Can we predict the conformational preference of amides?

To what extent, if any, is the conformation of secondary amides revealed by theory? This question has now been addressed by computational methods using calculations at the B3LYP/6-31G level of theory and (1)H NMR spectroscopy. Both gas-phase and solvent studies predict a Z-anti conformation to be the lowest in energy for an evaluated series of acetamides. Moreover, Z-anti conformations may also be inferred from the chemical shifts of the N-CH alpha protons determined by NMR spectroscopy. Thus, a proton situated anti to the N-H proton consistently appears approximately 0.8 ppm further downfield than a proton situated gauche to the N-H proton. This finding, which could only be derived by using the DFT calculations of conformational preference as a guide to interpret the NMR data, might prove to be useful as a simple and convenient methodology for establishing amide conformation experimentally.     

N’-苄基酰腙分子的氮-氮键旋转位阻及分子构象

采用动态核磁共振波谱(DNMR)和密度泛函理论(DFT)对N'-苄基酰腙化合物进行构象研究. 实验和理论计算表明, 1H NMR图谱中三组不同质子的双峰裂分是由N—N键旋转位阻造成的, 而这三个双峰裂分的化学位移差异随温度升高而减小. 通过模拟化学位移差异与温度的关系, 得到了交换速率常数, 采用Eyring方程计算出N—N键旋转位阻. 提出顺式和反式共存的模型来分析酰胺质子信号分裂的原因, 并利用DFT计算得出优化的异构体构象及其最低能量. 端甲基质子和次甲基质子信号裂分也来源于N—N键旋转受阻. N'-苄基酰腙通过缩合反应转变成1,3,4-二唑化合物, 消除了甲基空间取向的差异, 其信号变为单峰.     

Theoretical studies of the effect of thio substitution on orotidine monophosphate decarboxylase substrates

[reaction: see text] The effect of replacing carbonyl oxygens with sulfur in a series of orotidine 5'-monophosphate decarboxylase (ODCase) substrates was studied computationally. Previous experimental results indicate that while 2-thio-orotidine 5'-monophosphate (2-thio-OMP) is a poor substrate for ODCase, 4-thio-orotidine 5'-monophosphate (4-thio-OMP) binds to ODCase, and the resultant k(cat) is measurable. Energetics calculations on 2-thio-1-methyl-orotate and 4-thio-1-methyl-orotate (as models for the 2- and 4-thio-OMPs) indicate that mechanisms involving proton transfer to the 2- or 4-site, regardless of substrate and regardless of whether the 2- or 4-position is a carbonyl or thiocarbonyl, are energetically favorable, as compared to direct decarboxylation without proton transfer. Proton transfer to the 4-site during decarboxylation is found to be energetically more favorable than 2-protonation. Each thiocarbonyl is also found to be more basic than its carbonyl counterpart. Therefore, if 2- or 4-proton transfer is the operative catalytic pathway, energetics alone would not explain why 2-thio-orotidine 5'-monophosphate is a poor ODCase substrate. Conformational preferences for a series of ODCase substrates were also examined computationally. Specifically, the energies and Boltzmann probabilities of the conformers resulting from rotation about the C1'-N1 bond (O4'-C1'-N1-C2 rotation from 0 degrees to 360 degrees ) were calculated. It was found that a calculated preference for the syn versus the anti nucleoside conformation correlates to an experimentally better substrate: the OMP and 4-thio-OMP models show a preference for syn conformations, whereas the 2-thio-OMP (the only substrate of the three OMPs that is experimentally found to bind poorly) model shows a preference for an anti conformation. The same rough correlation was found for a series of ODCase inhibitors; that is, a preference for the syn conformation correlates to a better inhibitor. This result is of interest and points to the possibility that the ability for a substrate to bind well to ODCase may be related to its tendency to favor the syn conformation.     

