Journal of Theoretical and Computational Chemistry

In the last years, the development of small molecule antagonists of VLA-4 for the treatment of diseases, where cell trafficking and activation are important, has increased considerably. Among them, the MK-0617 ligand has proven to be a highly potent and orally active α4β1 antagonist. However, the binding mode of this ligand in the integrin binding site remains unknown. Herein we report a thermodynamic analysis of the interaction between MK-0617 (and one of its isomers) and the VLA-4 protein using molecular docking and the free energy perturbation calculations, based on a comparative model of the α4β1 receptor. Initial complex coordinates were taken from molecular docking assays and submitted to alchemical transformations. Free energy of binding ΔΔG values, derived from experimental IC₅₀ values, were taken as a parameter for determining the most likely binding mode. In addition, molecular dynamics simulations of these ligands within the α4β1 binding site were carried out to elucidate the binding energy profile and identify the most significant residues. Our results indicate that MK-0617 fits within the binding site in a stretched conformation, pointing the carboxylate group towards the MIDAS ion. We observe that, despite the fact that the main contribution to the energetic binding process is due to the electrostatic ion contribution, the nonpolar contribution is not negligible. Additionally, a network of hydrogen bonds participate in stabilizing the ligand-receptor interaction.

A new London–Eyring–Polanyi–Sato (LEPS) potential energy surface (PES) is employed in this work to study the stereo properties for the abstraction reaction of hydrogen with methane at its rovibrationally ground state using the quasiclassical trajectory method (QCT). A "quasi-triatomic" approximation is used to treat the CD₃ group of CD₄ as a pseudoatom. The calculated excitation function of the title reaction can give a good agreement to most experimental and theoretical data at collision energies (E_c =1.5 ~ 2.5 eV). Further investigation of the product HD in reaction H + CD₄(v = 0, j = 0) → HD + CD₃ and D + CH₄(v = 0, j = 0) → HD + CH₃ shows the dependence of the product rotational polarization on collision energies and mass factor, but P(θ_r) is not sensitive to both the collision energies and the mass factor.

Utilizing the quasiclassical trajectory method, the product rotational polarization of the reaction N(⁴S) + D₂ → ND + D has been calculated at different collision energies on the DMBE potential energy surface [Poveda LA et al., Phys Chem Chem Phys7:2867, 2005]. The distribution of the angle between k and j′, P(θ_r), the distribution of dihedral angle denoting k–k′–j′ correlation, P(ϕ_r), as well as the angular distribution of product rotational vectors in the form of polar plots P(θ_r, ϕ_r) are calculated. In addition, the four commonly used polarization-dependent differential cross sections, dσ₀₀/dω_t, dσ₂₀/dω_t, dσ₂₂₊/dω_t, and dσ_21-/dω_t with ω_t being the polar coordinates of the product velocity k′, are calculated in the center-of-mass frame. The effects of the collision energy on the product polarization are presented and discussed. In comparison with the result of Yu et al. [Yu YJ et al., Chin Phys B20:123402, 2011], significant isotope effects on the stereodynamics of N(⁴S) + D₂(H₂) → ND(H) + D(H) have also been revealed.

Dissipative particle dynamics (DPD) was initially used to simulate the polystyrene/nanoparticle composite microspheres (PNCM) in this paper. The coarse graining model of PNCM was established. And the DPD parameterization of the model was represented in detail. The DPD repulsion parameters were calculated from the cohesive energy density which could be calculated by amorphous modules in Materials Studio. The equilibrium configuration of the simulated PNCM shows that the nanoparticles were actually "modified" with oleic acid and the modified nanoparticles were embedded in the bulk of polystyrene. As sodium dodecyl sulfate (SDS) was located in the interface between water and polystyrene, the hydrophilic head of SDS stretched into water while the hydrophobic tailed into polystyrene. All simulated phenomena were consistent with the experimental results in preparation of polystyrene/nanoparticles composite microspheres. The effect of surface modification of nanoparticles on its dispersion in polystyrene matrix was also studied by adjusting the interaction parameters between the OA and NP beads. The final results indicated that the nanoparticles removed from the core of composite microsphere to the surface with increase of a_OA-NP. All the simulated results demonstrated that our coarse–grained model was reasonable.

