, the 1,3,4-thiadiazol moiety containing copper complex compounds 26 and 27 identified as the most promising based on their activity, were further evaluated for cytotoxicity against a panel of human cell lines. However, all metal complexes exhibited high cytotoxicity toward both normal and cancerous human cell lines, indicating a lack of selectivity (Rogolino vd., 2017). NN S N N N S N Cu Cl Cl 26 NN S N N N S N Cu Cl Cl Et Et Et Et 27 3.2. Anticancer activity Four coordination compounds based on copper(II) were synthesized by Lavrenova et al. using ligand (L1 - 2,5-bis(ethylthio)-1,3,4-thiadiazole) and (L2 - 2,5-bis(pyridylmethylthio)-1,3,4-thiadiazole) and the cytotoxicity of the L2-based complexes was assessed against cancer cell lines. The findings showed that the copper(II) halide complexes Cu(L2)Cl₂ (28) and Cu(L2)Br₂ (29) did not affect HepG2 cell viability but exhibited a cytotoxic effect on MCF-7 cells. The 112   AN OVERVIEW OF COORDINATION CHEMISTRY WITH METALS . . . IC₅₀ values showed no significant difference in cytotoxicity between the two copper(II) complexes against MCF-7 cells, with Cu(L2)Cl₂ at 41.7 ± 0.4 μM and Cu(L2)Br₂ at 39.0 ± 0.4 μM, indicating similar levels of activity (Lavrenova vd., 2023). NN S N N S Cu Cl Cl SS SS N N S S S Cu Cl Cl Cl Cu Cl 28 NN S N N S Cu Br Br SS SS Cu Br Br 29 Křikavová et al. reported two complexes based on Ruthenium and two complexes based on iridium, incorporating the thiadiazole ligand L1. Their biological activity was assessed in vitro using different cell lines. The Ir(III) complexes (32) and (33) showed no toxicity toward the healthy fibroblast cells, indicating good selectivity. Meanwhile, complexes (30) and (33) moderately inhibited the metabolism and proliferation of cancer cells. Selectivity indices (SI), calculated from IC₅₀ values in healthy and cancer cell lines, revealed that complexes 1(30) and (33) were more selective than cisplatin when tested on CCD-18Co cells, with SI values exceeding 5.8 and 3.4, respectively, compared to 2.6 for cisplatin. However, using the CCD-1072Sk cell line, complex (30) displayed poor selectivity (SI = 0.4), whereas complex (33) and cisplatin maintained higher selectivity, with SI values above 3.4 and 6.2, respectively (Křikavová vd., 2023). Fei et al. synthesized chiral copper(II) complexes from rosin as efficient anticancer agents. Their in vitro activities were evaluated against a panel of cancer cell lines. Half-maximal inhibitory concentration (IC₅₀) values showed that copper(II) coordination greatly enhanced the bioactivity of the ligand, with both complexes generally more potent than cisplatin and oxaliplatin. 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Crystal structure of tetra-μ-acetato-bis [(5-amino-2methylsulfanyl-1, 3, 4-thiadiazole-κN1) copper (II)]. Acta Crystallogr. Sect. E. 75(8), 1239-1242. https://doi.org/10.1107/S2056989019010272 Tunsrichon, S., Chainok, K., Promarak, V., Nalaoh, P., Youngme, S., & Boonmak, J. (2022). Simultaneous occurrence of vapochromism and METAL(MN+) – CARBOXYLATE(COO-) COMPLEXES: BONDING PROPERTIES . . .   135 anions in the precursor complex with carboxylate anions. This method allows the synthesis of mixed ligand complexes. Furthermore, precise control of the coordination sphere is possible. M(L1)m(L2)n + nR-COONa M(L1)m(R-COO)n + nNa(L2) 3.6. Electrochemical Synthesis Instead of using a metal salt, it relies on the direct electrochemical oxidation of the metal itself in the presence of a carboxylic acid or carboxylate salt. The electrolyte is a solution of the carboxylic acid or its salt in alcohol. The metal serves as the anode electrode. The reaction results in highly purified complexes. M (s) + 2 R-COOH (sol) / R-COONa (sol) M(R-COO) 2 + H 2(g) / Na (s) 3.7. Synthesis by Thermal Decomposition of Precursor Complexes Some metal carboxylate complexes are obtained by controlled heating of mixed-ligand metal carboxylate complexes containing volatile ligands. [M(RCOO)m(L2)n] [M(R-COO)m] + n L2 (volatile ligand) 4. Applications of Metal-Carboxylate Complexes Due to the variety of molecules containing the carboxylic acid group (-COOH), metal carboxylate complexes are versatile and have numerous applications in chemistry, materials, and industry. Some metal carboxylate complexes are used as catalysts in organic reactions (polymerization, oxidation), while others are used in biomedical applications (antimicrobial or anticancer effects, slow and targeted drug release). Now, let’s examine the applications of metal carboxylate complexes. 4.1. Catalysis Metal carboxylate complexes have found application in both homogeneous and heterogeneous catalysis due to their structural versatility, redox properties, and ability to stabilize reactive intermediates. Carboxylate ligands can adjust catalytic activity and selectivity by transferring electrons to the metal center. The main catalytic applications(Dhakshinamoorthy et al, 2011; Cotton et al., 1999; Corma et al., 2010; Kobayashi and Manabe, 2002; Dhakshinamoorthy et al., 2013; Ranocchiari and van Bokhoven, 2011; Wang and Xiao, 2025). 136   AN OVERVIEW OF COORDINATION CHEMISTRY WITH METALS . . . Oxidation Reactions: Alkene epoxidation, Alcohol oxidation, C–C and C–X Bond Formation: Cross-coupling (Suzuki, Heck, and Sonogashira reactions), C–H activation. Polymerization Catalysis: Olefin polymerization (Ziegler-Natta-type catalysis), Lactide polymerization. Photocatalysis: Photocatalytic water splitting, CO₂ reduction, and organic oxidation reactions. Lewis Acid Catalysis: Esterification, Transesterification, Aldol condensation, Diels-Alder reactions. Biomimetic (enzyme-like) catalysis: Superoxide dismutase (SOD) mimics, Hydrolase-like catalysis. 4.2. Advanced Materials Synthesis Due to their structural flexibility, thermal stability, and solubility, metal carboxylate complexes are ideal building blocks for producing advanced materials, including metal-organic frameworks (Furukawa et al., 2013; Corma et al., 2010; Ranocchiari and van Bokhoven, 2011), magnetic and electronic materials(Affronte, 2008), optical and photonic systems (luminescent materials, photonic crystals, nonlinear optical materials, optical sensors, photovoltaic devices, photonic circuits, optical memory devices, highefficiency LEDs, nanophotonic devices, microlasers), metal oxides, and hybrid nanomaterials(Allendorf et al, 2009; Kim et al., 2024; Gutiérrez et al., 2020; Gutiérrez et al., 2022). When metal carboxylates are heated, CO2 is released and metal-oxygen bonds are formed. This method enables the synthesis of TiO2, ZnO, and CuO nanoparticles. Homogeneous products are obtained at the molecular level by obtaining metal oxides through thermal decomposition. 4.3. Biomedical Applications Metal-carboxylate complexes are of great interest in biomedical applications due to their biocompatibility and tunable structural properties. These complexes can exhibit many biological activities, such as antimicrobial, anticancer, enzyme inhibitory, drug carrier, and antioxidant properties. Carboxylate complexes containing silver (Ag), copper (Cu), zinc (Zn), and cobalt (Co) exhibit strong antimicrobial properties (Miri et al., 2018; Mette et al., 2022; Tyagi et al., 2024; Scăețeanu et al., 2018; MorenoAlcántar and Casini, 2022; Bilal et al., 2025; Köse et al., 2012; Köse et al., 2007). These complexes can disrupt cell membranes, generate reactive oxygen species (ROS), or inhibit microbial enzymes. METAL(MN+) – CARBOXYLATE(COO-) COMPLEXES: BONDING PROPERTIES . . .   