Journal of Theoretical and Computational Chemistry

The electronic structures and stabilities of all benzenoid (enol) and quinonoid (keto) forms of 4-hydroxynaphthaldehyde (ALD-14) have been investigated using density functional theory (DFT) with a range of functionals and basis sets. The anti-enol form represents the global minimum energy structure. Low rotation barriers of both the hydroxyl and the aldehyde groups characterize this form. Fourier analysis of the potential energy function for rotation indicate that the conformational preference of ALD-14 is determined by both the dipole–dipole repulsion and bond moments interactions. Further, three different ALD-14 dimer complexes are investigated, i.e. head-to-tail (HT), head-to-head (HH), and stacked (S) forms. The analysis of natural bond order, quantum topology features of the Laplacian of the electron density, binding energies and structural parameters of these dimers point to comparable stabilities of the HT and S-dimers, with a preference for a stacking contact. The origin of its stability can be traced to π-conjugative, H-bonding and dispersion interactions.

Multistep dissociative chemisorption reactions of water with Pd₄ and Pd₇ clusters were studied using density functional theory. The adsorption energies and referred adsorption sites from water molecule (H₂O) to partially dissociative (H₂+O and OH+H), then to fully dissociative (O+H+H) configurations are carefully determined. It is found that the adsorption energies of three dissociative reactions are 5–6 times larger than that of water molecule. Atop sites of Pd₄ and Pd₇ clusters are found to be the most stable sites for the adsorbed H₂O molecule. For the coadsorption cases of partially and fully dissociated products, H₂ and OH molecules preferably tend to bind at the low coordination (atop or bridge) sites, and O and H atoms prefer to adsorb on the high coordination (hollow) sites. It is also found that the most favorable adsorption sites for the molecular adsorbates (H₂O, H₂ and OH) are adjacent to the Pd atoms with the largest site-specific polarizabilities. Therefore, site-specific polarizability is a good predictor of the favorable adsorption sites for the weakly bound molecules. The different directions of charge transfer between the Pd clusters and the adsorbate(s) is observed. Furthermore, the processes of the adsorption, dissociation, and the dissociative products diffusion of H₂O are analyzed.

In this study the anticancer properties of a series of benzimidazole drugs 1–9 and their interactions with DNA base pairs were investigated. The obtained theoretical results for anticancer activity of synthesized drugs 1–5 were compared to corresponding published experimental results. Based on theoretical and published experimental anticancer scales, drugs 2 and 4 have higher anticancer activity among drugs 1–5. Obtained results reveal that interactions of studied drugs with DNA base pairs are energetically favorable and solvent and electric field (EF) increase the binding energies in comparison to gas phase. The binding energies of drugs 2, 5 and 4 with DNA base pairs are more negative than corresponding values for drug 1. We propose the novel drugs 6–9 to synthesize with higher anticancer activity. Results show that binding energies of novel drugs 6–9 were more negative than drugs 1–5. Finally, results show that chemical potential, electrophilicity and global hardness can be considered as admissible theoretical anticancer indexes for studied benzimidazole drugs 1–9.

The catalytic coupling reaction mechanism for the transformation from p-aminothiophenol (PATP) to 4,4′-dimercaptoazobenzene (4,4′-DMAB) on silver cluster was studied by the density functional theory. All the reactants, intermediates, transition states and products were optimized with B3LYP method at 6-311+G (d, p) basis set (the LanL2DZ basis set was used for Ag atom). Transition states and intermediates have been confirmed by the corresponding vibration analysis and intrinsic reactions coordinate (IRC). In addition, nature bond orbital (NBO) and atoms in molecules (AIM) theories have been used to analyze orbital interactions and bond natures. Consistent with the conclusions reported in the literature, the core of obtaining the production of azobenzene according to the coupling reaction of PATP absorbed on Ag₅ clusters is the elimination of two H atoms. Meanwhile, we find that the effect of illumination in that reaction matters a lot. We also found in PATP molecular that the synergistic catalytic effect of S end absorbed on the catalyzer draws dramatically evident under no illumination conditions, while it draws less obvious under light. According to the paper's conclusion, PATP absorbed on the surface of Ag₅ tends to generate azobenzene easily.

