Quantification of hydrogen bond energy based on equations using spectroscopic, structural, QTAIM-based, and NBO-based descriptors which calibrated by the molecular tailoring approach.

CONTEXT: Hydrogen bonds critically influence the structure and properties of both organic molecules and biomolecules, as well as supramolecular assemblies. For this reason, the development and elaboration of methods for quantitative assessment of hydrogen bond energy is an urgent challenge. In this study, using a large series of hydroxycarbonyl aliphatic compounds with the O‒H···O = C intramolecular hydrogen bond, a bank of hydrogen bond descriptors was created, including spectroscopic, structural, QTAIM-based, and NBO-based parameters. It was shown that the O‒H vibration frequency, OH chemical shift as the spectroscopic descriptors, the O···H hydrogen bond length, O···O distance, and O‒H covalent bond length as the structural descriptors, the electron density and its Laplacian, electron potential energy density in the hydrogen bond critical point, the electron density at the ring critical point as the QTAIM-based descriptors change in a correlated manner. The same correlation is found in change of the charge transfer energy through a hydrogen bond, the occupancy of the O‒H bond antibonding orbital, the Wiberg indices of the O···H hydrogen bond, and the O‒H covalent bond, as well as the polarization of the O‒H bond, which are the NBO-based descriptors. It was also recognized that the specified descriptors from the spectroscopic, structural, QTAIM-based, and NBO-based categories are functionally related to the values of intramolecular hydrogen bond energy, quantified via the molecular tailoring approach. This allowed one to obtain a system of equations for quantitative estimation of intramolecular hydrogen bond energy based on the spectroscopic, structural, QTAIM, and NBO descriptors, which makes such quantification more dependable and reliable. METHODS: To obtain the spectroscopic descriptors, the vibrational spectra and shielding constants were calculated using the GIAO method. Structural descriptors were obtained for the equilibrium geometry of molecules, calculated at the MP2(FC)/6-311 + + (2d,2p) level using the Gaussian 09 program. The QTAIM-based descriptors were calculated using the AIMAll program within the framework of the quantum theory "Atoms in Molecules." The NBO-based descriptors were calculated using the NBO 3.1 program implemented into Gaussian 09. To quantify the energy of intramolecular hydrogen bonds, molecular fragmentation was used within the molecular tailoring approach.

Revealing the Reasons for Degeneration of Resonance-Assisted Hydrogen Bond on the Aromatic Platform: Calculations of Ortho-, Meta-, Para-Disubstituted Benzenes, and (Z)-(E)-Olefins.

The energies of the O-H∙∙∙O=C intramolecular hydrogen bonds were compared quantitatively for the series of ortho-disubstituted benzenes and Z-isomers of olefins via a molecular tailoring approach. It was established that the hydrogen bond energy in the former series is significantly less than that in the latter one. The reason for lowering the hydrogen bond energy in the ortho-disubstituted benzenes compared to the Z-isomers of olefins is the decrease in the π-contribution to the total energy of the complex interaction, in which the hydrogen bond per se is enhanced by the resonance effect. By the example of the para- and meta-disubstituted benzenes, as well as E-isomers of olefins, it was explicitly shown that the aromatic ring is a much poorer conductor of the resonance effect compared to the double bond. The hydrogen bond in the ortho-disubstituted benzenes has a lower energy than a typical resonance-assisted hydrogen bond because the aromatic moiety cannot properly assist the hydrogen bond with a resonance effect. Thus, a hydrogen bond on an aromatic platform should fall into a special category, namely an aromaticity-assisted hydrogen bond, which is closer by nature to a simple hydrogen bond rather than to a resonance-assisted one.

Digitization of the electron shell via the localized orbital locator formalism: trends in the size and electronegativity changes of atoms across the periodic table.

The parameters of the (3, -3) critical point in the topology of the localized orbital locator inside the electron shell reveal patterns that make it possible to recognize trends in the size, electronegativity, and ionization energy of atoms in the first four periods of the periodic table.

Molecular tailoring approach as tool for revealing resonance-assisted hydrogen bond: Case study of Z-pyrrolylenones with the NH⋯OС intramolecular hydrogen bond.

