Journal of Theoretical and Computational Chemistry

Alzheimer's disease (AD) is the most common cause of dementia in old aged people and clinically used drugs for treatment are associated with side effects. Thus, there is a current demand for the discovery and development of new potential molecules. However, the recent advances in drug therapy have challenged the predominance of the disease. In this manuscript, an attempt has been made to develop the 2D and 3D quantitative structure–activity relationship (QSAR) models for a series of rutaecarpine, quinazolines and 7,8-dehydrorutaecarpine derivatives to obtain insights to Acetylcholinesterase (AChE) inhibition. Five different QSAR models have been generated and validated using a set of 52 compounds comprising of varying scaffolds with IC₅₀ values ranging from 11,000 nM to 0.6 nM. These AChE-specific prediction models (M1–M5) adequately reflect the structure–activity relationship of the existing AChE inhibitors. Out of all developed models, QSAR model generated using ADME properties has been found to be the best with satisfactory statistical significance (regression (r²) of 0.9309 and regression adjusted coefficient of variation of 0.9194). The QSAR models highlight the importance of aromatic moiety as their presence in the structure influence the biological activity. Additional insights on the compounds show that acyclic amines attached to side chain have lower activity than cyclic amines. The QSAR models pinpointing structural basis for the AChEIs suggest new guidelines for the design of novel molecules.

The optical properties of two series of azobenzene derivatives were modulated by backbone modifications with the density functional theory (DFT) calculations. Compared to the short-chain molecule, the chromophore with an elongated π-bridge exhibits a greater extent of charge transfer during one-photon excitation and hence possesses a larger molecular first hyperpolarizability (β₀). Meanwhile, an evident red-shift in the maximum absorption was observed after extension of the π-conjugated backbone. The tendency of the static β₀ value derived from the two-state model is consistent with the result of the calculation at M06-2X/6–311++G(d,p) level by means of analytical derivative method. The dynamic perturbations were revealed to cause the obvious enhancement of the first hyperpolarizability. The more closer the foundational wavelength to two times the value of the maximum absorption in one-photon transition, the larger β_RHS value is observed for the chromophore. The nonlinear optical (NLO) properties augment with the introduction of the THF solvents by comparing the gas-phase values. With increasing the length of conjugated bridge, the dynamic β_RHS value increases more rapidly in THF solution than in vacuum.

Members of the genus Pseudomonas bacterium are of great interest because of their importance in plant disease. In this study, DNA fingerprints of 60 strains of Pseudomonas bacteria including three species of Pseudomonas syringae (Pseudomonas syringae pv. syringae (Pss) and Pseudomonas syringae pv. Lachrymans (Psl)), Pseudomonas savastanoi (Psa) and Pseudomonas tolaasii (Pt) were used for developing a robust predictive classification model. The DNA fingerprints were obtained by repetitive polymerase chain reaction (Rep-PCR) using enterobacterial repetitive intergenic consensus (ERIC), repetitive extragenic palindromes (REP), and BOXAIR primers. The classification results of counter propagation artificial neural network (CP-ANN) modeling indicated that a combination of Rep-PCR fingerprinting and chemometrics analysis can be used as an effective and powerful methodology to differentiate species of Pseudomonas and pathovars of P. syringae strains based on a predictive model.

A comprehensive theoretical study on the structure and stability of linear and triangular isomers of anionic clusters of zinc, cadmium and mercury and their binding with one and two alkali metal cations (X⁺ = Li⁺, Na⁺, K⁺) has been investigated at the density functional (BP86 and B₃LYP) and ab initio (MP₂, MP₄ and coupled cluster single and double (CCSD)) methods. The results showed that in all cases, the triangular geometry with D_3h symmetry is more stable than linear one. The calculated values of interaction energies (IE) between anions and two X⁺ cations, Wiberg bond indices (WBI) and the electron densities at bond critical points (BCP), ρ(BCP), for Y–X bonds show that among all complexes investigated here at all levels of theory Zn₃Li₂ and Hg₃K₂ have the largest and the smallest values of IE, WBI and ρ(BCP), respectively. The natural charges of the atoms and WBI involved in the bonding as well as the global value of the charge transfer ΔQ from to X⁺ cation in X₂Y₃ clusters, evaluated through natural population analysis, confirmed that covalent contribution in Y–X bond formation increases from K⁺ to Li⁺. Also the energy decomposition analyses (EDA) were used to detect the nature of interaction in the complexes. The results confirmed that the contribution of electrostatic interactions in present complexes is almost more than 70%.

