Journal of Theoretical and Computational Chemistry

Nineteen 10-substitued deoxoartemisinin derivatives and artemisinin with activity against D-6 strains of malarial falciparum designated as Sierra Leone are studied. We use molecular electrostatic potential maps in an attempt to identify key structural features of the artemisinins that are necessary for their activities and molecular docking to investigate the interaction with the molecular receptor (heme). Chemometric modeling: Principal Component Analysis (PCA), Hierarchical Cluster Analysis (HCA), K-Nearest Neighbor (KNN), Soft Independent Modeling of Class Analogy (SIMCA) and Stepwise Discriminant Analysis (SDA) are employed to reduce dimensionality and investigate which subset of descriptors are responsible for the classification between more active (MA) and less active (LA) artemisinins. The PCA, HCA, KNN, SIMCA and SDA studies showed that the descriptors LUMO (Lowest Unoccupied Molecular Orbital) energy, DFeO₁ (Distance between the O₁ atom from ligand and iron atom from heme), X1A (Average Connectivity Index Chi-1) and Mor15u (Molecular Representation of Structure Based on Electron Diffraction) code of signal 15, unweighted, are responsible for separating the artemisinins according to their degree of antimalarial activity. The prediction study was done with a new set of eight artemisinins by using the chemometric methods and five of them were predicted as active against D-6 strains of falciparum malaria. In order to verify if the key structural features that are necessary for their antimalarial activities were investigated for the interaction with the heme, we also carried out calculations of the molecular electrostatic potential (MEP) and molecular docking. MEP maps and molecular docking were analyzed for more active compounds of the prediction set.

This paper presents result of QSTR (quantitative structure–toxicity relationship) study obtained using the PRECLAV software. The dependent property is toxicity against rat (Rattus norvegicus), measured by TD₅₀ values. The calibration/training/learning set includes 49 molecules having a very high chemical diversity. There are five outliers in calibration set. In the presence of outliers the predictive power of QSTR is very low (r² = 0.5425, F = 10.4, ). After elimination of outliers the predictive power of QSTR is much higher (r² = 0.9078, F = 44.3, ). All eight predictors are nonlinear functions (parabolic and products) of descriptors. The LogP is not predictor. Presence of C = CH₂ and N–NO molecular fragments increases toxicity. Presence of C₆H₄ molecular fragment decreases toxicity.

Intermolecular charge transfer (ICT) enhanced resonance Raman scattering of charge transfer complex is investigated experimentally and theoretically. The evidence for intermolecular charge transfer on resonance electronic transition is visualized with charge difference density. The resonant Raman spectra reveal that the intensity of Raman peaks are strongly enhanced on the order of 10⁴, by comparing with the normal Raman scattering spectrum. ICT complexes can be used in fluorescence-, photoluminescence-, and electrochemistry-based techniques for sensing target molecules. These strong charge-transfer Raman peaks would enable discrimination of important target molecules from interferants that is normal Raman scattering for the isolated target molecules.

In this work, calculations of pK_b values have been performed for aniline and its substituted derivatives and sulfonamide drugs by using Gaussian 98 software package. Gas-phase energies were calculated with HF/6-31 G** and B3LYP/6-31 G** levels of theory. Free energies of solvation have been computed using the polarizable continuum model (PCM), conductor-like polarizable continuum model (CPCM) and the integral equation formalism-polarizable continuum model (IEFPCM) at the same levels which have been used for geometry determination in the gas-phase. The results show that the calculated pK_b values using the B3LYP/6-31 G** are better than those using the corresponding HF/6-31 G**. At first, the correlation equation was found to determine the pK_b values of the investigated anilines. Then, this correlation equation was used to calculate the pK_b values of the sulfonamide drugs. The results obtained indicate that the PCM model is a suitable solvation model for calculating pK_b values in comparison to the other solvation models. For the investigated compounds a good agreement between the experimental and the calculated pK_b values was also observed.

