Showing papers in "Journal of Theoretical and Computational Chemistry in 2007"

Model real-time quantum dynamical simulations of proton transfer in the green fluorescent protein (gfp)

Abstract: In this paper, we present the results from model real-time quantum dynamical calculations of the proton transfer in green fluorescent protein (GFP) regarding four electronic states (labeled A, A*, I, I*). A coupled-states quantum wavepacket method has been used, which involves split-operator and fast FFT algorithms. The model potential energy surfaces are based upon data derived from experimental results with some modifications. Several important processes in GFP have been simulated, which include the photo-absorption and proton transfer in the excited state, the isotope effect and the recurrence time for proton motion in the excited state. The origin of the early-time (prompt) stimulated emission is tentatively explained in terms of off-resonance excitation as well as the contribution from the fastest component for proton transfer in GFP.

Semiclassical electronegativity and chemical hardness

Abstract: The semiclassical path integral approach is undertaken to develop new definitions and atomic scales of electronegativity and chemical hardness. The considered quantum probability amplitude up to the fourth-order expansion provides intrinsic electronegativity and chemical hardness analytical expressions in terms of principal quantum number of the concerned valence shell and of the effective atomic charge including screening effects. The present electronegativity scale strikes on different orders of magnitude down groups of the periodic table, while still satisfying the main required acceptability criteria regarding the finite difference–based scale. The actual chemical hardness scale improves the trend across periods of the periodic system, avoiding the usual irregularities within the old-fashioned energetic picture. The current quest introduces the electronegativity of an element as the power by which the frontier electrons are attracted to the center of the atom being a stability measure of the atomic system as a whole.

Relationship between the lipophilicity and antifungal activity of some benzimidazole derivatives

Abstract: In the present paper, the antifungal activity of some 1-benzylbenzimidazole derivatives were evaluated against yeast Saccharomyces cerevisiae. The tested compounds displayed in vitro antifungal activity and minimum inhibitory concentration (MIC) was determined for all the compounds. Quantitative structure–activity relationship (QSAR) has been used to study the relationships between inhibitory activity and lipophilicity parameters (log P). A variety of lipophilicity parameters (log PHyper, CS log P, mi log P, A log P, IA log P, C log P, log PKow, and X log P) were calculated using different software products, and experimentally determined ("shake-flask" method). On the basis of correlations, the nonlinear structure–activity models were derived between the log 1/cMIC and two different lipophilicity parameters. Four high-quality QSAR models were found to have a good predictive ability and a close agreement between the experimental and predicted values was obtained.

Computational Characterization of Mutations in Cardiac Troponin T Known to Cause Familial Hypertrophic Cardiomyopathy

Abstract: Cardiac Troponin T (cTnT) is a central modulator of thin filament regulation of myofilament activation. The lack of structural data for the TNT1 tail domain, a proposed α-helical region, makes the functional implications of the FHC mutations difficult to determine. Studies have suggested that flexibility of TNT1 is important in normal protein-protein interactions within the thin filament. Our groups have previously shown through Molecular Dynamics (MD) simulations that some FHC mutations, Arg92Leu(R92L) and Arg92Trp(R92W), result in increased flexibility at a critical hinge region 12 residues distant from the mutation. To explain this distant effect and its implications for FHC mutations, we characterized the dynamics of wild type and mutational segments of cTnT using MD. Our data shows an opening of the helix between residues 105-110 in mutants. Consequently, the dihedral angles of these residues correspond to non-α-helical regions on Ramachandran plots. We hypothesize the removal of a charged residue decreases electrostatic repulsion between the point mutation and surrounding residues resulting in local helical compaction. Constrained ends of the helix and localized compaction results in expansion within the nearest non-polar helical turn from the mutation site, residues 105-109.

