Synthesis and antimicrobial activities of gold(I) sulfanylcarboxylates

ORIGINAL PAPER Synthesis and antimicrobial activities of gold(I) sulfanylcarboxylates Elena Barreiro &José S. Casas &María D. Couce & Agustín Sánchez &Rafael Seoane & Antonio Perez-Estévez &José Sordo Published online: 26 January 2012 #The Author(s) 2012. This article is published with open access at Springerlink.com Abstract Reaction of NaAuCl 4 ·H 2 O and thiodiglycol (1:3 molar ratio) with 3-(aryl)-2-sulfanylpropenoic acids, H 2 xspa0[x:p03-phenyl-, f03-(2-furyl)-, t03-(2-thienyl)-, o-py03-(2-pyridyl)-, Clp03-(2-chlorophenyl)-, -o-mp03- (2-methoxyphenyl)-, -p-mp03-(4-methoxyphenyl)-, -ohp03-(2-hydroxyphenyl)-, -p-hp03-(4-hydroxyphenyl)-, diBr-o-hp03-(3,5-dibromo-2-hydroxyphenyl)] and 2cyclopentylidene-2-sulfanylacetic acid (H 2 cpa) in a 1:1 metal/ligand molar ratio gave compounds of the type [Au(Hxspa)] or [Au(Hcpa)]. These compounds were reacted with diisopropylamine to afford [HQ][Au(xspa)] or [HQ][Au(cpa)] (HQ0diisopropylammonium) and with NaOH to afford Na[Au(xspa)]·H 2 O and Na[Au(cpa)]·H 2 O. All of the new compounds were isolated and characterised by IR and 1 H and 13 C NMR spectroscopy. The antimicrobial activities of the complexes against Escherichia coli,Staphylococcus aureus, Bacillus subtilis,Candida albicans,Pseudomonas aeruginosa and carbapenem-resistant P. a e ru g i no sa were evaluated and compared to those of the equivalent silver(I) complexes. The comparison shows that the gold compounds generally show better activity than the silver analogues against S. aureus and B. subtilis, but low sensitivity against E. coli, P. aeruginosa and C. albicans, suggesting a different mode of antimicrobial action for equivalent silver and gold compounds. Keywords Gold(I) complexes .Sulfanylpropenoic acids . 2-Cyclopentylidene-2-sulfanylacetic acid . Antimicrobial studies Introduction Silver(I) and gold(I) compounds present a variety of biological activities and have various medicinal uses, the study of which has increased in recent years. Silver compounds have mainly been studied for their widely known antibacterial effect; in fact, silver nitrate and certain silver complexes are still used against local infections [1–3]. From this perspective, compounds with Ag kernels have recently been prepared and studied, including examples containing Ag–N[4–7], Ag–O [8–10]andAg–S[11–15] bonds and some with other additional bonds. In previous papers, we have contributed [14,15] to the study of Ag–S by preparing compounds of the type [Ag (HL)], [Ag 2 (L)], [HQ][Ag(L)] (HQ0diisopropylammonium) and Na[Ag(L)]·xH 2 O, where H 2 L is a 3-(aryl)-2-sulfanylpropenoic acid or 2-cyclopentylidene-2-sulfanylacetic acid, which can be present as a monoor bideprotonated system in the complexes. The last two classes of compounds, especially the latter, show activity against certain Gram-positive and Gramnegative bacteria, and also against the yeast Candida albicans; this activity is similar to that shown by other compounds with Ag–Nand/orAg–O bonds except in the case of Escherichia coli, for which they show only low activity. Studies on gold complexes have mainly focused on antiarthritic properties [16–21], but growing interest is evident in antitumoral [22–24], antiparasitic [25] and antibacterial E. Barreiro :J. S. Casas :A. Sánchez :J. Sordo (*) Departamento de Química Inorgánica, Facultade de Farmacia, Universidade de Santiago de Compostela, 15782 Santiago de Compostela Galicia, Spain e-mail: [email protected] M. D. Couce Departamento de Química Inorgánica, Facultade de Ciencias, Universidade de Vigo, 36310 Vigo Galicia, Spain R. Seoane :A. Perez-Estévez Departamento de Microbiología, Facultade de Medicina, Universidade de Santiago de Compostela, 15782 Santiago de Compostela Galicia, Spain Gold Bull (2012) 45:23–34 DOI 10.1007/s13404-011-0040-7 activities. In this last field, the compounds under investigation include a major collection of the type R 3 PAuL, in which the gold atom is coordinated to a phosphine ligand and L is an O- [26,27], N- [28,29], Cl- [30] or S-[29,31–35] donor ligand. Complexes including S-donor ligands as the only ligand include the anionic complexes H[Au(Hmna) 2 ], Na 3 [Au(mna) 2 ](H 2 mna02-mercaptonicotinic acid) [13] and the cationic complexes [Au(L) 2 ](NO 3 ) 3 (L01-[2-(acridin-9-ylamino)ethyl]-1,3-dimethylthiourea) [34]. For the latter ligand, compounds of the type [Au(L)]Br, [Au(L)] SCN and [Au(L)]Cl were also prepared [34]andthe coexistence of an S-donor ligand and a Cl ligand was also described for [LAuCl] (where L02,3-diphenyl-1,3,4thiadiazolium-5-thiolato-S exo )[36]. The activity of some of these complexes is significant against some bacteria or mycobacteria; however, there is a limited number of gold(I) complexes of this class that have been studied and a broad comparative study with equivalent silver(I) complexes having similar ligand/metal stoichiometry has not been carried out. As mentioned above, we have