An ONIOM investigation on anion recognition of alkali–metal complexes with diurea calix[4]arene receptor

The ONIOM(B3LYP/6-31G(d):AM1) optimized structures of complexes of diurea calix[4]arene receptor (L) with alkali metals Li(+), Na(+) and K(+) and their complexes with halide ions F(-), Cl(-), Br(-), oxygen-containing anions HCO(3)(-), HSO(4)(-) and CH(3)COO(-) ions were obtained. Binding energies and thermodynamic properties of complex receptors LiL(+), NaL(+) and KL(+) with these anions were determined. The binding stabilities according to binding energies of LiL(+), NaL(+) and KL(+) associated with anions computed either at the ZPVE-corrected ONIOM(B3LYP/6-31G(d):AM1) or BSSE-corrected B3LYP/6-31 + G(d,p)//ONIOM(B3LYP/6-31G(d):AM1) are in the same order: F(-) > CH(3)COO(-) ≈ HCO(3)(-) > Br(-) ≈ HSO(4)(-) ≈ Cl(-). All the receptors LiL(+), NaL(+) and KL(+) were found to be selective toward fluoride ion.     

Conformational preferences of α,α-trehalose in gas phase and aqueous solution

This work presents an investigation on the conformational preferences of α,α-trehalose in gas phase and aqueous solution. Eighty-one systematically selected structures were studied at the B3LYP/6-311++G(d,p)//B3LYP/6-31G(d) level, giving rise to 40 unique conformers. The 19 lower energy structures and some selected other were further re-optimized at the B3LYP/6-311++G(d,p) level. The main factors accounting for the conformer’s stability were pointed out and discussed. NBO and QTAIM analyses were performed in some selected conformers in order to address the anomeric and exo-anomeric effects as well as intramolecular hydrogen bonding. The effect of solvent water on the relative stability of the conformers was accounted for by applying the conductor-like polarizable continuum model, CPCM.     

Quantum-chemical investigation of the elementary molecular mechanisms of pyrimidine-purine transversions

Purine-purine mispairs of DNA (thus involving template base in anti-conformation along the glycosidic bond and base of the incoming nucleotide - in syn-conformation) leading to pyrimidine-purine "transversions"-type point mutations were revealed and characterized at the MP2/6-311++G(2df,pd)//B3LYP/6-311++G(d,p) level of theory in vacuum approach adequately modeling hydrophobic environment of the active centre of high-fidelity replicative DNA-polymerases.     

Experimental and theoretical study on the 1:1 supramolecular complexes of formamide with adrenaline

The electron transfer properties were investigated for supramolecular complexes of formamide (FA) with adrenaline (Ad) at graphite electrode and paraffine soaked graphite electrode using cyclic voltammetry (CV). The experimental results show that FA affected the electron transfer properties of Ad. The formed supramolecular complexes by hydrogen bond (H-bond) interaction between FA and Ad slowed down the diffusion ability of adrenaline, which makes it hard to donate electron and be oxidized. The H-bond interaction energies calculation for the supramolecular complexes of FA with Ad at MP2/6-311+G(d,p)//B3LYP/6-311+G(d,p) level have also been performed. The calculational results confirm the experimental fact that FA can form stable supramolecular complexes with Ad.     

Unexpected role of 5-OH in DPPH radical-scavenging activity of 4-thiaflavans. Revealed by theoretical calculations

The O-H bond dissociation enthalpies (BDEs) of 4-thiaflavans were calculated by a combined density functional theory method (RO)B3LYP/6-311 + G(2d,2p)//AM1/AM1. The calculated BDEs not only gave a reasonable explanation on the DPPH radical-scavenging activity difference of 4-thiaflavans, but also revealed the unexpected role of 5-OH in enhancing the antioxidant activity of A-ring.     