Structural and dynamic studies on amido-bridged rhodium and iridium complexes

Treatment of [[M(mu-Cl)(diolefin)](2)] with the lithium salts of primary and secondary amines (LiNRR') in diethyl ether affords the complexes [[M(mu-NRR')(diolefin)](2)] (M=Rh, Ir; diolefin=1,5-cyclooctadiene (cod), tetrafluorobenzobarrelene (tfb); R'=H, R=tBu, Ph, 4-MeC(6)H(4); R=R'=Ph, 4-MeC(6)H(4)). Mixed-bridged chloro/amido complexes are intermediates in these syntheses, two of which, [[Rh(cod)](2)(mu-NHR)(mu-Cl)] (R=tBu, 4-MeC(6)H(4)), have been isolated. Replacement of the diolefin ligands by carbon monoxide or tert-butyl isocyanide in selected compounds takes place with retention of the binuclear structure to give the corresponding complexes [[M(mu-4-HNC(6)H(4)Me)(CO)(2)](2)], [[Rh(mu-4-HNC(6)H(4)Me)(CNtBu)(2)](2)] (12), and [[Rh(mu-NPh(2))(CNtBu)(2)](2)] (13). Single-crystal X-ray diffraction analyses of the complexes [[Rh(mu-NRR')(cod)](2)] (R'=H, R=4-MeC(6)H(4) (3); R=R'=4-MeC(6)H(4) (5)), 12, and 13 have shown that the conformation of the "RhN(2)Rh" four-membered metallacycle is planar in 5 and folded in 3, 12, and 13. The complexes with primary amides, 3 and 12, were found to exist as the syn,endo stereoisomers. The fluxionality of the complexes with secondary amides is due to rotation of the aromatic substituents about the N-C(ipso) bond and, in the case of 13, to the inversion of the "RhN(2)Rh" metallacycle as well. The complexes [[M(mu-NHR)(cod)](2)] (R=Ph, 4-MeC(6)H(4)) were found to exist as isomeric mixtures in solution, the syn/anti ratio being 2:3 for the rhodium derivatives and 1:1 for their iridium counterparts. Again, the motion detected was due to rotation of the aromatic substituents, and could be frozen only in the case of the syn isomers. The complex [[Rh(mu-NHtBu)(cod)](2)] with aliphatic amido ligands was found to be the anti folded isomer and proved to be nonfluxional. The most common conformation of the "RhN(2)Rh" metallacycle in these compounds is folded, and the preferred configuration varies from syn for the less encumbered compounds to anti on increasing the bulkiness of the bridging and ancillary ligands.     

Solvatochromic analysis of some N-nitroso oxime derivatives--Taft and Catalan approach

Some novel N-nitroso oxime derivatives were synthesized and characterized by (1)H, (13)C, (1)H-(1)H and (1)H-(13)C COSY NMR spectra. The spectra of all these N-nitroso oximes reveal the presence of two isomers labelled as E (-NOH group is anti to N-N=O moiety) and Z (-NOH group is syn to N-N=O moiety) in solution and the coupling constants ruled out the possibility of normal chair conformation. From the theoretical studies and coupling constant values it was found that both E (major) and Z (minor) isomers of N-nitroso oximes exist as an equilibrium mixture of CA and boat conformation (B(1)) and this was also supported by DFT calculation. The photophysical properties of these oxime derivatives were studied and the observed lower fluorescence quantum yield may be due to an increase in the non-radiative deactivation rate constant. This is attributed due to the presence of non-chair conformation of N-nitroso oxime derivatives.     

Ring current and anisotropy effects on OH chemical shifts in resonance-assisted intramolecular H-bonds

Ring current effects on resonance-assisted and intramolecularly bridged hydrogen bond protons for 10-hydroxybenzo[h]quinoline 1 and a number of related compounds were calculated and the through-space NMR shieldings (TSNMRS) obtained hereby visualized as iso-chemical-shielding surfaces (ICSS) of various size and direction. These calculations revealed that this through-space effect is comparably large (up to 2?ppm) dependent on the position of the intramolecularly bridged OH proton, and therefore, contribute considerably to the chemical shift of the latter making it questionable to use δ(OH)/ppm in the estimation of intramolecular hydrogen bond strength without taking this into account. Furthermore, the anisotropy effects of additional groups on the aromatic moiety (e.g. the carbonyl group in salicylaldehyde or in o-hydroxyacetophenone of ca. 0.6?ppm deshielding) should also be considered. These through-space effects need to be taken into account when using OH chemical shifts to estimate hydrogen bond strength.     