Determination of the oxidation potentials of pyrogallol and some of its derivatives: theory and experiment

Abstract: The Oxidation potentials of pyrogallol and some of its derivatives in aqueous solutions have been calculated. The calculations have been performed using ab initio molecular orbital calculations (HF), and density functional theory (DFT) with the inclusion of entropic and thermochemical corrections to yield free energies of redox reactions. The polarizable continuum model is used to describe the solvent. It was also obtained experimentally with the aid of an electrochemical technique (cyclic voltammetry). The theoretical and experimental values for the oxidation potential of the studied pyrogallol and some derivatives are in excellent agreement with each other and there is only a discrepancy of 0.025 V and 0.020 V for B3LYP and HF methods, respectively, between experimental and theoretical results. The agreement mutually verifies the accuracy of the experimental method and the validity of the applied mathematical model.

AB INITIO MOLECULAR DYNAMICS STUDY OF DISSOLVED SiO2 IN SUPERCRITICAL WATER

Abstract: Ab initio molecular dynamics simulations of SiO2 in supercritical water at temperatures of 900 K and 1200 K and a pressure of 1.5 GPa at concentrations of 5 wt% and 16 wt% have been carried out. The different polymeric forms SiO4H4, Si2O7H6, and Si3O10H8 are found to be energetically similar within the statistical error, suggesting that all three polymeric forms play an important role in solutions at the above conditions. However, neither spontaneous polymerization nor depolymerization has been observed during the 10-ps time span of the simulations. The dynamic and structural properties of the supercritical solutions have been analyzed in terms of diffusion coefficients, vibrational spectra, and radial pair distribution functions.

Topochemical models for the prediction of lipophilicity of 1,3-disubstituted propan-2-one analogs

Abstract: In the present study, the relationship between the topochemical indices and log P values of 1,3-disubstituted propan-2-one analogs has been investigated Three topochemical indices, Wiener's topochemical index — a distance-based topochemical descriptor, molecular connectivity topochemical index — an adjacency-based topochemical descriptor, and eccentric connectivity topochemical index — an adjacency-cum-distance-based topochemical descriptor, were used for the present investigation The values of the Wiener's topochemical index, molecular connectivity topochemical index, and eccentric connectivity topochemical index were computed for each of the 45 analogs constituting the data set using an in-house computer program The predicted log P values using leave-one-out (LOO) procedure exhibited a q2 of 072, 070, and 071 with reported log P values for Wiener's topochemical index, molecular connectivity topochemical index, and eccentric connectivity topochemical index, respectively Separate models were developed using training set and log P of each analog in the independent test set was predicted using these models The correlation of predicted log P values with the reported values, for independent test set, were in good agreement with those predicted using LOO procedure

Qsar and molecular design of benzo[b]acronycine derivatives as antitumor agents

Abstract: Quantitative structure-activity relationship (QSAR) studies of a series of benzo[b]acronycine derivatives as a novel class of antitumor agents have been carried out using the density functional theory (DFT), molecular mechanics (MM+) and statistical methods. Some calculated parameters of geometric structures, electronic structures and molecular properties of the compounds were adopted as generalized descriptors (variables). Via a stepwise regression analysis, some main independent factors affecting the activities of the compounds were selected out, and then the quantitative structure-activity relationship (QSAR) equation was established. The results suggest that the energy difference (Δ eL-H) between the lowest unoccupied molecular orbital and the highest occupied molecular orbital, the net charges of the nitrogen atom N11 and the first atom of the substituent R2, and the hydrophobic parameter (log P1) of the substituent R1 are the main independent factors contributing to the antitumor activities of the compounds. The fitting correlation coefficient (r2) and the cross-validation coefficient (q2) for the model established by this study are 0.865 and 0.721, respectively, showing this model with a good predictability. The QSAR equation can be used to estimate unknown antitumor activity of this kind of compound, and thus design new compounds with high antitumor activities. Here, based on this QASR study, 4 new compounds with predicted high antitumor activities have been theoretically designed and they are expecting experimental verification.

