Non-covalent interactions – QTAIM and NBO analysis

MP2(full)/6-311++G(3df,3pd) calculations were carried out on complexes linked through various non-covalent Lewis acid – Lewis base interactions. These are: hydrogen bond, dihydrogen bond, hydride bond and halogen bond. The quantum theory of ´atoms in molecules´ (QTAIM) as well as the natural bond orbitals (NBO) method were applied to analyze properties of these interactions. It was found that for the A-H…B hydrogen bond as well as for the A-X…B halogen bond (X designates halogen) the complex formation leads to the increase of s-character in the A-atom hybrid orbital aimed toward the H or X atom. In opposite, for the A…H-B hydride bond, where the H-atom possesses negative charge, the decrease of s-character in the B-atom orbital is observed. All these changes connected with the redistribution of the electron charge being the effect of the complex formation are in line with Bent´s rule. The numerous correlations between energetic, geometrical, NBO and QTAIM parameters were also found.

A B3LYP and MP2(full) theoretical investigation into the strength of the C-NO2 bond upon the formation of the molecule-cation interaction between Na+ and the nitro group of nitrotriazole or its methyl derivatives

The changes of bond dissociation energy (BDE) in the C–NO₂ bond and nitro group charge upon the formation of the molecule-cation interaction between Na⁺ and the nitro group of 14 kinds of nitrotriazoles or methyl derivatives were investigated using the B3LYP and MP2(full) methods with the 6-311++G**, 6-311++G(2df,2p) and aug-cc-pVTZ basis sets. The strength of the C–NO₂ bond was enhanced in comparison with that in the isolated nitrotriazole molecule upon the formation of molecule-cation interaction. The increment of the C–NO₂ bond dissociation energy (ΔBDE) correlated well with the molecule-cation interaction energy. Electron density shifts analysis showed that the electron density shifted toward the C-NO₂ bond upon complex formation, leading to the strengthened C-NO₂ bond and the possibly reduced explosive sensitivity.

New insights into the stability of alkenes and alkynes, fluoro-substituted or not: a DFT, G4, QTAIM and GVB study

Many undergraduate organic chemistry books do not agree with the order of relative stability of alkenes towards hydrogenation reactions. Although they ascribe the stability of alkenes to the number and spatial position of the alkyl groups attached to the vinyl carbon atoms, results from the quantum theory of atoms in molecules indicate that the influence of an alkyl substituent on the stability of unsaturated hydrocarbons arises from the slight removal of electron density of the π bond, not from donation of their charge density to unsaturated carbon atoms as stated in many text books. There is an inverse relation between delocalization index—the number of shared electrons between two atoms, or Wiberg bond index of C=C bond—and the number of methyl groups attached to the vinyl carbon atoms. Electron withdrawing groups (EWGs) attached to unsaturated carbon atoms of alkenes and alkynes have two different behaviors: slight EWGs (alkyl groups) stabilize unsaturated carbon atoms while the strong EWG destabilizes the unsaturated carbon atoms. Generalized valence bond theory was also used to study the ambiguous behavior of fluorine substituents bonded to vinyl carbon atoms.

Modulating weak intramolecular interactions through the formation of beryllium bonds: complexes between squaric acid and BeH2

The electronic structure of the two most stable isomers of squaric acid and their complexes with BeH₂ were investigated at the B3LYP/6-311?+?G(3df,2p)// B3LYP/6-31?+?G(d,p) level of theory. Squaric acid forms rather strong beryllium bonds with BeH₂, with binding energies of the order of 60 kJ?mol^?1. The preferential sites for BeH₂ attachment are the carbonyl oxygen atoms, but the global minima of the potential energy surfaces of both EZ and ZZ isomers are extra-stabilized through the formation of a BeH···HO dihydrogen bond. More importantly, analysis of the electron density of these complexes shows the existence of significant cooperative effects between the beryllium bond and the dihydrogen bond, with both becoming significantly reinforced. The charge transfer involved in the formation of the beryllium bond induces a significant electron density redistribution within the squaric acid subunit, affecting not only the carbonyl group interacting with the BeH₂ moiety but significantly increasing the electron delocalization within the four membered ring. Accordingly the intrinsic properties of squaric acid become perturbed, as reflected in its ability to self-associate.