In this paper we report the state of the art CCSD(T)//MP2 ab initio calculations for the activation of propane by cyclopentadienyl carbonyl rhodium, (Cp)Rh(CO), using the effective core potential of Hay and Wadt (LANL2DZ) for rhodium atom and the correlated consistent polarized valence double-ξ basis set (cc-pVDZ) for C, H and O atoms. The CCSD(T) energy values are used as reference to assess the effect of electron correlation on the reaction energies, as well as the performance of density functional theory (DFT) energy values using various functionals. An investigation on the accuracy of DFT results is relevant since their use in calculations involving large molecular systems is a computationally efficient strategy that enables us to tackle important problems in organometallics field and supramolecular chemistry. Our results for the small model system show that all DFT functionals used here correctly predict the CCSD(T) energy pattern and also reproduce very satisfactorily the MP2 geometrical parameters. The BP86, PBE1PBE and PW91 functionals exhibited the best agreement with structural parameters and relative energy values as compared with ab initio post-Hartree–Fock results, showing a potential use in theoretical investigations on larger systems.

The radical cations of DNA constituents generated by the ionizing radiation initiate an alteration of the bases, which is one of the main types of cytotoxic DNA lesions. These cation radical spices are known for their role in producing nucleic acid strand break. In this study, the gas-phase intrinsic chemical properties of the gaseous radical cations of cytosine and its base pair with guanine were examined by employing density functional theory (B3LYP) with the 6-311++G(d,p) basis set. Structures, geometries, adiabatic ionization energies, adiabatic electron affinities, charge distributions, molecular orbital analysis and proton-transfer process of these molecules were investigated. The influence of cation radical formation on acidities of multiple sites in cytosine molecule was investigated. Results of calculations revealed that cytosine radicals formed by deprotonation of cytosine cation radicals can exothermically abstract hydrogen atoms from thiol groups, phenol, and α-positions of amino acid. Furthermore, comparison of acidity value of N–H sites of cytosine cation radical with the known proton affinities (PA) of organic and biological molecules implied that cytosine cation radical can exothermically transfer onto basic sites of amino acids and peptides.

Molecular dynamics simulations for hLRH-1 (human liver receptor homologue-1) — DNA complexes were to investigate how the Ftz-F1 domain to regulate the transcriptional activity of hLRH-1. Comparative analyses of the three MD trajectories of hLRH-1 complexes suggest that the differential transcriptional activities of the wild-type hLRH-1, double-mutant and triple-mutant are due to alterative protein-DNA interactions. Further, the changes of position of Ftz–F1 domain can only exert limited effects on structures of the DBD (DNA binding domain), while the differences in the bound DNA's bending angles and helical parameters of key base pairs in the three systems result from the altering in distributions of the electrostatic potential surface, which varies with the positioning between the Ftz–F1 and the DBD. The disruptions or weakening of key interactions on several base pairs in the core sequence are mainly due to their distinct displacements from the helical axis in the mutant forms. So the Ftz-F1 domain can regulate the activity of the hLRH-1 by influencing conformations of the bound DNA.

The solvation structure and dynamics of alkali metal (Li⁺, Na⁺, K⁺, Rb⁺, Cs⁺) and halide (F^-, Cl^-, Br^-, I^-) ions in liquid N-methylacetamide (NMA) are calculated at two different temperatures T = 313 K and 453 K, by using classical molecular dynamics simulations. We have also considered and some larger cations such as I⁺, Me₄N⁺, and Et₄N⁺ in this study to investigate the size dependence solvation structure and dynamics of ions in liquid NMA. With the increase of ion size, the self-diffusion coefficients of cations are found to increase and the maximum is observed at Me₄N⁺, whereas for halide ions the increase of diffusion coefficient with ion size continues up to I^- and no maximum is observed. However, the relative increase of the diffusion coefficients of larger ion compared to those of Li⁺ and F⁺ are found to be significantly higher at low temperature. Results are very good in agreement with experimental observation.

Both Fukui's frontier orbital (FO) theory and Woodward–Hoffmann's orbital symmetry conservation (W–H) theory are based on the molecular orbital theory. However, there are some obvious inconsistencies between the two theories in explaining the electron movement. The process of chemical reactions has been explained by the potential surface analysis based on the time-independent Schrödinger equation. However, this approach is not always appropriate for describing unsteady states, because the variable of reaction coordinate should be time t by its very nature. When considering the time-scale of chemical reactions for molecules, there is inherent uncertainty in the energy levels for the midway state of chemical reactions owing to the Heisenberg uncertainty principle. The states which can be accurately described by quantum mechanics exist discontinuously in chemical reactions. Such quantization of chemical reactions solves all noncrossing problems. We also show that such an essential fact leads to new concepts and theories in chemical reactions such as stable molecule, elementary reaction and minimum deformation of orbital phases. Finally, taking the regularity in organic reactions as an example, we demonstrate that FO theory and W–H theory can be unified consistently by the universally applicable "dynamic correlation diagram method."

