Journal of Theoretical and Computational Chemistry

Indole derivatives represent an important class of privileged structures. Spectroscopic (Fourier transform infrared (FT-IR), FT-Raman, ¹H and ${}^{13}$C nuclear magnetic resonance (NMR)) investigations of the indole-bearing title compound, namely 5-methoxy-1-[(5-methoxy-1$H$-indol-2-yl)methyl]-1$H$-indole (MMIMI) have been carried out. The corresponding data of the MMIMI molecule were analyzed to understand its optimized geometry, and inter/intra-molecular interactions. The equilibrium geometry, harmonic vibrational wavenumbers, Frontier orbital energy, and natural bond orbital (NBO) analyses have been performed with the help of density functional theory (DFT) with B3LYP/6-311$++$G($d$,$p$) level of theory. The vibrational modes have been unequivocally assigned using potential energy distribution analysis. The theoretically predicted wavenumbers have good agreement with the experimental values. NBO has confirmed the intra-molecular charge transfer interactions. HOMO–LUMO analysis was carried out to explore charge delocalization on the MMIMI molecule. The immunomodulatory activity of the title molecule was predicted using molecular docking approach.

The urea inclusion compounds, a unique polar organic crystalline complex, are considered as a potential candidate for a molecular separator of long chain alkane molecule. A well-defined structure of the crystalline channel systems constructed from hydrogen bonding arrangement of the urea molecules, can be used to understand the fundamental aspects of the processes involving ions or molecules transportation. To do so, in our work, molecular dynamics approach is implemented to understand the behavioral pattern of the hexadecane-1,16-diol and hexadecane guests’ related to translational and rotational orientation along the urea tunnel. Our obtained results reveal that high interaction of hexadecane-1,16-diol with urea host molecules offers a restricted environment inside urea tunnel, resulting in slowing down the guest movement. Hexadecane guest system, on the contrary, exhibits lower interaction whereby the translational and rotational movement is faster. Moreover, as the distance increases (along $c$-axis) in the urea tunnel, both guest systems favor a clockwise rotational orientation. Preference of the respected orientation indicates the influence of chiral urea tunnel on achiral guests that is clathrate inside the tunnel structure.

A theoretical study on the antioxidant properties of two chalcone derivatives, kanakugiol and pedicellin, is performed by considering their Fe${}^{2+}$ and Fe${}^{3+}$ coordination ability. The objective of the study is to elucidate the factors influencing the stability of the isolated conformers, the nature of the complexes, metal$\cdots$ligand stability, metal ion affinities (MIA) and electronic properties of the cations before and after coordination to the ligand. The study is performed using the B3LYP/6–311$+$G(2d,p)//B3LYP/6–31$+$G(d,p) method. The LANL2DZ pseudopotential is selected to describe the Fe${}^{n+}$ ions. Time-dependent density functional theory (TDDFT) method is used to assess the electronic UV–Vis spectra of the isolated chalcones and their complexes with Fe${}^{n+}$ ions. The results suggest that the preferred complexes are those in which the Fe ion is coordinated at the hydroxyl-methoxy and hydroxyl-keto sites for kanakugiol and methoxy-keto site for pedicellin. Both kanakugiol and pedicellin have potential to chelate iron ions as demonstrated by their high MIA values in vacuo and in water solution. However, the ability of pedicellin to chelate iron is slightly lower than that of kanakugiol, indicating that the presence of the hydroxyl group has an effect of enhancing the metal binding abilities of the chalcone derivatives. In all the complexes obtained in vacuo, kanakugiol and pedicellin exhibit the ability to reduce the Fe${}^{n+}$ ion. In water solution (which mimics the environment in biological systems or studies performed in vivo), Fe${}^{3+}$ is reduced to Fe${}^{2+}$ upon coordination to the ligand while the oxidation number of Fe${}^{2+}$ upon coordination to the ligand remains virtually unchanged.

ONIOM studies were performed on the transition structure (TS) of organocatalytic direct aldol reaction by using ionic liquid supported benzoic acid (ILS-PhCO₂H) as an additive. Results obtained from this computation suggest direct involvement of ILS-PhCO₂H in the TS as a proton donor. It has also come out from the present study that, the counter ion of the ILS-acid additive may also play significant role to maintain the proper TS geometry by holding the organocatalyst and the acid additive close together during the course of reaction.