Both the experimental and calculated data reveal that a strong NH⋯OС intramolecular hydrogen bond closing the seven-membered quasi-cycle is formed in the Z-isomers of pyrrolylenones. Comparison of the NH⋯OС intramolecular hydrogen bonds energies in the pyrrolylenones, estimated via the molecular tailoring approach, with the similar data for reference malonaldehydes shows that the resonance-assisted hydrogen bonding occurs in both cases, the hydrogen bond energy being varied mainly within 10-20 kcal/mol. The combined application of function-based and molecular tailoring approaches makes it possible to decompose the NH⋯OС total hydrogen bond energy in the pyrrolylenones into the π- and σ-components. It is established that the contribution of the π-component to the total N(O)H⋯OС hydrogen bond energy in the pyrrolylenones and malonaldehydes is almost the same (6-7 kcal/mol). Comparison of the π-contribution to the total energy of the resonance-assisted hydrogen bonding in the Z-isomer of pyrrolylenones with the energy of the push-pull effect in the E-isomer of pyrrolylenones reveals that the resonance contribution to the total energy of the resonance-assisted hydrogen bond in the former significantly enhances with reference to the net resonance energy in the latter. The appearance of the resonance-assisted hydrogen bond in the pyrrolylenones is possible due to the participation in the interaction of 10 or 14 π-electrons satisfying the Hückel aromaticity rule.

Guide to tuning the chalcone molecular properties based on the push-pull effect energy scale created via the molecular tailoring approach.

Using the molecular tailoring approach, a total energy scale for the push-pull effect in the range from -40 to 100 kcal/mol is created for the wide series of neutral, charged and doubly charged compounds on the chalcone platform. Taking into account similar energy scale for hydrogen bonds, the strength of the push-pull effect is ranked in the seven categories, ranging from negative (anti-push-pull) to very weak and very strong push-pull effect. It is demonstrated that the molecular properties of chalcone can be tuned prior synthesis due to the created energy scale for the push-pull effect. The single bonds of the π-spacer in the chalcones are shortened, the double ones are lengthened, and the C=O bond vibrations are red shifted when the push-pull effect is enhanced along the energy scale. The HOMO and LUMO energies change systematically while the HOMO-LUMO energy gap narrows as the strength of the push-pull effect increases.

Localized orbital locator as a descriptor for quantification and digital presentation of lone pairs: benchmark calculations of 4-substituted pyridines.

The parameters of the (3,-3) critical point in the localized orbital locator topology near a heteroatom have been found to reflect the changes in the size, density and electron energy of the lone pair and correlate with the donor ability of the lone pair carrying heteroatom.

A molecular tailoring approach - a new guide to quantify the energy of push-pull effects: a case study on (E)-3-(1H-pyrrol-2-yl)prop-2-enones.

The molecular tailoring approach is recognized to be an efficient tool for quantifying the strength of the push-pull effect in molecules with internal charge transfer.

Acylacetylenes in multiple functionalization of hydroxyquinolines and quinolones.

The expected one-pot multiple functionalization of hydroxyquinolines and quinolones with acylacetylenes (20 mol% KOH, 5 equiv. H2O, MeCN, 55-60 °C), which, according to the previous finding, might involve the addition of OH and NH-functions to the triple bond and insertion of acylacetylenes into the quinoline scaffold, retains mainly on the formation of chalcone-quinoline ensembles in up 99% yield. The higher functionalized quinolines can be obtained in a synthetically acceptable yield, when the above ensembles are treated with the second molecule of acylacetylenes. Thus, the further insertion of second molecule of the acetylenes into the quinoline scaffold occurs as a much slower process indicating a strong adverse substituent effect of the remote chalcone moiety.

KOBut/DMSO-Mediated α-C-H Vinylation of N-Benzyl Ketimines with Acetylene Gas: Stereoselective Synthesis of (E,Z)-2-Azadienes.

Several imines, readily derived from aryl methyl ketones and benzylamines, react with acetylene gas in KOBut/DMSO system to afford 2-azadienes stereoselectively. This new C-C bond constructing reaction involves, instead of the expected ethynylation of the C═N bond, the addition of azaallyl anions to the triple bond of acetylene.

Quantitative decomposition of resonance-assisted hydrogen bond energy in ß-diketones into resonance and hydrogen bonding (π- and σ-) components using molecular tailoring and function-based approaches.

Using the molecular tailoring and function-based approaches allows one to divide the energy of the O─H⋯O═C resonance-assisted hydrogen bond in a series of the ß-diketones into resonance and hydrogen bonding components. The magnitude of the resonance component is assessed as about 6 kcal mol-1 . This value increases by ca. 1 kcal mol-1 on going from the weak to strong resonance-assisted hydrogen bonding. The magnitude of the hydrogen bonding component varies in the wide range from 2 to 20 kcal mol-1 depending on the structure of the ß-diketone in question.

