Interaction of angelicin with DNA‐bases (III) DFT and ab initio second‐order Moeller–Plesset study

Angelicin geometry was optimized at MP2/6‐31+G(d,p) level and compared with X‐ray experimental data. The highest π‐electron density was found to be localized on C1? C2 and on C13? C14 as confirmed by the calculated bond length and bond order values. Spectrophptometric properties of angelicin were measured and compared with the computed within the TD‐DFT. Quantum chemical methods were used to study the interaction of angelicin, as a nonlinear furocoumarin, with DNA bases and base pairs. The interactions with DNA bases and base pairs were studied to shade more light on the nature of the intercalation binding forces between angelicin and DNA. Comparing computed electronic properties of angelicin with that of linear psoralens show that the former is a weaker intercalator. The geometry of complexes of angelicin with adenine, thymine, adenine–thymine base pair, cytocine, guanine as well as cytocine–guanine base pair have been optimized in two main orientations, planar and stacked, at the levels of B3LYP/cc‐pVDZ, MP2/6‐31G(d,p) and MP2/cc‐pVDZ. Effect of vertical distance and rotational angle between the stacked molecules on the interaction energy were investigated by the aforementioned methods in gas phase and water media. It was found that ab initio methods which account for the electron correlation effects are the minimum level for studying the noncovalent interactions. © 2009 Wiley Periodicals, Inc. Int J Quantum Chem, 2010     

用离散-连续模型计算NH2-,NH3和NH4+的溶剂化自由能

通过理论计算推测NH2-,NH3和NH4+在水溶液第一溶剂化层中与之直接作用的水分子分别为2,4和4个,并采用离散-连续模型计算了NH2-,NH3,NH3和NH4+在水溶液中的溶剂化自由能.结果表明,由于离散-连续模型在从头算水平考虑了溶质分子与第一溶剂化层溶剂分子之间的作用,能更准确地描述溶剂化作用.此外,采用更加符合溶液中真实情况的溶剂化构型,能得到更准确的溶剂化性质.     

Computational Study of Proton Transfer in Tautomers of 3‐ and 5‐Hydroxypyrazole Assisted by Water

The tautomerism of 3‐ and 5‐hydroxypyrazole is studied at the B3LYP, CCSD and G3B3 computational levels, including the gas phase, PCM–water effects, and proton transfer assisted by water molecules. To understand the propensity of tautomerization, hydrogen‐bond acidity and basicity of neutral species is approached by means of correlations between donor/acceptor ability and H‐bond interaction energies. Tautomerism processes are highly dependent on the solvent environment, and a significant reduction of the transition barriers upon solvation is seen. In addition, the inclusion of a single water molecule to assist proton transfer decreases the barriers between tautomers. Although the second water molecule further reduces those barriers, its effect is less appreciable than the first one. Neutral species present more stable minima than anionic and cationic species, but relatively similar transition barriers to anionic tautomers.     

Hybrid supermolecule-polarizable continuum approach to solvation: Application to the mechanism of the Stevens rearrangement

Semiempirical molecular orbital theory has been used to study the effects of solvation by acetonitrile on the Stevens rearrangement of methylammonium formylmethylide to 2-aminopropanal. Three methods of solvation have been used to investigate both the electrostatic and specific solvent–solute effects of solvation: a supermolecule calculation involving the complete geometry optimization of up to six solvent molecules about the solute, the conductor-like screening model (COSMO) polarizable continuum method which allows for geometry optimization of the solute in a solvent defined by its dielectric constant, and a hybrid method in which up to five solvent molecules are incorporated inside the solute cavity and complete geometry optimization of the complex is carried out within the polarizable continuum. A comparison of the calculated geometries, rearrangement activation energies, and enthalpies of solvation from these approaches is presented, and the explicit versus bulk solvation effects are discussed. The overall effect of all methods for incorporating solvation effects is that the radical pair pathway is perferred over the concerted mechanism. © 1996 by John Wiley & Sons, Inc.     