137 Platinum (Pt), ruthenium (Ru), and titanium (Ti) carboxylate complexes can induce apoptosis in cancer cells by interacting with DNA or producing ROS. Carboxylate ligands may provide lower toxicity and higher selectivity than classical platinum-based drugs. Some metal–carboxylate complexes can mimic or inhibit metalloproteins or metalloenzymes (e.g., urease, carbonic anhydrase) in biological systems. These properties offer therapeutic potential in diseases associated with metabolic imbalances. Metal–carboxylate complexes and their derived metal–organic frameworks (MOFs) are used for controlled drug delivery and as contrast agents in magnetic resonance imaging (MRI). MOFs containing Fe or Zr have gained an important place in drug delivery systems due to their biocompatible structures. Some carboxylate complexes containing Mn, Cu, and Co can prevent cell damage by scavenging free radicals and regulate inflammatory processes. Such complexes are promising in the treatment of diseases associated with oxidative stress(Elattar et al., 2024; Liu et al., 2019; Sezgin et al., 2025). 4.4. Lubricants and Additives Certain metal carboxylate complexes (zinc, calcium, magnesium, and barium carboxylate) are widely used in engine oils, industrial machinery, and gear systems because they improve the flow properties of lubricants under temperature fluctuations, prevent lubricant degradation at high temperatures, keep engine surfaces clean, and prevent deposit formation. Bismuth, calcium, and magnesium carboxylates are used as friction modifiers, increasing the efficiency of engine and gear systems and reducing friction and energy loss(Totten et al., 2003; Mortier et al., 2011; Rudnick, 2013). 4.5. Flame Retardants Metal-carboxylate complexes exhibit flame retardancy through basic mechanisms such as the formation of a heat-resistant carbon layer, dilution of flammable gases, catalysis of carbonization reactions, and the formation of a protective metal oxide barrier. Zn(II), Al(III), and Fe(III) carboxylates exhibit flame retardancy through the carbonization mechanism, while Ca(II) and Mg(II) carboxylates exhibit flame retardancy through the endothermic mechanism. In the carbonization mechanism, metal ions catalyze the dehydration and cross-linking of polymer chains to form a heat-resistant carbon layer. In the endothermic mechanism, heat is absorbed during the decomposition of carboxylates, releasing non-flammable species such as CO₂ and H₂O. Metal 138   AN OVERVIEW OF COORDINATION CHEMISTRY WITH METALS . . . oxides (ZnO, Al₂O₃, Fe₂O₃) formed by the decomposition of metal carboxylates form a layer on the combustible material, preventing the transfer of heat and oxygen and slowing combustion. Metal carboxylate complexes contribute to the development of environmentally friendly formulations as effective and nontoxic flame retardant additives (Li et al., 2023; Hou et al., 2017; Wang et al., 2020; Nabipour et al., 2020). 4.6. Corrosion Inhibitors Metals are considered unreliable in the constantly changing Earth’s atmosphere and are susceptible to corrosion, which involves their transformation into low-energy inorganic oxides, carbonates, or sulfides. The industrial sector often uses metals in their metastable oxidation states, making them vulnerable to corrosion. Corrosion, a natural chemical process, involves the gradual deterioration of materials, particularly metals, due to their reactions with their environment. Corrosion is a significant threat that degrades metallic assets and the environment, shortening the lifespan of infrastructures and industrial facilities. The use of chemical inhibitors, primarily coordination compounds, as corrosion mitigation methods has the potential to extend the lifespan of infrastructures and provide significant cost savings in terms of equipment, materials, and structures. Metal carboxylate complexes are used as corrosion inhibitors due to their diverse capabilities. These complexes inhibit corrosion both by creating physical barriers and through chemical adsorption. Their ability to form protective films on metal surfaces, complexation reactions, and surface modifications ensure that the surface retains its properties. Metal carboxylate complexes generally inhibit corrosion through adsorption and film formation. Adsorption: Carboxylate groups (–COO⁻) protect the surface by binding to active sites on the metal surface. Film formation: The complex forms a thin, hydrophobic layer on the metal surface, preventing water and oxygen from reaching the surface. Complexation: Metal ions such as Zn²⁺, Co²⁺, and Ni²⁺ increase the stability of the protective layer by forming strong coordination bonds with the carboxylate ligands. Various factors influence the inhibitory effectiveness of metal carboxylate complexes. For example, if the alkyl group to which the carboxyl group is attached is long, hydrophobicity increases and the barrier effect is strengthened. The presence of electron-donating groups in the metal-carboxylate complex increases adsorption strength. Transition metals, especially Zn, Cu, Co, and METAL(MN+) – CARBOXYLATE(COO-) COMPLEXES: BONDING PROPERTIES . . .   139 Ni, exhibit high inhibitory effects because they provide stronger binding to the metal surface(Rudnick, 2013; Vithana et al., 2023; Junk et al., 2020; Akpan, 2023; Zarras and Stenger-Smith, 2020). 4.7. Ceramic and Oxide Precursors Metal carboxylate complexes have emerged as versatile precursors in the synthesis of ceramics and metal oxides due to their well-defined stoichiometry, structural tunability, and clean decomposition into metal-containing residues. These complexes provide precise control over the chemical composition and morphology of the resulting ceramic or oxide materials. Traditional methods (solid-state reactions, precipitation, or hydrothermal processes) often suffer from drawbacks such as high temperatures, long processing times, and low homogeneity. Therefore, metal carboxylate complexes are gaining increasing interest as molecular precursors for oxide and ceramic materials. These complexes, composed of metal ions coordinated to carboxylate ligands (RCOO⁻), can be thermally decomposed under controlled conditions to obtain metal oxides or ceramics. The molecular homogeneity, tunable stoichiometry, and low decomposition temperatures of these precursors enable the synthesis of phase-pure, nanostructured oxides with controlled morphology and particle size. Metal carboxylates offer several advantages over inorganic salts in the preparation of ceramics and oxides. Organic carboxylate ligands decompose at moderate temperatures, reducing the energy required for oxide formation. When thermally decomposed, they produce volatile CO₂ and hydrocarbons, leaving minimal carbon residue. The chain length and branching of the carboxylate ligands influence the particle size, porosity, and surface area of the final oxide. The decomposition of metal carboxylates generally occurs in three stages: dehydration, ligand cleavage, and complete oxidation. Metal carboxylate complexes are widely used in the preparation of simple metal oxides such as ZnO, TiO₂, CuO, and Fe₂O₃, spinel (NiFe₂O₄, CoFe₂O₄), perovskites (BaTiO₃), and multicomponent ceramics(Epifani et al., 2007; Slaughter et al., 2022; Szymańska et al., 2021; Patil, 1993; Zhu et al., 2023; Lu et al., 2020). 