Solvent Effects are Important in Elucidating Radical-Scavenging Mechanisms of Antioxidants. A Case Study on Genistein

Abstract

In two recent researches on antioxidant mechanisms of flavonoids and isoflavonoids, quantum chemical method was employed to calculate the proton dissociation energies, the bond dissociation energies and the ionization potentials for the phenols and derived radicals to help determine the radical-scavenging mechanisms. As the solvent effect was left out of consideration, the conclusion drawn from the calculation incurred some controversies. In the current study, we re-calculated the parameters for genistein and its anion by employing a B3LYP/6–311+G(d,p)//6–31G(d,p) method with solvent effect. Accordingly, a more reasonable explanation on the experimentally observed behavior of genistein as a radical scavenger was obtained. Therefore, solvent effect should be considered in the investigation of radical-scavenging mechanisms of antioxidants in polar solvents.     

Ab initio and DFT study of the inner mechanism and dynamic stereochemistry of electrophilic addition reaction of bromine to bisbenzotetracyclo[6.2.2.23,6.02,7]tetradeca-4,9,11,13-tetraene

The inner mechanism and dynamic stereochemistry of electrophilic addition of bromine to bisbenzotetracyclo[6.2.2.2(3,6).0(2,7)]tetradeca-4,9,11,13-tetraene(BBTT) molecule have been investigated by the methods of quantum chemistry. The structure of the BBTT molecule has been studied by ab initio and DFT/B3LYP methods using the 6-31G(d) and 6-311G(d) basis sets. The double bonds of BBTT molecule are endo-pyramidalized. The structure and stability of the cationic intermediates and products of the addition reaction have been investigated by HF/6-311G(d), HF/6-311G(d,p), B3LYP/6-311G(d) and B3LYP/6-311++G(2d,p)//B3LYP/6-311G(d) methods. The bridged bromonium cation isomerized into the more stable nonclassical delocalized N- and U-type cations and the difference between the stability of these cations is small. For the determination of the direction of addition reaction and the stereochemistry of the products, the stability of nonclassical delocalized N- and U-type ions and the structure of their cationic centres play a vital role. Since the cationic centre of the N-type ion is in interaction with the benzene ring from the exo face, the nucleofilic attackof the bromide anion to this centre occurs from the endo face and the exo,endo-isomer of the N-type product is obtained. The attack of bromide anion, towards the cationic centre of U-type ion from the endo face is sterically hindered by the hydrogen atom therefore the attack occurs from the exo face, which interacts with the benzene ring and the more stable exo,exo-isomer of U-type product is formed. Although, the U-type cation was 2.232 kcal mol(-1) more stable than the N-type cation, the U-type product was 0.587 kcal mol(-1) less stable than the N-type product.     

Ionic interactions for substituted MCH1R inhibitors studied by pKa values

MCH1R inhibitors with the quinoline moiety having the aromatic amine and aliphatic amine chain were selected, and then the effect of substituents of the quinoline ring on the ionic interaction were studied by calculating pK_a values for these amines at the B3LYP/6-311++G(d,p)//B3LYP/6-31+G(d) level in the gas phase and in water. For substituent with C, N, O, and S atoms next to the quinoline ring, respectively, the pK_a values of aromatic amines are estimated to be 8.98, 12.19, 4.64, and 4.33 and those of the aliphatic amines are 12.65, 10.82, 9.94, and 11.55, respectively.     

ONIOM DFT/PM3 calculation on the interaction between STI-571 and abelson tyrosine kinase

The ONIOM2 (B3LYP/6–31G (d, p): PM3) and B3LYP/6–31G (d, p) methods were applied to investigate the interaction between STI-571 and abelson tyrosine kinase binding site. The complex of N-[4-methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)- phenyl]-benzamide (part of STI-571) and related 16 amino acid residues were found at B3LYP/6–31G (d, p) level to have hydrogen bonds and π....π stacking interaction, their binding energy via HAF optimization was −20.4 kcal mol⁻¹. The results derived from this study agreed well with the reported observation. Figure Optimized structure of STI-571 and Thr315 in abelson tyrosine kinase based on ONIOM2 method     

Comparative theoretical study of the UV/Vis absorption spectra of styrylpyridine compounds using TD-DFT calculations