Determination of the electronic ground state of molecular systems with the multi-configuration time-dependent hartree–fock method

Abstract: In this paper, we present progress in the application of the explicitly time-dependent multi-configuration time-dependent Hartree–Fock (MCTDHF) method. The spin–orbitals and equations of motion are expressed in the basis of Gaussian Type Orbitals. MCTDHF is then applied to the calculation of the electronic ground state of various small molecules by imaginary time propagation. We were able to take between four and 12 active electrons into account. We discuss the suitability of a core guess as initial wave function, the possibility to obtain excited states, as well as the consequences of a neglect of core excitations.

PHOTODETACHMENT ofH- NEAR A SOFT WALL

Abstract: We investigate the photodetachment of H- near an inelastic interface semiclassically. It is found that the inelasticity of an interface has significant influence on the photodetachment process. We have derived an analytical formula of the cross section of photodetachment. The spectrum of photodetachment consists of a smooth background and a sinusoidal oscillation whose frequency depends on the electronic energy, the reflection of the wall and the distance between the ion and the wall.

Theoretical and experimental study of electrical and electrochemical properties of (e)-3-(4, 5-dihydroxy-2-(phenylsulphonyl) phenyl) acrylic acid as a new caffeic acid derivative

Abstract: The electrode potentials of (E)-3-(4,5-dihydroxy-2-(phenylsulphonyl) phenyl) acrylic acid (DPA), as a new caffeic acid derivative, in aqueous solution have been calculated. DPA has two geometric structures, cis and trans. Since the cis structure of caffeic is unstable, it cannot be found in nature, but in this research, its electrode potential have been calculated theoretically. The calculations have been performed using ab initio molecular orbital calculations (HF), and density functional theory (DFT) with the inclusion of entropic and thermochemical corrections to yield free energies of redox reactions. The electrode potential was also obtained experimentally by means of an electrochemical technique (cyclic voltammetry) and it was 335 mV for trans structure. The theoretical and experimental values for the electrode potential of the studied molecule are in excellent agreement. Geometric parameters and vibrational frequencies values of DPA and (2E)-3-(3,4-dioxo-6-(phenylsulfonyl) cyclohexa-1,5-dienyl)acrylic acid (DPDA is the oxidized form of DPA), were computed using same methods. The calculated IR spectrum of DPA used for the assignment of IR frequencies was observed in the experimental FT-IR spectrum. Correlations between theoretical and experimental vibrational frequencies of DPA molecule were 0.996. The agreement mutually verifies the accuracy of the experimental method and the validity of the applied mathematical model.

Heterocyclic hydrogen bonded complexes involving three and five members: a quantum chemical study about the case of the nonlinearity on the hydrogen bonding

Abstract: B3LYP/6-311++G(d,p) and B3LYP/6-31G(d,p) theoretical levels combined with topological calculations based on the theory of atoms in molecules (AIM) were used to study the formation of intermolecular interactions on heterocyclic hydrogen-bonded complexes formed by ethylene oxide, sulfide oxide, 2,5-dihydrofuran, thiophene, and the hydrofluoric acid As observed, the electrophilic attack of the hydrofluoric acid occur aligned to the n lone pair of the heteroatom of the cyclic systems, the modeled structure of the hydrogen-bonded complexes is interpreted in terms of the intermolecular parameters of the (n ⋯ HF) hydrogen bond, such as its R(n ⋯ HF) distance, ΔEC binding energy, and the new υ(n ⋯ HF) stretching vibrational mode From these criteria, a relationship between the strength (R, ΔEC and υ) of the hydrogen bonds and its nonlinearity deviation was verified, which is formed by a secondary interaction between the hydrofluoric acid and axial hydrogen atoms of the cyclic structure Moreover, even though the Bader's electronic density partitioning has been projected with low dependence from ab initio wave functions, it is shown here that the 6-31G(d,p) basis sets characterized the secondary interaction in geometrical point of view, as well as by means of the AIM protocol through the specific calculation of bond critical points between the fluoride and the axial hydrogen atoms

Study on complexes of trypsin and its inhibitors by means of atom-bond electronegativity equalization method fused into molecular mechanics (abeem/mm)