A DFT study of solvation effects on the tautomeric equilibrium and catalytic ylide generation of thiamin models

Thiamin diphosphate (ThDP) is the biologically active form of vitamin B1 and an essential cofactor for a number of enzymes. The effect of solvent polarity on the tautomeric equilibria of ThDP using three model systems of the 4'-aminopyrimidine ring is studied by density functional theory calculations (B3LYP/6-311+G(d,p)//B3LYP/6-31G(d)) in the gas phase and selected solvents (cyclohexane, ether, dichloroethane, and water). Solvation effects are investigated using three different schemes: implicit solvation by a continuum model, explicit solvation by inclusion of three water molecules mimicking the first solvation shell of the enzymatic environment, and by a mixed implicit/explicit solvation model. The 4'-aminopyrimidine tautomer is more stable than the 1',4'-iminopyrimidine tautomer in all solvation schemes employed; however, the trend for the stabilities of the 1',4'-iminopyrimidine tautomer in the solvents depends on the specific ThDP-model. Formation of the catalytic important ylide for ThDP-dependent enzymes by deprotonation of ThDP(C2) is also investigated by localization of transition states for two possible pathways. Only the less stable tautomer, 1',4'-iminopyrimidine ThDP, is able to form the catalytic active ylide. Generation of the ylide through a direct intramolecular proton transfer from ThDP(C2) to the ThDP(N4') nitrogen lone pair is favored by 6 kcal/mol in the gas phase, as compared to a water-mediated ylide generation. However, inclusion of a dielectric medium reduces this difference dramatically. Furthermore, inclusion of two water molecules to model the apoenzymatic environment lowers the activation energies of both direct and water-mediated ylide generation.     

Ab initio structural study of some substituted ibuprofen derivatives as possible anti‐inflammatory agents

The formation energies of a series of substituted derivatives in α‐position of ibuprofen (2‐p‐isobutyl‐phenyl‐propionic acid) are determined, at the ab initio level RHF/6‐311G** with full geometry optimization, in their neutral and anionic forms and in the gas phase and water solution to correlate their physical–chemical properties with their anti‐inflammatory activity. Conformational calculations on the acidic moiety were also performed on five of them. The ab initio methods foresee that all these molecules present two preferred conformations in which the substituting atom in α‐position is lying approximately in the aromatic ring plane, in contrast with the results obtained with semiempirical methods. In this article, the protonation energy in solution, the solvation energy, the HOMO energy of the neutral form, and the lipophilicity will be considered as possible factors of anti‐inflammatory activity. The protonation energy in solution, together with the lipophilicity, are verified to be good activity factors: The smaller the protonation energy and the lipophilicity, the larger the anti‐inflammatory activity. In contrast, the larger the solvation energy, the smaller the activity. © 2003 Wiley Periodicals, Inc. Int J Quantum Chem, 2004     

Pathway dependence of the efficiency of calculating free energy and entropy of solute–solute association in water

In this study we investigate two alternative pathways to compute the free energy and the entropy of small molecule association (ΔF_assoc and ΔS_assoc) in water. The first route (direct pathway) uses thermodynamic integration as function of the distance R between the solutes. The mean force and the mean covariance of the force with the energy in solution are calculated from molecular dynamics simulation followed by integration of these quantities with respect to the reaction coordinate R. The alternative approach examined (solvation pathway) would first remove the solutes from the solution using thermodynamic integration as function of a solvation coupling parameter λ, change the solute–solute distance in vacuo and then solvate back the solute pair at the new separation distance. The system studied was a pair of CH₄ molecules in water. We investigate the influence of the CH₄–water interaction strength on the obtained ΔF_assoc and ΔS_assoc values by changing van der Waals and Coulomb interaction and evaluated the accuracy and efficiency for the two pathways. We find that the direct route seems more suitable for the calculation of free energies of hydrophobic solutes while the solvation pathway performs better when calculating entropy changes for solutes that have a stronger interaction with the solvent.     

Hydrogen-bonded nucleic acid base pairs containing unusual base tautomers: complete basis set calculations at the MP2 and CCSD(T) levels