This study examined absorption properties of 2-styrylpyridine, trans-2-(m-cyanostyryl)pyridine, trans-2-[3-methyl-(m-cyanostyryl)]pyridine, and trans-4-(m-cyanostyryl)pyridine compounds based on theoretical UV/Vis spectra, with comparisons between time-dependent density functional theory (TD-DFT) using B3LYP, PBE0, and LC-ωPBE functionals. Basis sets 6–31G(d), 6–31G(d,p), 6–31+G(d,p), and 6–311+G(d,p) were tested to compare molecular orbital energy values, gap energies, and maxima absorption wavelengths. UV/Vis spectra were calculated from fully optimized geometry in B3LYP/6–311+G(d,p) in gas phase and using the IEFPCM model. B3LYP/6–311+G(d,p) provided the most stable form, a planar structure with parameters close to 2-styrylpyridine X-ray data. Isomeric structures were evaluated by full geometry optimization using the same theory level. Similar energetic values were found: ～4.5 kJ?mol^?1 for 2-styrylpyridine and ～1 kJ?mol^?1 for derivative compound isomers. The 2-styrylpyridine isomeric structure differed at the pyridine group N-atom position; structures considered for the other compounds had the cyano group attached to the phenyl ring m-position equivalent. The energy difference was almost negligible between m-cyano-substituted molecules, but high energy barriers existed for cyano-substituted phenyl ring torsion. TD-DFT appeared to be robust and accurate approach. The B3LYP functional with the 6–31G(d) basis set produced the most reliable λ_max values, with mean errors of 0.5 and 12 nm respect to experimental values, in gas and solution, respectively. The present data describes effects on the λ_max changes in the UV/Vis absorption spectra of the electron acceptor cyano substituent on the phenyl ring, the electron donor methyl substituent, and the N-atom position on the electron acceptor pyridine ring, causing slight changes respect to the 2-styrylpyridine title compound.     

Molecular structure,vibrational spectra and HOMO,LUMO analysis of 4-piperidone by density functional theory and ab initio Hartree–Fock calculations

Vibrational frequencies and geometrical parameters of 4-piperidone (4-PID) in the ground state have been calculated by using the Hartree–Fock (HF) and density functional methods (B3LYP) with 6-311++G(d,p) and 6-311+G(3df,2p) basis sets. These methods are proposed as a tool to be applied in the structural characterisation of 4-PID (C₅H₉NO). The title molecule has C _s point group symmetry, thus providing useful support in the interpretation of experimental IR and Raman data. The DFT-B3LYP/6-311+G(3df,2p) calculations have been found more reliable than the ab initio HF/6-311++G(d,p) calculations for the vibrational study of 4-PID. The calculated highest occupied molecular orbital and lowest unoccupied molecular orbital energies show that charge transfer occurs within the molecule. The theoretical spectrograms for FT-IR and FT-Raman spectra of the title molecule have been constructed.     

A density functional theory study on the kinetics and thermodynamics of N-glycosidic bond cleavage in 5-substituted 2'-deoxycytidines

B3LYP/6-311+G(2d,p)//B3LYP/6-31+G(d) density functional theory calculations were employed to explore the kinetics and thermodynamics of gas-phase N-glycosidic bond cleavage induced by nucleophilic attack of C1' with a hydroxide ion in 5-substituted 2'-deoxycytidines. The results showed that, among the 5-substituted 2'-deoxycytidine derivatives examined [XdC, where X = H (dC), CH(3) (medC), CH(2)OH (hmdC), CHO (fmdC), COOH (cadC), F (FdC), or Br (BrdC)], fmdC and cadC exhibited the lowest energy barrier and largest exothermicity for N-glycosidic bond cleavage. These results paralleled previously reported nucleobase excision activities of human thymine DNA glycosylase (hTDG) toward duplex DNA substrates harboring a thymine and 5-substituted cytosine derivatives when paired with a guanine. Our study suggests that the inherent chemistry associated with the nucleophilic cleavage of N-glycosidic bond constitutes a major factor contributing to the selectivity of hTDG toward 5-substituted dC derivatives. These findings provided novel insights into the role of TDG in active cytosine demethylation.     