4.8. Agricultural Applications Metal carboxylate complexes have gained significant importance in the agricultural sector in recent years due to their solubility, stability, bioavailability, and controlled release properties. Compared to traditional inorganic salts, carboxylate complexes are considered more environmentally friendly, 140   AN OVERVIEW OF COORDINATION CHEMISTRY WITH METALS . . . biodegradable, and more effective metal nutrient carriers. The purpose of using these complexes in agricultural applications is to provide more effectively the micronutrients plants need, thereby increasing yield, improving soil health, and controlling disease. Metal carboxylates are used for various purposes in agriculture. The most common uses are to address common micronutrient deficiencies in plants (Zn, Fe, Mn, and Cu carboxylates); as natural pesticides or fungicides against plant pathogens (Cu and Ag carboxylates); as growth regulators by directly affecting plant metabolism (Mn, Fe, Co, and Ni carboxylates); in soil pollution control thanks to the chelating properties of carboxylate groups; and in controlled release systems by encapsulating them in nanocapsules or polymer matrices(Clemens et al., 1990; Álvarez-Fernández et al., 2014; Nieto-Cantero et al., 2025; Staunton and Pistocchi, 2025; Wei et al., 2022; Wang et al., 2023). 4.9. Photovoltaics and Solar Cells Metal-carboxylate complexes, particularly in the form of organometallic complexes (OMCs) and metal-organic cages (MOFs), show great potential for photovoltaic (PV) and solar cell applications. These complexes are available as active systems or auxiliary systems in various solar cell systems, such as dyesensitized solar cells (DSSCs), organic solar cells (OSCs), and perovskite solar cells (PSCs), to expand device utilization. The main roles of metal-carboxyl complexes in photovoltaic applications are as follows: Dye-Sensitized Solar Cells (DSSCs): Photosensitizing dyes, one of the key components of DSSCs, are generally composed of metal complexes. In the structure of these complexes, carboxylate (COO-) groups serve as holding groups, enabling the dye to bind to the semiconductor (usually TiO2) surface. Ruthenium (Ru) Polypyridyl Complexes are the most well-known dyes for efficient DSSCs. The carboxylate groups in these complexes bind the dye to the conduction band of TiO2 to facilitate electron injection. Perovskite Solar Cells (PSCs): Carboxylate-containing metal complexes and Metal-Organic Framework (MOF) materials are used in various layers of PSCs. MOFs or carboxylate-containing metal complexes can be added as dopants to the perovskite layer to improve device long-term stability and reduce lead Pb2+ leaching. Organic Solar Cells (OSCs): Metal carboxylate complexes are used as light absorbers or interlayer materials in organic solar cells. Transition metal complexes, such as rhenium complexes, can sensitize photovoltaic devices by METAL(MN+) – CARBOXYLATE(COO-) COMPLEXES: BONDING PROPERTIES . . .   141 enhancing optical absorption and providing long-lived excited states. Metalcontaining polymers containing carboxylate-based ligands have been studied to enhance light absorption (Kakiage et al., 2015; Nazeeruddin et al., 1993; Yang et al., 2011; ,Tomara et al., 2020; Shahroosvand et al., 2014; Lv et al. 2023). 4.10. Piezoelectric and Ferroelectric Materials Metal-carboxylate complexes (metal–OOC–R) are an important class of crystalline structures capable of forming non-centrosymmetric (NCS) structures, thanks to the flexibility of the organic linkers and the coordination geometry of the metal centers. A key requirement for piezoelectric and ferroelectric properties is that the crystal lacks an inversion center; therefore, NCS metal-carboxylate structures are natural candidates for these properties. Piezoelectricity is the ability of a material to produce an electric charge when mechanical stress (pressure) is applied if it has a non-centrosymmetric (NCS) crystal structure. The piezoelectric effect was first observed by Jacques and Pierre Curie in 1880. It refers to the distortion of a piezoelectric material when a force is applied in an unsymmetrical direction. Many MOFs and coordination polymers can naturally form NCS structures through the ordered association of metal nodes and carboxylate-containing organic linkers. Thanks to the flexibility of the organic components and the choice of the metal center, it is possible to produce piezoelectric devices (nanogenerators and sensors) that are more flexible and biocompatible than traditional ceramics. Metal carboxylate complexes may exhibit piezoelectric properties for the following reasons: asymmetric coordination environment (monodentate, syn–anti, chelating, etc.); directional alignment of organic ligands; hydrogen bonds and weak interactions forming three-dimensional polar networks; and the natural crystallization of some MOFs and coordination polymers in polar space group systems. Ferroelectricity is the ability of a material to exhibit reversible spontaneous polarization even in the absence of an external electric field. All ferroelectric materials also exhibit piezoelectric properties. Ferroelectric behavior in metal carboxylate complexes arises through ligand conformational changes (order-disorder phase transitions), dipole moment imbalance around the metal center, and polar alignment of asymmetrically bridged carboxylate groups. Piezoelectric materials, which can convert mechanical energy into chemical energy, have emerged as promising catalysts in the fields of environmental wastewater treatment and clean energy production(Tu et al., 2020; Du et al., 2025; Xu, 1991; Jaffe et al., 2012; Haertling, 1999). 142   AN OVERVIEW OF COORDINATION CHEMISTRY WITH METALS . . . 5. Spectroscopic Properites of Metal-Carboxylates Complexes Spectroscopic properties of metal carboxylate complexes are determined by FT-IR and UV spectroscopies, and structural properties are determined using techniques such as XRD and thermal analysis. 5.1. FT-IR Spectroscopy IR spectroscopy is the most important spectroscopic method for characterizing the coordination mode of the carboxylate group to the metal center. The coordination mode of the carboxylate group (–COO−) is understood by the difference Δʋ (ʋas – ʋs) (Table 1)(Nakamoto, 2009). Table 1. Relationship between coordination mode and IR vibrations Coordination Mode ʋas (COO-) (cm-1) ʋs (COO-) (cm-1)Δʋ (ʋas -ʋs ) Monodentate 1650-1550 1350-1300 ~200 cm-1 Bidentate 1620-1550 1400-1300 ~100 cm-1 Bridging 1650-1540 1450-1300 140-200 cm-1 Ionic 1560-1540 1400-1360 ~200 The Metal-O bond is between 400-600 cm-1. Table 2 shows the asymmetric and symmetric vibration values of the COOgroup in the complexes formed by some carboxylic acids with Fe, Mn and Zn metals (Justi et al., 2021). METAL(MN+) – CARBOXYLATE(COO-) COMPLEXES: BONDING PROPERTIES . . .   