We analyze the antioxidant property of four phenolic compounds i.e., gallic acid, methyl gallate, ethyl gallate, and 4, 5-dihydroxy 3-methoxy benzoic acid through the determination of bond dissociation enthalpy (BDE), vertical ionization potential (IP_v) in gas phase as well as in six different solvent medium. The theoretical trends of these phenolic compounds, based on BDE and IP, is compared with the scavenging activity towards HOCl. In addition, we compute and analyze the values of the density-based reactivity descriptors such as chemical potential, hardness, electrophilicity, and local softness.

In this paper, electronic structures and third-order nonlinear optical (NLO) properties of a series of Pt–Pt bond-containing metal complexes have been calculated by using the density functional theory (DFT) combining with the sum-over-states (SOS) method. In order to check the reliability of this method, the electron correlations and basis sets have been compared. Our calculated results show that introduction of electron donor, thiophene ring and lengthing of organic conjugated ligand can enhance third-order NLO responses. The electronic structure analysis shows that the [Pt–Pt(H₂P(CH₂)PH₂)₂] fragment displays strong electron-withdrawing character in these systems. Meanwhile, the third-order NLO response of Pt–Pt bond also has been estimated by using TDDFT–SOS method. An enhancement of third-order NLO response has been observed because of the introduction of the Pt–Pt bond. This is mainly due to the intense and low-lying metal-to-ligand charge transfer (MLCT) and intraligand (IL) CT transitions.

The hydrogen-bonding dynamics in both singlet and triplet excited states of the trans-acetanilide (AA) in methanol (MeOH) solvent was investigated using the time-dependent density functional theory (TDDFT) method. Geometric optimizations of the hydrogen-bonded AA–MeOH complexes considered here as well as the isolated AA and MeOH molecules were performed using density functional theory (DFT) method. At the same time, the TDDFT method was performed to calculate the electronic transition energies and corresponding oscillation strengths of all the compounds in the low-lying electronically excited states. In this study, only the intermolecular hydrogen bonds C=O⋯H–O and N–H⋯O–H can be formed. A theoretical forecast that changes of hydrogen bonds in the low-lying electronic excited states was proposed. We discussed not only ground-state geometric structures and electronic excitation energies but also frontier molecular orbitals and electron density transition. The intermolecular hydrogen bonds between AA and MeOH molecules play an important role in the geometric structures and electronic excitation energies. Zhao et al. have put forward the relationship between the electronic spectra and hydrogen bonding dynamics for the first time. According to Zhao's rule, a redshift of the relevant electronic spectra will appear if hydrogen bond is strengthened, while the hydrogen bond weakening can make an electronic spectra shift to blue.

Recently, Xiong et al. reported an activation of ammonia by p-dimethylaminopyridine (DMAP) coordinated silanone (DMAP→Si(L)=O, DS) affording a unique pair of sila-hemiaminal (SH) and silanoic amide (SA) tautomers (Xiong Y, Yao S, Müller R, Kaupp M, Driess M, J Am Chem Soc132:6912, 2010). In this paper, the mechanisms of the activation of ammonia affording SH and SA, the successive generation of hydrogen bonded complex pair SH–SA and the tautomerization between SH and SA have been intensively investigated computationally for the first time at MP2/6-311+G(2d,p)//B3LYP/6-31+G(d,p) level in toluene. The concerted Paths C and D with ammonia assistance are determined by our calculations to be the dominant pathways corresponding to forming SH and SA from DS, respectively. The free energy barrier of Path C affording SH from DS is 14.45 kcal/mol, and that of Path D affording SA is 21.46 kcal/mol. So it is determined theoretically that Path C is dynamically dominant over Path D. And the pair SH–SA is formed then spontaneously by intermolecular hydrogen bond (O–H ⋯ O′) without any barrier. While the tautomerization between SH and SA is nonsignficant resulting from the corresponding relative high barriers (23.79 kcal/mol for process from SH to SA and 26.52 kcal/mol for process from SA to SH). Our results are in good agreement with and good interpretation of the experimental results by Xiong et al.