Racemization of the gastrointestinal antisecretory chiral drug esomeprazole magnesium via the pyramidal inversion mechanism: A theoretical study

The pyramidal inversion mechanisms of the 6‐methoxy and the 5‐methoxy tautomers of (S)‐omeprazole were studied, employing ab initio and DFT methods. The conformational space of the model molecule (S)‐2‐[(3‐methyl‐2‐pyridinyl)methyl]sulfinyl‐1H‐benzimidazole was calculated, with respect to rotations around single bonds, at the B3LYP/6‐311G(d,p) level. All of the resulting conformations were used as starting points for full optimizations of (S)‐omeprazole, at B3LYP/6‐31G(d), B3LYP/6‐311G(d,p), B3LYP/6‐311++G(d,p), B3LYP/6‐311G(2df,2pd), MP2/6‐31G(d), and MP2/6‐311G(d,p) levels. Four distinct pathways were found for enantiomerization via the pyramidal inversion mechanism for each of the tautomers of (S)‐omeprazole. Each transition state, in which the sulfur, the oxygen and the two carbon atoms connected directly to the sulfur are in one plane, connects two diastereomeric minima. The enantiomerization is completed by free rotation around the sulfur–methylene bond, and around the methylene–pyridine ring bond. The effective Gibbs' free energy barrier for racemization ΔG of the two tautomers of (S)‐omeprazole are 39.8 kcal/mol (5‐methoxy tautomer) and 40.0 kcal/mol (6‐methoxy tautomer), indicating that the enantiomers of omeprazole are stable at room temperature (in the gas phase). The 5‐methoxy tautomer of (S)‐omeprazole was found to be slightly more stable than the 6‐methoxy tautomer, in the gas phase. The energy barrier (ΔG^?) for the(S,M) (S,P) diastereomerization of (S)‐omeprazole due to the rotation around the pyridine chiral axis was very low, 5.8 kcal/mole at B3LYP/6‐311G(d,p). Chirality 2010. © 2010 Wiley‐Liss, Inc.     

Solvent effects are important in elucidating radical-scavenging mechanisms of antioxidants. A case study on genistein

In two recent researches on antioxidant mechanisms of flavonoids and isoflavonoids, quantum chemical method was employed to calculate the proton dissociation energies, the bond dissociation energies and the ionization potentials for the phenols and derived radicals to help determine the radical-scavenging mechanisms. As the solvent effect was left out of consideration, the conclusion drawn from the calculation incurred some controversies. In the current study, we re-calculated the parameters for genistein and its anion by employing a B3LYP/6-311+G(d,p)//6-31G(d,p) method with solvent effect. Accordingly, a more reasonable explanation on the experimentally observed behavior of genistein as a radical scavenger was obtained. Therefore, solvent effect should be considered in the investigation of radical-scavenging mechanisms of antioxidants in polar solvents.     

A computer-aided quantum chemical study of the N<Stack><Subscript>15</Subscript><Superscript>−</Superscript></Stack> cluster

Ab initio (RHF, MP2) and Density Functional Theory (DFT) methods have been used to examine six isomers of the N15m cluster with the 6-31+G* basis set. Different from the known odd-numbered anionic N7m, N9m, and N11m clusters, in which the open-chain structures are the most stable species, the most stable N15m isomer is structure 1 (C1), which may be considered as a complex between the fragments cyclic N5m (D5h) and staggered N10 (D2d). The decomposition pathways of structure 2 (CS), containing two aromatic N5 rings connected by a N5 chain, and the open-chain structure 3 (C2v) were studied at the B3LYP/6-31+G* level of theory. Relative energies were refined at the level of B3LYP/6-311+G(3df,2p)//B3LYP/6-31+G*+ZPE (B3LYP/6-31+G*). The barriers for N2 and N5m (D5h) fission reactions for structure 2 are predicted to be 18.2 and 14.2 kcal x mol(-1), respectively. The corresponding N2+N3m fission barrier for structure 3 is predicted to be 11.2 kcal x mol(-1). Supplementary material is available for this article if you access the article at http://dx.doi.org/10.1007/s00894-003-0118-0. A link in the frame on the left on that page takes you directly to the supplementary material. Figure Structure 1 of the N15m cluster, showing bond distances in A and bond angles in degrees     

