Journal of Theoretical and Computational Chemistry

The purpose of our work is to characterize and present a theoretical comparative study of a variety of compounds based on DNA base pairs linked with some transition metal ions in gas phase: C–M–G (Cytosine–metal–Guanine) where $\text{M}=\text{Ag}$(I), Zn(II), Cd(II) and A–M–T (Adenine–metal–Thyminate) where $\text{M}=\text{Co}$(II), Ru(I), Ni(I), Y(II), Zn(I), Cd(I), Cu(II). Geometry optimization and frequency calculations were carried out at DFT/ZORA/BLYP-D/TZ2P level. M–N and M–O bonds were investigated with the quantum chemical topology (QCT): Quantum theory of atoms in molecules (QTAIM) and electron localization functions (ELF). The hydrogen bonds: N10–H$\dots$O7 for A–M–T complexes and N7–H$\dots$O10 for C–M–T ones were visualized and discussed, QTAIM and ELF prove the existence of O7–H$\dots$N10 hydrogen bond for some A–M–T systems, since the bond critical point (BCP) of N7–H having ${\nabla }^2\rho (r)<0$, so it has a covalent character confirming the existence of a tautomer process of these complexes. Bonding energy $E_{(\mathrm{\text{bond}})}$, Pauli repulsion $E_{(\mathrm{\text{Pauli}})}$, electrostatic $E_{(\mathrm{\text{elect}})}$, and orbital $E_{(\mathrm{\text{orb}})}$ interactions were represented and compared together. Hirschfeld’s charges showed the existence of charge transfer process in the bridge moieties. It seems that, in contrast to natural base pairs that are stabilized by hydrogen bonding, Hoogsteen-type base pairs are held together by coordinative bond with metal ions.

Bilirubin is an insoluble yellow pigment produced from heme catabolism and serves as a diagnostic marker of liver and blood disorders. Here, a systematic study of several interactions and arrangements between different forms of natural bilirubin and poly-5, 2${}^{\prime }$-5${}^{\prime }$, 2${}^{\prime \prime }$-terthiophene-3-carboxylic acid/Mn(II)₂ complex, PTTCA–Mn(II)₂, as a biosensor of bilirubin has been investigated extensively. The PTTCA–Mn(II)₂ biosensor detects natural bilirubin through the mediated electron transfer by the Mn${}^{2+}$. Initially, density functional theory (DFT) using B3LYP and different basis sets including 6-31G* and 6-311G** has been employed to calculate the details of electronic structure and electronic energies of natural biliverdin and $\delta$-, $\beta$- and $\gamma$-bilirubin. Next, the interaction of the PTTCA–Mn(II)₂ biosensor, being in three possible spin states, with $\delta$-, $\beta$- and $\gamma$-natural bilirubin with 1:1 and 1:2 stoichiometry using UB3LYP/6-31G* method has been investigated. Natural population analysis (NPA) calculations have been used to derive more suitable interaction sites of bilirubin with Mn${}^{2+}$ ions in PTTCA–Mn(II)₂ biosensor. Investigation of different manganese complexes with bilirubin shows that the most stable complex is high spin state (total electron spin $S=5∕2$) rather than intermediate and low spin states with 1:2 stoichiometry. Also, the temperature effect and interferences from other biological compounds such as ascorbic acid, L-glutamic acid, uric acid, creatine, glucose and dopamine have been investigated. The nature of the interaction between manganese metal cations and natural bilirubin is also discussed employing NPA, molecular orbital (MO) analysis and Bader’s Atoms in Molecule (AIM) theory.

The electronic properties, polarizabilities, first and second hyperpolarizabilities of YO_n clusters of $n=1$–12 were studied using the quantum chemical method. The vertical ionization potential (VIP) values for the anionic clusters increase monotonically with the cluster size. Among the neutral clusters YO₃ and YO₈ have the least chemical hardness values, where in anionic clusters with size $n<4$ possesses the least chemical hardness. Anionic clusters have more electrons attracting tendency than the neutral clusters. The computed static mean polarizability of neutral yttrium oxides has positive values but is close to zero. The incorporation of oxygen atom quenches the polarizability of yttrium. The computed polarizability anisotropy of neutral clusters shows an oscillatory effect both at static and at dynamic conditions. The first hyperpolarizability for many YO_n clusters are close to zero. The existence of high symmetry in these clusters reduces the first hyperpolarizability values which was supported by the small dipole moments. The computed $\gamma$ values for the static neutral and anionic clusters show only a small variation. The decrease in the polarizability and second hyperpolarizability with size can be interpreted in terms of the electronic delocalization and chemical bonding in the clusters.

The molecular structure and properties of 1,4-diformylpiperazine (1,4-dfp, C₆H${}_{10}$N₂O₂) were investigated by Fourier transform infrared (FT-IR) spectroscopy, Raman spectroscopy and density functional theory (DFT). The Becke-3-Lee–Yang–Parr (B3LYP) functional was used with the 6-31$++$G(d,p) basis set. Total energy distribution (TED) analysis of normal modes was performed to identify characteristic frequencies by the scaled quantum mechanical (SQM) method. Halogeno-analogs of 1,4-dfp were studied to understand the halogen effect. Computations were focused on five conformational isomers of the compounds in the gas phase and in solutions. The computed and experimental frequencies of the C$=$O stretching vibration of 1,4-dfp were correlated with the empirical solvent parameters such as the Kirkwood–Bauer–Magat (KBM) equation, the solvent acceptor number (AN), Swain parameters and linear solvation energy relationships (LSER). The electronic properties of the compounds were also examined. The findings from the present work may be useful to understand systems involving the halogens and conformational changes analogous to the compounds investigated.