Cyanoacetylenes as Triggers and Partners in KOH-Assisted Assemblies of Quinoline-Based Dihydropyrimido[1,2-a]quinolin-3-ones on Water.

Arylcyanoacetylenes trigger the assembly of dihydropyrimido[1,2-a]quinolin-3-ones in good to excellent yields on the platform of quinolines in the presence of KOH in aqueous media at room temperature. This green on-water methodology provides a simple one-pot access to a novel family of the pharmaceutically prospective compounds.

Study of spontaneous E/Z isomerization of bis[(Z)-cyanomethylidene]-diazapentacyclodienedicarboxylates by 1 H, 13 C, and 15 N NMR spectroscopy, X-ray, and quantum chemical calculation data.

X-ray data show that the diethyl 6,13-bis[(Z)-cyanomethylidene]-5,5,14,14-tetramethyl-4,15-dioxa-7,12-diazapentacyclo[9.5.2.02,10 .03,7 .012,16 ]octadeca-8,17-diene-10,17-dicarboxylate is formed as the ZZ isomer and diastereomer with the (1R*,2R*,3R*,10S*,11R*,12R*,16R*) configuration. The 1 H, 13 C, and 15 N NMR data exhibit that on standing in chloroform-d solution, there is a spontaneous isomerization of this compound resulting in a thermodynamically stable mixture of the ZZ, ZE, EE, and EZ isomers with the same backbone. Using the 2D [1 H-1 H] COSY, [1 H-13 C] HSQC, and [1 H-13 C, 1 H-15 N] HMBC NMR techniques and quantum chemical calculations makes it possible a complete assignment of signals in the 1 H, 13 C, and 15 N NMR spectra of each of the isomers. Such isomerization does not occur for similar compounds with the more bulky substituents at the 1,3-oxazolidine rings. Copyright © 2016 John Wiley & Sons, Ltd.

Estimating the energy of intramolecular hydrogen bonds from 1H NMR and QTAIM calculations.

The values of the downfield chemical shift of the bridge hydrogen atom were estimated for a series of compounds containing an intramolecular hydrogen bond O-HO, O-HN, O-HHal, N-HO, N-HN, C-HO, C-HN and C-HHal. Based on these values, the empirical estimation of the hydrogen bond energy was obtained by using known relationships. For the compounds containing an intramolecular hydrogen bond, the DFT B3LYP/6-311++G(d,p) method was used both for geometry optimization and for QTAIM calculations of the topological parameters (electron density ρBCP and the density of potential energy V in the critical point of the hydrogen bond). The calculated geometric and topological parameters of hydrogen bonds were also used to evaluate the energy of the hydrogen bond based on the equations from the literature. Comparison of calibrating energies from the 1H NMR data with the energies predicted by calculations showed that the most reliable are the linear dependence on the topological ρBCP and V parameters. However, the correct prediction of the hydrogen bond energy is determined by proper fitting of the linear regression coefficients. To obtain them, new linear relationships were found between the calculated ρBCP and V parameters and the hydrogen bond energies obtained from empirical 1H NMR data. These relationships allow the comparison of the energies of different types of hydrogen bonds for various molecules and biological ensembles.

Experimental and theoretical study of the intramolecular C-H···N and C-H···S hydrogen bonding effects in the 1H and 13C NMR spectra of the 2-(alkylsulfanyl)-5-amino-1-vinylpyrroles: a particular state of amine nitrogen.

In the (1)H NMR spectra of the 1-vinylpyrroles with amino- and alkylsulfanyl groups in 5 and 2 positions, an extraordinarily large difference between resonance positions of the HA and HB terminal methylene protons of the vinyl group is discovered. Also, the one-bond (1)J(C(ß),H(B)) coupling constant is surprisingly greater than the (1)J(C(ß),H(A)) coupling constant in pyrroles under investigation, while in all known cases, there was a reverse relationship between these coupling constants. These spectral anomalies are substantiated by quantum chemical calculations. The calculations show that the amine nitrogen lone pair is removed from the conjugation with the π-system of the pyrrole ring so that it is directed toward the HB hydrogen. These factors are favorable to the emergence of the intramolecular C-HB •••N hydrogen bonding in the s-cis(N) conformation. On the other hand, the spatial proximity of the sulfur to the HB hydrogen provides an opportunity of the intramolecular C-HB •••S hydrogen bonding in the s-cis(S) conformation. Presence of the hydrogen bond critical points as well as ring critical point for corresponding chelate ring revealed by a quantum theory of atoms in molecules (QTAIM) approach confirms the existence of the weak intramolecular C-H•••N and C-H•••S hydrogen bonding. Therefore, an unusual high-frequency shift of the HB signal and the increase in the (1)J(C(ß),H(B)) coupling constant can be explained by the effects of hydrogen bonding.