The oxidation mechanism of diethyl ethers by NO₂ was carried out using density functional theory (DFT) at the B3LYP/6-31+G (d, p) level. The oxidation process of ether follows four steps. First, the diethyl ether reacts with NO₂ to produce HNO₂ and diethyl ether radical with an energy barrier of 20.62 kcal ⋅ mol^-1. Then, the diethyl ether radical formed in the first step directly combines with NO₂ to form CH₃CH(ONO)OCH₂CH₃. In the third step, the CH₃CH(ONO)OCH₂CH₃ was further decomposed into the CH₃CH₂ONO and CH₃CHO with a moderately high energy barrier of 32.87 kcal ⋅ mol^-1. Finally, the CH₃CH₂ONO continues to react with NO₂ to yield CH₃CHO, HNO₂ and NO with an energy barrier of 28.13 kcal ⋅ mol^-1. The calculated oxidation mechanism agrees well with Nishiguchi and Okamoto's experiment and proposal.

In this work, the molecular structures of single-walled carbon nanotube (SWCNT), cyclophosphamide and cyclophosphamide–SWCNT complex were optimized B3LYP/6–31G* level of theory. The nanotube used in this study was a (5,5) SWCNT including 150 C atoms. The NBO analysis showed that the transfer electron can be occurred from the lone pair of oxygen (donor atom) in the cyclophosphamide to the σ* or π* orbitals of the carbon atoms (acceptor atoms) in the SWCNT. The highest occupied molecular orbital (HOMO), lowest unoccupied molecular orbital (LUMO) and energy gap (HOMO–LUMO) were calculated for the studied structures and the results indicated the stability of the complex. In addition, the calculated chemical shift isotropy (σ) and the chemical shift anisotropy (Δσ) confirmed the interaction between cyclophosphamide and SWCNT. Also, the results of the atoms in molecule (AIM) theory indicated that the H₁₄₅–O₁₆₄ bond is a partial covalent bond.

In this work, the structural, electronic properties, ¹³C and ¹H NMR parameters and first hyperpolarizability of a chromium carbene (OC)₅Cr=C(OEt)(–C≡C–Ph) complex were theoretically computed in gas phase and different solvents. Also, the solvent effect on structural parameters, frontier orbital energies, –C≡C– and C≡O stretching frequencies of complex has been carried out based on polarizable continuum model (PCM). The results indicate that the polarity of solvents has played a significant role on the structures and properties of complex. ¹H and ¹³C NMR chemical shifts were calculated by using the gauge-independent atomic orbital (GIAO) method. In analyzing the structural characteristics of this structure, Cr–CO and Cr–C_carbene bonds were identified and characterized in detail by topological parameters such as electron density ρ(r) and Laplacian of electron density ∇²ρ(r) from Bader's atom in molecules theory.

How a mutation affects the binding free energy of a ligand is a fundamental problem in molecular biology/biochemistry with many applications in pharmacology and biotechnology, e.g. design of drugs and enzymes. Free energy change due to a mutation can be determined most accurately by performing alchemical free energy calculations in molecular dynamics (MD) simulations. Here we discuss the necessary conditions for success of free energy calculations using toxin peptides that bind to ion channels as examples. We show that preservation of the binding mode is an essential requirement but this condition is not always satisfied, especially when the mutation involves a charged residue. Otherwise problems with accuracy of results encountered in mutation of charged residues can be overcome by performing the mutation on the ligand in the binding site and bulk simultaneously and in the same system. The proposed method will be useful in improving the affinity and selectivity profiles of drug leads and enzymes via computational design and protein engineering.