143 Table 2. Carboxylate symmetric and asymmetric stretching frequencies for different metal carboxylic acid complexes Metal-Organic Acid Stoichiometry ʋ(COO-)asym ʋ(COO-)sym Δʋ(COO-) Citrate - 1559 1357 202 Fe 1:1 1580 1380 200 1:2 1578 1377 201 Mn 1:1 1587 1364 223 1:2 1586 1365 221 Zn 1:1 1573 1380 193 1:2 1575 1375 200 Tartrate - 1578 1394 184 Fe 1:1 1587 1358 236 1:2 1592 1358 234 Mn 1:1 1584 1380 204 1:2 1585 1374 211 Zn 1:1 1589 1379 210 1:2 1586 1375 211 Malate - 1582 1375 207 Fe 1:1 1611 1371 240 1:2 1588 1365 223 Mn 1:1 1592 1383 209 1:2 1604 1375 228 Zn 1:1 1590 1358 231 1:2 1602 1354 248 Oxalate - 1573 1306 267 Fe 1:1 1634 1311 323 1:2 1629 1312 317 Mn 1:1 1628 1310 318 1:2 1636 1307 329 Zn 1:1 1650 1315 335 1:2 1637 1338 299 5.2. Single Crystal X-Ray Diffraction (SCXRD) X-ray analysis of metal carboxylate complexes is one of the most widely used methods to determine the structures, crystallographic properties and bond geometries of such complexes. Using SCXRD in metal-carboxylate complexes, the coordination geometry of the metal center (octahedral, tetrahedral, square 144   AN OVERVIEW OF COORDINATION CHEMISTRY WITH METALS . . . planar, etc.), the bonding modes of the carboxylate group (Monodentate, Bidentate, and Bridging), crystal symmetry, and possible non-centric structures (important for piezoelectric applications) can be determined. 5.3. Thermal Analysis Thermal analysis of metal carboxylate complexes is typically performed using TGA (Thermogravimetric Analysis), DSC (Differential Scanning Calorimetry) and DTG(Derivative TGA) . These methods are used to determine the thermal stability of the complexes, their decomposition behavior, and the loss of ligands or water molecules they contain. The TGA curve shows which components the complex loses at different temperatures: Adsorbed water loss occurs around 50–150 °C, crystalline water loss (coordinated water) occurs around 150–250 °C, and organic ligand decomposition occurs around 250– 450 °C. The metal oxide residue is the mass that remains constant above 500 °C. Thermal Analysis provides information such as Thermal stability (up to which temperature the complex maintains its structure), Ligand number and coordination (Mass loss and temperature regions can indicate the type and number of ligands), Coordination water presence (Initial losses in TGA confirm the presence of coordinated water) and Metal oxide formation (Final mass stabilization can determine which metal oxide is formed). 5.4. UV Spectroscopy In metal–carboxylate complexes, three basic types of electronic transitions are usually found in the UV-Vis spectra: intraligand transitions(Π→Π*), charge transfer transitions(LMCT), and d-d transitions(for transition metals). If the carboxylate group (–COO⁻) is attached to an aromatic ring or a conjugated system, very strong (high ε, λ: 190–240 nm) π→π* transitions are generally observed. Because the O atom in the carboxylate group is an electron donor, moderate/ strong charge transfer is common in the O → Metal direction (λ: 250–350 nm). This transition is most pronounced in metals with high oxidation states (Co(III), Fe(III), etc.). The coordination mode of the carboxylate group (asymmetric or bidentate/bridging) can shift the LMCT bands. d–d transitions typically occur in the visible region, producing a variable number of bands depending on the metal center. Their intensity is weak and appears between 450 and 800 nm. If the carboxylate group is monodentate, the LMCT band shifts to higher energy (shorter wavelength). If it is chelated/ CRYSTAL STRUCTURES OF METAL(II) METHOXYBENZOATO COMPLEXES   247 two 3-methoxybenzoato anions and two nitrogen atoms of the 2,2′-bipyridine molecule coordinate the Cu(II) ion. Here, a monomeric complex is formed as a result of the carboxylate groups’ monodentate bridging coordination behavior as opposed to bidentate bridging coordination behavior (Figure 1).(Lin et al., 2011). Figure 1. Molecular structure of [Cu(C₈H₇O₃)₂(C₁₀H₈N₂)]·H₂O (Lin et al., 2011). The water molecules in the complex do not participate in coordination and are only located within the crystal lattice; the distance between the Copper(II) cation and the O atom of the aqua ligand was determined to be 4.019(2) Å. This allows the complex to crystallize as independent (monomeric) molecular units. Through H-bonding of the O–H···O and C–H···O types, the molecules create a 1D chain that grows into two-dimensional layers and threedimensional networks. However, these interactions are non-coordinative weak supramolecular bonds, thus preserving the monomeric structure. This complex represents a monomeric, distorted octahedral Copper(II) structure formed by the monodentate coordination of 3-methoxybenzoate ligands and the coordination of 2,2′-bipyridine ligands through their nitrogen atoms. Since 248   AN OVERVIEW OF COORDINATION CHEMISTRY WITH METALS . . . the water molecule is not involved in coordination, the complex exists as an independent monomeric unit within the crystal lattice (Lin et al., 2011). Sundberg et al. conducted a comparative investigation of the structures of trans-di(4-methoxybenzoato-O)-bis(1,3-diaminopropane-N,N′)M(II) [M = Cu(II), Ni(II)] compounds. The complexes consist of discrete monomeric units interconnected through hydrogen bonds formed via amino and carboxylate groups. A metal ion on an inversion origin is the center of both complexes (Figure 2). The central Cu(II) or Ni(II) cation is coordinated equatorially by two 1,3-diaminopropane ligands and axially by two 4-methoxybenzoato anions. The methoxybenzoato anions are bonded monodentately through a single oxygen atom, which results in the crystallization of the complexes as independent monomeric structures (Sundberg et al., 1997). Figure 2. Crystal structures of trans-di(4-methoxybenzoato-O)-bis(1,3diaminopropane-N,N′)M(II) [M = Cu(II), Ni(II)] (Sundberg et al., 1997). In both complex units, hydrogen bonds have also been identified between the carboxylate oxygen atoms and the NH2groups. These bonds hold the complex units together only through weak intermolecular interactions without CRYSTAL STRUCTURES OF METAL(II) METHOXYBENZOATO COMPLEXES   249 altering the metal-centered coordination structure. Therefore, these compounds are considered independent monomeric metal complexes within the crystal structure (Sundberg et al., 1997). The trans-di(4-methoxybenzoato-O)-bis(1,3-diaminopropane-N,N′)Cu(II) and Ni(II) complexes are independent monomeric structures formed through the monodentate coordination of carboxylate ligands. Both complexes exhibit a distorted octahedral coordination geometry; a Jahn–Teller elongation is observed in the Copper(II) complex, while a compression related to the highspin configuration is observed in the Nickel(II) complex. These characteristics clearly demonstrate the tendency of methoxybenzoate ligands to form stable monomeric coordination units with metal ions (Sundberg et al., 1997). Hökelek et al. synthesized a monomeric [Zn(C₈H₇O₃)₂(C₆H₆N₂O)₂] complex consisting of three crystallographically independent molecules (Figure 3). Each Zn(II) center is surrounded by three oxygen atoms of two 4-methoxybenzoato anions and the nitrogen atoms of two nicotinamide ligands. (Hökelek, Saka, et al., 2010). Figure 3. Molecular structure of [Zn(C₈H₇O₃)₂(C₆H₆N₂O)₂] (Hökelek, Saka, et