Molecular docking and charge density analysis were carried out to understand the geometry, charge density distribution and electrostatic properties of one of newly synthesized 4-substituted-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylates (PDE), which is regarded as the best $\alpha$-Glucosidase inhibitor among the hydropyridine dicarboxylate derivatives. The different bonding models of the PDE molecule in the active sites of proteins Human serum albumin (HSA) and Saccharomyces cerevisiae $\alpha$-glucosidase (SAG) are firstly compared, which is important to understand the different intermolecular interactions between drug-transport protein and drug-target protein. The deformation density maps suggest that the electron densities of the PDE molecule are redistributed when it presents in the active sites. When the molecule presents in the active site of the SAG, it is evident to find that the negative region does not appear at the vicinity of the oxygen atoms on one of the carboxylic acid dimethyl ester group. Frontier molecular orbital density distributions for the PDE molecule are similar in all forms. The highest occupied molecular orbital (HOMO) and lowest occupied molecular orbital (LUMO) energy gaps in the active sites are higher than that of the molecule in pure solution phase. It is generally noticed that all of the orientations of the dipole moment vectors are reoriented in both active sites. These fine details at electronic level allow to better understand the exact drug-transport protein and drug-target protein interactions.

The effect of external perturbations, namely solvent and external electric field on potential energy surface (PES) and bond dissociation energy of C–X (X$=$F, Cl, Br, N, O) bonds has been studied in the light of density functional theory (DFT). The study reveals that presence of solvent as well as external electric field changes the curvature of the PES significantly. Bond dissociation energy significantly drops in presence of both the external perturbation.

3,5-Dicaffeoylquinic acid (diCQA) is a part of the chlorogenic acid group of compounds, largely isolated from food sources and possessing potent antioxidant activity. Only the trans–trans isomer exists in nature, however, abiotic stresses, such as UV-radiation, give rise to cis isomers. There have been no reports on the antioxidant activity of the cis isomers. The current study, performed using the B3LYP/6-311$+$G(d,p) method, is aimed at investigating and comparing the antioxidant properties of the geometrical isomers of 3,5-diCQA. The study is conducted by checking the molecules’ ability for two main radical scavenging mechanisms, hydrogen atom transfer (HAT) and electron transfer (ET). A separate DPPH assay experimental study performed in this study shows that all the geometrical isomers are potent radical scavengers. The lowest O$-$H bond dissociation enthalpy value (70.599 kcal/mol) corresponds to the trans–trans isomer and is comparable to that of gallic acid, a commercially available antioxidant. The lowest ionization potential value corresponds to the cis–cis isomer (149.54kcal/mol), indicating that it is best antioxidant, in terms of ET mechanism.

The ladder transitions controlled by two harmonic pulses are investigated theoretically using a time-dependent quantum wave packet method for the ground electronic state of HF molecule. By choosing $\omega +2\omega$, $\omega +3\omega$ and $\omega +4\omega$ schemes, the population can be transferred to target states $|\nu ,j〉$. The population distribution can be controlled by the average amplitude of total electric field which depends on the relative phase of two pulses. With the variation of the relative phase between $\omega$ and $3\omega$ pulses, the variation of population has a period of $2\pi$. For $\omega +2\omega$ and $\omega +4\omega$ schemes, the population distributions show oscillation behavior with a period of $\pi$ by varying the relative phase. The two harmonic pulses can realize a nearly complete population transfer to the target state.

Cisplatin and oxaliplatin are two widely-used anti-cancer drugs which covalently bind to a same location in DNA strands. Platinum agents make intrastrand and interstrand cross-links with the N7 atoms of guanine nucleotides which prevent DNA from polymerization by causing a distortion in the double helix. Molecular dynamics simulations and free energy calculations were carried out to investigate the binding of two platinum-based anti-cancer drugs with DNA. We compared the binding of these drugs which differ in their carrier ligands, and hence their potential interactions with DNA. When a platinum agent binds to nucleotides, it causes a high amount of deformation in DNA structure. To find the extent of deformation, torsion angles and base pair and groove parameters of DNA were considered. These parameters were compared with normal B-DNA which was considered as the undamaged DNA. The formation of hydrogen bonds between drugs and DNA nucleotides was examined in solution. It was shown that oxaliplatin forms more hydrogen bonds than cisplatin. Our results confirm that the structure of the platinated DNA rearranges significantly and cisplatin tries to deform DNA more than oxaliplatin. The binding free energies were also investigated to understand the affinities, types and the contributions of interactions between drugs and DNA. It was concluded that oxaliplatin tendency for binding to DNA is more than cisplatin in solvent environment. The binding free energy was calculated based on the MM/PBSA and MM/GBSA methods and the results of QM/MM calculations verified them.