How Aromatic Are Molecular Nanorings? The Case of a Six-Porphyrin Nanoring**

Aromaticity Hot Paper HowAromatic Are Molecular Nanorings?The Case of aSix-Porphyrin Nanoring** Irene Casademont-Reig,RaffllGuerrero-Avil8s, EloyRamos-Cordoba,* Miquel Torrent-Sucarrat,* and EduardMatito* Dedicated to the memory of our friend and colleague,Prof.Istv#nMayer,whose works have been acontinuous inspiration Angewandte Chemie A ngewandte Chemie Research Articles How to cite: Angew.Chem. Int. Ed. 2021,60,24080–24088 International Edition: doi.org/10.1002/anie.202108997 German Edition: doi.org/10.1002/ange.202108997 24080 T2021 TheAuthors.AngewandteChemieInternational Editionpublished by Wiley-VCHGmbH Angew.Chem. Int.Ed. 2021,60,24080–24088 Abstract: Large conjugated rings with persistent currents are novel promising structures in molecular-scale electronics.A six-porphyrin nanoring structure that allegedly sustained an aromatic ring current involving 78pelectrons was recently synthesized.Weprovide here compelling evidence that this molecule is not aromatic,contrary to what was inferred from the analysis of 1H-NMR data and computational calculations that suffer from large delocalization errors.The main reason behind the absence of an aromatic ring current in these nanorings is the low delocalization in the transition from the porphyrins to the bridging butadiyne linkers,which disrupts the overall conjugated circuit. These results highlight the importance of choosing asuitable computational method to study large conjugated molecules and the appropriate aromaticity descriptors to identify the part of the molecule responsible for the loss of aromaticity. Introduction Benzene is the paradigm of an organic aromatic molecule, exhibiting bond-length equalization, cyclic electron delocalization, and exalted magnetic susceptibility.Assuch, benzene is just the smallest neutral annulene that presents p-conjugated aromaticity;o ther annulenes possessing 4n+2p electrons are also considered aromatic. It is well established that large annulenes suffer out-of-plane distortions and exhibit apoor overlap between porbitals,thus favoring non-symmetric conformations that are much less aromatic.[1–3] Thelarger the annulene,the less aromatic the molecule is expected to be.For this reason, it is difficult to find large aromatic macrocycles.[2,4,5] Geometrical constraints are imposed in some large macrocyclic structures with the hope to preserve conjugation, aromaticity,and quantum coherence. Among the molecules with the largest aromatic rings,itis worth highlighting the dodecaphyrin structures synthesized by Osuka and co-workers,[6,7] which adopt twisted Mçbius and Hgckel conformations,the annulene-with-an-annulene aromatic super-ring structure of Wu et al.,[8] and the p-conjugated six-porphyrin nanoring of Anderson and co-workers (see Figure 1).[9] Thelatter work synthesized and analyzed the aromaticity of asix-porphyrin nanoring (c-P6·T6) in four different oxidation states (c-P6·T6, c-P6·T64+,c-P6·T66+,and c-P6·T612+), concluding from 1H-NMR, NICS,and ACID analyses that the neutral and the c-P6·T612+species are nonaromatic,whereas c-P6·T64+and c-P6·T66+are,respectively, antiaromatic and aromatic.[9,10] These molecules were the first of aseries of similar large macrocyclic structures exhibiting (anti)aromaticity.[9,11–14] Porphyrin nanorings are very attractive compounds because they offer an end-free p-conjugated system with remarkable properties such as photophysical and guestencapsulating,which might lead to amyriad of applications in the field of single-molecule electronics,[15,16] serve as lightharvesting antennas,[17] or investigate energy transfer in biomimetic systems,[18] among others.