al., 2010). The bis(4-methoxybenzoato)-κ²O,O′;κO-bis(nicotinamide-κN1) zinc(II) complex exhibits a monomeric structure in which the coordination number of the Zn(II) center is five, displaying a distorted trigonal- 250   AN OVERVIEW OF COORDINATION CHEMISTRY WITH METALS . . . bipyramidal geometry. The mixed monodentate and bidentate binding modes of the methoxybenzoato ligands enable the complex to crystallize as a stable monomeric unit without transforming into dimeric or polynuclear structures (Hökelek, Saka, et al., 2010). Cai et al. synthesized a monomeric Cu(H₂O)(C₈H₇O₃)₂(C₃N₂H₄)₂ complex with a distorted octahedral geometry, containing one coordinated water molecule, two imidazole ligands, and two 4-methoxybenzoate ligands. The fact that one of the methoxybenzoate ligands acts in a monodentate and the other in a bidentate coordination mode allows the structure to remain stable in a monomeric form without exhibiting polynuclear bridging. Although weak intermolecular hydrogen bonds stabilize the crystal structure in three dimensions, the coordinative monomeric structure remains intact (Cai et al., 2010). Figure 4. Molecular structure of the Cu(H₂O)(C₈H₇O₃)₂(C₃N₂H₄)₂ complex (Cai et al., 2010). Hökelek et al. synthesized a monomeric [Co(C₈H₇O₃)₂(C₆H₆N₂O)(H₂O)₂] complex in which a Co(II) cation is coordinated by two methoxybenzoato anions (one bidentate and the other monodentate), one isonicotinamide ligand, and two aqua molecules, exhibiting a distorted octahedral geometry. This coordination mode prevents the formation of polynuclear networks due to the absence of bridging ligands, thereby maintaining the independence of the monomeric complex. Intermolecular H-bonds and π…π interactions support the three-dimensional stability of the crystal lattice, while the cobalt-centered coordination core retains its completely monomeric character (Hökelek, Süzen, et al., 2010a). CRYSTAL STRUCTURES OF METAL(II) METHOXYBENZOATO COMPLEXES   251 Figure 5. Crystal structure of the [Co(C₈H₇O₃)₂(C₆H₆N₂O)(H₂O)₂] complex (Hökelek, Süzen, et al., 2010a). In the [Co(C₈H₇O₃)₂(C₆H₆N₂O)₂(H₂O)₂]·2H₂O complex synthesized by Hökelek et al., the cobalt(II) ion is located at a crystallographically inverted point (Figure 6). The asymmetric unit consists of one 4-methoxybenzoato anion, one coordinated aqua ligand, one uncoordinated water molecule, and one nicotinamide (NA) ligand. Each ligand has properties related to monodentate binding. (Hökelek, Dal, et al., 2010b). Figure 6. Crystal structure of the Cobalt complex (Hökelek, Dal, et al., 2010b). 252   AN OVERVIEW OF COORDINATION CHEMISTRY WITH METALS . . . An intramolecular O–H···O H-bonds bind the uncoordinated aqua ligand to the carboxylato group inside the compound. The molecules can form a 3D network in the crystal structure as a result of intermolecular O–H···O, N–H···O, and C–H···O H-bonds. These hydrogen bonds support the crystal packing, yet each Co(II) complex unit basically retains its unique monomeric character. (Hökelek, Dal, et al., 2010b). The [Ni(C₈H₇O₃)₂(C₆H₆N₂O)₂(H₂O)₂]·2H₂O compound synthesized by Hökelek et al. (Figure 7) is a monomeric Ni(II) complex with a distorted octahedral geometry, containing two monodentately bound 4-methoxybenzoato anions, two nicotinamide ligands, and two aqua ligands. The monodentate coordination of all ligands prevents the formation of polynuclear or bridging structures, allowing the complex to remain stable in its independent monomeric form. Intermolecular H-bonds and π…π contacts contribute to the 3D crystal stability of the structure; however, these interactions do not affect the monomeric coordination core of the complex (Hökelek, Dal, et al., 2010a). Figure 7. Crystal structure of the Nickel complex (Hökelek, Dal, et al., 2010a). 2.2. Dimeric Complexes Methoxybenzoate ligands, containing two oxygen atoms in the carboxylate group, are capable of coordinating in both monodentate and bidentate fashions. CRYSTAL STRUCTURES OF METAL(II) METHOXYBENZOATO COMPLEXES   253 This flexibility allows the formation of μ-carboxylato (bridging) bonds between two metal centers. Consequently, dimeric complexes are typically formed by the bridging of two metal ions through the oxygen atoms of the carboxylato groups (Kar et al., 2011; D.-Y. Zhao, 2010; L.-P. Zhao, 2010). The [Cu₂(C₈H₇O₃)₄(C₁₀H₈N₂)₂] complex, synthesized by Adelskold et al. (Figure 8), exhibits a dimeric, distorted octahedral structure in which two Cu(II) ions are interconnected by μ₂–O,O′ bridging 4-methoxybenzoate ligands. Copper(II) cations is coordinated by four bridging O atoms and two N atoms from the bipy ligands. The Cu···Cu separation (~2.63 Å) confirms the presence of metal–metal interactions between the cores. These features clearly demonstrate the tendency of 4-methoxybenzoate ligands to form stable dinuclear (dimeric) complexes through the carboxylate oxygen atoms (Adelskold et al., 1989). Figure 8. Crystal structure of the [Cu₂(C₈H₇O₃)₄(C₁₀H₈N₂)₂] complex (Adelskold et al., 1989). The [Cu₂(C₈H₇O₃)₄(CH₃CN)₂] complex, synthesized by Kar et al. (Figure 9), possesses a classical paddle-wheel type dimeric structure composed of two Cu(II) cations bridged by four 3-methoxybenzoate ligands through a μ₂–O,O′ 254   AN OVERVIEW OF COORDINATION CHEMISTRY WITH METALS . . . coordination mode. Each Cu(II) ion exhibits a distorted square-pyramidal coordination geometry involving four bridging O atoms and one N atom from an acetonitrile molecule. Weak metal–metal interactions are supported by the small Cu···Cu distance, and the carboxylate bridges’ stability is improved by the methoxy group’s inductive effect. This structure clearly reveals the tendency of 3-methoxybenzoate ligands to form dimeric Cu(II) complexes (Kar et al., 2011). Figure 9. Crystal structure of the [Cu₂(C₈H₇O₃)₄(CH₃CN)₂] complex (Kar et al., 2011). The [Cd₂(C₈H₇O₃)₄(C₂₀H₂₂N₄O)₂] complex, synthesized by Dian-Ying Zhao forms a paddle-wheel type dimer placed on a crystallographic inversion center. The Cd(II) cation is hexacoordinated by four carboxylato O atoms from two chelating 4-methoxybenzoato anions and two nitrogen atoms from a chelating 2,2′-dimethyl-3,3′-(oxydiethylene)bis(1H-benzimidazole) ligand. The crystal structure connects molecules via a weak intermolecular C—H···O H-bond and an intermolecular C—H···π contacts (Figure 10) (D.- Y. Zhao, 2010). CRYSTAL STRUCTURES OF METAL(II) METHOXYBENZOATO COMPLEXES   255 Figure 10. Molecular structure of the [Cd₂(C₈H₇O₃)₄(C₂₀H₂₂N₄O)₂] (D.-Y. Zhao, 2010). The [Co₂(C₈H₇O₃)₄(C₂₀H₂₂N₄O)₂] complex, synthesized by Lian-Peng Zhao, is a paddle-wheel type dimer located by inversion center. The Cobalt(II) cation is pentacoordinated by three oxygen atoms from two 4-methoxybenzoato anions (one bidentate and one monodentate) and two nitrogen atoms from two 2,2′-bis(2-methyl-1H-benzimidazole)ether ligands. The coordination results in a highly distorted trigonal bipyramidal geometry for the metal cation, with both nitrogen atoms occupying equatorial positions. The molecular configuration is stabilized via intramolecular C—H···O H-bonds (Figure 11) (L.-P. Zhao, 2010). 256   AN OVERVIEW OF COORDINATION CHEMISTRY WITH METALS . . . Figure 11. Structure of the [Co₂(C₈H₇O₃)₄(C₂₀H₂₂N₄O)₂] molecule (L.