previously prepared [14, 15] several silver(I) complexes containing a variety of sulfanylcarboxylate ligands, thus enabling the aforementioned comparative study. In order to carry out this comparison, we have prepared and characterised equivalent gold(I) complexes of the type [Au(HL)], [HQ][Au(L)] (HQ0diisopropylammonium) and Na[Au(L)]·H 2 O. The activities of these complexes were determined and analysed in light of the results obtained for the equivalent silver(I) complexes. Experimental Materials and methods The 3-(aryl)-2-sulfanylpropenoic acids (Scheme 1)were prepared by condensation of the appropriate aldehyde with rhodanine, subsequent hydrolysis in an alkaline medium and acidification with aqueous HCl. In the preparation of 2cyclopentylidene-2-sulfanylacetic acid, a ketone (cyclopentanone) was used in the condensation reaction instead of an aldehyde [14,15,37]. NaAuCl 4 ·2H 2 O(Aldrich),S (CH 2 CH 2 OH) 2 (Aldrich), diisopropylamine (Merck) and NaOH (Probus) were all used as supplied. Elemental analyses were performed on a Fisons 1108 microanalyser. Melting points were determined with a Büchi apparatus. IR spectra (KBr pellets or Nujol mulls) were recorded on a Bruker IFS66V FT-IR spectrophotometer and are reported in the synthesis section using the following abbreviations: vs0very strong, s0strong, m0medium, w0 weak, sh0shoulder, br0broad. 1 H, 13 C and DEPT NMR spectra in solution were recorded in dimethyl sulfoxide (DMSO)-d 6 at room temperature on a Bruker AMX 300 spectrometer operating at 300.14 MHz ( 1 H) and 75.40 MHz ( 13 C), using 5-mm o.d. tubes; chemical shifts are reported relative to TMS using the solvent signal (δ 1 H02.50 ppm; δ 13 C039.50 ppm) as reference. The splitting of proton resonances in the reported 1 H NMR spectra are defined as s0 singlet, d0doublet, t0triplet, m0multiplet, pst0pseudotriplet and br0broad. The numbering scheme is shown in Scheme 1. Antimicrobial activity Antibacterial activity was initially assayed by Müller– Hinton agar diffusion methods. Compounds 1–11 were suspended in water containing 0.1% of DMSO, the ligands and compounds 12–22 were dissolved in ethanol and compounds 23–33 were dissolved in water. Paper discs (5 mm in diameter) were impregnated with 20 μL of a 2 mg/cm 3 solution or suspension of the substance to be tested and control discs were impregnated with solvent alone. The discs were then placed on dishes of Müller–Hinton agar inoculated with Staphylococcus aureus (ATCC29213), Bacillus subtilis (ATCC6633), Escherichia coli (ATCC25922), Pseudomonas aeruginosa (ATCC27853) and a carbapenemresistant strain of P. aeruginosa (hereafter “resistant P. aeruginosa”). After incubation for 24 h at 37°C, the diameters of the bacterial growth inhibition zones were measured. All assays were carried out in duplicate. For products that showed activity, serial dilutions in Müller–Hinton broth were used as described in the literature [38] to determine the minimum inhibitory concentration (MIC), which is defined as the lowest concentration of the substance under test that inhibits the visible growth of the test organism when the latter is at optimal concentration. Minimum bactericidal concentration (MCB) was also determined for active compounds. Briefly, after MIC determination (24 h of exposure to compounds) bacterial cultures were subcultured in plates of solid medium without test compounds and incubated for 24 h. MCB was defined as the lowest concentration able to prevent bacterial growth in the first 24 h after compound removal. Synthesis Complexes of the type [Au(HL)] Complexes 1–11 were prepared by adding a stirred solution of NaAuCl 4 ·H 2 OandS (CH 2 CH 2 OH) 2 (thiodiglycol) in a 1:3 molar ratio in water to a solution of the appropriate sulfanylcarboxylic acid (metal/ ligand molar ratio 1:1) in ethanol. The mixture was stirred at room temperature for 1 h and the resulting solid was filtered off, washed with ethanol, water and ether and dried in vacuo. [Au(Hpspa)] (1). H 2 pspa (0.07 g, 0.38 mmol), NaAuCl 4 ·3H 2 O (0.15 g, 0.38 mmol), thiodiglycol (0.11 cm 3 ), ethanol (3 cm 3 ), H 2 O(5cm 3 ), yellow solid. 24 Gold Bull (2012) 45:23–34 Yield: 75%; mp: 190°C. (Found: C 28.5, H 1.7, S 8.7%. Calc. for C 9 H 7 O 2 SAu: C 28.7, H 1.9, S 8.5%). IR (cm −1 ): 1,680 vs, ν(C0O); 1,446 s, δ(OH); 1,253 vs, ν(C–O). NMR (DMSO-d 6 ): 1 H, δ13.14 (s, 1H, C(1) OH), 7.84 (s, 1H, C(3)H), 7.67 (d, 2H, C(5)H, C(9)H), 7.41 (pst, 2H, C(6)H, C(8)H), 7.28 (m, 1H, C(7)H); 13 C, δ166.0 C(1), 128.8 C(2), 144.3 C(3), 133.7 C(4), 130.6 C(5) and C(9), 128.3 C(6) and C(8), 129.9 C(7). [Au(Hfspa)] (2). H 2 fspa (0.06 g, 0.38 mmol), NaAuCl 4 ·3H 2 O (0.15 g, 0.38 mmol), thiodiglycol Scheme 1 The numbering scheme of 3-(aryl)- 2-sulfanylpropenoic acids and 2-cyclopentylidene-2sulfanylacetic acid and synthesis of complexes Gold Bull (2012) 45:23–34 25 (0.11 cm 3 ), ethanol (3 cm 3 ), H 2 O(5cm 3 ), brown solid. Yield: 86%; mp: 182°C. (Found: C 22.8, H 1.4, S 8.5%. Calc. for C 7 H 5 O 3 SAu: C 23.0, H 1.4, S 8.8%). IR (cm −1 ): 1,663 vs, ν(C0O); 1,466 vs, δ(OH); 1,281 vs br, ν(C–O). NMR (DMSO-d 6 ): 1 H, δ12.97 (brs, 1H, C (1)OH), 7.61 (s, 1H, C(3)H), 7.25 (d, 1H, C(5)H), 6.68 (m, 1H, C(6)H), 7.89 (d, 1H, C(7)H); 13 C, δ165.9 C(1), 124.0 C(2), 131.5 C(3), 149.4 C(4), 118.4 C(5), 113.0 C(6), 146.3 C(7). [Au(Htspa)] (3). H 2 tspa (0.07 g, 0.38 mmol), NaAuCl 4 ·3H 2 O (0.15 g, 0.38 mmol), thiodiglycol (0.11 cm 3 ), ethanol (3 cm 3 ), H 2 O(5cm 3 ), green solid. Yield: 85%; mp: 207°C. (Found: C 22.3, H 1.2, S 16.5%. Calc. for C 7 H 5 O 2 S 2 Au: C 22.0, H 1.3, S 16.8%). IR (cm −1 ): 1,674 vs, ν(C0O); 1,408 s, δ(OH); 1,270 vs, ν(C–O). NMR (DMSO-d 6 ): 1 H, δ12.57 (brs, 1H, C(1)OH), 8.19 (s, 1H, C(3)H), 7.67 (d, 1H, C(5)H), 7.17 (pst, 1H, C(6)H), 7.89 (d, 1H, C(7)H); 13 C, δ 166.1 C(1), 123.0 C(2), 137.6 C(3), 137.6 C(4), 140.3 C(5), 127.1 C(6), 134.2 C(7). [Au(H-o-pyspa)] (4). H 2 -o-pyspa (0.07 g, 0.38 mmol), NaAuCl 4 ·3H 2 O (0.15 g, 0.38 mmol), thiodiglycol (0.11 cm 3 ), ethanol (3 cm 3 ), H 2 O(5cm 3 ), pale yellow solid. Yield: 85%; mp: 190°C. (Found: C 25.4, H 1.5, N 3.4, S 8.3%. Calc. for C 8 H 6 O 2 SNAu: C 25.5, H 1.6, N 3.7, S 8.5%). IR (cm −1 ): 1,694 s, ν(C0O); 1,466 m br, δ(OH); 1,250 vs, ν(C–O). NMR (DMSO-d 6 ): 1 H, δ7.00 (s, 1H, C(3)H), 8.30 (d, 1H, C(5)H), 8.10 (pst t, 1H, C(6) H), 7.22 (pst, 1H, C(7)H), 8.55 (d, 1H, C(8)H); 13 C, δ 165.1 C(1), 136.0 C(2), 134.1 C(3), 154.5 C(4), 150.0 C (5), 134.0 C(6), 121.0 C(7), 124.0 C(8). [Au(HClpspa)] (5). H 2 Clpspa (0.08 g, 0.38 mmol), NaAuCl 4 ·3H 2 O (0.15 g, 0.38 mmol), thiodiglycol (0.11 cm 3 ), ethanol (3 cm 3 ), H 2 O(5cm 3 ), yellow solid. Yield: 84%; mp: 183°C. (Found: C 26.6, H 1.3, S 7.5%. Calc. for C 9 H 6 O 2 SClAu: C 26.3, H 1.5, S 7.8%). IR (cm −1 ): 1,689 vs, ν(C0O); 1,436 s, δ(OH); 1,247 s, ν(C–O). NMR (DMSO-d 6 ): 1 H, δ13.53 (brs, 1H, C (1)OH), 7.86 (s, 1H, C(3)H), 7.46 (d, 1H, C(6)H), 7.31 (pst t, 2H, C(7)H), 7.38 (pst, 2H, C(8)H), 7.61 (d, 1H, C (9)H); 13 C, δ166.6 C(1), 127.8 C(2), 139.7 C(3), 132.5 C(4), 133.5 C(5), 130.7 C(6), 131.3 C(7), 126.9 C(8), 129.3 C(9). [Au(H-o-mpspa)] (6). H 2 -o-mpspa (0.08 g, 0.38 mmol), NaAuCl 4 ·3H 2 O (0.15 g, 0.38 mmol), thiodiglycol (0.11 cm 3 ), ethanol (3 cm 3 ), H 2 O(5cm 3 ), pale yellow solid. Yield: 77%; mp: 203°C. (Found: C 29.2, H 2.5, S 8.0%. Calc. for C 10 H 9 O 3 SAu: C 29.6, H 2.2, S 7.9%). IR (cm −1 ): 1,685 vs, ν(C0O); 1,463 s, δ(OH); 1,249 vs, ν(C–O). NMR (DMSO-d 6 ): 1 H, δ13.15 (brs, 1H, C(1) OH), 8.00 (s, 1H, C(3)H), 7.70 (d, 1H, C(6)H), 6.97 (pst, 1H, C(7)H), 7.40 (t, 1H, C(8)H), 7.05 (d, 1H, C(9) H), 3.79 (s, 3H, OCH 3 ); 13 C, δ167.1 C(1), 128.8 C(2), 139.4 C(3), 122.3 C(4), 157.5 C(5), 111.1 C(6), 131.6 C(7), 119.8 C(8), 130.3 C(9), 55.5 C(OCH 3 ). [Au(H-p-mpspa)] (7). H 2 -p-mpspa (0.08 g, 0.38 mmol), NaAuCl 4 ·3H 2 O (0.15 g, 0.38 mmol), thiodiglycol (0.11 cm 3 ), ethanol (3 cm 3 ), H 2 O(5cm 3 ), yellow solid. Yield: 92%; mp: 215°C. (Found: C 29.5, H 2.2, S 7.5%. Calc. for C 10 H 9 O 3 SAu: C 29.6, H 2.2, S 7.9%). IR (cm −1 ): 1,674 vs, ν(C0O); 1,438 m, δ(OH); 1,256 vs br, ν(C–O). NMR (DMSO-d 6 ): 1 H, δ13.10 (brs, 1H, C (1)OH), 7.79 (s, 1H, C(3)H), 7.83 (d, 2H, C(5)H, C(9) H), 6.95 (d, 2H, C(6)H, C(8)H), 3.80 (s, 3H, OCH 3 ); 13 C, δ166.5 C(1), 125.1 C(2), 144.8 C(3), 126.2 C(4), 133.0 C(5) and C(9), 113.8 C(6) and C(8), 160.7 C(7), 55.3 C(OCH 3 ). [Au(H-o-hpspa)] (8). H 2 -o-hpspa (0.07 g, 0.38 mmol), AuCl 4 Na·3H 2 O (0.15 g, 0.38 mmol), thiodiglycol (0.11 cm 3 ), ethanol (3 cm 3 ), H 2 O(5cm 3 ), orange solid. Yield: 91%; mp: 190°C. (Found: C 27.6, H 1.8, S 8.6%. Calc. for C 9 H 7 O 3 SAu: C 27.6, H 1.8, S8.2%).IR(cm −1 )1,686vs,ν(C0O); 1,452 s, δ(OH); 1,250 vs, ν(C–O). NMR (DMSO-d 6 ): 1 H, δ13.16 (brs, 1H, C(1)OH), 7.97 (s, 1H, C(3)H), 9.99 (s, 1H, C(5)OH), 7.84 (d, 1H, C(6)H), 7.10 (pst,1H,C(7)H),6.82(pst,1H,C(8)H),7.75(d, 1H, C(9)H); 13 C, δ167.5 C(1), 121.4 C(2), 139.0 C(3), 123.2 C(4), 156.0 C(5), 115.4 C(6), 131.1 C(7), 118.2 C(8), 130.9 C(9). [Au(H-p-hpspa)] (9). H 2 -p-hpspa (0.07 g, 0.38 mmol), NaAuCl 4 ·3H 2 O (0.15 g, 0.38 mmol), thiodiglycol (0.11 cm 3 ), ethanol (3 cm 3 ), H 2 O(5cm 3 ), orange solid. Yield: 65%; mp: 205°C. (Found: C 27.5, H 2.0, S 8.2%. Calc. for C 9 H 7 O 3 SAu: C 27.6, H 1.8, S 8.2%). IR (cm −1 ): 1,675 vs, ν(C0O); 1,433 m, δ(OH); 1,245 s br, ν(C–O). NMR (DMSO-d 6 ): 1 H, δ12.91 (brs, 1H, C (1)OH), 7.74 (s, 1H, C(3)H), 7.77 (d, 2H, C(5)H, C(9) H), 6.77 (d, 2H, C(6)H, C(8)H), 10.18 (s, 1H, C(7)OH); 13 C, δ166.7 C(1), 123.6 C(2), 145.4 C(3), 124.7 C(4), 133.4 C(5) and C(9), 115.3 C(6) and C(8), 159.7 C(7). [Au(H-diBr-o-hpspa)] (10). H 2 diBr-o-hpspa (0.13 g, 0.38 mmol), NaAuCl 4 ·3H 2 O (0.15 g, 0.38 mmol), thiodiglycol (0.11 cm 3 ), ethanol (3 cm 3 ), H 2 O(5cm 3 ), yellow solid. Yield: 83%; mp: 238°C. (Found: C 19.8, H 0.8, S 5.5%. Calc. for C 9 H 5 O 3 SBr 2 Au: C 19.6, H 0.9, S5.8%).IR(cm −1 ): 1,690 vs, ν(C0O); 1,448 vs, δ(OH); 1,255 vs, ν(C–O). NMR (DMSO-d 6 ): 1 H, δ 13.30 (brs, 1H, C(1)OH), 7.87 (s, 1H, C(3)H), 9.95 (brs, 1H, C(5)OH), 7.75 (s, 1H, C(7)H), 7.59 (s, 1H, C(9)H); 13 C, δ166.7 C(1), 126.5 C(2), 132.1 C(3), 127.0 C(4), 151.3 C(5), 112.8 C(6), 137.4 C(7), 110.6 C(8), 135.1 C(9). [Au(Hcpa)] (11). H 2 cpa (0.06 g, 0.38 mmol), NaAuCl 4 ·3H 2 O (0.15 g, 0.38 mmol), thiodiglycol (0.11 cm 3 ), ethanol (3 cm 3 ), H 2 O(5cm 3 ), brown solid. 