A B3LYP and MP2(full) theoretical investigation into the strength of the C–NO2 bond upon the formation of the intermolecular hydrogen-bonding interaction between HF and the nitro group of nitrotriazole or its methyl derivatives

The changes of bond dissociation energy (BDE) in the C–NO₂ bond and nitro group charge upon the formation of the intermolecular hydrogen-bonding interaction between HF and the nitro group of 14 kinds of nitrotriazoles or methyl derivatives were investigated using the B3LYP and MP2(full) methods with the 6-311++G**, 6-311++G(2df,2p) and aug-cc-pVTZ basis sets. The strength of the C–NO₂ bond was enhanced and the charge of nitro group turned more negative in complex in comparison with those in isolated nitrotriazole molecule. The increment of the C–NO₂ bond dissociation energies correlated well with the intermolecular H-bonding interaction energies. Electron density shifts analyses showed that the electron density shifted toward the C–NO₂ bond upon complex formation, leading to the strengthened C–NO₂ bond and the possibly reduced explosive sensitivity.

Microsolvation of Mg2+, Ca2+: strong influence of formal charges in hydrogen bond networks

A stochastic exploration of the quantum conformational spaces in the microsolvation of divalent cations with explicit consideration of up to six solvent molecules [Mg (H ₂ O) _n )]²⁺, (n?=?3, 4, 5, 6) at the B3LYP, MP2, CCSD(T) levels is presented. We find several cases in which the formal charge in Mg²⁺ causes dissociation of water molecules in the first solvation shell, leaving a hydroxide ion available to interact with the central cation, the released proton being transferred to outer solvation shells in a Grotthus type mechanism; this particular finding sheds light on the capacity of Mg²⁺ to promote formation of hydroxide anions, a process necessary to regulate proton transfer in enzymes with exonuclease activity. Two distinct types of hydrogen bonds, scattered over a wide range of distances (1.35–2.15 Å) were identified. We find that in inner solvation shells, where hydrogen bond networks are severely disturbed, most of the interaction energies come from electrostatic and polarization+charge transfer, while in outer solvation shells the situation approximates that of pure water clusters.

Electron density reactivity indexes of the tautomeric/ionization forms of thiamin diphosphate

The generation of the highly reactive ylide in thiamin diphosphate catalysis is analyzed in terms of the nucleophilicity of key atoms, by means of density functional calculations at X3LYP/6–31++G(d,p) level of theory. The Fukui functions of all tautomeric/ionization forms are calculated in order to assess their reactivity. The results allow to conclude that the highly conserved glutamic residue does not protonate the N1′ atom of the pyrimidyl ring, but it participates in a strong hydrogen bonding, stabilizing the eventual negative charge on the nitrogen, in all forms involved in the ylide generation. This condition provides the necessary reactivity on key atoms, N4′ and C2, to carry out the formation of the ylide required to initiate the catalytic cycle of ThDP- dependent enzymes. This study represents a new approach for the ylide formation in ThDP catalysis.

Structural elucidation of supramolecular alpha-cyclodextrin dimer/aliphatic monofunctional molecules complexes

The structural elucidation of 2α-cyclodextrin/1-octanethiol, 2α-cyclodextrin/1-octylamine and 2α-cyclodextrin/1-nonanoic acid inclusion complexes by nuclear magnetic resonance (NMR) spectroscopy and molecular modeling has been achieved. The detailed spatial configurations are proposed for the three inclusion complexes based on 2D NMR method. ROESY experiments confirm the inclusion of guest molecules inside the α-cyclodextrin (α-CD) cavity. On the other hand, the host-guest ratio observed was 2:1 for three complexes. The detailed spatial configuration proposed based on 2D NMR methods were further interpreted using molecular modeling studies. The theoretical calculations are in good agreement with the experimental data.

Natures of benzene-water and pyrrole-water interactions in the forms of σ and π types: theoretical studies from clusters to liquid mixture

A combined and sequential use of quantum mechanical (QM) calculations and classical molecular dynamics (MD) simulations was made to investigate the σ and π types of hydrogen bond (HB) in benzene-water and pyrrole-water as clusters and as their liquid mixture, respectively. This paper aims at analyzing similarities and differences of these HBs resulted from QM and MD on an equal footing. Based on the optimized geometry at ωb97xD/aug-cc-pVTZ level of theory, the nature and property of σ and π types of HBs are unveiled by means of atoms in molecules (AIM), natural bond orbital (NBO) and energy decomposition analysis (EDA). In light of the above findings, MD simulation with OPLS-AA and SPC model was applied to study the liquid mixture at different temperatures. The MD results further characterize the behavior and structural properties of σ and π types HBs, which are somewhat different but reasonable for the clusters by QM. Finally, we provide a reasonable explanation for the different solubility between benzene/water and pyrrole/water.

A molecular dynamics study on sI hydrogen hydrate

A molecular dynamics simulation is carried out to explore the possibility of using sI clathrate hydrate as hydrogen storage material. Metastable hydrogen hydrate structures are generated using the LAMMPS software. Different binding energies and radial distribution functions provide important insights into the behavior of the various types of hydrogen and oxygen atoms present in the system. Clathrate hydrate cages become more stable in the presence of guest molecules like hydrogen.