1H NMR spectroscopic criteria for the configuration of N-acyl-alpha,beta-dehydro-alpha-amino acid esters

The diagnostic values of the following three spectral criteria for the configuration of N-acyl-alpha,beta-dehydro-alpha-amino acid esters were examined: (i) the proton at the beta-position at the double bond of a Z-isomer is shielded if compared with the respective E-isomer (delta(beta)Z < delta(beta)E); (ii) the proton at the nitrogen atom is shielded in a Z-isomer in comparison with the corresponding E-isomer (delta(NH)Z < delta(NH)E); and (iii) changing of the solvent from CDCl3 to deuterated trifluoroacetic acid (TFA) causes shielding of the H(beta) vinylic proton of an E-isomer or deshielding of the respective proton of the Z-isomer (delta(CDCl3)E > delta(TFA)E or delta(CDCl3)Z < delta(TFA)Z). The investigations were based on a set of 22 (Z)- and (E)-N-acyl-alpha,beta-dehydro-alpha-amino acid esters of diverse structures, with aliphatic, aromatic and heteroaromatic substituents at the vinylic beta-carbon; most of the examined compounds were hitherto unknown. The application of the substituent effect additivity rule given by Pascual et al. for olefinic protons leads to evidently erroneous configuration assignments of N-acyl-alpha,beta-dehydro-alpha-amino acid esters. The considered criteria were fulfilled for all the examined cases with one exception [the second criterion for the alpha-pivaloylamino-beta-(2-furyl)acrylates]. The comparison of changes in the chemical shifts of H(beta) vinylic protons in CDCl3 and deuterated TFA seems to be the most reliable and useful configuration criterion, as it can be used in the case of a single isomer.     

1H NMR spectra part 31: 1H chemical shifts of amides in DMSO solvent

The ¹H chemical shifts of 48 amides in DMSO solvent are assigned and presented. The solvent shifts Δδ (DMSO‐CDCl₃) are large (1–2 ppm) for the NH protons but smaller and negative (?0.1 to ?0.2 ppm) for close range protons. A selection of the observed solvent shifts is compared with calculated shifts from the present model and from GIAO calculations. Those for the NH protons agree with both calculations, but other solvent shifts such as Δδ(CHO) are not well reproduced by the GIAO calculations. The ¹H chemical shifts of the amides in DMSO were analysed using a functional approach for near ( ≤ 3 bonds removed) protons and the electric field, magnetic anisotropy and steric effect of the amide group for more distant protons. The chemical shifts of the NH protons of acetanilide and benzamide vary linearly with the π density on the αN and βC atoms, respectively. The C=O anisotropy and steric effect are in general little changed from the values in CDCl₃. The effects of substituents F, Cl, Me on the NH proton shifts are reproduced. The electric field coefficient for the protons in DMSO is 90% of that in CDCl₃. There is no steric effect of the C=O oxygen on the NH proton in an NH…O=C hydrogen bond. The observed deshielding is due to the electric field effect. The calculated chemical shifts agree well with the observed shifts (RMS error of 0.106 ppm for the data set of 257 entries). Copyright © 2014 John Wiley & Sons, Ltd.     

Conformations and energetics of sulfur and selenium diimides

The geometries and energetics of different conformations of sulfur and selenium diimides E(NR)(2) (E = S, Se; R = H, Me, (t)Bu, C(6)H(3)Me(2)-2,6, SiMe(3)) have been studied by using various ab initio and DFT molecular orbital techniques. The syn,syn conformation is found to be most stable for parent E(NH)(2), but in general, the preferred molecular conformation for substituted chalcogen diimides is syn,anti. In the case of E(NH)(2) the present calculations further confirm that syn,syn and syn,anti conformations lie energetically close to each other. From the three different theoretical methods used, B3PW91/6-31G proved to be the most suitable method for predicting the geometries of chalcogen diimides. The optimized geometrical parameters are in a good agreement with all available experimental data. While qualitative energy ordering of the different conformations is independent of the level of theory, the quantitative energy differences are dependent on the method used. The performance and reliability of higher level ab initio calculations and DFT methods using large basis sets were tested and compared with experimental information where available. All of the higher level ab inito methods give very similar results, but the use of large basis sets with the B3PW91 method does not increase the reliability of the results. The combination of CCSD(T)/cc-pVDZ with the B3PW91/6-31G-optimized geometries is found to be the method of choice to study energetic properties of chalcogen diimides.     