[9,13,19–25] In this sense, the interest and the utility of the compounds synthesized by the group of Anderson are beyond question. However,inthis work, we demonstrate that the aromaticity of these large macrocycles is questionable.Weperform athroughout analysis of these species using several density functional approximations (DFAs) and various tools to analyze the aromaticity, providing compelling evidence that the conclusions are highly sensitive to the level of calculation employed. In particular, [*] Dr.I.Casademont-Reig, R. Guerrero-Avil8s, Dr.E.Ramos-Cordoba, Dr.M.Torrent-Sucarrat, Dr.E.Matito Donostia International Physics Center (DIPC) 20018 Donostia,Euskadi (Spain) E-mail:eloy[email protected] [email protected]m [email protected] Dr.I.Casademont-Reig, Dr.E.Ramos-Cordoba Polimero eta Material Aurreratuak:Fisika, Kimika eta Teknologia, Kimika Fakultatea,Euskal Herriko Unibertsitatea UPV/EHU P.K. 1072, 20080 Donostia, Euskadi (Spain) R. Guerrero-Avil8s Centro de F&sica de Materiales, CFM-MPC CSIC-UPV/EHU 20018 Donostia,Euskadi (Spain) Dr.M.Torrent-Sucarrat, Dr.E.Matito Ikerbasque, Basque Foundationfor Science Plaza Euskadi 5, 48009 Bilbao, Euskadi (Spain) Dr.M.Torrent-Sucarrat Department of Organic Chemistry I, Universidad del Pais Vasco/ Euskal Herriko Unibertsitatea (UPV/EHU) 20018 Donostia,Euskadi (Spain) [**] Aprevious version of this manuscript has been deposited on apreprint server (https://doi.org/10.26434/chemrxiv.14035919). Supporting information and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.org/10.1002/anie.202108997. T2021 The Authors. AngewandteChemie International Edition published by Wiley-VCH GmbH. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is noncommercialand no modifications or adaptations are made. Figure 1. Structure of c-P6. Forthe nanoring structure with the aryl group substituents (orange) and the encapsulated template (purple) we will use the notation c-P6·T6. In Ref. [9],they synthesized the compound with Ar=(3,5-bis(trihexylsilyl))phenyl, whereas the computational studies used Ar=Ph for c-P6·T6 and Ar=Hfor c-P6. A ngewandte Chemie Research Articles 24081Angew.Chem. Int.Ed. 2021,60,24080–24088 T2021 TheAuthors.AngewandteChemieInternational Editionpublished by Wiley-VCHGmbH www.angewandte.org B3LYP presents large delocalization errors that artificially enhance the aromaticity of c-P66+,whereas CAM-B3LYP provides an excellent agreement with the experimental data available.Through careful computational analysis and the judicious examination of the 1H-NMR data, we conclude that c-P66+is not aromatic. Additionally,weperform acomplete electronic structure study of the four oxidation states of the nanoring and analyze the aromaticity of these molecules.Bystudying the local aromaticity of the six porphyrins that compose the belt structure and the conjugated linkers (the butadiyne fragments linking the porphyrins), we identify the parts of the molecule that are responsible for the absence of the global aromatic ring current. Finally,weprovide some hints that might aid in the synthesis of large aromatic nanorings. Results and Discussion Thesynthesized molecules consist of abelt nanoring structure of six porphyrins with aryl groups and an encapsulated template (c-P6·T6, see Figure 1). There,Anderson et al.[9] computationally analyzed the aromaticity of the nanoring structure without the aryl groups and the template (i.e., c-P6) because the nanoring belt structure is the one responsible for the aromaticity of these compounds.Inthis work, we have also analyzed the effect of adding the encapsulated template and the aryl groups to the c-P66+ structure. DFAs with alow percentage of Hartree–Fock (HF) exchange (typically,HF[%]!50) at long interelectronic ranges are prone to present large delocalization errors,[27] leading to the unphysical overdelocalization of electrons, the underestimation of reaction barriers and charge-transfer excitation energies,[27] the overestimation of the conductance of molecular junctions,optical responses,[28,29] the magnetizability of strong antiaromatic molecules,[30] electron conjugation,[31] and aromaticity,[32,33] especially in large conjugated macrocycles.[2,3,34–37] Anderson et al.