26 Gold Bull (2012) 45:23–34 Yield: 80%; mp: 207°C. (Found: C 23.5, H 2.6, S 9.3%. Calc. for C 7 H 9 O 2 SAu: C 23.7, H 2.6, S 9.0%). IR (cm −1 ): 1,668 vs, ν(C0O); 1,413 vs, δ(OH); 1,274 vs, ν(C–O). NMR (DMSO-d 6 ): 1 H, δ12.52 (brs, 1H, C(1) OH), 2.67 (m, 2H, C(4)H 2 ), 1.67 (m, 2H, C(5)H 2 ), 1.57 (m, 2H, C(6)H 2 ), 2.56 (m, 2H, C(7)H 2 ); 13 C, δ171.3 C (1), 119.7 C(2), 166.5 C(3), 36.0 C(4), 26.5 C(5), 25.0 C(6), 35.0 C(7). Complexes of the type [HQ][Au(L)] Complexes 12–22 (HQ0diisopropylammonium) were prepared by adding diisopropylamine to a suspension of the appropriate [Au(HL)] complex in ethanol. The mixture was stirred at room temperature for 24 h. The resulting solid was filtered off and dried in vacuo, and the ethanol was evaporated from the filtrate at room temperature. [HQ][Au(pspa)] (12). [Au(Hpspa)] (0.08 g, 0.20 mmol), diisopropylamine (0.03 cm 3 0.20 mmol), ethanol (9 cm 3 ), white solid. Yield: 75%; mp: 207°C. (Found: C 37.5, H 4.2, S 6.5, N 2.8%. Calc. for C 15 H 22 O 2 SNAu: C 37.7, H 4.6, S 6.7, N 2.9%). IR (cm −1 ): 1,629 s, ν(NH 2+ ); 1,569 s, ν asym (CO 2 − ); 1,345 vs, ν sym (CO 2 − ). NMR (DMSO-d 6 ): 1 H, δ7.60 (s, 1H, C(3)H), 7.42 (d, 2H, C(5)H, C(9)H), 7.33 (pst, 2H, C(6)H, C(8)H), 7.20 (m, 1H, C(7)H), 1.19 (d, 12H, [Q]CH 3 ), 3.23 (m, 2H, [Q] CH); 13 C, δ171.9 C(1), 127.4 C(2), 143.0 C(3), 136.8 C (4), 130.3 C(5) and C(9), 128.2 C(6) and C(8), 129.6 C (7), 46.1 CH[HQ], 19.6 CH 3 [HQ]. [HQ][Au(fspa)] (13). [Au(Hfspa)] (0.07 g, 0.20 mmol), diisopropylamine (0.03 cm 3 0.20 mmol), ethanol (8 cm 3 ), brown solid. Yield: 63%; mp: 194°C. (Found: C 33.2, H 4.3, S 6.9, N 2.8%. Calc. for C 13 H 20 O 3 SNAu: C 33.4, H 4.3, S 6.9, N 3.0%). IR (cm −1 ): 1,621 s br, ν(NH 2+ ); 1,553 s br, ν asym (CO 2 − ); 1,339 vs, ν sym (CO 2 − ). NMR (DMSO-d 6 ): 1 H, δ7.40 (s, 1H, C(3)H), 7.13 (d, 1H, C(5)H), 6.55 (m, 1H, C(6)H), 7.66 (d, 1H, C(7)H), 1.24 (d, 12H, [Q]CH 3 ), 3.29 (m, 2H, [Q]CH), 8.97 (s, 2H, [Q]NH 2+ ); 13 C, δ170.2 C(1), 34.8 C(2), 122.8 C(3), 152.6 C(4), 111.8 C(5), 110.5 C(6), 141.8 C(7), 5.3 CH [HQ], 19.3 CH 3 [HQ]. [HQ][Au(tspa)] (14). [Au(Htspa)] (0.07 g, 0.16 mmol), diisopropylamine (0.024 cm 3 0.16 mmol), ethanol (8 cm 3 ), brown solid. Yield: 53%; mp: 203°C. (Found: C 32.0, H 4.3, S 13.4, N 2.6%. Calc. for C 13 H 24 O 2 S 2NAu: C 32.3, H 4.2, S 13.3, N 2.9%). IR (cm −1 ): 1,622 vs, ν(NH 2+ ); 1,565 vs, ν asym (CO 2 − ); 1,334 vs, ν sym (CO 2 − ). NMR (DMSO-d 6 ): 1 H, δ7.77 (s, 1H, C(3) H), 7.31 (d, 1H, C(5)H), 7.04 (pst, 1H, C(6)H), 7.54 (d, 1H, C(7)H), 1.24 (d, 12H, [Q]CH 3 ), 3.27 (m, 2H, [Q] CH), 9.07 (s, 2H, [Q]NH 2+ ); 13 C, δ169.9 C(1), 24.9 C(2), 36.1 C(3), 41.9 C(4), 132.5 C(5), 126.7 C(6), 126.2 C(7), 5.6 CH[HQ], 18.9 CH 3 [HQ]. [HQ][Au(-o-pyspa)] (15). [Au(H-o-pyspa)] (0.06 g, 0.17 mmol), diisopropylamine (0.026 cm 3 , 0.17 mmol), ethanol (7 cm 3 ), orange solid. Yield: 76%; mp: 194°C. (Found: C 34.9, H 4.6, S 6.5, N 5.6%. Calc. for C 14 H 21 O 2 SN 2 Au: C 35.1, H 4.4, S 6.7, N 5.9%). IR (cm −1 ): 1,610 m sh, ν(NH 2+ ); 1,579 vs, ν asym (CO 2 − ); 1,354 vs, ν sym (CO 2 − ). NMR (DMSO-d 6 ): 1 H, δ6.99 (s, 1H, C(3)H), 7.63 (d, 1H, C(5)H), 7.82 (pst, 1H, C(6)H), 7.20 (pst, 1H, C(7)H), 8.32 (d, 1H, C(8)H), 3.18 (d, 12H, [Q]CH 3 ), 1.19 (m, 2H, [Q]CH); 13 C, δ170.3 C(1), 134.8 C(2), 137.2 C(3), 152.0 C(4), 143.5 C(5), 130.3 C(6), 122.3 C(7), 126.8 C(8), 45.9 CH[HQ], 18.8 CH 3 [HQ]. [HQ][Au(Clpspa)] (16). [Au(HClpspa)] (0.05 g, 0.16 mmol), diisopropylamine (0.024 cm 3 0.16 mmol), ethanol (6 cm 3 ), white solid. Yield: 88%; mp: 179°C. (Found: C 34.9, H 4.2, S 6.4, N 2.8%. Calc. for C 15 H 21 O 2 SNClAu: C 35.2, H 4.1, S 6.3, N 2.7%). IR (cm −1 ): 1,623 vs, ν(NH 2+ ); 1,570 vs br, ν asym (CO 2 − ); 1,346 vs, ν sym (CO 2 − ). NMR (DMSO-d 6 ): 1 H, δ7.66 (s, 1H, C(3)H), 7.40 (d, 1H, C(6)H), 7.13 (m, 1H, C(7)H, C(8)H), 7.47 (d, 1H, C(9)H), 1.21 (d, 12H, [Q]CH 3 ), 3.29 (m, 2H, [Q]CH), 9.10 (s, 2H, [Q]NH 2+ ); 13 C, δ 171.8 C(1), 125.8 C(2), 136.5 C(3), 135.1 C(4), 134.3 C(5), 130.2 C(6), 131.0 C(7), 136.6 C(8), 128.9 C(9), 45.8 CH[HQ], 19.2 CH 3 [HQ]. [HQ][Au(-o-mpspa)] (17). [Au(H-o-mpspa)] (0.07 g, 0.17 mmol), diisopropylamine (0.027 cm 3 , 0.17 mmol), ethanol (8 cm 3 ), beige solid. Yield: 66%; mp: 177°C. (Found: C 37.4, H 4.5, S 6.8, N 2.5%. Calc. for C 16 H 24 O 3 SNAu: C 37.9, H 4.8, S 6.3, N 2.8%). IR (cm −1 ): 1,620 vs, ν(NH 2+ ); 1,565 vs, ν asym (CO 2 − ); 1,346 vs, ν sym (CO 2 − ). NMR (DMSO-d 6 ): 1 H, δ7.53 (s, 1H, C(3)H), 7.67 (d, 1H, C(6)H), 6.90 (m, 2H, C(7) H and C(9)H), 7.15 (pst, 1H, C(8)H), 3.75 (s, 3H, OCH 3 ), 1.21 (d, 12H, [Q]CH 3 ), 3.24 (m, 2H, [Q]CH), 8.80 (s, 2H, [Q]NH 2+ ); 13 C, δ168.7 C(1), 129.0 C(2), 