-P. Zhao, 2010). The [Tb₂(C₈H₇O₃)₆(C₁₂H₈N₂)₂] complex, synthesized by Gao et al. (Figure 12), is a dimeric terbium(III) complex in which two Tb³⁺ ions are interconnected through four μ₂-bridging 4-methoxybenzoate groups. Each terbium center is eight-coordinated with oxygen and nitrogen donor atoms, exhibiting a distorted square antiprismatic geometry. The differing bond lengths of the bridging and terminal carboxylates reflect the flexible binding modes of the ligands. In addition, π…π contacts and C–H···O hydrogen bonds serve as significant supramolecular factors contributing to the stability of the crystal structure (Gao et al., 2009). Figure 12. Structure of the [Tb₂(C₈H₇O₃)₆(C₁₂H₈N₂)₂] molecule (Gao et al., 2009). STRUCTURAL ASPECTS OF NAPROXEN COMPLEXES OF TRANSITION METALS   263 anions, two pyridine ligands, and two aqua molecules, forming a distorted octahedral geometry. The Co–O bond lengths are quite similar (2.090–2.103 Å) and shorter than the Co–N bonds (2.179–2.181 Å). The two pyridine nitrogen atoms occupy the axial locations in the octahedral surroundings, whilst the two naproxenato anions and two aqua molecules occupy the basal plane. The ligand pairs (naproxenato, water, and pyridine) are arranged in trans positions relative to each other. The carboxylate groups of the naproxenato ligands exhibit asymmetric bonding, with C–O distances ranging from approximately 1.24 to 1.29 Å. The crystal structure exhibits polymeric chains made of carboxylate oxygen atoms and aqua ligands, which extend parallel to the a-axis. Additionally, the uncoordinated carboxylate oxygens engage in intramolecular hydrogen bonding with coordinated water molecules. This complex represents the first crystallographically characterized cobalt(II)–naproxenato structure reported in the literatüre (Dimiza et al., 2012). Figure 2. Molecular structure of [Co(nap)₂(py)₂(H₂O)₂] (Dimiza et al., 2012). The cobalt(II) naproxenato complex containing the neocuproine ligand (Fig. 3) is a mononuclear Co(II) complex in which the naproxenato ligands coordinate to the cobalt center in an asymmetric bidentate chelate mode, that is, through both O atoms of the carboxylate group. The complex consists of two naproxenato and one bidentate neocuproine (neoc) ligand, and the cobalt(II) ion is in a six-coordinate geometry. Consequently, the coordination sphere is defined by a CoN₂O₄ chromophore, and the structure exhibits a distorted octahedral geometry. The largest bond angle in the complex, 160.99(9)°, indicates a clear deviation from ideal octahedral symmetry. In one of the naproxenato anions, the Co–O bond lengths differ significantly (Co–O₁ = 2.031(2) Å, Co–O₂ = 2.260(2) Å), which is characteristic of asymmetric chelation. For the other naproxenato anion, the Co–O bond distances are more similar (2.151(2) Å and 2.172(2) Å). The Co–N bond lengths fall in the range of 2.0966(18)–2.126(2) Å. The structural features of this complex are comparable to those of other NSAIDderived Co(II)–neocuproine complexes, such as those containing tolfenamate 264   AN OVERVIEW OF COORDINATION CHEMISTRY WITH METALS . . . and mefenamate ligands, all of which share the common characteristics of bidentate carboxylate coordination and distorted octahedral geometry (Perontsis et al., 2024). Figure 3. Molecular structure of cobalt(II) naproxenato complex containing the neocuproine ligand (Perontsis et al., 2024). In the same study, a cobalt(II) naproxenato complex containing imidazole ligands was also reported, although its structure was characterized using FT-IR spectroscopy, magnetic susceptibility measurements, and related methods. The reported complex is a mononuclear Co(II) compound (consistent with μ_eff ≈ 4.29–4.40 BM). The naproxenato ligand coordinates to the Co(II) ion in a monodentate coordination, through a single oxygen atom of the carboxylate group. The complex also contains two coordinated imidazole (Himi) co-ligands. The cobalt center has a four-coordinate CoN₂O₂ chromophore and a distorted tetrahedral structure. The Δν(COO) values observed in the IR spectra (≈190–216 cm⁻¹) support the monodentate coordination mode of the carboxylate, while the characteristic C–H vibrational band of imidazole (ρ(C– H)_Himi ≈ 749–755 cm⁻¹) confirms the presence of coordinated imidazole ligands (Perontsis et al., 2024). 2.2. Copper(II) Naproxenato Complexes The [Cu₂(nap)₄(DMSO)₂] complex (Figure 4) possesses a binuclear structure, with each Cu(II) center being five-coordinated. Each Cu(II) ion is surrounded by four carboxylate oxygen atoms and one DMSO oxygen atom, forming a {CuO₅} coordination sphere with a distorted square-pyramidal geometry. Cu–O (carboxylato) bond lengths range from 1.958–1.995 Å, while Cu–O (DMSO) bond distances are 2.155 Å for Cu1–O(A) and 2.123 Å for Cu2– O(B), indicating that DMSO acts as a terminal, weakly coordinating ligand. The Cu-Cu distance between the two copper centers is 2.629(1) Å, supporting the presence of bridging carboxylate ligands. The Cu atoms are slightly displaced STRUCTURAL ASPECTS OF NAPROXEN COMPLEXES OF TRANSITION METALS   265 from the carboxylate plane to the DMSO ligand (0.210 Å for Cu1, 0.196 Å for Cu2), reflecting a distortion consistent with square-pyramidal geometry. Overall, the structure consists of two five-coordinated Cu(II) centers linked by bridging carboxylates, forming a terminal-DMSO binuclear copper(II) system. (Dendrinou-Samara et al., 1990). Figure 4. Molecular structure of [Cu₂(Nap)4(DMSO)₂] (Dendrinou-Samara et al., 1990). Single-crystal X-ray diffraction confirmed the crystal architecture of the compound [Cu(nap)₂(3-pyridylmethanol)₂] (Figure 5). The complex features a Cu(II) center with a distorted tetragonal bipyramidal coordination environment. The copper atom is surrounded in the equatorial plane by the carboxylato O atoms of two monodentate naproxenato ligands (Cu–O = 1.943–1.954 Å) and the pyridine nitrogen atoms of two 3-pyridylmethanol molecules (Cu–N = 2.066–2.070 Å). In the axial positions, O atoms from the methanol groups of the same 3-pyridylmethanol ligands originating from adjacent molecules are located, exhibiting longer Cu–O_axial distances (2.397–2.490 Å). Consequently, a tetragonal bipyramidal coordination environment is formed around the Cu(II) cation. The hydrogen atoms of methanolic –OH groups engage in H-bonding with non-coordinated carboxylate O atoms of the naproxenato ligands, resulting in six-membered metallacyclic rings that enhance the structural stability. Furthermore, the 3-pyridylmethanol ligands act as bridging units between neighboring Cu(II) centers, leading to a chain-like polymeric network formed by [Cu(naproxenato)₂(3-pyridylmethanol)₂] units. The angles around the Cu(II) center (O–Cu–O_trans ≈ 177.8°, N–Cu–N_trans ≈ 176.7°) indicate a slightly distorted geometry, closely approaching an ideal bipyramidal arrangement (Abuhijleh & Khalaf, 2010). 