Journal of Theoretical and Computational Chemistry

The physiological role of human cystatin C (HCC) in the brain of individuals suffering from Alzheimer’s disease (AD) is currently an uncertainty in the scientific community. The protein complex interface between HCC and amyloid$\beta$ (A$\beta$), an aggregated protein in the AD brain, is of great interest due to the potential roles of HCC as an agonist and/or antagonist in AD progression. Thus, to understand the molecular details of HCC–A$\beta$ interactions, all-atom molecular dynamic simulations were performed in explicit water under physiological conditions. Rigid body protein–protein docking was utilized to obtain the best modes of interactions between A$\beta$ and HCC by using energy functions that comprise pairwise shape complementarity with desolvation and electrostatics. Subsequently, two top docking structures were simulated and evaluated for molecular interactions. A detailed trajectory analysis indicates favorable binding conformations between A$\beta$ and HCC where A$\beta$ goes through major conformational rearrangements while HCC retains its major secondary structures throughout the simulations. Root mean square deviation, radius of gyration and solvent accessible surface area analyses also suggest a larger conformational sampling for A$\beta$ in comparison to HCC. Moreover, hydrogen bonding and hydrophobic interactions were found to have important roles in the stability of complexes between A$\beta$ and HCC. Overall, the results obtained from this study provide molecular insight into the interaction pathways of A$\beta$ and HCC and emphasize the importance of noncovalent forces in biomolecular interactions of therapeutic significance.

Density functional theory has been performed on the step-defect Al₂O₃ film surfaces with the OH, Cl and H₂O molecules coadsorption. Three kinds of step-defect (Al, O2, Al3) surfaces are optimized and the adsorption energy, the binding energies of film and adsorbates are calculated. The energy properties are similar in H₂O or Cl coadsorption configurations, but have obvious differences for the OH group coadsorption configuration due to large numbers of adsorbate species and numbers. After structural relaxation, most of the step-defect surfaces could be easily hydroxylated. The Al3 step-defect surfaces are easier to be corroded by H₂O and coadsorption molecules due to lots of unsaturated dangling bonds, some H₂O molecules are located into the step-defect, surface Al atoms collapse inside the steps and several inner O atoms move outside the film. When the Cl exists in the aqueous solution, it would restrict H₂O molecules from dissociating into OH groups. Moreover, the dissociation and recombination of H₂O molecules could be promoted by OH groups.

In this study, the interactions between nitrile oxide (fulminic acid) and azide (hydrazoic acid) with the C${}_{20}$ fullerene were investigated and their priority in reacting and functionalizing surface of this fullerene were compared with each other. The results show that the 1,3-dipolar cycloaddition reaction between fulminic acid and C${}_{20}$ fullerene could occur faster than this reaction by hydrazoic acid. Therefore, nitrile oxide group as a dipole is much preferred compared to the azide functional group in reacting with the surface of C${}_{20}$ fullerene. In addition, the calculated adsorption energy and electronic density of state, DOS plots for the related species confirmed that the C${}_{20}$ fullerene can be used as sensors for sensing the hydrazoic acid and fulminic acid molecules.

Density functional theory (DFT) at the B3LYP-6-311$++$G(3df,2p)//6-311$++$G(d,p) level of theory in the gas phase and solution was performed to investigate the relative stabilities of all possible tautomers of 2-amino-2-oxazolin-4-one. Five different paths have been proposed to investigate the amino/oxo $\leftrightarrow$ imino/oxo proton transfer (PT) process. These paths are direct, mono-, di- and tri-water-assisted and self-assistance (dimerization) PT process. A clear catalytic effect has been observed when the introduction of water molecules and self-dimerization are taken place. Furthermore, barrier energies, equilibrium constants and reaction rate constants of the PT process between amine/oxo and imine/oxo tautomers of the self-assistance and in the presence of one, two and three water-assisted molecules were calculated. The computed activation barriers in the presence of water molecules are about 35–45 kcal/mol lower than those in the isolated case. In addition, the effective rate of the T1 $\leftrightarrow$ T2 processes were also recorded, compared and discussed. Finally, time-dependent–DFT (TD–DFT) was performed to determine the electronic absorption spectra of all species under probe. A reasonable agreement with the available experiments was also achieved.