Structural characterization of the (MeSH)4 potential energy surface

A random walk on the PES for (MeSH)₄ clusters produced 50 structural isomers held together by hydrogen-bonding networks according to calculations performed at the B3LYP/6–311++G** and MP2/6–311++G** levels. The geometric motifs observed are somewhat similar to those encountered for the methanol tetramer, but the interactions responsible for cluster stabilization are quite different in origin. Cluster stabilization is not related to the number of hydrogen bonds. Two distinct, well-defined types of hydrogen bonds scattered over a wide range of distances are predicted.

Low-energy conformers of pamidronate and their intramolecular hydrogen bonds: a DFT and QTAIM study

Extensive DFT and ab initio calculations were performed to characterize the conformational space of pamidronate, a typical pharmaceutical for bone diseases. Mono-, di- and tri-protic states of molecule, relevant for physiological pH range, were investigated for both canonical and zwitterionic tautomers. Semiempirical PM6 method were used for prescreening of the single bond rotamers followed by geometry optimizations at the B3LYP/6-31++G(d,p) and B3LYP/6-311++G(d,p) levels. For numerous identified low energy conformers the final electronic energies were determined at the MP2/6-311++G(2df,2p) level and corrected for thermal effects at B3LYP level. Solvation effects were also considered via the COSMO and C-PCM implicit models. Reasonable agreement was found between bond lengths and angle values in comparison with X-ray crystal structures. Relative equilibrium populations of different conformers were determined from molecular partition functions and the role of electronic, vibrational and rotational degrees of freedom on the stability of conformers were analyzed. For no level of theory is a zwitterionic structure stable in the gas-phase while solvation makes them available depending on the protonation state. Geometrically identified intramolecular hydrogen bonds were analyzed by QTAIM approach. All conformers exhibit strong inter-phosphonate hydrogen bonds and in most of them the alkyl-amine side chain is folded on the P-C-P backbone for further hydrogen bond formation.

Study on the role of SBA-15 in the oxidative dehydrogenation of n-butane over vanadia catalyst using density functional theory

The first step in the mechanism of n-butane oxidative dehydrogenation (ODH) on a V₄O₁₀ cluster and V₄O₁₀ supported SBA-15 is examined using DFT method. The activation and adsorption energies, oxidation state of V atoms are calculated. Over V₄O₁₀ the obtained results indicate that the activation of C-H bond of methylene group can occur at both the terminal and the bridging oxygen atoms with similar barrier (21.5–22.5 kcal mol^?1). The role of SBA-15 (with and without modification by Al) in n-butane adsorption step has been studied in detail. SBA-15 itself has mild effect on the reaction process, but the substitution of silicon atoms by aluminum atoms results in an active supporter for V₂O₅ in ODH reaction. In that, the ratio of Si/Al will decide the direction of initial interaction steps between n-butane and catalyst surface and it will result in the selectivity of the reaction products.

Effects of trimethylaluminium and tetrakis(ethylmethylamino) hafnium in the early stages of the atomic-layer-deposition of aluminum oxide and hafnium oxide on hydroxylated GaN nanoclusters

We calculate the interactions of two atomic layer deposition (ALD) reactants, trimethylaluminium (TMA) and tetrakis(ethylmethylamino) hafnium (TEMAH) with the hydroxylated Ga-face of GaN clusters when aluminum oxide and hafnium oxide, respectively, are being deposited. The GaN clusters are suitable as testbeds for the actual Ga-face on practical GaN nanocrystals of importance not only in electronics but for several other applications in nanotechnology. We find that TMA spontaneously interacts with hydroxylated GaN; however it does not follow the atomic layer deposition reaction path unless there is an excess in potential energy introduced in the clusters at the beginning of the optimization, for instance, using larger bond lengths of various bonds in the initial structures. TEMAH also does not interact with hydroxylated GaN, unless there is an excess in potential energy. The formation of a Ga—N(CH₃)(CH₂CH₃) bond during the ALD of HfO₂ using TEMAH as the reactant without breaking the Hf—N bond could be the key part of the mechanism behind the formation of an interface layer at the HfO₂/GaN interface.

Synthetic and quantum chemical study on the regioselective addition of amines to methyl maleamate

Synthetic and theoretical studies were performed to gain insight into the regioselectivity in the mechanism of aspartyl-isoaspartyl formation, modeled by additions of ammonia and primary amines to methyl maleamate. Reactions between maleamate and aliphatic, araliphatic amines or O-methyl acetimidate lead to the formation of N-substituted isoasparaginates. The size of the amine and the activating effect of the amide and ester group on the double bond are the determining factors of the site of addition. The formation of both isomers was observed only in the case of ammonia addition. The regioselectivity was predicted on the basis of the charge distribution for low-energy methyl maleamate conformers, calculated at the B3LYP/6-311++G(2df,2pd)//B3LYP/6-31+G(d) level, both in gas phase and in methanol. The methyl isoasparaginate over methyl asparaginate product ratio was computed based on the free energy Boltzmann distribution of their conformers. The calculated 2 : 1 ratio is in agreement with the experimental regioselectivity of the addition of nitrogen nucleophiles.