Based on the density functional theory, the structural information and energetic property of Ni–Cu–Al ternary layered double hydroxides were investigated by periodic lattice calculation as a function of cationic substitution. The results revealed that the incorporated Ni^II could improve the structural stability and crystalline perfection of the material. When the content of Ni increased, the charge of the metal cations would transfer to the hydroxyl groups, and the electronic configuration of Cu^II and Ni^II would both change from their ideal states. Therefore, as Cu^II cations were progressively replaced by Ni^II, the distortion of Cu(OH)₆ and Ni(OH)₆ octahedra would be weakened by enlarging the four short M–O bonds and shortening the two long ones. What is more, the distorted O–M–O bond angle changed to adapt the variety of M–O bond lengths. As a result, all the M(OH)₆ octahedra could share their edges more conveniently to format the LDHs structure. At last, we conclude that the averaged length of M–O bond and the electron configuration of the metal cations play a significant role in the synthesis of LDHs materials.

Density functional theory (DFT) method and B3LYP/6-311++G(d,p) basis set were used to determine coordination geometries, binding strength, and metal ion affinity (MIA) for interaction of 2′-deoxythymidine (dT) with alkali metal cations including Li⁺, Na⁺, and K⁺. Calculations demonstrated that the interaction of dT with these cations is tri-coordinated η (O2, O4′, O5′). Among these cations, Li⁺ cation exhibited the most tendency for interaction with dT. Cations via their interaction with dT can affect the N-glycosidic bond length, the values of pseudorotation of the sugar ring, the orientation of base unit with respect to sugar ring and the acidity of O5′H, O3′H, and N3H groups in 2′-dT nucleoside. Natural bond orbital (NBO) analysis was performed to calculate the charge transfer and natural population analysis of the complexes. Quantum theory of atoms in molecules (QTAIM) was also applied to determine the nature of interactions. It was shown that in these complexes, (dT-Li⁺, dT-Na⁺, and dT-K⁺), the bonds are an electrostatic (closed-shell) interaction in the nature.

A quantitative structure-property relationship (QSPR) study for the prediction of the absorption maxima (λ_max) of organic dyes used in solar cells was carried out using different computational methods. Three-dimensional (3D) descriptors were calculated using Codessa and Dragon softwares to represent the dye molecules. Then, different chemometric tools such as multivariate adaptive regression splines (MARS) and adaptive neuro-fuzzy inference system (ANFIS) combined with Monte Carlo (MC) sampling technique were utilized for selecting the most important descriptors and predicting the absorption maxima of the dyes. Various evaluation techniques such as leave-one-out, leave-multiple-out cross-validation procedures, randomization tests, and validation through the external test set were performed to validate the performance of the model. The results revealed that the calculated absorption maxima values are in good agreement with the experimental ones. This theoretical method provides an accurate and alternative method to obtain λ_max of dyes before they are actually synthesized.

The properties of the ground and excited states of AsH₂, and have been investigated by using symmetry-adapted-cluster (SAC)/symmetry-adapted-cluster configuration interaction (SAC-CI) method. The geometry of the ground state of AsH₂ is optimized at SAC method with different basis sets. The calculated results with cc-pVTZ and cc-pVQZ basis sets are in very good agreement with the experimental and previous theoretical data. The geometry and the properties of eight low-lying electronic excited states of AsH₂ are obtained at SAC-CI/cc-pVTZ and SAC-CI/cc-pVQZ level, including geometries, vertical excitation energies, adiabatic excitation energies, transition dipole moments, and oscillation strengths. Employing the same theoretical level as AsH₂, the geometries, adiabatic ionization potentials (AIPs), and vertical ionization potentials (VIPs) of the ground and eight low-lying electronic states of are investigated as well as the geometries, vertical detachment energies (VDEs) and adiabatic detachment energies (ADEs) of nine electronic states of . Comparing with the available experimental or previous theoretical data, the SAC/SAC-CI/cc-pVTZ and SAC/SAC-CI/cc-pVQZ results are reliable for AsH₂, and . The predicted results can afford the useful information for one to deeply investigate them from the spectral experiment.