Abstract: Trypsin is one of the most important enzymes and plays important roles in the regulation of biological processes. The newly developed trypsin–inhibitor interaction potential model based on atom-bond electronegativity equalization method fused into molecular mechanics (ABEEM/MM) was employed to study complexes of trypsin and its inhibitors. Some structural properties, including root-mean-square deviations (RMSD) of bond length, bond angle and key dihedral, and coordinated RMS Shifts of atoms and hydrogen bond, were studied using ABEEM/MM method and compared with OPLS-AA force-field. At the same time, comparative study on the charges of the hydrogen atoms at the tail of the ligand was also discussed in order to investigate the effect of hydrogen bond between trypsin and its ligand. This work demonstrates that ABEEM/MM model can well reproduce good structures for these trypsin–inhibitor complexes with rather small RMSD of bond length, bond angles, key dihedrals, and RMS Shifts of atomic coordinates with respect to the experimental crystal structures, compared with the results from the OPLS-AA method. The charges obtained by ABEEM/MM model are in good accordance with those from an ab initio calculation. Moreover, both the polarization and the salt-bridge effects have been taken into account. It is shown that ABEEM charges can properly describe the electrostatic interactions between the protein trypsin and its inhibitors.

Qsar and action mechanism of troxacitabine prodrugs with antitumor activity

Abstract: The quantitative structure–activity relationship (QSAR) of troxacitabine prodrugs with antitumor activity has been studied by using the density functional theory (DFT), molecular mechanics (MM2), and statistical methods. The established QSAR model shows not only significant statistical quality, but also predictive ability, with the square of adjusted correlation coefficient and the square of the cross-validation coefficient (q2 = 0.807). The antitumor activity is expressed as pIC50, which is defined as the negative value of the logarithm of necessary molar concentration of a compound to cause 50% growth inhibition against the human non-small-cell lung cancer cell line SW1573. It appears to be mainly governed by two factors (or original variables), i.e. the calculated hydrophobic coefficient (C log P) of whole molecule and the net charges of the first atom of substituent R (QFR), although three descriptors, i.e. C log P, (C log P)2, and QFR, were selected in our multiple linear regression model. The factor C log P shows parabolic relation to pIC50 and its suitable range is around 5.6, and the other factor QFR shows a significant negative correlation with pIC50. In this paper, a detailed discussion on these two factors was carried out, and their close correlation with the action mechanism of these prodrugs was reasonably revealed. Such results can offer some useful theoretical references for understanding the action mechanism and directing the molecular design of this kind of compound with antitumor activity.

Development and numerical analysis of "black-box" counterpropagating wave algorithm for exact quantum scattering calculations

Abstract: In a recent series of papers,1-3 a bipolar counter-propagating wave decomposition, Ψ = Ψ+ + Ψ-, was presented for stationary bound states Ψ of the one-dimensional Schrodinger equation, such that the components Ψ± approach their semiclassical WKB analogs in the large action limit. The corresponding bipolar quantum trajectories are classical-like and well-behaved, even when Ψ has many nodes, or is wildly oscillatory. In this paper, the earlier results are used to construct an universal "black-box" algorithm, numerically robust, stable and efficient, for computing accurate scattering quantities of any quantum dynamical system in one degree of freedom.

COMPUTER-AIDED MOLECULAR DESIGN OF NOVEL HMG-CoA REDUCTASE INHIBITORS FOR THE TREATMENT OF HYPERCHOLESTEROLEMIA

Abstract: Elevated cholesterol levels are a primary risk factor for the development of coronary artery disease. Dietary changes associated with drug therapy can reduce high serum cholesterol levels and dramatically decrease the risk of stroke and overall mortality. HMG-CoA reductase is an important molecular target of hypolipemic drugs, known as statins, which are effective in the reduction of cholesterol serum levels, attenuating cholesterol synthesis in-liver by competitive inhibition regarding the substrate HMG-CoA. In this paper, we have focused on computer-aided molecular design using density functional theory, flexible docking, molecular dynamics as well as ADME, and synthetic accessibility analyses in order to propose novel potential HMG-CoA reductase inhibitors, designed by bioisosteric modifications which are promising for the treatment of hypercholesterolemia.