A sensitive colorimetric L-chemosensor 1,3-dimethyl-5-(thien-2-ylmethylene)-pyrimidine-2,4,6-(1$H,3H,5H)$-trione was developed by Knoevenagel combination of barbituric acid with thiophene aldehyde chelating moiety. The sensor displayed a high colorimetric Cu(II)X₂ response; a dramatic methanol color change was recorded depending on anion type ($X={\mathrm{\text{Br}}}^{-1}$, Cl${}^{-1}$, ClO${}_4^{-1}$, NO${}_3^{-1}$, OAc${}^{-1}$, and SO${}_4^{-2})$. Off-on-off decolorized halochromism of the L-chemosensor/CuBr₂ was recorded in an acidic medium. The structure of the L-chemosensor was confirmed by single-crystal X-ray diffraction, elemental analysis, and molecular spectroscopic tools such as UV–Vis, Fourier transform infra-red, ¹H, and ${}^{13}$C nuclear magnetic resonance (NMR) spectroscopy. The thermal stability of the L-chemosensor was experimentally evaluated by thermogravimetric analysis. The structural optimized parameters of the ligand matched the crystallographic data, and the intermolecular forces were computed by Hirshfeld surface analysis. Electronic absorption in several solvents and ¹H NMR were correlated with the computed spectra in the gaseous state. The HOMO/LUMO, global reactivity descriptor quantum parameters, Mulliken charge population, and molecular electrostatic potential of the L-chemosensor were also computed.

The global aromaticity of dithienopyridine and dithienobenzene isomers was investigated using the topological resonance energy (TRE) and percentage topological resonance energy (%TRE) methods. The effect of variations in the positions of sulfur and nitrogen atoms on $\pi$-electron delocalization is analyzed. The local aromaticity of these isomers is described based on the bond resonance energy (BRE) and circuit resonance energy (CRE) methods. Our BRE and CRE results show that structure of the central six-membered rings has a strong effect on global aromaticity. The aromaticity of these dithienopyridine isomers is enhanced when a complete pyridine unit exists in their middle ring structure, while the aromaticity of the dithienobenzene isomers is enhanced when a complete benzene unit exists in their middle ring structure. For dithienopyridines, our results obtained using the TRE method correlate well with the Bird aromaticity index as reported in the literature. Our ring-current results show that all these compounds are diatropic systems.

Computational chemistry with the data from more detailed X-ray diffraction (XRD) oxygen evolving complex (OEC) structure has been used extensively of late in exploring the mechanisms of water oxidation in the OEC. The study reported in this paper involves density functional theory (DFT) calculations to investigate whether the data are in agreement with the four manganese ions in the OEC, being organized as a ‘3$+$1’ (trimer plus one) model [Gatt et al. Angewandte Chemie International Edition, 51, 12025–12028, 2012; Petrie et al. Chemistry - A European Journal, 21, 6780–6792, 2015; Terrett et al. Chemical Communications, 50, 3187–3190, 2014] or ‘dimer of dimers’ model. [Terrett et al. Journal of Inorganic Biochemistry, 162, 178–189, 2016]. The data analysis method used involves quantum chemical DFT calculations on relevant models of the OEC cluster. DFT calculations were performed using both the so-called ‘open’ and ‘closed’ forms [Terrett et al. Journal of Inorganic Biochemistry, 162, 178–189, 2016] of the S₂ OEC structure models with total spin ($S_T$) 1/2, 7/2, 9/2 and 15/2 within the Mn^III Mn^IV Mn^III Mn^III ‘low’ oxidation paradigm to examine exchange coupling within the OEC cluster. The results show that the $J$-coupling in the ‘closed’ form: $J_{23}=-23.4$cm${}^{-1}$, $J_{13}=43.66$cm${}^{-1}$, $J_{12}=126.1$cm${}^{-1}$ and $J_{34}=70$–$81.67$cm${}^{-1}$. In the ‘closed’ form, $J_{12}$ and $J_{34}$ represent the two largest exchange interactions within the manganese cluster, whereas $J_{23}$ and $J_{13}$ are small and almost net cancel. The magnetic coupling between the four Mn ions is close to ‘dimer of dimers’, with both dimers anti-ferromagnetically coupled internally and with weak inter-dimer net coupling.