137.3 C(3), 125.0 C(4), 156.8 C(5), 110.5 C(6), 133.4 C(7), 119.3 C(8), 130.6 C(9), 55.1 C(OCH 3 ), 45.5 CH [HQ], 19.0 CH 3 [HQ]. [HQ][Au(-p-mpspa)] (18). [Au(H-p-mpspa)] (0.07 g, 0.17 mmol), diisopropylamine (0.027 cm 3 , 0.17 mmol), ethanol (8 cm 3 ), pale orange solid. Yield: 67%; mp: 198°C. (Found: C 37.9, H 4.6, S 6.2, N 2.6%. Calc. for C 16 H 24 O 3 SNAu: C 37.9, H 4.8, S 6.3, N 2.8%). IR (cm −1 ): 1,627 m, ν(NH 2+ ); 1,570 vs, ν asym (CO 2 − ); 1,348 vs, ν sym (CO 2 − ). NMR (DMSO-d 6 ): 1 H, δ7.41 (s, 1H, C(3)H), 7.66 (d, 2H, C(5)H, C(9)H), 6.88 (d, 2H, C(6)H, C(8)H), 3.70 (s, 3H, OCH 3 ), 1.22 (d, 12H, [Q]CH 3 ), 3.24 (m, 2H, [Q]CH), 9.09 (s, 2H, [Q]NH 2+ ); 13 C, δ169.0 C(1), 114.2 C(2), 134.9 C(3), 131.1 C(4), 131.4 C(5) and C(9), 113.2 C(6) and C(8), 158.5 C(7), 54.9 C(OCH 3 ), 45.5 CH[HQ], 19.1 CH 3 [HQ]. Gold Bull (2012) 45:23–34 27 [HQ][Au(-o-hpspa)] (19). [Au(H-o-hpspa)] (0.06 g, 0.17 mmol), diisopropylamine (0.027 cm 3 , 0.17 mmol), ethanol (7 cm 3 ), pale orange solid. Yield: 70%; mp: 192°C. (Found: C 36.3, H 4.2, S 6.6, N 2.6%. Calc. for C 15 H 22 O 3 SNAu: C 36.5, H 4.5, S 6.5, N 2.8%). IR (cm −1 ): 1,600 vs, ν(NH 2+ ); 1,558 vs, ν asym (CO 2 − ); 1,350 vs, ν sym (CO 2 − ). NMR (DMSO-d 6 ): 1 H, δ7.70 (s, 1H, C(3)H), 8.52 (s, 1H, C(5)OH), 6.86 (d, 1H, C(6) H), 7.05 (pst, 1H, C(7)H), 6.68 (pst, 1H, C(8)H), 7.87 (d, 1H, C(9)H), 3.21 (d, 12H, [Q]CH 3 ), 1.20 (m, 2H, [Q]CH); 13 C, δ171.3 C(1), 122.3 C(2), 136.6 C(3), 128.2 C(4), 155.7 C(5), 115.0 C(6), 131.3 C(7), 118.6 C(8), 131.5 C(9), 45.5 CH[HQ], 18.7 CH 3 [HQ]. [HQ][Au(-p-hpspa)] (20). [Au(H-p-hpspa)] (0.05 g, 0.11 mmol), diisopropylamine (0.016 cm 3 0.11 mmol), ethanol (6 cm 3 ), pale yellow solid. Yield: 82%; mp: 207°C. (Found: C 36.3, H 4.7, S 6.6, N 2.6%. Calc. for C 15 H 22 O 3 SNAu: C 36.5, H 4.5, S 6.5, N 2.8%). IR (cm −1 ): 1,606 vs, ν(NH 2+ ); 1,558 vs, ν asym (CO 2 − ); 1,345 vs, ν sym (CO 2 − ). NMR (DMSO-d 6 ): 1 H, δ7.57 (s, 1H, C (3)H), 7.82 (d, 2H, C(5)H, C(9)H), 6.75 (d, 2H, C(6)H, C (8)H), 8.90 (s, 1H, C(7)OH), 3.27 (d, 12H, [Q]CH 3 ), 1.19 (m, 2H, [Q]CH), 9.60 (s, 2H, [Q]NH 2+ ); 13 C, δ171.2 C (1), 124.3 C(2), 129.0 C(4), 131.5 C(5) and C(9), 114.5 C (6) and C(8), 158.4 C(7), 45.5 CH[HQ], 20.0 CH 3 [HQ]. [HQ][Au(-diBr-o-hpspa)] (21). [Au(H-diBr-o-hpspa)] (0.07 g, 0.20 mmol), diisopropylamine (0.03 cm 3 0.20 mmol), ethanol (8 cm 3 ), yellow solid. Yield: 76%; mp: 189°C. (Found: C 34.9, H 4.5, S 5.5, N 5.5%. Calc. for C 15 H 20 O 3 SBr 2 NAu: C 27.7, H 3.1, S 4.9, N 2.1%). IR (cm −1 ): 1,605 s br, ν(NH 2+ ); 1,566 vs br, ν asym (CO 2 − ); 1,347 vs, ν sym (CO 2 − ). NMR (DMSO-d 6 ): 1 H, δ7.67 (s, 1H, C(3)H), 0.80 (br, 1H, C(5)OH), 7.54 (s, 1H, C(7)H), 7.32 (s, 1H, C(9)H), 3.20 (d, 12H, [Q]CH 3 ), 1.13 (m, 2H, [Q]CH); 13 C, δ171.6 C(1), 126.0 C(2), 135.6 C(3), 126.8 C(4), 155.3 C(5), 116.4 C(6), 136.3 C(7), 113.0 C(8), 132.8 C(9), 45.8 CH[HQ], 19.8 CH 3 [HQ]. [HQ][Au(cpa)] (22). [Au(Hcpa)] (0.07 g, 0.18 mmol), diisopropylamine (0.028 cm 3 0.18 mmol), ethanol (8 cm 3 ), beige solid. Yield: 58%; mp: 172°C. (Found: C 34.3, H 5.1, S 6.8, N 3.2%. Calc. for C 13 H 24 O 2 SNAu: C 34.3, H 5.3, S 7.0, N 3.1%). IR (cm −1 ): 1,617 vs, ν(NH 2+ ); 1,543 vs, ν asym (CO 2 − ); 1,357 vs, ν sym (CO 2 − ). NMR (DMSO-d 6 ): 1 H, δ2.57 (m, 2H, C(4)H 2 ), 1.65 (m, 2H, C(5)H 2 ), 1.65 (m, 2H, C(6)H 2 ), 2.57 (m, 2H, C(7) H 2 ), 3.22 (d, 12H, [Q]CH 3 ), 1.13 (m, 2H, [Q]CH); 13 C, δ 171.5 C(1), 133.2 C(2), 61.3 C(3), 37.2 C(4), 28.0 C(5), 26.1 C(6), 35.1 C(7), 45.5 CH[HQ], 19.2 CH 3 [HQ]. Complexes of the type Na[Au(L)]·H 2 OComplexes 23–33 were prepared by adding NaOH to a suspension of the appropriate [Au(HL)] complex in water. The mixture was stirred at room temperature for 24 h, the solution was passed through a folded filter paper (Whatman No. 42) and the solvent was evaporated at room temperature. Na[Au(pspa)]·H 2 O(23). [Au(Hpspa)] (0.05 g, 0.13 mmol), NaOH (0.005 g, 0.13 mmol), H 2 O(5cm 3 ), pale yellow solid. Yield: 55%; mp: 215°C. (Found: C 26.0, H 1.8, S 7.2%. Calc. for C 9 H 8 O 3 SAuNa: C 26.0, H 1.9, S 7.7%). IR (cm −1 ): 1,573 vs, ν asym (CO 2 − ); 1,368 vs, ν sym (CO 2 − ). NMR (DMSO-d 6 ): 1 H, δ7.58 (s, 1H, C(3) H), 7.85 (d, 2H, C(5)H, C(9)H), 7.34 (t, 2H, C(6)H, C(8) H), 7.15 (m, 1H, C(7)H); 13 C, δ173.9 C(1), 127.2 C(2), 140.2 C(3), 133.8 C(4), 129.9 C(5) and C(9), 128.0 C(6) and C(8), 128.7 C(7). Na[Au(fspa)]·H 2 O(24). [Au(Hfspa)] (0.10 g, 0.27 mmol), NaOH (0.011 g, 0.27 mmol), H 2 O(8cm 3 ), brown solid. Yield: 67%; mp: 210°C (Dec.). (Found: C 20.1, H 1.8, S 7.8%. Calc. for C 7 H 8 O 5 SAuNa: C 19.8, H 1.9, S 7.6%). IR (cm −1 ): 1,596 vs, ν asym (CO 2 − ); 1,382 s, ν sym (CO 2 − ). NMR (DMSO-d 6 ): 1 H, δ7.58 (s, 1H, C(3) H), 7.28 (d, 1H, C(5)H), 6.52 (t, 1H, C(6)H), 7.60 (d, 1H, C(7)H); 13 C, δ172.4 C(1), 135.0 C(2), 121.8 C(3), 153.2 C(4), 111.8 C(5), 111.4 C(6), 141.7 C(7). Na[Au(tspa)]·H 2 O(25).