Theoretical investigation of 42 cation-π complexes formed by the alkali metal (Li⁺, Na⁺, K⁺), alkaline-earth cations (Be²⁺, Mg²⁺, Ca²⁺) and π-system of the pyrazine and its derivatives have been performed at density functional theory (DFT) (B3LYP functional) and MP2 methods with 6-311++G** basis set in the gas phase and the polarized continuum model (PCM)-water solvation. The following substituents have been taken into consideration: Br, Cl, CH₃, OH, OCH₃ and SH. The interactions present in these complexes have been investigated by means of the natural bond orbital (NBO) and the Bader's quantum theory of atoms in molecules (QTAIMs) approaches. The effects of the interactions on NMR data have been probed using the GIAO-based method to extend investigation of the studied compounds. The calculated highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) energies show that charge transfer occurs within each complex. Vibrational frequencies and physical properties such as dipole moment, chemical potential, chemical hardness and chemical electrophilicity of these compounds have been systematically explored. The aromaticity of aromatic rings has been measured using several well-established indices of aromaticity such as nucleus-independent chemical shift, harmonic oscillator models of the aromaticity, para-delocalization index, average two-center indices, aromatic fluctuation index and π-fluctuation aromatic index.

3,6-pyridazinedione and two of its derivatives where oxygen atoms of the molecule are substituted by two sulfur or selenium (N₂C₄Y₂H₄) were studied with the goal of answering the following question: "Which N₂C₄Y₂H₄ compounds are unstable in their planar configuration?" Additionally, the origin of the twisting instability of 3,6-pyridazinedione planar configuration and three of its 1,2-dihalo derivatives (N₂C₄H₂O₂Z₂) were rationalized by employing the pseudo Jahn–Teller effect (PJTE) to explain the difference between N₂C₄H₂O₂Z₂ structures in series. Therefore, the structures of six 3,6-pyridazinediones (N₂C₄H₂Y₂Z₂) were optimized in both equilibrium and planar configurations, and their vibrational frequencies were calculated. Then the adiabatic potential energy surface (APES) profiles along the a₂ distortion coordinates were calculated. Based on the calculation results, N₂C₄S₂H₄ and N₂C₄Se₂H₄ compounds were stable in the planar structure; but, due to the vibronic coupling interaction between the ¹A₁ ground state and the first excited state ¹A₂, the twisting instability occurred in planar N₂C₄H₂O₂Z₂ series. The (¹A₁ + ¹A₂) ⊗ a₂ problem was found to be the reason of the breaking symmetry phenomena in all the four N₂C₄H₂O₂Z₂ in series from unstable planar configuration (highest-symmetry C_2v) to the stable twisted geometry with C₂ symmetry. Finally, the vibronic coupling constants of the PJTE of the compounds in series were estimated by fitting the secular equation roots along the normal coordinates of distortion.

Quantum chemical calculations have been performed to analyze the intermolecular interactions in the ternary NCLi⋯NCX⋯HMgY complexes (X = F, Cl, Br; Y = H, F, Cl, Br, Li). A cooperative effect is observed between the lithium and halogen–hydride bonds in these complexes. The cooperative energy ranges from -1.81 kJ/mol to -5.21 kJ/mol, -3.59 kJ/mol to -9.86 kJ/mol and -4.77 kJ/mol to -14.27 kJ/mol for X = F, Cl and Br, respectively (at MP2/6-311++G(d,p) level). The geometrical and interaction energies analysis reveal that the lithium bond has a greater enhancing effect on the halogen–hydride bond. The results of many-body analysis indicate that two- and three-body interaction energies have a positive contribution to the total interaction energy. The electronic characteristics of the complexes have been analyzed through molecular electrostatic potential (MEP), atoms in molecules (AIM), electron localization function (ELF) and natural bond orbital (NBO) methodologies.