[9] performed B3LYP (HF[%]=19), M06-2X (HF[%]=54), and wB97X (HF[%] = 0–100) calculations with the 6-31G* basis set but mostly employed the B3LYP results to analyze the aromaticity of these compounds.Wehave performed additional calculations with CAM-B3LYP (HF[%]=19–65) and LC-wHPBE (HF- [%]=0–100), wbeing 0.1 and 0.2 (the larger w,the larger HF[%] at long range). Although all methods give qualitatively the same structure for the neutral and the c-P612+ species,c-P64+and c-P66+present significantly different geometries depending on the amount of long-range HF exchange present in the DFA. While CAM-B3LYP,M06-2X, and LC-wHPBE(w=0.2) give aless symmetric structure for c-P66+,B3LYP and LC-wHPBE(w=0.1) yield asymmetric aromatic species (see Tables 1and S2). Thefirst group of DFAs has alarge percentage of HF exchange at long range, indicating that the latter DFAs may be suffering from delocalization errors.This is further reinforced by singlepoint DLPNO-CCSD(T)/def-SVP-C calculations that attribute much lower energy to the less symmetric c-P66+ structures of M06-2X and CAM-B3LYPgeometries compared to the B3LYP one (see Table 2), and the fact that CAMB3LYP identifies the symmetric structure as atransition state (TS) connecting to equivalent minimal structures with nonequivalent linkers (see Figure 2). Indeed, the B3LYP minimal geometry has agreat resemblance with the geometry of this TS (see Table 1). Thesituation is reminiscent of the error committed by B3LYP in the potential energy surface of extended porphyrins,[34] and casts ashadow of doubt over the conclusions obtained using this B3LYP geometry.[9] In the case of c-P64+,single-point DLPNO-CCSD(T)/def-SVP-C calculations identify the B3LYP geometry as the lowest-lying one.Although, in the latter case,the energy differences are so Table 1: Comparison of CAM-B3LYP and M06-2X ground state geometries against the B3LYP one.[a] Species RMSD(CAM-B3LYP) RMSD (M06-2X) c-P6 0.05 0.04 c-P64+0.66 0.20 c-P66+0.22 0.21 c-P612+0.04 0.04 TS c-P66+0.06 0.07 [a] All root mean square deviations (RMSD)[26] are given with respect to the B3LYP minimum.TSc-P66+corresponds to the transition state of cP66+connecting two energy minima (see Figure 2). Table 2: c-P64+and c-P66+DLPNO-CC/Def-SVP/C relative energy values with respect to the corresponding lowest value.[a] Species Optimization Geometry DECCSD DECCSD(T) c-P64+B3LYP min 0.0 0.0 CAM-B3LYPmin @5.2 7.8 M06-2X min @1.8 5.5 c-P66+M06-2X min 0.0 0.0 B3LYP min 81.9 68.4 CAM-B3LYPmin 8.3 10.9 CAM-B3LYPTS32.4 25.0 M06-2X TS 28.2 18.8 [a] All T1diagnostic[38] values are below 0.017. DFTcalculations employed the 6-31G* basis set. Energy in kcalmol@1. Figure 2. Sketch of the potential energy surface of c-P66+around the energy minimum as described by different DFAs. A ngewandte Chemie Research Articles 24082 www.angewandte.org T2021 TheAuthors.AngewandteChemieInternational Edition publishedbyWiley-VCH GmbH Angew.Chem. Int.Ed. 2021,60,24080–24088 small with respect to other DFAs (2–8 kcalmol@1), that one cannot unequivocally draw any conclusion about the geometries (see below for an assessment of the aromaticity of cP64+calculated with different geometries). Thus far,wehave analyzed the isolated nanoring model. At the B3LYP level of theory,the addition of the template and the aryl groups breaks the D6hsymmetry that was originally predicted by the naked nanoring,providing an overall geometry that is much closer to the CAM-B3LYP C3h geometry.For B3LYP,M06-2X, and CAM-B3LYPgeometries,the root mean square deviations (RSMD) of the 1HNMR chemical shifts of various relevant hydrogen atoms are collected in Table 3(see Figure S1). Reproducing experimental 1H-NMR values is avery challenging computational task because they depend not only on the moleculeQsgeometry but also on the solvent and the temperature.[39] However,CAMB3LYP geometry provides the closest agreement with the experiment for all compounds tested, whereas B3LYP’s provides the worst agreement (see Table 3), especially in the case c-P66+.Hence,wecan safely conclude that CAMB3LYP geometries and the 1H-NMR of c-P6, c-P66+,and cP612+conform to the experimental data, whereas,inthe case of c-P64+,there are large discrepancies between the experimental data and all the examined DFAs.Asweshall see in the following sections,obtaining the right geometry is crucial to correctly assess the aromaticity of c-P66+.Hereafter,unless otherwise explicitly indicated, we will refer to the results obtained from CAM-B3LYPgeometries. We focus now on the local aromaticity of the porphyrins, which is assessed by studying the circular conjugation pathways that go through C@CorC @Nbonds around each porphyrin. Thepathway going through the C@Nbonds of the imine group is labeled as “i”, whereas the one following the C@Cbonds of the imine group is labeled as “o”. There are 16 pathways for each porphyrin but some of them are equivalent by symmetry.Weemploy ACID plots[40] as amagnetic criterion of aromaticity,aswellasseveral electron-delocalization measures of aromaticity.