Spectroscopic investigations and hydrogen bond interactions of 8-aza analogues of xanthine, theophylline and caffeine: a theoretical study

The structure, spectral properties and the hydrogen bond interactions of 8-aza analogues of xanthine, theophylline and caffeine have been studied by using quantum chemical methods. The time-dependent density functional theory (TD-DFT) and the singly excited configuration interaction (CIS) methods are employed to optimize the excited state geometries of isolated 8-azaxanthine, 8-azatheophylline tautomers and 8-azacaffeine in both the gas and solvent phases. The solvent phase calculations are performed using the polarizable continuum model (PCM). The absorption and emission spectra are calculated using the time-dependent density functional theory (TD-DFT) method. The results from the TD-DFT calculations reveal that the excitation spectra are red shifted relative to absorption in aqueous medium. These changes in the transition energies are qualitatively comparable to the experimental data. The examination of molecular orbital reveals that the molecules with a small H→L energy gap possess maximum absorption and emission wavelength. The relative stability and hydrogen bonded interactions of mono and heptahydrated 8-azaxanthine, 8-azatheophylline tautomers and 8-azacaffeine have been studied using the density functional theory (DFT) and Møller Plesset perturbation theory (MP2) implementing the 6-311++G(d,p) basis set. The formation of strong N-H…O bond has resulted in the highest interaction energy among the monohydrates. Hydration does not show any significant impact on the stability of heptahydrated complexes. The atoms in molecule (AIM) and natural bonding orbital (NBO) analyses have been performed to elucidate the nature of the hydrogen bond interactions in these complexes.

Why tazobactam and sulbactam have different intermediates population with SHV-1 β-lactamase: a molecular dynamics study

The imine intermediates of tazobactam and sulbactam bound to SHV-1 β-lactamase were investigated by molecular dynamics (MD) simulation respectively. Hydrogen bond networks around active site were found different between tazobactam and sulbactam acyl-enzymes. In tazobactam imine intermediate, it was observed that the triazolyl ring formed stable hydrogen bonds with Asn170 and Thr167. The results suggest that conformation of imine determined the population of intermediates. In imine intermediate of tazobactam, the triazolyl ring is trapped in Thr_Asn pocket, and it restricts the rotation of C5-C6 bond so that tazobactam can only generate trans enamine intermediate. Further, conformational cluster analyses are performed to substantiate the results. These findings provide an explanation for the corresponding experimental results, and will be potentially useful in the development of new inhibitors.

Insight into substituent effects in Cal-B catalyzed transesterification by combining experimental and theoretical approaches

Candida antarctica lipase B (Cal-B) is one of the most recognized biocatalysts because of its high degree of selectivity in a broad range of synthetic applications of industrial importance. Herein, the substituent effects involved in transesterification catalyzed by Cal-B are explored in detail using a combination of experimental analysis and theoretical modeling. The transesterification ability of Cal-B was experimentally determined with 22 vinyl ester analogs and ribavirin as substrates and, on this basis, a series of quantitative structure-activity relationship (QSAR) models are developed using various structural parameters characterizing the variation in substituent groups of the substrate molecules. The resulting models exhibit a good stability and predictive power, from which five most important properties are highlighted and engaged to ascertain the structural basis and reaction mechanism underlying the transesterification. From the modeling analysis it is seen that the size, geometry, and charge distributions of substrate exert a significant effect on reaction yield, where, the size of the substituent group was the most significant impact factor on the reaction yield, the charge distribution was the second, and then the topological structure of the substrate.

Macrocyclic conjugation in N-fused porphyrins and related species

Macrocyclic aromaticity is the most important concept in porphyrin chemistry. We propose a general graph-theoretical procedure for predicting the main macrocyclic conjugation pathway in porphyrinoids. This procedure, based on calculated bond resonance energies (BREs), can be applied not only to natural and expanded porphyrins but also to porphyrinoids with fused rings. Main macrocyclic conjugation pathways predicted with this procedure are exactly the same as those proposed by porphyrin chemists. Macrocyclic aromaticity can be estimated readily from the BRE for any of the π-bonds linking adjacent pyrrolic rings. It was found that N-fusion often gives rise to anti-aromatic tripentacyclic subunits with negative BREs. Thus, our procedure properly characterizes macrocyclic conjugation and macrocyclic aromaticity in a wide variety of porphyrinoids.