[Au(Htspa)] (0.12 g, 0.31 mmol), NaOH (0.013 g, 0.31 mmol), H 2 O(10cm 3 ), brown solid. Yield: 68%; mp: 221°C (Dec.). (Found: C 19.6, H 1.2, S 15.1%. Calc. for C 7 H 6 O 3 S 2 AuNa: C 19.9, H 1.4, S 15.2%). IR (cm −1 ): 1,571 vs, ν asym (CO 2 − ); 1,368 vs, ν sym (CO 2 − ). NMR (DMSO-d 6 ): 1 H, δ7.78 (s, 1H, C(3) H), 7.35 (d, 1H, C(5)H), 7.04 (t, 1H, C(6)H), 7.45 (d, 1H, C(7)H); 13 C, δ172.6 C(1), 125.2 C(2), 135.3 C(3), 142.2 C(4), 130.7 C(5), 126.3 C(6), 125.9 C(7). Na[Au(-o-pyspa)]·H 2 O(26). [Au(H-o-pyspa)] (0.05 g, 0.13 mmol), NaOH (0.005 g, 0.13 mmol), H 2 O(5cm 3 ), brown solid. Yield: 48%; mp: 224°C. (Found: C 22.8, H 1.7, S 7.9, N 3.2%. Calc. for C 8 H 7 O 3 SNAuNa: C 23.0, H 1.7, S 7.7, N 3.3%). IR (cm −1 ): 1,574 vs, ν asym (CO 2 − ); 1,381 vs, ν sym (CO 2 − ). NMR (DMSO-d 6 ): 1 H, δ7.10 (s, 1H, C(3)H), 7.58 (d, 1H, C(5)H), 7.81 (pst, 1H, C(6)H), 7.19 (pst, 1H, C(7)H), 8.56 (d, 1H, C(8)H); 13 C, δ172.5 C(1), 135.9 C(2), 133.4 C(3), 153.2 C(4), 139.6 C(5), 29.2 C(6), 121.6 C(7), 125.6 C(8). Na[Au(Clpspa)]·H 2 O(27). [Au(HClpspa)] (0.10 g, 0.24 mmol), NaOH (0.01 g, 0.24 mmol), H 2 O (8 cm 3 ), yellow solid. Yield: 60%; mp: 227°C. (Found: C 23.8, H 1.4, S 7.0%. Calc. for C 9 H 7 O 3 SClAuNa: C 24.0, H 1.6, S 7.1%). IR (cm −1 ): 1,589 vs, 1,575 vs, ν asym (CO 2 − ); 1,384 vs, 1,367 vs, ν sym (CO 2 − ). NMR (DMSO-d 6 ): 1 H, δ7.70 (s, 1H, C(3)H), 7.42 (d, 1H, C(6)H), 7.19 (t, 1H, C(7)H), 7.31 (t, 1H, C(8)H), 7.90 (d, 1H, C(9)H); 13 C, δ172.3 C(1), 127.0 C(2), 133.2 C (3), 138.1 C(4), 135.2 C(5), 129.5 C(6), 129.9 C(7), 126.2 C(8), 128.2 C(9). 28 Gold Bull (2012) 45:23–34 Na[Au(-o-mpspa)]·H 2 O(28). [Au(H-o-mpspa)] (0.10 g, 0.25 mmol), NaOH (0.01 g, 0.25 mmol), H 2 O(8cm 3 ), yellow solid. Yield: 63%; mp: 220°C (Dec.). (Found: C 27.1, H 2.3, S 7.2%. Calc. for C 10 H 10 O 4 SAuNa: C 26.9, H 2.3, S 7.2%). IR (cm −1 ): 1,566 vs, ν asym (CO 2 − ); 1,372 vs, ν sym (CO 2 − ). NMR (DMSO-d 6 ): 1 H, δ7.73 (s, 1H, C(3)H), 8.00 (d, 1H, C(6)H), 6.89 (t, 1H, C(7)H), 7.16 (t, 1H, C(8)H), 7.91 (d, 1H, C(9)H), 3.72 (s, 3H, OCH 3 ); 13 C, δ173.3 C(1), 127.6 C(2), 137.5 C(3), 125.5 C(4), 156.4 C(5), 110.2 C(6), 130.7 C(7), 119.3 C(8), 129.2 C(9), 55.3 C(OCH 3 ). Na[Au(-p-mpspa)]·H 2 O(29). [Au(H-p-mpspa)] (0.08 g, 0.2 mmol), NaOH (0.01 g, 0.2 mmol), H 2 O (6 cm 3 ), orange solid. Yield: 68%; mp: 209°C (Dec.). (Found: C 26.7, H 2.1, S 6.9%. Calc. for C 10 H 10 O 4 SAgNa: C 26.9, H 2.3, S 7.2%). IR (cm −1 ): 1,570 s, ν asym (CO 2 − ); 1,383 s, ν sym (CO 2 − ). NMR (DMSO-d 6 ): 1 H, δ7.56 (s, 1H, C(3)H), 7.93 (d, 2H, C(5)H), (C(9)H), 6.87 (d, 2H, C(6)H, C(8)H), 3.72 (s, 3H, OCH 3 ); 13 C, δ173.4 C(1), 115.0 C(2), 134.5 C(3), 130.4 C(4), 131.2 C(5) and C(9), 113.3 C(6) and C(8), 158.7 C(7), 54.9 C(OCH 3 ). Na[Au(-o-hpspa)]·H 2 O(30). [Au(H-o-hpspa)] (0.06g,0.15mmol),NaOH(0.006g,0.15mmol), H 2 O(5cm 3 ), orange solid. Yield: 66%; mp: 225°C (Dec.). (Found: C 24.7, H 1.8, S 7.0%. Calc. for C 9 H 8 O 4 SAuNa: C 25.0, H 1.9, S 7.4%). IR (cm −1 ): 1,566 vs, ν asym (CO 2 − ); 1,363 vs, ν sym (CO 2 − ). NMR (DMSO-d 6 ): 1 H, δ7.84 (s, 1H, C(3)H), 9.63 (s, 1H, C(5)OH), 6.79 (m, 2H, C(6)H and C(8)H), 7.00 (pst, 1H, C(7)H), 8.10 (d, 1H, C(9)H); 13 C, δ173.6 C(1), 123.9 C(2), 132.8 C(3), 155.3 C(5), 114.8 C(6), 130.4 C(7), 118.0 C(8), 129.8 C(9). Na[Au(-p-hpspa)]·H 2 O(31). [Au(H-p-hpspa)] (0.08 g, 0.2 mmol), NaOH (0.008 g, 0.2 mmol), H 2 O(6cm 3 ), orange solid. Yield: 60%; mp: 217°C (Dec.). (Found: C 24.8, H 2.1, S 7.2%. Calc. for C 9 H 8 O 4 SAuNa: C 25.0, H 1.9, S 7.4%). IR (cm −1 ): 1,563 vs, ν asym (CO 2 − ); 1,360 vs, ν sym (CO 2 − ). NMR (DMSO-d 6 ): 1 H, δ7.56 (s, 1H, C(3)H), 7.87 (d, 2H, C(5)H, C(9)H), 6.71 (d, 2H, C(6)H, C(8)H), 9.50 (s, 1H, C(7)OH); 13 C, δ172.6 C(1), 122.2 C(2),127.9 C(4), 131.5 C(5) and C(9), 114.8 C(6) and C(8), 156.3 C(7). Na[Au(-diBr-o-hpspa)]·H 2 O(32). [Au(H-diBr-ohpspa)] (0.05 g, 0.09 mmol), NaOH (0.007 g, 0.09 mmol), H 2 O(5cm 3 ), yellow solid. Yield: 48%; mp: 219°C. (Found: C 17.9, H 1.1, S 5.2%. Calc. for C 9 H 6 O 4 SBr 2 AuNa: C 18.3, H 1.0, S 5.4%). IR (cm −1 ): 1,565 vs br, ν asym (CO 2 − ); 1,361 vs br, ν sym (CO 2 − ). NMR (DMSO-d 6 ): 1 H, δ7.90 (s, 1H, C(3)H), 7.75 (d, 1H, C(7)H), 7.20 (d, 1H, C(9)H); 13 C, δ172.8 C(1), 125.6 C(2), 133.8 C(3), 126.3 C(4), 155.6 C(5), 115.9 C(6), 137.2 C(7), 112.5 C(8), 130.2 C(9). Na[Au(cpa)]·H 2 O(33). [Au(Hcpa)] (0.1 g, 0.28 mmol), NaOH (0.012 g, 0.28 mmol), H 2 O(8cm 3 ), brown solid. Yield: 68%; mp: 222°C. (Found: C 21.5, H 2.8, S 8.2%. Calc. for C 7 H 10 O 3 SAuNa: C 21.3, H 2.6, S 8.1%). IR (cm −1 ): 1,570 vs, ν asym (CO 2 − ); 1,387 vs br, ν sym (CO 2 − ). NMR (DMSO-d 6 ): 1 H, δ2.65 (m, 2H, C(4)H 2 ), 1.56 (m, C(5)H 2 ), 1.56 (m, C(6)H 2 ), 2.36 (m, 2H, C(7)H 2 ); 13 C, δ172.0 C(1), 129.6 C(2), 160.3 C(3), 38.2 C(4), 26.1 C(5), 24.8 C(6), 36.0 C(7). Results and discussion Synthesis and characterization Complexes were prepared as described in the “Experimental” section. The [Au(HL)] complexes were obtained in high yields (close to 80% in most cases), whereas the reactions that afforded [HQ][Au(L)] and Na[Au(L)]·H 2 O gave lower yields. The three types