266   AN OVERVIEW OF COORDINATION CHEMISTRY WITH METALS . . . Figure 5. Molecular structure of [Cu(nap)₂(3-pyridylmethanol)₂] (Abuhijleh & Khalaf, 2010). The [Cu₂(μ-nap)₄(3-pic)₂] and [Cu(nap)₂(py)₂(H₂O)] complexes (Figures 6 and 7) are described as diand mononuclear copper(II) naproxenato complexes, respectively. In [Cu₂(μ-nap)₄(3-pic)₂], four deprotonated naproxenato (nap) ligands adopt a bridging mode, connecting two neighboring Cu(II) ions via eight carboxylate oxygen atoms. Each copper center is five-coordinated, displaying a distorted square-pyramidal geometry. The calculated structural distortion indices (τ) for Cu1 and Cu2 are 0.125 and 0.118, respectively, indicating geometries close to square-pyramidal (τ = 0 for ideal square-pyramidal, τ = 1 for trigonal-bipyramidal). Cu–N bond lengths range from 2.164(3)–2.180(3) Å, while Cu–O bond lengths range from 1.935(3)–2.029(3) Å. Hydrogen bonds between methoxy groups of naproxenato ligands further stabilize interactions between complex units (Caglar et al., 2014). Figure 6. Molecular structure of [Cu₂(μ-nap)₄(3-pic)₂] (Caglar et al., 2014). STRUCTURAL ASPECTS OF NAPROXEN COMPLEXES OF TRANSITION METALS   267 The [Cu(nap)₂(py)₂(H₂O)] complex is mononuclear, with the Cu(II) ion coordinated by the oxygen atoms of two monodentate naproxenatos, two 4-picoline nitrogens, and one water oxygen. This complex also exhibits squarepyramidal geometry, with a distortion index τ = 0.13. An intramolecular O–H···O H-bond occurred between the hydroxyl proton of the coordinated water molecule and a naproxenato carboxylate oxygen. Additionally, intermolecular O–H···O and C–H···O H-bonds form a supramolecular network. Cu–N(4-picoline) bond lengths range from 2.017(8)–2.062(9) Å, and Cu–O(nap) distances range approximately from 1.96–2.42 Å. These 3-picolineand 4-picoline-containing copper(II) naproxenato complexes display different nuclearities (diand mononuclear), yet both are characterized by square-pyramidal coordination, similar Cu–O and Cu–N bond lengths, and three-dimensional crystal networks stabilized by hydrogen bonding (Caglar et al., 2014). Figure 7. Molecular structure of [Cu(nap)₂(py)₂(H₂O)] (Caglar et al., 2014). The [Cu(4’-(4-methylphenyl)-2,2’:6’,2’’-terpyridine)(nap)Cl]·CH₃OH ((4’-(4-methylphenyl)-2,2’:6’,2’’-terpyridine= L1 and 4’-(2-furyl)-2,2’:6’,2’’- terpyridine= L6) and [Cu(L6)(nap)Cl]·H₂O·½CH₃OH complexes (Figures 8 and 9) have been characterized by single-crystal X-ray method, revealing that both are Cu(II) complexes with distorted octahedral coordination geometries. The [Cu(L1)(nap)Cl]·CH₃OH complex crystallizes in the monoclinic P2₁ space group, with the asymmetric unit containing two independent molecules and two lattice methanol molecules. The Cu(II) center is coordinated by three nitrogen atoms from a terpyridine derivative ligand, one carboxylate oxygen, and one chloride ion, while the second carboxylate oxygen interacts weakly at a distance of 2.959 Å. Cu–N bond lengths range from 1.939–2.087 Å, Cu–O(carboxylate) 268   AN OVERVIEW OF COORDINATION CHEMISTRY WITH METALS . . . is 1.948 Å, and Cu–Cl is 2.427 Å. O–H···O and C–H···Cl H-bonds stabilize intermolecular contacts and the crystal packing. The phenyl ring of the terpyridine ligand is coplanar, and methanol molecules act as bridges within the crystal lattice (Mahendiran et al., 2015). The [Cu(4’-(2-furyl)-2,2’:6’,2’’-terpyridine)(nap)Cl]·H₂O·½CH₃OH compound crystallizes in the triclinic P1 space group, with the asymmetric unit containing two independent complexes along with two water and half a methanol molecule. The Cu(II) ion is coordinated by three nitrogen atoms, one chloride, and carboxylate oxygens. Due to the bulky ligand and bidentate nature of the carboxylate group, a distorted octahedral geometry is observed. Cu–N bond lengths range from 1.92–2.06 Å, Cu–Cl is approximately 2.51 Å, and the second carboxylate oxygen coordinates at 2.73 Å. Water molecules form hydrogen-bonded chains bridging Cl and carboxylate oxygens, stabilizing intermolecular packing. The methoxy group of the naproxen ligand is coplanar with the naphthalene ring, while the furan ring is nearly coplanar with the terpyridine ligand (Mahendiran et al., 2015). Figure 8. Molecular structure of [Cu(4’-(4-methylphenyl)-2,2’:6’,2’’-terpyridine) (nap)Cl]·CH₃OH (Mahendiran et al., 2015). Both complexes maintain the octahedral coordination tendency, but slight distortions arise due to ligand size and geometric constraints. Hydrogen bonding and crystal packing result in a three-dimensional stable arrangement, and the metal–ligand bond lengths and angles are optimized according to the electronic and steric properties of the complexes (Mahendiran et al., 2015). STRUCTURAL ASPECTS OF NAPROXEN COMPLEXES OF TRANSITION METALS   269 Figure 9. Molecular structure of [Cu(4’-(2-furyl)-2,2’:6’,2’’-terpyridine)(nap) Cl]·H₂O·½CH₃OH (Mahendiran et al., 2015). The [Cu(H₂O)₂(C₂H₈N₂)₂(nap)₂·2H₂O] complex, synthesized by Jamil and research groups(2020), contains two different ionic species and features a Cu(II) center with a distorted octahedral coordination geometry. The coordination sphere of the copper(II) ion is defined by a planar N₄ base formed by four N atoms from two ethylenediamine (1,2-diaminopropane) molecules and two axial oxygen atoms provided by water molecules. Cu–N bond lengths are in the range of 2.015(3)–2.024(3) Å, while Cu–O bonds range from 2.495(3)–2.536(3) Å, consistent with typical [CuN₄O₂] octahedral Cu(II) chromophores. The deviation of the Cu1 atom from the equatorial plane is only 0.0204 Å, indicating a nearly regular octahedral environment. The crystal structure contains two naproxen anions. In both naproxen ligands, the acetyl (C=O) group and naphthalene ring adopt planar conformations (r.m.s. deviations 0.0045–0.0235 Å). In the first naproxen anion, the dihedral angle between these two planes is 73.27(13)°, whereas in the other it is 74.27(13)°, indicating only a small torsional difference between the ligands. Moreover, the methoxy group in the first naproxen unit is planar, while in the other it is slightly twisted. N–H···O and O–H···O H-bonds stabilize the molecule, forming a 2-dimensional polymeric network on the (001) plane that extends along the [010] and [100] directions. This supramolecular arrangement maintains the three-dimensional integrity and stability of the crystal lattice (Jamil et al., 2020). 270   AN OVERVIEW OF COORDINATION CHEMISTRY WITH METALS . . . Figure 10. Molecular structure of [Cu(H₂O)₂(C₂H₈N₂)₂(np)₂·2H₂O] (Jamil et al., 2020) 2.3. Manganese(II) Naproxenato Complexes The [Mn(nap)₂(py)(H₂O)₂] and [Mn(nap-O)(nap-O, O’)(phen)(H₂O)] complexes (Figures 11 and 12) are mononuclear and exhibit distorted octahedral coordination geometries. In the [Mn(nap)₂(py)(H₂O)₂] complex, through the carboxylate oxygen atoms, the two naproxen ligands are deprotonated and coordinate to the Mn(II) cation in a monodentate coordination type. The manganese center is additionally coordinated by two pyridine molecules (originating from 2,2’-bipyridine) and two water molecules. The Mn–O bond lengths range from 2.155 to 2.175 Å, while Mn–N bonds are between 2.307 and 2.310 Å. The complex is stabilized through intramolecular and intermolecular H-bonds: the non-coordinated carboxylate O atoms (O12 and O32) form hydrogen bonds with the H atoms of the aqua ligands, while the other hydrogens of the aqua ligands interact with coordinated carboxylate O atoms of neighboring molecules, forming chains along the b crystallographic axis (Dimiza et al., 2018). STRUCTURAL ASPECTS OF NAPROXEN COMPLEXES OF TRANSITION METALS   271 Figure 11. Molecular structure of [Mn(nap)₂(py)(H₂O)₂] (Dimiza et