Structural peculiarities of configurational isomers of 1-styrylpyrroles according to 1Н, 13С and 15N NMR spectroscopy and density functional theory calculations: electronic and steric hindrance for planar structure.

Comparative analysis of the (1)Н and (13)С NMR data for a series of the E and Z-1-styrylpyrroles, E and Z-1-(1-propenyl)pyrroles, 1-vinylpyrroles and styrene suggests that the conjugation between the unsaturated fragments in the former compounds is reduced. This is the result of the mutual influence of the donor p-π and π-π conjugation having opposite directions. According to the NMR data combined with the density functional theory calculations, the Z isomer of 1-styrylpyrrole has essentially a nonplanar structure because of the steric hindrance. However, the E isomer of 1-styrylpyrrole is also an out-of-plane structure despite the absence of a sterical barrier for the planar one. Deviation of the E isomer from the planar structure seems to be caused by an electronic hindrance produced by a mutual influence of the p-π and π-π conjugation. The structure of the E isomer of the 2-substituted 1-styrylpyrroles is similar to that of the 2-substituted 1-vinylpyrroles. The steric effects in the Z isomer of the 2-substituted 1-styrylpyrroles result in the large increase of the dihedral angle between planes of the pyrrole ring and double bond.

Stereoselective tandem ring opening of imidazoles with electron-deficient acetylenes and water: synthesis of functionalized (Z,Z)-1,4-diaza-2,5-dienes.

1-Substituted imidazoles undergo exceptionally facile stereoselective ring opening under the influence of electron-deficient acetylenes and water (equimolar ratio of the reactants) in MeCN at 45-60 °C without any catalysts to afford functionalized (Z,Z)-1,4-diaza-2,5-dienes, (Z,Z)-propenylaminoethenylformamides, in up to 80% yields. The reaction is rationalized to proceed in a tandem manner via zwitterionic vinyl carbanions formed by nucleophilic addition of imidazole to the triple bond. The carbanionic center is then quenched with water followed by the rearrangement of the intermediate 2-hydroxy-3-alkenylimidazolines.

Stereospecificity of (1) H, (13) C and (15) N shielding constants in the isomers of methylglyoxal bisdimethylhydrazone: problem with configurational assignment based on (1) H chemical shifts.

In the (13) C NMR spectra of methylglyoxal bisdimethylhydrazone, the (13) C-5 signal is shifted to higher frequencies, while the (13) C-6 signal is shifted to lower frequencies on going from the EE to ZE isomer following the trend found previously. Surprisingly, the (1) H-6 chemical shift and (1) J(C-6,H-6) coupling constant are noticeably larger in the ZE isomer than in the EE isomer, although the configuration around the -CH═N- bond does not change. This paradox can be rationalized by the C-H⋯N intramolecular hydrogen bond in the ZE isomer, which is found from the quantum-chemical calculations including Bader's quantum theory of atoms in molecules analysis. This hydrogen bond results in the increase of δ((1) H-6) and (1) J(C-6,H-6) parameters. The effect of the C-H⋯N hydrogen bond on the (1) H shielding and one-bond (13) C-(1) H coupling complicates the configurational assignment of the considered compound because of these spectral parameters. The (1) H, (13) C and (15) N chemical shifts of the 2- and 8-(CH(3) )(2) N groups attached to the -C(CH(3) )═N- and -CH═N- moieties, respectively, reveal pronounced difference. The ab initio calculations show that the 8-(CH(3) )(2) N group conjugate effectively with the π-framework, and the 2-(CH(3) )(2) N group twisted out from the plane of the backbone and loses conjugation. As a result, the degree of charge transfer from the N-2- and N-8- nitrogen lone pairs to the π-framework varies, which affects the (1) H, (13) C and (15) N shieldings.

Study of stereospecificity of 1H, 13C, 15N and 77Se shielding constants in the configurational isomers of the selenophene-2-carbaldehyde azine by NMR spectroscopy and MP2-GIAO calculations.