An oniom study on the crosslinked base pairs in dna reacted with chloroethylnitrosoureas

Abstract: Chloroethylnitrosoureas (CENUs) are clinically useful anticancer agents Their cytotoxicity is associated with the generation of DNA interstrand crosslinks QM/MM computations are carried out to investigate DNA crosslinks by CENUs with ONIOM hybrid method The crosslinked DNA are subdivided into three layers, each of which are described at B3LYP/6-311+G(d,p), AM1, and UFF level of theory, respectively The result shows that the deformation of DNA with dG(N1)–dC(N3) crosslink is much less than the other crosslinks, which indicate that the most favorable crosslink is between the N1 atom of guanine and the N3 atom of the complementary cytosine

Computational study of unimolecular decomposition mechanism of rdx explosive

Abstract: This study investigated the RDX (1,3,5-Trinitro-1,3,5-triazine) molecule to elucidate its possible decomposition species and the corresponding energies by performing the density-functional theory (DFT) calculations. Reasonable decomposition mechanisms are proposed based on the bond energy calculated using the differential overlap (INDO) program, which yields the weakest bonding site for reference and determines the site of easy cleavage. Computational results indicate that the activation energy of direct cis-form HONO elimination is lower than that of direct trans-form HONO elimination and that of a two-stage elimination of two forms of HONO (N–N bond fission combined with C–H bond breaking) in the initial decomposition step, which are 213.9 kJ/mol and 93.8–101.8 kJ/mol, respectively. Two possible pathways are proposed; (1) N–N bond homolytic cleavage followed by elimination of cis-form HONO, and (2) N–N bond homolytic cleavage followed by elimination of trans-form HONO.

ARBITRARY ℓ-STATE SOLUTION OF THE HELLMANN POTENTIAL

Abstract: We present an alternative and accurate solution of the radial Schrodinger equation for the Hellmann potential within the framework of the asymptotic iteration method. We show that the bound state energy eigenvalues can be obtained easily for any n and l values without using any approximations required by other methods. Our results are compared with the findings of other methods.

B3lyp-svm method for the estimation of molecular enthalpies of formation

Abstract: Support vector machine (SVM) is used to predict the enthalpies of formation at 298 K for 261 molecules based on B3LYP/6-311g (3df,2p) results. With data randomly separated into two parts: 195 for training set and 66 for test set, the resulting mean absolute deviation (MAD) and maximum deviation (MD) for training set are 1.51 kcal/mol and 9.23 kcal/mol (correlation coefficient R = 0.9995), and for test set they become to 1.78 kcal/mol and 7.31 kcal/mol (R = 0.9990). The result is improved according to G2 method.

Theoretical studies on heats of formation for some thiol compounds by density functional theory and cbs-q method

Abstract: The heats of formation (HOFs) for 15 thiol compounds are calculated by employing the hybrid density functional theory (B3LYP, B3PW91, B3P86) methods with 6-311G** basis set and the complete basis set (CBS-Q) method. It is demonstrated that the B3P86 and CBS-Q methods are accurate to compute the reliable HOFs for thiol compounds. In order to test whether the B3P86 method has a low basis set sensitivity, the HOFs for six thiol compounds are also calculated by using the B3P86 method with 6-31+G*, 6-31+G**, and 6-311+G** basis sets for comparison. We also extend our study by employing the nonlocal BLYP method together with 6-31+G* basis set to calculate the HOFs for thiol compounds. The obtained results are compared with the experimental results. It is noted that the B3P86 method is not sensitive to the basis sets. Considering the inevitably computational cost of CBS-Q method and the reliability of the B3P86 calculation, the B3P86 method with a moderate or a larger basis set such as 6-311G** and 6-311+G** may be more suitable to calculate the HOFs of thiol compounds. In addition, we believe that the maximum error associated with the calculated HOFs is less than 6 kcal/mol for the B3P86/6-311G** method and it is expected that the error bar is more likely 1–5 kcal/mol for the HOFs of thiol compounds.