al., 2018) The [Mn(nap-O)(nap-O, O’)(phen)(H₂O)] complex contains two naproxenato ligands coordinated to the Mn(II) cations in different coordination types: one ligand is monodentate, while the other binds in an asymmetric bidentate fashion. The remaining coordination sites of the manganese center are occupied by two nitrogen atoms from the 1,10-phenanthroline ligand and one oxygen atom from a water molecule. This complex also features intermolecular H-bonds forming chains along the b crystallographic axis. Additionally, π···π interactions are observed between the aromatic rings of adjacent 1,10-phenanthroline ligands, with an average plane-to-plane distance of 3.466 Å, further stabilizing the crystal packing. Mn–O bond distances vary from 2.057 to 2.398 Å, Mn–N bond distances range from 2.263 to 2.277 Å, and Mn–O–O angles span 57–148°, reflecting the distortion caused by the bidentate ligand (Dimiza et al., 2018). Figure 9. Molecular structure of [Mn(nap-O)(nap-O,O’)(phen)(H₂O)] (Dimiza et al., 2018) 272   AN OVERVIEW OF COORDINATION CHEMISTRY WITH METALS . . . Both complexes form three-dimensional stable arrangements in the crystal lattice through the binding modes of the ligands and hydrogen bonding, while the octahedral coordination geometry of manganese is slightly distorted due to steric and electronic effects of the ligands (Dimiza et al., 2018). 2.4. Nickel(II) Naproxenato Complexes The compounds [Ni(nap-O)(nap-O,O′)(bipy)(MeOH)] (Figure 13) and [Ni(nap-O)(nap-O,O′)(phen)(H₂O)] (Figure 14) exhibit similar structural features. In both cases, the Ni(II) ion is six-coordinated, forming a NiN₂O₄ chromophore and adopting a distorted octahedral geometry. The two naproxen ligands coordinate differently: one binds via both carboxylate oxygen atoms (O1, O2) in a bidentate chelate mode, while the other coordinates in a monodentate mode through a single oxygen atom (O4). The bond lengths clearly reflect these different coordination modes. Ni–O4 is the shortest (≈2.02 Å), while Ni–O2 is the longest (≈2.19–2.20 Å), showing the strain induced by the chelate ring and the flexibility of the ligand. Intramolecular H-bonds between carboxylate oxygens and the MeOH/H₂O solvent molecules are observed in both structures, contributing to the stabilization of the crystal lattice. Ni–N bond lengths (2.05–2.09 Å) show minor variations depending on the electronic and steric impacts of the bipy and phen molecules. The O–C distances in the carboxylate groups range from 1.23 to 1.27 Å, confirming delocalized carboxylate character due to resonance. Overall, the structural comparison of these two complexes demonstrates that the auxiliary N-donor ligand (bipy vs. phen) and the coordinated solvent molecule (MeOH vs. H₂O) slightly alter the geometric parameters around the metal center. Such subtle differences reflect the delicate balance among bonding nature, hydrogen-bonding effects, and ligand field strength in Ni(II) complexes (Totta et al., 2017). Figure 13. Molecular structure of [Ni(nap-O)(nap-O,O′)(bipy)(MeOH)] (Totta et al., 2017). STRUCTURAL ASPECTS OF NAPROXEN COMPLEXES OF TRANSITION METALS   279 Complex M–O Bond Lengths (Å) M–N Bond Lengths (Å) Notes Reference [Cu(H₂O)₂(C₂H₈N₂)₂(np)₂·2H₂O] 2.495–2.536 2.015–2.024 Octahedral; Mononuclear; two independent naproxen anions; polymeric 2D network (Jamil et al., 2020) [Mn(nap)₂(py)(H₂O)₂] 2.155–2.175 2.307–2.310 Distorted octahedral; Mononuclear; monodentate naproxen (Dimiza et al., 2018) [Mn(nap-O)(nap-O,O’)(phen) (H₂O)] 2.057–2.398 2.263–2.277 Mononuclear; asymmetric bidentate, and monodentate naproxen. (Dimiza et al., 2018) [Ni(1,10-phen)(nap)(solvent)] 2.041–2.196 2.064–2.096 Distorted octahedral Mononuclear; bidentate and monodentate naproxen. (Mirzaei-Kalar et al., 2021). [Ni(nap-O)(nap-O,O′)(bipy) (MeOH)] 2.02–2.19 2.05–2.09 Distorted octahedral; Mononuclear; monodentate naproxen. (Totta et al., 2017) [Ni(nap-O)(nap-O,O′)(phen) (H₂O)] 2.02–2.20 2.05–2.09 Distorted octahedral; Mononuclear; bidentate naproxen. (Totta et al., 2017) [Zn(L)₂(MeOH)₂] 2.00–2.48 – Distorted octahedral Mononuclear; bidentate and monodentate naproxen. (Khandar et al., 2016) [Zn(nap)₂(2,9-dmphen)] 1.927–2.241 2.05–2.09 Tetrahedral and distorted squarepyramidal; bidentate and monodentate naproxen. (Abu Ali et al., 2015) [Zn(nap)₂(dap)] 1.970 2.025 Distorted tetrahedral; Mononuclear; monodentate naproxen. (Chu et al., 2019) 280   AN OVERVIEW OF COORDINATION CHEMISTRY WITH METALS . . . 3. Conclusion Naproxen, a widely recognized non-steroidal anti-inflammatory drug (NSAID), demonstrates not only significant pharmacological relevance but also remarkable versatility as a ligand in the coordination chemistry of transition metals. The comprehensive structural analysis of various metalnaproxen complexes—including cobalt, copper, manganese, nickel, and zinc— highlights how the incorporation of auxiliary ligands profoundly influences the coordination environment, geometry, and supramolecular architecture of these compounds. Across the examined complexes, common structural motifs emerge, such as distorted octahedral or square-pyramidal geometries, diverse modes of naproxen coordination (monodentate, bidentate, or asymmetric chelation), and extensive hydrogen-bonding networks that stabilize the crystal lattice. These features underscore the pivotal role of auxiliary ligands—ranging from pyridine, neocuproine, and 1,10-phenanthroline derivatives to simple solvents like water and methanol—in fine-tuning both the steric and electronic properties of the metal center. Across all studied naproxenato complexes, the M–O(carboxylate) distances generally fall within 1.92–2.20 Å, and the geometries vary from tetrahedral (Zn, Ni) to octahedral (Cu, Mn, Co) depending on the coordination number and the auxiliary ligand. Non-covalent interactions, including hydrogen bonding and π–π stacking, play a key role in the stabilization of the crystal packing and in the formation of supramolecular frameworks. The flexibility of the naproxenato ligand, along with the steric and electronic effects of co-ligands, enables fine-tuning of the coordination geometry and crystal architecture across different metal centers. The findings also reveal that subtle variations in metal identity, auxiliary ligand structure, and solvent coordination can lead to pronounced differences in bond lengths, angles, and overall geometry, reflecting the delicate balance between ligand field effects, steric constraints, and intermolecular interactions. Such tunability not only enriches our understanding of coordination chemistry principles but also positions metal-naproxen complexes as promising candidates for pharmaceutical research, with potential applications in drug design, delivery systems, and bioinorganic investigations. Despite the extensive diversity of complexes reported in the literature, there remains a substantial opportunity for further exploration. The design and synthesis of biologically active metal-naproxen complexes incorporating novel or multifunctional auxiliary ligands could yield new entities with STRUCTURAL ASPECTS OF NAPROXEN COMPLEXES OF TRANSITION METALS   281 enhanced stability, targeted activity, or improved pharmacokinetic profiles. 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