[41] In Table 4, the results for all the possible pathways in the porphyrins of the neutral species are collected. Thedelocalization indices[47] do not show significant differences between neighboring C@Nand C@Cbonds in the imine group, indicating no clear preferential pathway in the porphyrins of c-P6 (see Figure S3). AVmin,[46] which measures the least delocalized fragment along the pathway,does not find significant differences among the paths either,afact which is further confirmed by the ACID plot of Figure 3a.Other aromaticity measures like FLU[42,43] or HOMA[44] find some differences between the pathways,but one should keep in mind that, unlike AVmin,these indices failed to identify the most aromatic pathway in simple porphyrins.[3,35] In Table 5, we collect the results of the most aromatic pathway of the porphyrins for all the oxidation states of the nanoring according to different aromaticity descriptors.All the indices find that the porphyrins of c-P6 are less aromatic than those of porphin (see Table S6) but aromatic nonetheless.Although the indices do not agree on the most aromatic pathway of the porphyrins (see Tables S7 and S9), there is Table 3: Selected 1H-NMR chemicalshift differences (in ppm).[a] Method data c-P6·T6 c-P6·T64+c-P6·T66+c-P6·T612+ CAM-B3LYP b-a2.40 0.09 @0.79 @2.15 o’-o 0.09 0.41 @0.19 @0.91 a-atemp @6.34 @1.92 @0.97 1.88 b-btemp @2.54 @0.44 @0.36 1.13 RMSD 0.16 –1.35 0.45 B3LYP b-a1.95 @12.75 0.99 @4.37 o’-o 0.31 36.36 @7.23 @2.67 a-atemp @5.34 60.43 @12.26 5.63 b-btemp @1.97 49.10 @9.85 2.68 RMSD 0.30 –5.36 1.41 Experimental b-a2.58 @2.80 @0.44 @2.48 o’-o 0.26 – @1.87 @0.74 a-atemp @6.31 14.16 @2.83 2.77 b-btemp @2.34 12.57 @2.06 1.50 [a] RMSD are based on nine 1H-NMR differences with respect to the experimental data available in Ref. [9].Data for c-P6·T64+is taken from Ref. [13]. atemp and btemp are the corresponding data calculated on the isolated template (see Figure 1). See Figure S1 and Tables S3 and S4 for computational details, proton labels, and all 1H-NMR values. Table 4: Aromaticity indices for the different pathways within the porphyrins of c-P6 calculated at the CAM-B3LYP/6-31G* level of theory.[a] Pathway FLU[42,43] BOA HOMA[44] BLA AV1245[45] jAVmin j[46] oooo 0.023 0.235 0.658 0.050 1.64 0.57 iiii 0.007 0.071 0.927 0.017 0.92 0.52 ioio (2) 0.016 0.162 0.778 0.036 1.32 0.52 iiio (4) 0.012 0.119 0.848 0.027 1.13 0.52 iioo (2) 0.016 0.162 0.778 0.036 1.32 0.52 iooi (2) 0.016 0.162 0.778 0.036 1.32 0.52 oooi (4) 0.020 0.200 0.715 0.043 1.49 0.52 [a] The number in brackets indicates the numberofequivalent pathways. Figure 3. ACID isosurface plots (isocontour value 0.06) for a) c-P6, b) c-P64+,c)c-P66+,and d) c-P612+at the CAM-B3LYP/6-31G* level of theory. Table 5: Aromaticity indices for the most aromatic pathway of porphyrins calculated at the CAM-B3LYP/6-31G* level of theory. Species FLU HOMA AV1245 jAVmin jACID c-P6 0.007 0.927 1.64 0.57 A c-P64+0.016 0.784 1.45 0.32 A c-P66+0.017 0.760 1.33 0.24 NA c-P612+0.027 0.426 0.63 0.04 NA/AA porphin 0.006 0.968 2.16 1.28 A A ngewandte Chemie Research Articles 24083Angew.Chem. Int.Ed. 2021,60,24080–24088 T2021 TheAuthors.AngewandteChemieInternational Editionpublished by Wiley-VCHGmbH www.angewandte.org aconsensus among the descriptors concerning the aromatic character of the porphyrins in c-P6 and the fact that c-P64+’s, c-P66+’s, and c-P612+’sporphyrins are much less aromatic than those of c-P6. ACID plots (see Figure 3) concur with these results,even though they identify the porphyrins in c-P64+as aromatic. 1H-NMR results were also used by Anderson et al.