of compound differ in solubility. The [HQ] [Au(L)] complexes are soluble in ethanol, methanol, acetone, chloroform and DMSO, the Na[Au(L)] H 2 O complexes are soluble in water and DMSO, and the [Au(HL)] complexes are only soluble in DMSO. The IR spectra of [Au(HL)] complexes do not show the ν(SH) band present at around 2,550 cm −1 in the spectra of the free ligands. Furthermore, the vibrations of the COOH group are slightly shifted from their positions in the spectra of the free ligands [14,15]. These features suggest that, as in other complexes in which the COOH group is present, this group is not deprotonated and remains uncoordinated, with the complexes probably being polymeric species supported by Au–S bonds, as previously suggested for equivalent silver complexes [14,15,39,40]. In the case of [HQ][Au(L)], the common features for the complexes are the absence of the ν(SH) band and of the bands due to the COOH group; both of these observations are consistent with the bideprotonation of the ligand in all cases. The existence of the diisopropylammonium cation is confirmed by the presence, at around 1,600 cm −1 , of a band due to the NH 2+ group [41], which was previously identified in equivalent complexes with the same ligands [14,15]. The ν asym (CO 2 − ) and ν sym (CO 2 − ) bands are located in similar positions in the spectra of all the complexes, suggesting the same coordination mode for the carboxylate group, which, in all cases, acts as a monodentate group that is hydrogen bonded to the HQ cations [14,15,42] The IR spectra of Na[Au(L)]·H 2 O complexes do not contain the ν(SH) band or the bands due to the COOH group. The positions of the ν asym (CO 2 − ) and ν sym (CO 2 − ) bands are again similar in all of the complexes and these positions are again compatible with the same kind of Gold Bull (2012) 45:23–34 29 monodentate coordination mode for the carboxylate group, which, in these cases, can be hydrogen bonded to the H 2 O molecule instead of the diisopropylammonium cation. NMR studies For complexes of the type [Au(HL)] (1–11), the broad signal at around 13 ppm in the 1 H NMR spectra of the ligands persists, an observation consistent with the presence of the protonated COOH group. This signal is not present in the spectrum of the [Au(H-o-pyspa)] complex, probably due to an interchange with the deuterium of the solvent. In the 1 H spectrum of H 2 -o-pyspa the presence of a broad singlet at 17.85 ppm is consistent with protonation of the pyridine nitrogen, which, together with the presence of only one proton on C(3)H, suggests that this compound is in the thione form in solution and not in the enethiol form. Coordination to gold causes significant changes in the 1 HNMR spectrum; the signal attributed to N–H does not appear for the complex, a fact that reflects deprotonation of this group and the evolution of the ligand to the thiol form. The 13 C NMR spectra of these complexes show the C(3) signal shifted to higher field with respect to that in the free ligand [14,15], suggesting that the S-coordination found in the solid state, as in other complexes with these ligands [43,44], is retained in solution. For [HQ][Au(L)] (12–22) and Na[Au(L)]·H 2 O(23–33) compounds the 1 H NMR spectra show a shift in the ligand C (3)H signal to higher field on complexation, which again suggests the persistence of the S–Au bond in solution; the disappearance of the broad signal located at around 13 ppm in the spectra of each free acid evidences the deprotonation of the COOH group in the complexes. The persistence of the S-coordination was confirmed by the shift in the C(3) signal in the 13 C NMR spectra. In these spectra, the C(1) peaks are in positions close to those found in compounds with a coordinated carboxylate group [45,46] and, in particular, in the equivalent silver complexes [14,15]. Antimicrobial activity Antibacterial and antifungal activities are listed in Tables 1 and 2, as estimated by minimum inhibitory concentration (MIC; microgrammes per millilitre) and minimum bactericidal concentration (MBC; microgrammes per millilitre). Remarkable activity was not exhibited by either diisopropylammonium chloride [42], the ligands or complexes of the type [Au(HL)] (1–11), which in the case of the complexes can be attributed to the low solubility. The majority of these new complexes showed better activity against the Gram (+) bacteria S. aureus and B. subtilis than against the Gram (−)E. coli and P. aeruginosa (the lower activity is shown against this latter bacterium even though the values are similar to those for E. coli). However, there are differences between the two classes of compounds and also between the compounds included in the [HQ][Au(L)] or Na[Au(L)]·H 2 O classes. Among the HQ derivatives, which in general are more active than the Na derivatives, [HQ][Au(fspa)] (13), [HQ] [Au(-o-pyspa)] (15) and [HQ][Au(-diBr-o-hpspa)] (21) show higher activity against the Gram (+) bacteria; however, the wider spectrum