In the (1)H and (13)C NMR spectra of selenophene-2-carbaldehyde azine, the (1)H-5, (13)C-3 and (13)C-5 signals of the selenophene ring are shifted to higher frequencies, whereas those of the (1)H-1, (13)C-1, (13)C-2 and (13)C-4 are shifted to lower frequencies on going from the EE to ZZ isomer or from the E moiety to the Z moiety of EZ isomer. The (15)N chemical shift is significantly larger in the EE isomer relative to the ZZ isomer and in the E moiety relative to the Z moiety of EZ isomer. A very pronounced difference (60-65 mg/g) between the (77)Se resonance positions is revealed in the studied azine isomers, the (77)Se peak being shifted to higher frequencies in the ZZ isomer and in the Z moiety of EZ isomer. The trends in the changes of the measured chemical shifts are reasonably reproduced by the GIAO calculations at the MP2 level of the (1)H, (13)C, (15)N and (77)Se shielding constants in the energy-favorable conformation with the syn orientation of both selenophene rings relative to the C = N groups. The NBO analysis suggests that such an arrangement of the selenophene rings may take place because of a higher energy of some intramolecular interactions.

GIAO, DFT, AIM and NBO analysis of the N-H...O intramolecular hydrogen-bond influence on the 1J(N,H) coupling constant in push-pull diaminoenones.

In the series of diaminoenones, large high-frequency shifts of the (1)H NMR of the N-H group in the cis-position relative to the carbonyl group suggests strong N-H...O intramolecular hydrogen bonding comprising a six-membered chelate ring. The N-H...O hydrogen bond causes an increase of the (1)J(N,H) coupling constant by 2-4 Hz and high-frequency shift of the (15)N signal by 9-10 ppm despite of the lengthening of the relevant N-H bond. These experimental trends are substantiated by gauge-independent atomic orbital and density functional theory calculations of the shielding and coupling constants in the 3,3-bis(isopropylamino)-1-(aryl)prop-2-en-1-one (12) for conformations with the Z- and E-orientations of the carbonyl group relative to the N-H group. The effects of the N-H...O hydrogen-bond on the NMR parameters are analyzed with the atoms-in-molecules (AIM) and natural bond orbital (NBO) methods. The AIM method indicates a weakening of the N-H...O hydrogen bond as compared with that of 1,1-di(pyrrol-2-yl)-2-formylethene (13) where N-H...O hydrogen bridge establishes a seven-membered chelate ring, and the corresponding (1)J(N,H) coupling constant decreases. The NBO method reveals that the LP(O) --> sigma*(N-H) hyperconjugative interaction is weakened on going from the six-membered chelate ring to the seven-membered one due to a more bent hydrogen bond in the former case. A dominating effect of the N-H bond rehybridization, owing to an electrostatic term in the hydrogen bonding, seems to provide an increase of the (1)J(N,H) value as a consequence of the N-H...O hydrogen bonding in the studied diaminoenones.

Study of conformations and hydrogen bonds in the configurational isomers of pyrrole-2-carbaldehyde oxime by 1H, 13C and 15N NMR spectroscopy combined with MP2 and DFT calculations and NBO analysis.

The (1)H, (13)C and (15)N NMR studies have shown that the E and Z isomers of pyrrole-2-carbaldehyde oxime adopt preferable conformation with the syn orientation of the oxime group with respect to the pyrrole ring. The syn conformation of E and Z isomers of pyrrole-2-carbaldehyde oxime is stabilized by the N-H...N and N-H...O intramolecular hydrogen bonds, respectively. The N-H...N hydrogen bond in the E isomer causes the high-frequency shift of the bridge proton signal by about 1 ppm and increase the (1)J(N, H) coupling by approximately 3 Hz. The bridge proton shows further deshielding and higher increase of the (1)J(N, H) coupling constant due to the strengthening of the N-H...O hydrogen bond in the Z isomer. The MP2 calculations indicate that the syn conformation of E and Z isomers is by approximately 3.5 kcal/mol energetically less favorable than the anti conformation. The calculations of (1)H shielding and (1)J(N, H) coupling in the syn and anti conformations allow the contribution to these constants from the N-H...N and N-H...O hydrogen bondings to be estimated. The NBO analysis suggests that the N-H...N hydrogen bond in the E isomer is a pure electrostatic interaction while the charge transfer from the oxygen lone pair to the antibonding orbital of the N-H bond through the N-H...O hydrogen bond occurs in the Z isomer.