The total interaction energies of altogether 15 hydrogen-bonded nucleic acid base pairs containing unusual base tautomers were calculated. The geometry properties of all selected adenine-thymine and guanine-cytosine hydrogen-bonded base pairs enable their incorporation into DNA. Unusual base pairing patterns were compared with Watson-Crick H-bonded structures of the adenine-thymine and guanine-cytosine pairs. The complete basis set (CBS) limit of the MP2 interaction energy and the CCSD(T) correction term, determined as the difference between the CCSD(T) and MP2 interaction energies, was evaluated. Extrapolation to the MP2 CBS limit was done using the aug-cc-pVDZ and aug-cc-pVTZ results, and the CCSD(T) correction term was determined with the 6-31G*(0.25) basis set. Final interaction energies were corrected while taking into account both tautomeric penalization determined at the CBS level and solvation/desolvation free energies. The situation for the adenine-thymine pairs is straightforward, and tautomeric pairs are significantly less stable than the Watson-Crick pair consisting of the canonical forms. In the case of the guanine-cytosine pair, the Watson-Crick structure made by canonical forms is again the most stable. The other two structures are, however, energetically rather similar (by 5 and 6 kcal/mol), which provides a very small but non-negligible chance of detecting these structures in the DNA double helix (1:5000). Due to the fact that DNA bases and base pairs incorporated into DNA are solvated less favorably than in isolated systems, this probability represents the very upper limit. The results clearly show how precisely the canonical building blocks of DNA molecules were chosen and how well their stability is maintained.     

Base pairing in RNA structures: A computational analysis of structural aspects and interaction energies

The base pairing patterns in RNA structures are more versatile and completely different as compared to DNA. We present here results of ab-initio studies of structures and interaction energies of eight selected RNA base pairs reported in literature. Interaction energies, including BSSE correction, of hydrogen added crystal geometries of base pairs have been calculated at the HF/6-31G** level. The structures and interaction energies of the base pairs in the crystal geometry are compared with those obtained after optimization of the base pairs. We find that the base pairs become more planar on full optimization. No change in the hydrogen bonding pattern is seen. It is expected that the inclusion of appropriate considerations of many of these aspects of RNA base pairing would significantly improve the accuracy of RNA secondary structure prediction.     

An investigation of keto–enol tautomerism in N-vinyl-2-, and 3-pyrrolidinones using ab initio and density functional theory calculations

We investigated the protomeric tautomerism of N-vinyl-2-pyrrolidinone (NV2P) and N-vinyl-3-pyrrolidinone (NV3P) molecules, and considered the three neutral tautomers for NV2P (1a, 1b, 1c) and the five for NV3P (2a, 2b, 2c, 2d, 2e). Full geometry optimizations were carried out at the HF/6-31G**, HF/6-31+G** and B3LYP/6-31+G** levels in the gas phase and in water. Additionally, single-point MP2/6-31+G** calculations were performed on the HF/6-31+G** optimized geometries. The tautomerization processes in water (=78.54) were studied using the self-consistent reaction field theory. According to our estimations, the tautomerization of NV2P and NV3P molecules are not strongly influenced by the polar solvents, the improvement of the basis set quality and the electron correlation effects in the gas phase and in water. The calculated relative free energies (ΔG) predict that 1a and 2a are the energetically preferred tautomers in the gas phase and in water.     

Hydration of DNA Bases and Compounds Containing Small Rings—A Model for Interactions of the Ricin Toxin A-Chain. A Theoretical Ab Initio Study

Ab initio quantum chemical calculations were performed for four neutral gas phase adenine and four pterin tautomers along with guanine and formycin bases. The water complexes of the lowest energy tautomers of these bases have been studied to mimic their interaction with the ricin toxin A chain (RTA). The water molecules create a full first hydration shell around the bases. Full geometry optimizations without any constraints on the planarity of these hydrated complexes were carried out at the HF/6-31G(d,p) level. Single point calculations were also performed at the correlated MP2/6-31G(d,p)//HF/6-31G(d,p) level of theory. Hydration energies were corrected for the basis set superposition error. Hydration energies of adenine and formycin are predicted to be lower (in magnitude) than those for the pterin and guanine. Due to these properties, two pterin tautomers can be considered as potentially useful inhibitors of RTA.     

A simple model of solvation within the molecular orbital theory

A simple model of solvation within the molecular orbital method is proposed whereby the effect of solvent molecules is simulated by the inclusion of fractional point charges at the solvent atomic centers. The method is applied to three solvation problems: the hydration of Li⁺ and F^? and the solvation effect on the interaction between NH₃ and HF. The results of the first two calculations indicate that the point charge model is capable of reliably predicting solvation energies. The calculations for H₃N···HF demonstrate that the hydration has a profound effect on the potential energy surface favoring a proton transfer structure H₃NH⁺···F^?.     