[9] to assess the aromaticity of the porphyrins.According to the experiment (see Table 3), the differences between the shielding of aand bprotons of the template (see Figure S1) are 2.58, @2.80, @0.44, and @2.48 ppm for c-P6·T6, c-P6·T64+,cP6·T66+,and c-P6·T612+,respectively.The latter values are associated with aromatic,antiaromatic,non-aromatic,and antiaromatic porphyrins.CAM-B3LYP values are 2.40, 0.09, @0.79, and @2.15 ppm, in good agreement with the experimental values,whereas the B3LYP values for c-P6·T64+,cP6·T66+,and c-P6·T612+show larger discrepancies. Finally,westudy how the constituent parts of the compound change upon oxidation of the nanoring.Wehave performed an effective oxidation state (EOS)[48,49] analysis of three different fragments of the nanoring:the zinc atoms (Zn), the porphyrins (P), and the linkers (L). Thecarbon shared by the porphyrin and the linkers is assigned to the porphyrin. Ther esults of this analysis are collected in Table 6. In all species,the Zn atom has an EOS of +2, indicating that the oxidized electrons never come from the Zn atom. In cP64+,the electrons are subtracted from the butadiyne linkers, distorting the overall symmetry that the linkers had in the neutral species.Interestingly,incompounds with higher oxidation states,c-P66+and c-P612+,the electrons are subtracted from the porphyrins,restoring the symmetry of the neutral species.These results agree with the decrease of local aromaticity we have found with the aromaticity descriptors and help to explain the loss of symmetry in the case of c-P64+. Now,weassess the global aromatic character of the nanoring structure,i.e., we focus on finding aclosed conjugation pathway that goes around the nanoring belt. This pathway involves both the porphyrins and the linkers that bridge them. Since we have already studied the aromaticity of the porphyrins,wefirst focus on the butadiyne linkers and, afterward, we analyze the whole conjugated pathway involving both structures. In Table 7, we collect the MCI[50] of the six carbons that compose each linker.MCI values measure the extent of electron delocalization along the carbon atoms in the linker,[51] which is rather small for c-P6 and c-P612+,indicating that the linkers cannot contribute to forming acompletely delocalized circuit along the nanoring belt (hence,c-P6 and cP612+cannot be considered aromatic molecules). MCI values for c-P64+and c-P66+exhibit an alternated pattern, i.e., an uneven delocalization of the linkers,which also precludes the appearance of aglobal conjugated pathway that can be connected with aromaticity.This picture is corroborated by the ACID plots shown in Figure 4, where we can see disconnected sections around the position of the linkers for all oxidation states.From this analysis and the local aromaticity of the porphyrins,wecan construct the schematic model of the four nanoringsQaromaticity that we collect in the first row of Figure 5. Table 6: Effective oxidation States (EOS) of several fragments of the nanoring at the CAM-B3LYP/6-31G* level of theory. Species Zn Porphyrins Linkers c-P6 +20@2 c-P64++20(@1)W4, (@2)W2 c-P66++2+1@2 c-P612++2+2@2 Table 7: MCI (W1000) values for the six carbon atoms that form the linker bridging two porphyrins. Species/Linker L1L2L3L4L5L6 c-P6 111111 c-P64+20 4420 44 c-P66+121121 121 c-P612+111111 Figure 4. ACID isosurface plots (isocontour value 0.06) for a) c-P6, b) c-P64+,c)c-P66+,and d) c-P612+. Figure 5. The global aromatic character of the nanoringfrom its constituentparts according to the optimized geometries obtained with different DFAs. Full, half-full, and empty circles represent aromatic, weakly aromatic, and non-aromatic porphyrins, respectively.The electron delocalization in the linkers increasesfrom single solid lines (no delocalization)tosolid-dashed lines and, finally,double lines. A ngewandte Chemie Research Articles 24084 www.angewandte.org T2021 TheAuthors.AngewandteChemieInternational Edition publishedbyWiley-VCH GmbH Angew.Chem. Int.Ed. 2021,60,24080–24088 Theglobal aromaticity of the nanoring can be further analyzed using several aromaticity criteria (for further details see the Supporting Information). We rely here on AVmin,[46] which measures the electron delocalization along the different aromatic pathways of the nanoring.[2,35] Forc-P612+,AV min is negligible for all the conjugation pathways,clearly establishing the non-aromatic character of this molecule.For c-P6, c-P64+,and c-P66+,the values of AVmin are negligible for most pathways except the one that passes through the nitrogen atoms of imine groups of each porphyrin. In this pathway, AVmin is also low but not negligible,which is reminiscent of some expanded porphyrin structures,which were considered very weakly aromatic or antiaromatic.