THEORETICAL STUDY ON PARTIAL POTENTIAL SURFACE AND SCATTERING RESONANCE STATE OF THE ASYMMETRICAL H EXCHANGING X + H2O → XH + OH (X = Cl, F, H) REACTIVE SYSTEM

Abstract: In the course of an extensive investigation aimed at understanding the detailed mechanism of a prototypical polyatomic reaction, several remarkable observations were uncovered. To interpret these findings, we surmise the existence of a reactive resonance in this polyatomic reaction. The system of concern is X + H2O → XH + OH (X = Cl, F, H), and it belongs to a type of asymmetrical H exchanging reaction. Because the concerned electronic number is quite small, it is usually regarded as a template constructed the model of theory or experiment. In this paper, compared with the symmetrical systems, we constructed the partial potential surfaces of asymmetrical systems in order to research their resonance states. All results are in good agreement with previous theoretical and experimental works.

Theoretical study on internal rotation of nitrosoureas and toxicological analysis

Abstract: A theoretical study has been carried out for internal rotation of nitrosoureas at the B3LYP/6-311G* level of theory. For each nitrosourea compound, two ground state structures have been found and the E isomer is predicted to be more stable than the Z isomer. Two transition state conformations for the isomerization have also been obtained and the calculated results show that the isomerization through TS1 is easier than that through TS2. The relationship between energy barrier and toxicity has also been investigated. It is concluded that the carcinogenic potency increases along with the decrease of rotational energy barrier.

ELECTRONIC STRUCTURES OF S-DOPED ANATASE AND RUTILE TiO2

Abstract: The electronic structures of S-doped TiO2 have been carried out by first-principles calculations based on density functional theory with plane-wave ultrasoft pseudopotential method. Comparing anion doping with cation doping in anatase and rutile, we found different energy band structures and origins of photoactivity of S-doped TiO2. For anion-doped TiO2, new S–3p bands appear and which lie slightly above the top of the O–2p valence band. It plays a significant role in increasing absorbance in the visible region, resulting in improvement in photocatalytic activity under visible-light irradiation. For cation-doped TiO2, the potential of the O–2p valence band shift much downwards, yielding the stronger oxidative power than that of undoped and S anion-doped TiO2. Nevertheless, the deep impurity states in BG (bond gap) that originate from the S-dopant have negative effects on the recombination of the photoexcited electrons and holes. From our calculated results, we can explain their differences in photocatalyt...

Theoretical, empirical and experimental electron affinities of sf6: solving the density functional enigma

Abstract: We postulate that the adiabatic electron affinity of SF6 is 2.40(10) eV, obtained from the photodetachment onset, 3.2(1) eV and a rearrangement energy of 0.8(1) eV. This eliminates the perceived "SF6 density functional enigma". All of the experimental electron affinities are evaluated and 14 significantly different values selected to construct empirical anionic Morse potentials. These values are (in eV): 2.40(10) 2.20(10), 2.00(10), 1.80(10), 1.60(10), 1.20(10), 1.07(7), 0.93(10), 0.80(10), 0.63(10), 0.43(10), 0.30(10), 0.10(10), and 0.0(2). Comparisons are made to theoretical calculations and relative bond orders. The calculated electron affinities of SF6 are: density functional, 1.6–3.0 eV; ab initio, -1.0–2.2 eV; semiempirical, 0.1–2.2 eV, and for SF5 is 0.3–3.8 eV. Curves calculated using semiempirical, density functional and ab initio procedures are similar to the anionic Morse potentials. This work attempts to correct for differences in the EA calculated for this species.