Solvatochromism and preferential solvation of Brooker's merocyanine in water–methanol mixtures

The excitation energy of Brooker's merocyanine in water–methanol mixtures shows nonlinear behavior with respect to the mole fraction of methanol, and it was suggested that this behavior is related to preferential solvation by methanol. We investigated the origin of this behavior and its relation to preferential solvation using the three‐dimensional reference interaction site model self‐consistent field method and time‐dependent density functional theory. The calculated excitation energies were in good agreement with the experimental behavior. Analysis of the coordination numbers revealed preferential solvation by methanol. The free energy component analysis implied that solvent reorganization and solvation entropy drive the preferential solvation by methanol, while the direct solute–solvent interaction promotes solvation by water. The difference in the preferential solvation effect on the ground and excited states causes the nonlinear excitation energy shift. © 2017 Wiley Periodicals, Inc.     

Role of twisting and sliding on the solvation of a stacked cytosine dimer: an ab initio study

Ab initio calculations with inclusion of correlation effects at the MP2/6-31G* level have been used to predict the interaction energy of stacked cytosine dimer (C/C) as a function of twisting and sliding in the gas phase. Systematic calculations have also been carried out on the solvation free energies of various rotated and translated C/C dimers using a polarized continuum model approach at the HF/6-31G* level with a view to probe the role of various degrees of freedom on the free energy of solvation of the C/C dimer. The interaction energy of the C/C dimer decreases upon changing from a parallel to an antiparallel conformation in the gas phase. The 180°-rotated conformation has been found to be the most stable arrangement when compared to other rotated positions. The rotated and translated dimers exhibit lower solvation free energy than the parallel conformation. The decrease in the dipole moment upon rotation from the parallel to the antiparallel conformation indicates the cancellation of charge distribution upon rotation in the z direction of one cytosine base with respect to the other. The calculation reveals that the present approach could not yield association energy, ΔΔG _Asso, in a solvent medium. This may be due to the fact that in the case of floppy molecules the contribution from translational, rotational and vibrational free energies plays a significant role in the calculation of ΔΔG _Asso. Received: 13 December 2001 / Accepted: 25 March 2002 / Published online: 13 June 2002     

BSSE‐corrected geometry and harmonic and anharmonic vibrational frequencies of formamide–water and formamide–formamide dimers

The basis set superposition error (BSSE) influence in the geometry structure, interaction energies, and intermolecular harmonic and anharmonic vibrational frequencies of cyclic formamide–formamide and formamide–water dimers have been studied using different basis sets (6‐31G, 6‐31G**, 6‐31++G**, D95V, D95V**, and D95V++**). The a posteriori “counterpoise” (CP) correction scheme has been compared with the a priori “chemical Hamiltonian approach” (CHA) both at the Hartree–Fock (HF) and second‐order Møller–Plesset many‐body perturbation (MP2) levels of theory. The effect of BSSE on geometrical parameters, interaction energies, and intermolecular harmonic vibrational frequencies are discussed and compared with the existing experimental data. As expected, the BSSE‐free CP and CHA interaction energies usually show less deep minima than those obtained from the uncorrected methods at both the HF and MP2 levels. Focusing on the correlated level, the amount of BSSE in the intermolecular interaction energies is much larger than that at the HF level, and this effect is also conserved in the values of the force constants and harmonic vibrational frequencies. All these results clearly indicate the importance of the proper BSSE‐free correlation treatment with the well‐defined basis functions. At the same time, the results show a good agreement between the a priori CHA and a posteriori CP correction scheme; this agreement is remarkable in the case of large and well‐balanced basis sets. The anharmonic frequency correction values also show an important BSSE dependence, especially for hydrogen bond stretching and for low frequencies belonging to the intermolecular normal modes. © 2005 Wiley Periodicals, Inc. Int J Quantum Chem, 2005     