[35] There is,however, an important difference concerning the latter case:in aromatic expanded porphyrins,the minimal value of electron delocalization was achieved twice or three times during the whole pathway (see Figure S4), whereas in the case of c-P64+ and c-P66+there are multiple (over twenty) low-delocalization fragments,aswe can see in the delocalization profile of Figure 6. Forthis reason, all the nanorings in the present study are considered non-aromatic,according to AVmin.Interestingly,for c-P64+,c-P66+,and c-P612+,the vast majority of these disconnection points occur in the transition from the porphyrin to the linker,whereas for c-P6, the least delocalized fragment corresponds to an internal fragment inside the porphyrin. ACID confirms the most aromatic pathway indicated by AVmin,and its discontinuous isosurfaces (see Figure 4) also suggest that the molecules are non-aromatic, especially c-P66+,for which large discontinuities also occur in the vicinity of the linkers.Finally,wehave performed twodimensional NICS profiles[52,53] and collected them in l.h.s.of Figure 7. In all cases,the values of the NICS inside and outside the nanoring belt are very close to zero,further confirming the global non-aromatic character of these molecules. Figure 5, provides aqualitative comparison of the aromaticity analyses performed on CAM-B3LYP(or M06-2X) and B3LYP geometries.There are no significant differences for cP6 and c-P612+,asexpected from the similarity of these geometries regardless of the DFAemployed for the optimization. In fact, only for c-P66+,weobtain acompletely different picture of the aromaticity from different methods. Thelarge negative number of the two-dimensional NICS profile in the vicinity of the nanoring center (see the r.h.s.of Figure 7) and the continuous ACID plots (Figure S14) indicate that the B3LYP geometry is globally aromatic.This is further corroborated by the larger AVmin value and, most importantly,bythe 1245-index distribution profiles (FigFigure 6. The 1245-index distribution along the most aromatic path. Figure 7. NICS(0)iso[54] grid plots for c-P6, c-P64+,c-P66+,and c-P612+ species from top to bottom, respectively.a)–d) corresponding to the CAM-B3LYP optimized geometries and e)–h) to the B3LYP ones. See Figure S15 and Table S14 for further details of this computation. A ngewandte Chemie Research Articles 24085Angew.Chem. Int.Ed. 2021,60,24080–24088 T2021 TheAuthors.AngewandteChemieInternational Editionpublished by Wiley-VCHGmbH www.angewandte.org ure 8), where we observe the drastic reduction in the number of fragments with alow delocalization. Thecomparison of the aromaticity measures between B3LYP and CAM-B3LYP cP64+geometries also suggests that B3LYP overestimates the global antiaromaticity of this molecule,asthe NICS (see Figure 7and Table S14) shows alarge positive value in the center of the ring and the ACID plots exhibit acontinuous paratropic ring current (Figure S14). These results align with the recent results of Sundholm and co-workers,which identify CAM-B3LYP as agood method to calculate magnetizabilities[55] and the fact that B3LYP tends to overestimate the paramagnetic ring currents.[56] On the other hand, AVmin and the 1245-index distribution profiles (Figure S8) are consistent with c-P64+being arather antiaromatic or aweakly aromatic molecule,regardless of the geometry.Since the results of no DFAsatisfactorily conform to the experimental data, the results of c-P64+should be taken with caution. Anderson and co-workersQstrongest experimental evidence to assess the global aromaticity of c-P66+comes from the NMR data. They study the (de)shielding of the trihexylsilyl groups (see Figure 1), the ortho protons (o and o’)in the aryl groups (see Figure S1), and the shielding difference between the a(or b)proton of the bound template and the free template, Dda=da@datemp (Ddb=db@dbtemp ).