N-二茂铁甲酰基-N'-对乙酰基苯基硫脲的晶体及分子结构

合成的标题化合物晶体属单斜晶系, 空间群为P2~1/α, 晶胞参数为:α=0.9771(2), b=1.6752(6), c=1.1552(3)nm; β=109.23(2)°, 体积V=1.785(2)nm^3, Z=4, D~x=1.42g/cm^3, 最终偏差因子R=0.047, R~ω=0.051。结构分析表明, 在N'H-C(S)-NH-C(O)中的羰基氧和N'上的氢之间生成分子内氢键, 其为包括氢原子在内的平面六元环, 并且在二茂铁中的两个茂环平行。结合^1HNMR, IR谱矛以确证, 指出N原子上的氢应在高场(～8.0)N'上的氢原子化学位移应在低场(～12,0)。     

Ab initio and NMR studies on the effect of hydration on the chemical shift of hydroxy protons in carbohydrates using disaccharides and water/methanol/ethers as model systems

Density functional theory (DFT) and Hartree-Fock (HF) quantum mechanical calculations have been performed on the disaccharides, [small beta]-l-Fucp-(1[rightward arrow]4)-[small alpha]-d-Galp-OMe, [small beta]-l-Fucp-(1[rightward arrow]4)-[small alpha]-d-Glcp-OMe, and [small beta]-l-Fucp-(1[rightward arrow]3)-[small alpha]-d-Glcp-OMe. The [capital Delta][small delta]-values (difference between the chemical shift in the disaccharide and the corresponding monosaccharide methyl glycoside) for the exchangeable hydroxy protons have been calculated and compared to experimental values previously measured by NMR spectroscopy for samples in aqueous solutions. The calculations performed on molecules in vacuum showed that hydroxy protons hydrogen bonded to the neighboring ring oxygens have large positive [capital Delta][small delta]-values, indicating that they are deshielded relative to those in the corresponding methyl glycoside. The NMR experiments showed instead that these hydroxy protons close to the neighboring ring oxygens were shielded. This discrepancy between calculated and experimental data was attributed to solvent effects, and this hypothesis has been confirmed in this work by monitoring the chemical shift of the hydroxy proton of methanol in water, ethers and water/ether solutions. Shielding of the hydroxy proton of methanol is observed for increased ether concentrations, whereas deshielding is observed for increased concentration of water. The shielding observed for hydroxy protons in disaccharides is a consequence of reduced hydration due to intermolecular hydrogen bonding or steric effects. In strongly hydrated systems such as carbohydrates, the hydration state of a hydroxy proton is the key factor determining the value of the chemical shift of its NMR signal, and the [capital Delta][small delta] will be a direct measure of the change in hydration state.     

A conformational study of phospha(III)- and phospha(V)-guanidine compounds

Spectroscopic, crystallographic, and computational studies of the substituent distribution about the "NCN" unit in a series of phospha(III)- and phospha(V)-guanidines, R(2)PC{NR'}{NHR'} and R(2)P(E)C{NR'}{NHR'} (R = Ph, Cy; R' = (i)Pr, Cy; E = S, Se), are reported. In the phosphorus(III) systems, the P-diphenyl substituted compounds are observed as only one isomer, shown by NMR spectroscopy to be the E(syn)-(alpha) configuration. In contrast, the corresponding P-dicyclohexyl derivatives exist as a mixture of E(syn)-(alpha) and Z(anti) in solution. Spectroscopic techniques are unable to determine whether the latter isomer exists as the alpha- or beta-conformer relative to rotation about the P-C(amidine)() bond; however, DFT calculations indicate a low-energy structure for the N,N'-dimethyl model complex in the beta-conformation. In their oxidized sulfo and seleno forms, the P-diphenyl compounds are present as an interconverting equilibrium mixture of the E(syn)-(beta) and Z(syn)-(beta) isomers in solution ( approximately 3:2 ratio), whereas for the P-dicyclohexyl analogues, the latter configuration (in which the nitrogen substituents are in a more sterically unfavorably cisoid arrangement about the imine double bond) is the dominant form. Intramolecular E...HN (E = S, Se) interactions are observed in solution for the Z(syn)-(beta) configuration of both P-substituted species, characterized by J(SeH) coupling in the NMR spectrum for the P(V)-seleno compounds and a bathochromic shift of the NH absorption in the infrared spectrum. An X-ray crystallographic analysis of representative Ph(2)P(E)- and Cy(2)P(E)-substituted species shows exclusively the E(syn)-(beta) configuration for the P-diphenyl substituted compounds and the Z(syn)-(beta) form for the P-dicyclohexyl derivatives, independent of the chalcogen and the nitrogen substituents. Results from a DFT analysis of model compounds fail to identify a compelling electronic argument for the observed preferences in substituent orientation, suggesting that steric factors play an important role in determining the subtle energetic differences at work in these systems.     