Neutral hydrolyses of carbon disulfide: An ab initio study of water catalysis

The water-catalyzed hydrolysis reaction of carbon disulfide (CS(2)) has been investigated at the levels of HF and MP2 with the basis set of 6-311++G(d,p) using the combined supramolecular/continuum models, in which up to six water molecules are involved in the hydrolysis and the effect of water bulk solvent is taken into account according to the polarizable continuum model (PCM). The activation Gibbs free energies in water solution, DeltaG(sol) (not equal) (298 K), for the rate-determining steps of one up to six water hydrolyses are 247.9, 184.2, 152.3, 141.8, 134.4, and 118.9 kJ/mol, respectively. The most favorable hydrolysis path of CS(2) involves a sort of eight-membered ring transition structure formed by six water molecules, among which three water molecules are not involved in the proton transfer, two near to the nonreactive sulfur atom, and one below the parent carbon disulfide. This suggests that the hydrolysis of CS(2) can be mediated with the water molecule(s) and be significantly facilitated by the cooperative effects of the water molecule(s) in the nonreactive region. The catalytic effects of water molecule(s) due to the alleviation of ring strain in the proton transfer process may result from the synergistic effects of rehybridization and charge reorganization from the prereaction complex to the rate-determining transition state structure induced by water molecule(s). PCM solvation models could significantly lower the rate-determining activation Gibbs free energies by 20-38 kJ/mol when two up to six explicit water molecules involved in the neutral hydrolysis of CS(2).     

Kramers' unrestricted Hartree–Fock and second-order Møller–Plesset perturbation methods using relativistic effective core potentials with spin–orbit operators: Test calculations for HI and CH3I

The Kramers' restricted Hartree–Fock (KRHF) and second-order Møller–Plesset perturbation (KRMP2) methods using relativistic effective core potentials (RECP) with spin–orbit operators and two-component spinors are extended to the unrestricted forms, KUHF and KUMP2. As in the conventional unrestricted methods, the KUHF and KUMP2 methods are capable of qualitatively describing the bond breaking for a single bond. As a result, it is possible to estimate spin–orbit effects along the dissociation curve at the HF and MP2 levels of theory as is demonstrated by the test calculations on the ground states of HI and CH₃I. Since the energy lowering due to spin–orbit interactions is larger for the I atom than for the closed-shell molecules, dissociation energies are reduced and bond lengths are slightly elongated by the inclusion of the spin–orbit interactions. © 1998 John Wiley & Sons, Inc. Int J Quant Chem 66 : 91–98, 1998     

Insights into the dynamics of evaporation and proton migration in protonated water clusters from Large‐scale Born–Oppenheimer direct dynamics

Large‐scale on‐the‐fly Born–Oppenheimer molecular dynamics simulations using recent advances in linear scaling electronic structure theory and trajectory integration techniques have been performed for protonated water clusters around the magic number (H₂O)_nH⁺, for n = 20 and 21. Besides demonstrating the feasibility and efficiency of the computational approach, the calculations reveal interesting dynamical details. Elimination of water molecules is found to be fast for both cluster sizes but rather insensitive to the initial geometry. The water molecules released acquire velocities compatible with thermal energies. The proton solvation shell changes between the well‐known Eigen and Zundel motifs and is characterized by specific low‐frequency vibrational modes, which have been quantified. The proton transfer mechanism largely resembles that of bulk water but one interesting variation was observed. © 2012 Wiley Periodicals, Inc.     

Extension of the platform of applicability of the SM5.42R universal solvation model

We present eight new parameterizations of the SM5.42R solvation model: in particular we present parameterizations for HF/MIDI!, HF/6-31G^*, HF/6-31+G^*, HF/cc-pVDZ, AM1, PM3, BPW91/MIDI!, and B3LYP/MIDI!. Two of the new cases are parameterized using the reaction-field operator presented previously, and six of the new cases are parameterized with a simplified reaction-field operator; results obtained by the two methods are compared for selected examples. For a training set of 2135 data for 275 neutral solutes containing H, C, N, O, F, S, P, Cl, Br, and I in 91 solvents (water and 90 nonaqueous solvents), seven of the eight new parameterizations give mean unsigned errors in the range 0.43–0.46 kcal/mol, and the eighth – for a basis set containing diffuse functions – gives a mean unsigned error of 0.53 kcal/mol. The mean unsigned error for 49 ionic solutes (containing the same elements) in water is 3.5–3.9 kcal/mol for the Hartree–Fock, Becke–Perdew–Wang-1991 and Becke three-parameter Lee–Yang–Parr cases and 4.1 and 4.0 kcal/mol for parameterized model 3 and Austin model 1, respectively. The methods are tested for sensitivity of solvation free energies to geometry and for predicting partition coefficients of carbonates, which were not included in the training set. Received: 24 November 1998 / Accepted: 31 December 1998 / Published online: 7 June 1999