[13] Theformer data cannot be studied in the present paper due to the computational limitations that pose such large structure. However,wecan analyze a,b,and ortho protons.The B3LYP geometry finds that do’@dois @7.23 ppm, whereas CAMB3LYP and M06-2X results are @0.19 ppm and @0.36 ppm, respectively,which are in closer agreement with the experiment,[9] 1.87 ppm (see Tables 3and S3). TheCAM-B3LYP values of Ddaand Ddbare in much better agreement with the experimental data than the B3LYP ones.Rikhaus et al.[13] argue that Dda<0and Ddb<0are an indication of the presence of aglobal aromatic current (while the opposite is evidence of an antiaromatic current). However,this would indicate not only that c-P6·T66+is globally aromatic,but also that c-P6·T6 is even more aromatic than the former,which is not supported by any other experimental or computational data. We have also calculated Ddaand Ddbin abound template in which we have eliminated the alleged current (by removing the bridging butadiyne linkers), and we have found negative and positive Ddaand Ddb,which would support the presence of aring current even in the absence of connectivity among the porphyrins (see Supporting Information). These results bring about two important conclusions.First of all, it reinforces the idea that CAM-B3LYP(or M06-2X) are more adequate methods to obtain the geometry of potential aromatic molecules than B3LYP,which incurs large delocalization errors.Second, through various aromaticity probes,we have shown that the B3LYP geometry of c-P66+corresponds to aquite aromatic molecule with do’@[email protected] ppm, and [email protected] ppm. Hence,ifthe corresponding experimental values are only @1.87 ppm and @2.83 ppm, respectively,this is clearly suggesting that c-P6·T66+is either very weakly aromatic or non-aromatic,asthe CAM-B3LYP results indicate.This result is further reinforced by arecent finding[57] that the experimental aromatic stabilization energy of cP6·T66+is ca. 1.2 kcalmol@1,which is relatively small for an aromatic molecule. Conclusion We have provided compelling evidence that the B3LYP description of c-P66+suffers from severe delocalization errors that result in the overestimation of the aromaticity of this species.This is yet another proof[2,3,31–35] that DFAs with alow percentage of long-range HF exchange should not be used to analyze aromatic compounds,especially large conjugated circuits.Computational results at the CAM-B3LYP level conform with the experimental data for c-P6, c-P66+,and cP612+,whereas,for c-P64+,none of the DFAs we have employed provides asatisfactory agreement with the experiment. Through careful computational analysis and the judicious examination of the 1H-NMR data, we conclude that cP66+is not aromatic and that 1H-NMR data cannot be used to unequivocally assess the aromaticity of this species.Hence, none of the large nanorings studied can be considered aromatic,and the quest for large aromatic nanorings should be continued. Although an enhanced conjugation of some pathways passing through the porphyrins would help to increase the global aromaticity of these nanorings,our results show that the main reason behind the absence of an aromatic ring current in these nanorings is the low delocalization in the transition from the porphyrins to the bridging butadiyne linkers,which disrupts the overall conjugated circuit. Acknowledgements This work has been supported by grants from the Spanish government MICINN (PGC2018-098212-B-C21, PID2019104772GB-I00, EUR2019-103825, PID2019-105488GB-I00, and PCI2019-103657), DiputacilnForal de Gipuzkoa (2019CIEN-000092-01), and Gobierno Vasco (IT1346-19, IT125419, PRE_2016_1_0159, and PIBA19-0004). E.R.C.acknowledges funding from the Juan de la Cierva program IJCI-201734658. Figure 8. The 1245-index distribution along the most aromatic path of c-P6·T66+.See Figure 6tolocate the points of the molecule represented in the x-axis. A ngewandte Chemie Research Articles 24086 www.angewandte.org T2021 TheAuthors.AngewandteChemieInternational Edition publishedbyWiley-VCH GmbH Angew.Chem. Int.Ed. 2021,60,24080–24088 Conflict of Interest Theauthors declare no conflict of interest. Keywords: aromaticity ·delocalization error ·nanoring [1] C. Gellini, P. R. Salvi, Symmetry 2010,2,1846–1924. [2] I. Casademont-Reig,E.Ramos-Cordoba, M. Torrent-Sucarrat, E. 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