Occurrence of electron transfer was studied for different combinations of polycyclic aromatic hydrocarbons (PAHs) and DNA bases as electron donors or acceptors and free radicals only as electron acceptors. Geometries of all the molecules and radicals were optimized in aqueous medium employing the polarizable continuum model. Single electron transfer (SET) and sequential proton loss electron transfer mechanisms were investigated employing Gibbs free energies of the appropriate neutral, anionic and cationic species. Barrier energies involved in these phenomena were calculated using the Marcus theory. The SET barrier energies were found to be linearly correlated with $\mathrm{\Delta }E=$ (Electron affinities of acceptors – Ionization potentials of donors). SET barrier energies from the DNA bases to the PAHs follow the order Cy $>$ Th $\approx$ Ad $>$ Gu, whereas SET barrier energies from the PAHs to the DNA bases follow the order Gu $>$ Ad $>$ Th $\approx$ Cy. Thus, guanine, among the DNA bases, is the best electron donor to the PAHs and worst electron acceptor from the same.

In this work, density functional theory is applied to understand the conformational stability and solvent effects on glycolic acid conformers in different solvents. In addition, the role of intramolecular hydrogen bond (H-bond) interactions in the stability of conformers are investigated. The molecular geometries of selected conformers are optimized using B3LYP and PBE0 functionals with 6-311$++$G(d,p) basis set. The effects of solvent on the geometrical parameters, relative stability, dipole moment, chemical hardness, chemical potential, etc. are studied for the conformers of glycolic acid. Our calculations show that the order of stability of the SSC and AAT conformers does not change in liquid phase. However, the energy of SSC and AAT conformers is very close to each other in water media. In water media, strong intramolecular H-bond interaction is present in AAT conformer which causes the energy of AAT conformer to be very close to that of SSC conformer. This may be due to the influence of water media.

Porous materials are commonly used to decrease or regulate thermal transport in insulating materials due to the very low thermal conductivity of the pores. More pores can achieve a better insulating effect; however, this can also be a shortcoming when the materials are directly involved in physical movement with friction, such as an interior wall of a cylinder in an automobile engine intended to prevent heat loss. Thus, it is important to clarify the mechanisms of the pore-dependent thermal properties of porous materials. In this study, the effects of the number and size of pores in silica quartz on thermal conductivity were investigated using nonequilibrium molecular dynamics simulations. The results revealed that the thermal conductivity of porous silica quartz decreased in all cases with an increase in the volume fraction of pores. A lower number of pores in the system showed higher thermal conductivity in the range of low volume fractions. We also showed that the interstitial distance between pores mostly governs thermal conduction at low volume fractions $<8.0$ vol.%. Additionally, the mechanism of thermal conduction was assessed with respect to several theoretical models.

The mechanism of gold(III)-catalyzed 1,3-dipolar [$3+3$] cycloaddition reactions of 2-(1-alkynyl)-2-alken-1-ones with nitrones to afford highly-substituted furo [3,4-d] [1,2] oxazines, which are useful as structural skeletons in biologically active compounds and as synthetic building blocks in organic synthesis, have been studied computationally. The results show that the reaction proceeds via the formation of a $\pi$-complex in which the gold moiety coordinates to the triple bond of the 2-(1-alkynyl)-2-alken-1-ones, resulting in an intramolecular cyclization of the gold intermediate to generate a carbocation intermediate which is trapped by the nucleophilic oxygen of the nitrone to form a furanyl–gold complex, which upon subsequent cyclization affords the furo [3,4-d] [1,2] oxazine as well as regenerates the gold catalyst. The highest activation barrier in the entire cycle is 19.5kcal/mol which accompanies the intramolecular cyclization step. The activation barriers for the reactions of 2-(1-alkynyl)2-alken-1-ones with electron-donating and cyclic substituents are generally lower compared to those of the parent 2-(1-alkynyl)2-alken-1-one while the reactions of 2-(1-alkynyl)2-alken-1-ones with electron-withdrawing substituents have higher activation barriers. Preliminary exploratory calculations on the possibility of replacing gold, an expensive and rare metal, with a copper-based catalyst for the reaction, show that for the key elementary steps, the Cu (III) catalyst is at least as active as the Au (III) complex, thus providing a cheaper route to furo [3,4-d] [1,2] oxazine.