Theoretical Vibrational Spectra Studies: The Effect of Ring Size on the Carbonyl Vibrational Frequencies

Abstract: In this paper, molecular structures and vibrational frequencies of cycloketone, cyclopropanone, cyclobutanone, cyclopentanone, and cyclohexanone have been investigated by density functional theory (DFT) and the second order Moller and Plesset (MP2) levels of theory, using 6-311G, 6-311G**, 6-311++G, and 6-311++G** basis sets. The calculations predict a planar structure for cyclopropanone. The cyclobutanone ring is puckered and according to the calculations at B3LYP/6-311++G** and MP2/6-311++G** levels of theory, it deviates from planarity by 5.0° and 15.7°, respectively. The calculated barrier height between puckered and planar conformer, at MP2/6-311G** level of theory, is 196.7 cm-1. The puckering frequency at B3LYP/6-311G** and MP2/6-311G** levels are 47.5 cm-1 and 121.2 cm-1. Cyclopentanone has twisted conformations (C2 symmetry) in which carbons C1 and C2 are out-of-plane with a torsional angle of 11.5° (MP2/6-311G**) and the molecule goes from one conformation to the other via an envelope transition conformation (Cs symmetry). or planar hilltop conformation (C2v symmetry). The most stable conformation of the cyclohexanone is Cs chair, which has no ring strain, is used as land mark.

Topological study of reactive potential-energy surfaces from model diabatic states coupled to surrounding media

Abstract: Reaction paths are studied with the help of diabatic potential-energy surfaces coupled in a generic external field. We show that all putative geometrical and topological features of two-dimensional ...

Theoretical calculation of bond dissociation energies and heats of formation for alkyl nitrate and nitrite compounds with density functional theory and complete basis set method

Abstract: The N–O bond dissociation energies (BDEs) and the heats of formation (HOFs) of alkyl nitrate and nitrite compounds in gas phase at 298.15 K were theoretically calculated. Density functional theory (B3LYP and PBE1PBE) with 6-311+g** and 6-311g** basis sets was employed. It is found that PBE1PBE functional has an average increased BDE of 4.03 kcal/mol from B3LYP functional. What is more, we find the reverse trend in ab initio approach, which is slightly smaller than PBE1PBE. The B3LYP functional is found to be sufficiently reliable to compute the BDEs of alkyl nitrate compounds without the presence of diffusion functions. The BDEs of alkyl nitrite compounds appear to be a constant. The functionals (B3LYP and PBE1PBE) with 6-311g** and 6-311+g** basis sets and CBS-4M ab initio method can all yield good results with respect to the experimental HOFs with the deviation less than 2.0 kcal/mol. As the number of methylene group increases, the HOFs of alkyl nitrate and nitrite compounds increase. In addition, the conclusion of Ventural et al. (J Phys Chem A105:9912, 2001 and Phys Lett245:488, 1995) is confirmed again by our computational results.

Acidity and basicity of alkoxides: attainment of hydration clusters using the agoa methodology

Abstract: The optimized geometries of the methoxy, ethoxy, iso-propoxy and tert-butoxy anions were calculated using the B3LYP/6-311++G(d, p) theoretical level. Thereby, these structures were used to explore their hydration clusters by means of the AGOA methodology. Analyzing the molecular electrostatic potential of the solute and using the TIP4P model to locate the water molecules over the alkoxide anions, it was observed that the energies of the hydration clusters decrease in order from methoxy to the tert-butoxy. These results corroborate the experimental acidity of the correspondent conjugate alcohols, indicating that the AGOA methodology can be used as an efficient computational methodology to appraise the structures of molecules in aqueous media.

Comparison of three 3d-qsar methods using a novel class of murf inhibitors

Abstract: MurF was considered as an attractive target for new antibacterial discovery. In this paper, three QSAR methods were employed, viz. comparative molecular field analysis (CoMFA), comparative molecular similarity indices analysis (CoMSIA) and hologram QSAR (HQSAR), to derive highly predictive QSAR models for designing novel MurF inhibitors and comparing different 3D-QSAR/alignment methods. QSAR models with high predictive ability for MurF inhibitors were successfully constructed in terms of cross-validation q2, standard error and predictive coefficient r2, which were around 0.70, 0.55 and 0.99, respectively. All the models from different methods were in good agreement with each other. Compounds with indeterminate activities were used as a test set; results showed that CoMSIA had the best predictive ability, followed by HQSAR and CoMFA. Based on these models, some key features for designing new MurF inhibitors were identified. A virtual database screen process was proposed based on the combination of these models.