In this paper the reaction enthalpies of three antioxidant action mechanisms, HAT, SET–PT, and SPLET, for mono-substituted Stobadines were calculated in gas-phase and water. Results show that electron-withdrawing substituents increase the bond dissociation enthalpy (BDE), ionization potential (IP), and electron transfer enthalpy (ETE), while electron-donating ones cause a rise in the proton dissociation enthalpy (PDE) and proton affinity (PA). In comparison to gas-phase, water attenuates the substituent effect on all reaction enthalpies. Results show that IP and BDE values can be successfully correlated with the indolic N–H bond length after electron abstraction, R(N–H^+•), and the partial charge on the indolyl radical nitrogen atom, q(N). Furthermore, calculated IP and PA values for mono-substituted Stobadines show linear dependence on the energy of the highest occupied molecular orbital (E_HOMO) of studied molecules in the two environments. SPLET represents the thermodynamically preferred mechanism in water.

The equilibrium structure, spectroscopy constants and anharmonic force field of O³⁵ClO have been calculated at B3PW91 and B3LYP levels of theory with two basis sets 6-311++G(2df,2pd) and 6-311++G(3df,3pd), respectively. The computed geometries, dipole moment, rotational constants, vibration–rotation interaction constants, vibrational band origins, anharmonic constants, quartic, and sextic centrifugal distortion constants are compared with the available experimental data. The cubic and quartic force constants are predicted. The calculated results show that the B3PW91 results are in excellent agreement with experiment and represent a substantial improvement over the results obtained from B3LYP.

The second harmonic generation (SHG) hyperpolarizabilities of phenylalanine and homopolypeptides are investigated by configuration interaction among singly excited configurations (CIS) technique combined with the sum-over-states (SOS) method. The geometries of peptides containing phenylalanine (Phe)_n(n = 1–8) are optimized by B3LYP/6-31g(d) method, and they form the special structures like β-sheet (a common protein secondary structure). It is found that the energy gaps of various peptides are reduced and the hyperpolarizabilities are increased with the peptide chains lengthened. We discuss the origin of the second-order nonlinear optical response in phenylalanine homopolypeptides and confirm that the π → π* transitions in the aromatic residue of phenylalanine make the most important contributions to the second-order polarizability. Our results strongly suggest that the hyperpolarizabilities are dominated from the propagation direction of peptide chains.

The hydrogen abstraction reaction of CF₃CHFCF₃ (HFC-227ea) by Cl atom is studied theoretically over a temperature range of 50–2000 K. The reaction path information such as geometries, gradients, etc. are initially obtained at the BB1K/6-31+G (d,p) level. In order to improve the energies, high level single point energy (SPE) calculations are carried out at BB1K/MG3S on BB1K/6-31+G(d,p) geometries. The rate coefficients are obtained by dual-level direct dynamics approach with the interpolated SPE method at BB1K/MG3S//BB1K/6-31+G(d,p) level. Aforementioned rate coefficients are calculated based on canonical variational transition state theory (CVT) with small-curvature tunneling (SCT) correction. The results show that for the title reaction, variational effect is small while the tunneling effects are significant at low temperature. In order to investigate the reliability of improved BB1K potential energy surface in predicting barrier height of the reaction, different quantum models built such as QCISD(T)/6-311++G(d,p)//MP2/6-31G(d,p), QCISD(T)/aug-cc-pv-DZ//MP2/6-31G(d,p), and MP4SDQ/aug-cc-pv-DZ//MP2/6-31G(d,p) are applied to calculate the rate coefficients of the reaction. The results show the rate coefficients calculated based on MP2 potential energy surface are underestimated as compared to the experimental value. Finally three models are applied to fit the calculated rate coefficients over the temperature range of 50–2000 K. It is shown that the new four-parameter model provided a better temperature dependence than the other expressions. It is expected that obtained theoretical results can be useful for modeling the kinetics nature of the reaction of HFC-227ea and Cl atom over temperature range where no experimental data is accessible.