Synthesis and characterization of two isomeric, self-assembled arsenic-thiolate macrocycles

The use of labile As-S bond formation in the self-assembly of discrete supramolecular structures is extended. Macrocyclic structures of chemical formula As2L2Cl2 (H2L=alpha,alpha'-dimercapto-p-xylene) were prepared and characterized. Diastereomeric syn and anti isomers of these macrocycles were selectively crystallized and characterized in the solid state using single-crystal X-ray diffraction. Both the syn and anti macrocycles show close contacts between the arsenic(III) ions and the aromatic carbons, consistent with intramolecular arsenic-pi interactions. The dynamic behavior of the isomers in solution is also investigated. anti-As2L2Cl2.AsCl3 crystallizes in monoclinic space group P2(1)/c (No. 14) with a=10.6194(5) A, b=16.7780(9) A, c=8.5725(4) A, beta=100.6830(10) degrees, and Z=2. syn-As2L2Cl2 crystallizes in orthorhombic space group Pnma (No. 62) with a=10.8881(8) A, b=19.3511(14) A, c=9.9524(7) A, and Z=4.     

Are ring currents still useful to rationalize the benzene proton magnetic shielding?

[structure: see text] The conventional interpretation of proton NMR chemical shifts is supported by large basis set ab initio quantum mechanical calculations. The benzene protons are predicted to lie within the deshielding zone defined in terms of the out-of-plane magnetic shielding domain. However, ring currents by themselves are not sufficient to account quantitatively for the observed benzene proton downfield chemical shift. sigma-Electron contributions must also be taken into account. The conventional explanation for the ethyne proton chemical shift is valid.     

Bifurcated hydrogen-bonding effect on the shielding and coupling constants in trifluoroacetyl pyrroles as studied by 1H, 13C and 15N NMR spectroscopy and DFT calculations

According to the (1)H, (13)C and (15)N NMR spectroscopic data and DFT calculations, bifurcated N--H...N and N--H...O intramolecular hydrogen bond is shown to be present in 2-trifluoroacetyl-5-(2'-pyridyl)-pyrrole. This bifurcated hydrogen bond causes an increase in the absolute size of the (1)J(N,H) coupling constant by about 6 Hz, and the deshielding of the bridge proton by 2 ppm. DFT calculations show that the influence of the N--H...N and N--H...O intramolecular hydrogen bonds on the (1)J(N,H) coupling and proton shielding is almost additive, although the components of the bifurcated hydrogen bond slightly weaken each other. In 2-trifluoroacetyl-5-(2'-pyridyl)-pyrrole, the coupling constants involving the fluorine and the N--H covalent bond nuclei depend dramatically on the spatial position of the pyridine ring. The pyridine ring rotation operates as a quantum switch controlling the spin information transfer between the (19)F and (15)N nuclei, as well as the proton.     

Azolium-linked cyclophanes: effects of structure, solvent, and counteranions on solution conformation behavior

This paper describes the synthesis, structural characterization, and solution behavior of some xylyl-linked imidazolium and benzimidazolium cyclophanes decorated with alkyl or alkoxy groups. The addition of alkyl/alkoxy chains to the cyclophanes allows for studies in chlorinated solvents, whereas previous solution studies of azolium cyclophanes have generally required highly polar solvents. The azolium cyclophanes may exist in a syn/syn conformation (azolium rings mutually syn, arene rings mutually syn) or a syn/anti conformation (azolium rings mutually syn, arene rings mutually anti). The preferred conformation is significantly affected by (i) binding of bromide (ion pairing) to the protons on the imidazolium or benzimidazolium rings, which occurs in solutions of bromide salts of the cyclophanes in chlorinated solvents, and (ii) the addition of alkoxy groups to the benzimidazolium cyclophanes. These structural modifications have also led to cyclophanes that adopt conformations not previously identified for similar azolium cyclophane analogues. Detailed (1)H NMR studies for one cyclophane identified binding of bromide at two independent sites within the cyclophane.     