DFT studies on the intrinsic conformational properties of non-ionic pyrrolysine in gas phase

B3LYP/6-31G(d,p) level of theory is used to carry out a detailed gas phase conformational analysis of non-ionized (neutral) pyrrolysine molecule about its nine internal back-bone torsional angles. A total of 13 minima are detected from potential energy surface exploration corresponding to the nine internal back-bone torsional angles. These minima are then subjected to full geometry optimization and vibrational frequency calculations at B3LYP/6-31++G(d,p) level. Characteristic intramolecular hydrogen bonds present in each conformer, their relative energies, theoretically predicted vibrational spectra, rotational constants and dipole moments are systematically reported. Single point calculations are carried out at B3LYP/6-311++G(d,p) and MP2/6-31++G(d,p) levels. Six types of intramolecular H-bonds, viz. O…H–O, N…H-O, O…H–N, N…H–N, O…H–C and N…H–C, are found to exist in the pyrrolysine conformers; all of which contribute to the stability of the conformers. The vibrational frequencies are found to shift invariably toward the lower side of frequency scale corresponding to the presence of intramolecular H-bond interactions in the conformers.     

Density functional theory study of N-H...O, O-H...O and C-H...O hydrogen-bonding effects on the 14N and 2H nuclear quadrupole coupling tensors of N-acetyl-valine

Hydrogen-bonding effects in the crystalline structure of N-acetyl-valine, NAV, were studied using the (14)N and (2)H quadrupole coupling tensors via density functional theory. The calculations were carried out at the B3LYP level with the 6-311++G(d,p) and 6-311+G(d) basis sets. The theoretical quadrupole coupling components and their relative orientation in the molecular frame axes at the nitrogen site are compared to experimental values. This nucleus is involved in a rather strong intermolecular O=CNH...O=CNH hydrogen bond, r(N-H...O(1))=2.04 A and angleN-H...O(1)=171.53 degrees. A reasonably good agreement between the experimentally obtained (2)H quadrupole coupling tensors and the B3LYP/6-311++G(d,p) calculations is achievable only in molecular model where a complete hydrogen-bonding network is considered.     

Key role of hydrazine to the interaction between oxaloacetic against phosphoenolpyruvic carboxykinase (PEPCK): ONIOM calculations

The interactions between oxaloacetic (OAA) and phosphoenolpyruvic carboxykinase (PEPCK) binding pocket in the presence and absence of hydrazine were carried out using quantum chemical calculations, based on the two-layered ONIOM (ONIOM2) approach. The complexes were partially optimized by ONIOM2 (B3LYP/6-31G(d):PM6) method while the interaction energies between OAA and individual residues surrounding the pocket were performed at the MP2/6-31G(d,p) level of theory. The calculated interaction energies (INT) indicated that Arg87, Gly237, Ser286, and Arg405 are key residues for binding to OAA with the INT values of ?1.93, ?2.06, ?2.47, and ?3.16 kcal mol^?1, respectively. The interactions are mainly due to the formation of hydrogen bonding interactions with OAA. Moreover, using ONIOM2 (B3LYP/6-31G(d):PM6) applied on the PEPCKHS complex, two proton transfers were observed; first, the proton was transferred from the carboxylic group of OAA to hydrazine while the second one was from Asp311 to Lys244. Such reactions cause the generation of binding strength of OAA to the pocket via electrostatic interaction. The orientations of Lys243, Lys244, His264, Asp311, Phe333, and Arg405 were greatly deviated after hydrazine incorporation. These indicate that hydrazine plays an important role in terms of not only changing the conformation of the binding pocket, but is also tightly bound to OAA resulting in its conformation change in the pocket. The understanding of such interaction can be useful for the design of hydrazine-based inhibitor for antichachexia agents.