Human butyrylcholinesterase (BChE) is a bioscavenger that protects the enzyme which is critical for the central nerve system, acetylcholinesterase, from poisoning by organophosphorus agents. Elucidating the details of the hydrolysis reaction mechanism is important to understand how the phosphorylated BChE can be reactivated. Application of the QM(DFTB)/MM(AMBER) method to construct the minimum energy pathways for the hydrolysis reaction of the diethylphosphorylated BChE allowed us to suggest a mechanism of reactivation of the wild-type and the G117H mutated enzyme. Unlike previous approaches assuming that either His438 or His117 serves as a general base in the catalysis, in our proposal the Glu197 residue is responsible for activation of the nucleophilic water molecule (Wat) leading to the chemical transformations that restore the catalytic Ser198 residue in BChE. In agreement with the experimental data, it is shown that the G117H mutation facilitates the reactivation of the inhibited enzyme.

In the present work, a theoretical study of the geometrical structures and spectroscopic (IR, ¹H and ${}^{13}$C NMR, UV-visible) properties, and anti-cancer activity of cis-fused tetrahydrochromeno[4,3-b]quinolines have been performed. The equilibrium geometries have been optimized at the B3LYP/6-31G(d) computational level and the present study puts in evidence the stability preference of the cis stereoisomers in comparison with the trans ones as expected experimentally. The vibrational frequencies and IR spectra were calculated at the same level of theory and compared to experimental FT-IR spectra and the spectral peaks have been assigned on the basis of potential energy distribution results. UV-visible absorption bands were calculated using the TD-DFT/B3LYP/6-31G(d) method. The ${}^{13}$C nuclear magnetic resonance chemical shifts and the coupling constants were calculated at the B3LYP level using the gauge independent atomic orbital (GIAO) method in chloroform solvent. The ¹H chemical shifts were calculated using the recently proposed WP04/6-31G(d) DFT functional. The visualization of the molecular electrostatic potential (MEP) surfaces and the docking simulation show that the absence of the methyl group at 2-position of tetrahydrochromeno[4,3-b]quinoline moiety is responsible of the potential anti-cancer activity of this compound.

Three possible catalytic cycles for ebselen have been comprehensively modeled by theoretical calculations using density functional theory (DFT) at a mixed basis set level; the 6-31G(d) basis set for hydrocarbon fragments and the 6-31$++$G(d,p) basis set for other atoms. The 2$\to 3\to 3^{\prime }\to 3^{\prime }{}^{\prime }\to 4^{\prime }\to 4\to 2$ cycle is the main pathway in the glutathione peroxidase (GPx) cycle (cycle A), and IM3$\to$TS3 is the rate controlling process. The 1$\to 5\to 8\to 8^{\prime }{}^{\prime }\to$1 cycle is the main pathway for the oxidation cycle (cycle B), and the rate controlling step is the $8^{\prime }{}^{\prime }\to 1$ step. Ebselen reacts with the selenol 3 to form the diselenide 9, and this is the rate controlling step for cycle C. The extremely high energy barrier for the IM9$\to$TS9 process indicates that cycle C is unlikely to occur in vivo. Although cycle B is favored based on the energy analysis, with a maximum energy barrier of only 26.68kcal/mol at the mixed basis set level, it is generally unlikely to have very high concentrations of peroxides present in vivo. The results indicate that in order to improve the antioxidant activity of ebselen, it would be necessary to suitably modify the molecular structure of ebselen to reduce the energy barrier of the IM3$\to$TS3 process.

A quantum mechanical molecular mechanics (QM/MM) implementation for periodic systems is reported. This is done for the case of molecules and for systems with two and three-dimensional periodicity, which is suitable to model electrolytes in contact with electrodes. Tests on different water-containing systems, ranging from the water dimer up to liquid water indicate the correctness of the scheme. Furthermore, molecular dynamics simulations are performed, as a possible direction to study realistic systems.

In order to probe the effects of substituents (F and CN) attached to benzo[1,2-b:3,4-$b^{\prime }$:5,6-$b^{\prime }{}^{\prime }$]tristhianaphthene (BTTP) on their charge carrier transport properties, we investigated the characteristics of molecular structures and charge transport properties of BTTP and its derivatives (BTTP1, BTTP2, BTTP3, BTTP4, and BTTP5). Six crystal structures were predicted by the Monte Carlo-simulated annealing method with the embedded electrostatic potential charges method. Even a subtle change of geometrical structures may result in a great change of the reorganization energy. With increasing numbers of substituted fluorine atoms, the reorganization energy of the BTTP derivative increases, which is disadvantageous to the electron transport. In contrast, the attachment of the electron-withdrawing cyano groups to BTTP decreases the reorganization energy and raises the electron affinity, which is beneficial to electron injection and charge carrier stabilization. The introduction of cyano groups also results in an enhancement of $\pi$–$\pi$ interaction and leads to an increase in the transfer integrals. Among the six compounds, the novel compound BTTP4 has the largest electron mobility (1.154cm${}^2\cdot {\mathrm{\text{V}}}^{-1}\cdot {\mathrm{\text{s}}}^{-1}$) on account of its larger transfer integral and smaller reorganization energy, indicating that BTTP4 is a promising high-performance n-type organic semiconductor and worth to synthesize. The analysis of angular-resolution anisotropic mobilities for the BTTP and BTTP4 shows that it is helpful to control the orientations of the conducting channels for a better charge transport efficiency. This work provides a rational strategy for the design of high-performance n-type organic semiconductors from molecule to crystal structure.