Phospholes with Reduced Pyramidal Character from Steric Crowding. 1. Synthesis and NMR Characterization of 1-(2,4-Di-tert-butyl-6-methylphenyl)-3-methylphosphole

The sterically crowded 1-(2,4-di-tert-butyl-6-methylphenyl)-3-methylphosphole was synthesized by dehydrohalogenation of the corresponding 3,4-dibromophospholane, in order to probe the possibility that the steric congestion would cause some flattening of the phosphorus pyramid and an increase in electron delocalization. The phosphole was a recrystallizable solid with (31)P NMR delta 1.8. Semiempirical calculations indicated that the pyramidal shape was retained but was noticeably flatter than in 1-phenylphosphole. In the low energy conformation, the phosphole and phenyl ring planes are approximately orthogonal, with the 2-tert-butyl group in the less crowded position that is syn to the lone pair on phosphorus. The 6-methyl group is positioned under the phosphole ring. This conformational prediction was amply confirmed by several chemical shift and coupling effects in the (13)C NMR spectrum. The (1)H NMR spectrum displayed an unusually large four-bond coupling (6 Hz) of (31)P to the m-phenyl proton syn to the lone pair (and none to the anti-meta proton), consistent with the orthogonal conformation. The oxide of the phosphole showed more stability than that of less crowded phospholes and gave a (31)P NMR signal that was detectable over a several hour period at room temperature. The oxide proceeded to give the usual Diels-Alder dimer and also formed a cycloadduct with N-phenylmaleimide. The phosphoryl group of the latter was reduced with trichlorosilane to give the phosphine. This new 7-phosphanorbornene derivative gave the most downfield (31)P NMR shift (delta 153.3) of any member of this family, all of which are characterized by remarkable deshielding in the syn isomer.     

Molecular orbital studies of the NMR hydrogen bond shift

Magnetic shielding constants are calculated for the protons in XOH and XOH…OH₂ (XH, CH₃, NH₂, OH and F) molecules using a slightly extended set of atomic functions modified by gauge factors. These results are used to determine theoretical values for the NMR hydrogen bond shifts in the XOH…OH₂ systems. Such theoretical data are consistent with the few available experimental data. An analysis of the theoretical results reveals that there are three major types of shielding contribution to the NMR hydrogen bond shift; (a) a deshielding change due to the variation of the local currents on the hydrogen bonded proton; (b) a reduction in shielding from currents localized on the oxygen atom of the proton donor; (c) a deshielding contribution from currents induced on the oxygen atom of the proton acceptor. Except for the water dimer, contributions (a), (b) and (c) are of comparable importance for changes in isotropic shielding. For (H₂O)₂ contributions (a) and (c) are somewhat more important than contribution (b). Contribution (c) is almost totally responsible for the changes in the anistropies of the shielding tensors associated with the hydrogen bonded protons. The proton shielding anisotropy changes which occur on hydrogen bond formation are generally much larger than the corresponding variations in the isotropic values of the shielding tensors. This suggests that proton magnetic shielding anisotropies may be more sensitive measures of features of hydrogen bonding than are isotropic proton shielding constants.     

Amidolithium and amidoaluminum catalyzed synthesis of substituted guanidines: an interplay of DFT modeling and experiment

The synthesis of substituted guanidines is of significant interest for their use as versatile ligands and for the synthesis of bioactive molecules. Lithium amides supported by tetramethylethylenediamine have recently been shown to catalyze the guanylation of amines with carbodiimide. In this report, density functional theory (DFT) calculations are used to provide insight into the mechanism of this transformation. The mechanism identified through our calculations is a carbodiimide insertion into the lithium-amide bond to form a lithium guanidinate, followed by a proton transfer from the amine. The proton transfer transition state requires the dissociation of one of the chelating nitrogen centers of the lithium guanidinate, proton abstraction from the amine, and bond formation between the lithium center and the amine nitrogen. On the basis of this mechanism, further calculations predicted that aluminum amides would also function as active catalysts for the guanylation of amines. We confirm this experimentally and report the development of aluminum amides as a new main group catalyst for the guanylation of a range of electron-poor amines with carbodiimide.     

Conformational changes of functionalised indole receptors upon their interaction with anions

The conformational analysis of four C2-amido and C7-ureido functionalised indole anion receptors was performed by a combination of heteronuclear NMR spectroscopy and ab initio quantum mechanical calculations. NOE experiments showed that anti–anti conformation across C2–C2α and C7–N7α bonds is predominant in acetone solution in the absence of anions. Upon anion binding to receptors, syn–syn conformation becomes predominant. The conformational changes upon anion binding are in good agreement with energetic preferences established by ab initio calculations. Chemical shift changes induced by interaction of anions suggest that binding of chloride and bromide anions occurs primarily to H1 and H7α protons. Nitrate anions favour interaction with H7α and H7γ ureido protons, whereas acetate anions interact strongly with all four available hydrogen bond donor groups.