of activity within this class corresponds to [HQ][Au(tspa)] (14), which shows significant activity against the assayed Gram (+) and Gram (−) bacteria. Among the Na derivatives, the worst values were measured for Na[Au(cpa)]·H 2 O(33), which showed a low activity against all the tested bacteria, whereas Na[Au(Clpspa)]·H 2 O (27) showed significant activity against all the bacteria; furthermore, Na[Au(pspa)]·H 2 O(23) showed better activity against the Gram (−) bacteria and Na[Au(-o-hpspa)]·H 2 O(30)andNa [Au(-diBr-o-hpspa)]·H 2 O(32) showed good values against the two Gram (+) bacteria and E. coli. In an attempt to assess the bactericidal or bacteriostatic activity of these compounds, we also determined the MBC values for most of the synthesised compounds (Table 2). In the range of concentrations studied, we found bactericidal activity for some complexes and, as can be seen in Table 2, this activity is particularly relevant against E. coli and B. subtilis. In the first case, among the HQ complexes, [HQ][Au(pspa)] (12), [HQ][Au(fspa)] (13), [HQ][Au(-o-hpspa)] (19) and [HQ] [Au(-p-hpspa)] (20) showed only bacteriostatic activity. The complexes [HQ][Au(tspa)] (14), [HQ][Au(-o-pyspa)] (15), [HQ][Au(Clpspa)] (16), [HQ][Au(-diBr-o-hpspa)] (21) and [HQ][Au(cpa)] (22) showed bactericidal activity but only at concentrations higher than those at which the initial growth inhibition was observed; for [HQ][Au(-o-mpspa)] (17)and [HQ][Au(-p-mpspa)] (18), the bacteriostatic and bactericidal activity was observed at the same concentration. Bactericidal activity was not observed for the Na complexes Na[Au(fspa)]·H 2 O(24), Na[Au(tspa)]·H 2 O(25), Na [Au(-o-mpspa)]·H 2 O(28), Na[Au(-o-hpspa)]·H 2 O(30), Na [Au(-p-hpspa)]·H 2 O(31), Na[Au(-diBr-o-hpspa)]·H 2 O(32) and Na[Au(cpa)]·H 2 O(33), whereas this activity was observed for Na[Au(pspa)]·H 2 O(23), Na[Au(-o-pyspa)]·H 2 O (26), Na[Au(Clpspa)]·H 2 O(27) and Na[Au(-p-mpspa)]·H 2 O (29) at slightly higher concentrations than those at which the bacteriostatic activity was observed. The wider expression of activity over the range of concentrations tested was identified against B. subtilis. With the exception of Na[Au(fspa)]·H 2 O(24), Na[Au(-o-mpspa)]·H 2 O (28) and Na[Au(cpa)]·H 2 O(33),allofthecomplexesshowed bactericidal activity—albeit at higher concentrations than those at which bacteriostatic activity was observed. In any case, none of the microorganisms tested showed tolerance to these products because the MIC/MBC ratio was less than 32 in all cases. 30 Gold Bull (2012) 45:23–34 Only three compounds showed bactericidal activity against S. aureus, and these were [HQ][Au(fspa)] (13), [HQ][Au (-diBr-o-hpspa)] (21) and Na[Au(-diBr-o-hpspa)]·H 2 O(32); interestingly, for [HQ][Au(fspa)] (13) and [HQ][Au(-diBr-ohpspa)] (21), bactericidal activity was detected at low concentrations, indicating a lack of tolerance to these compounds. Against P. aeruginosa, only three HQ derivatives, [HQ][Au(tspa)] (14), [HQ][Au(Clpspa)] (16) and [HQ] Table 1 Antimicrobial activities (MICs) of the complexes Compound E. coli S. aureus B. subtilis P. aeruginosa ATCC 27853 P. aeruginosa Resistant C. albicans [HQ][Au(pspa)] (12)252525 50 25 50 [HQ][Au(fspa)] (13) 100 <6.25 <6.25 100 100 50 [HQ][Au(tspa)] (14) 25 12.5 25 12.5 12.5 100 [HQ][Au(-o-pyspa)] (15) 50 12.5 <6.25 25 50 200 [HQ][Au(Clpspa)] (16) 50 12.5 12.5 50 50 25 [HQ][Au(-o-mpspa)] (17) 50 12.5 25 25 25 50 [HQ][Au(-p-mpspa)] (18) 50 12.5 25 25 25 50 [HQ][Au(-o-hpspa)] (19) 50 50 25 50 50 >200 [HQ][Au(-p-hpspa)] (20) 50 12.5 100 50 50 200 [HQ][Au(-diBr-o-hpspa)] (21) 50 12.5 <6.25 50 50 50 [HQ][Au(cpa)] (22) 50 12.5 12.5 50 50 200 Na[Au(pspa)]·H 2 O(23) 25 50 50 25 12.5 >200 Na[Au(fspa)]·H 2 O(24) 100 12.5 200 100 100 200 Na[Au(tspa)]·H 2 O(25) 50 25 50 100 100 200 Na[Au(-o-pyspa)]·H 2 O(26) 25 12.5 50 100 100 200 Na[Au(Clpspa)]·H 2 O(27) 12.5 12.5 12.5 25 12.5 >200 Na[Au(-o-mpspa)]·H 2 O(28) 25 25 25 100 100 100 Na[Au(-p-mpspa)]·H 2 O(29) 50 25 50 50 50 >200 Na[Au(-o-hpspa)]·H 2 O(30) <6.25 <6.25 12.5 50 50 100 Na[Au(-p-hpspa)]·H 2 O(31) 50 50 25 50 50 >200 Na[Au(-diBr-o-hpspa)]·H 2 O(32) 12.5 <6.25 <6.25 50 50 200 Na[Au(cpa)]·H 2 O(33) >200 >200 >200 >200 >200 >200 Minimum inhibitory concentration (microgrammes per millilitre) Table 2 MBC values for the complexes Minimum bactericidal concentration (microgrammes per millilitre) Compound E. coli S. aureus B. subtilis P. aeruginosa ATCC 27853 P. aeruginosa Resistant [HQ][Au(pspa)] (12)50 [HQ][Au(fspa)] (13) 6.25 50 [HQ][Au(tspa)] (14) 100 100 50 [HQ][Au(-o-pyspa)] (15) 100 50 [HQ][Au(Clpspa)] (16) 100 25 100 [HQ][Au(-o-mpspa)] (17)50 50 [HQ][Au(-p-mpspa)] (18) 50 100 100 [HQ][Au(-diBr-o-hpspa)] (21) 100 12.5 6.25 [HQ][Au(cpa)] (22) 100 50 Na[Au(pspa)]·H 2 O(23) 50 100 100 200 Na[Au(tspa)]·H 2 O(25) 100 Na[Au(-o-pyspa)]·H 2 O(26) 200 200 200 Na[Au(Clpspa)]·H 2 O(27) 50 50 100 50 Na[Au(-p-mpspa)]·H 2 O(29) 100 100 Na[Au(-diBr-o-hpspa)]·H 2 O(32) 25 12.5 200 200 Gold Bull (2012) 45:23–34 31