Vudhichai Parasuk

An n-Channel Two-Dimensional Covalent Organic Framework

Co-condensation of metallophthalocyanine with an electron-deficient benzothiadiazole (BTDA) block leads to the formation of a two-dimensional covalent organic framework (2D-NiPc-BTDA COF) that assumes a belt shape and consists of AA stacking of 2D polymer sheets. Integration of BTDA blocks at the edges of a tetragonal metallophthalocyanine COF causes drastic changes in the carrier-transport mode and a switch from a hole-transporting skeleton to an electron-transporting framework. 2D-NiPc-BTDA COF exhibits broad and enhanced absorbance up to 1000 nm, shows panchromatic photoconductivity, is highly sensitive to near-infrared photons, and has excellent electron mobility as high as 0.6 cm(2) V(-1) s(-1).

Theoretical Investigations on the Stereoselectivity of the Proline Catalyzed Mannich Reaction in DMSO

The stereocontrol steps of the (S)-proline catalyzed Mannich reaction of cyclohexanone, formaldehyde, and aniline were theoretically investigated. The geometries of reactants, products, and transition states were optimized using density functional theory using the B3LYP functional with the 6-31++G(d,p) basis set. The energies of these compounds were then more accurately determined at the MP2 level, and the effect of DMSO as the solvent was included using a polarizable continuum model (PCM). The reaction was modeled from the previously proposed mechanism that cyclohexanone reacts with (S)-proline to generate an enamine, while formaldehyde reacts with aniline to produce an imine, and that the conformation around the C-N bond of the enamine 1 is crucial for the further enantioselective step. The formation of two conformations of the enamine via a proton transfer process was examined, revealing activation barriers for syn- and anti-enamine proton transfer of 10.2 and 17.9 kcal/mol, respectively. The transformation of syn- to anti-enamine through C-N bond rotation, however, was predicted to require only 4.2 kcal/mol, while the (S)- and (R)-intermediates could be obtained from subsequent reactions between enamine and imine with energy barriers of 8.5 and 12.4 kcal/mol, respectively. The difference between these barriers, but not the C-N rotation energy, becomes larger at the MP2 level and when DMSO as a solvent is included. This predicted enantioselective reaction, through the kinetic and thermodynamic favoring of the (S)-pathway, is in agreement with experimental results, which have reported the (S)-configuration as the major product.

Source of High Pathogenicity of an Avian Influenza Virus H5N1: Why H5 Is Better Cleaved by Furin

The origin of the high pathogenicity of an emerging avian influenza H5N1 due to the -RRRKK- insertion at the cleavage loop of the hemagglutinin H5, was studied using the molecular dynamics technique, in comparison with those of the noninserted H5 and H3 bound to the furin (FR) active site. The cleavage loop of the highly pathogenic H5 was found to bind strongly to the FR cavity, serving as a conformation suitable for the proteolytic reaction. With this configuration, the appropriate interatomic distances were found for all three reaction centers of the enzyme-substrate complex: the arrangement of the catalytic triad, attachment of the catalytic Ser(368) to the reactive S1-Arg, and formation of the oxyanion hole. Experimentally, the--RRRKK--insertion was also found to increase in cleavage of hemagglutinin by FR. The simulated data provide a clear answer to the question of why inserted H5 is better cleaved by FR than the other subtypes, explaining the high pathogenicity of avian influenza H5N1.

Accurate torsional potentials in conjugated systems: ab initio and density functional calculations on 1,3-butadiene and monohalogenated butadienes

Accurate calculations of the torsional potentials for rotation around the carbon–carbon single bond of all conceivable monohalogenated 1,3-butadienes C4 H 5X, (X ∈ [F, Cl, Br]), are presented. The parent compound, 1,3-butadiene, is also included as a benchmark and reference case. Large-scale ab initio calculations were performed at the second-order Møller–Plesset perturbation theory (MP2) and the coupled cluster, CCSD(T), levels. Additionally, density functional methods were applied. In all compounds considered, the anti- or s-trans-conformation is the most stable. For all three halogens, the 2-halo-1,3-butadiene is the most stable isomer, followed by the cis-1-halo-1,3-butadiene. Depending on the position and the type of halogen, the original 1,3-butadiene torsional potential is modified in a different manner. The modifications are particularly visible in the region of the syn- or s-cis and the gauche structures and in the barrier heights.

QSAR study of antimalarial activities and artemisinin-heme binding properties obtained from docking calculations.

The quantitative structure-activity relationships (QSAR) between antimalarial activities and artemisinin-heme binding properties were studied by means of docking calculations. Automated molecular dockings of 30 artemisinin derivatives to heme revealed a significant relationship between biological activity and binding energy (ra ˇ0:93) and less significantly with the O1-Fe distance (raˇ0:55). The QSAR models were constructed and the predicted biological activities were in good agreement with the corresponding experimental values. The docking also showed that artemisinin compounds approach heme by pointing O1 at the endoperoxide linkage toward the iron center, a mechanism controlled by the steric hindrance.

Comparative molecular field analysis of artemisinin derivatives: Ab initio versus semiempirical optimized structures

Based on the belief that structural optimization methods, producing structures more closely to the experimental ones, should give better, i.e. more relevant, steric fields and hence more predictive CoMFA models, comparative molecular field analyses of artemisinin derivatives were performed based on semiempirical AM1 and HF/3-21G optimized geometries. Using these optimized geometries, the CoMFA results derived from the HF/3-21G method are found to be usually but not drastically better than those from AM1. Additional calculations were performed to investigate the electrostatic field difference using the Gasteiger and Marsili charges, the electrostatic potential fit charges at the AM1 level, and the natural population analysis charges at the HF/3-21G level of theory. For the HF/3-21G optimized structures no difference in predictability was observed, whereas for AM1 optimized structures such differences were found. Interestingly, if ionic compounds are omitted, differences between the various HF/3-21G optimized structure models using these electrostatic fields were found.

Glucose transformation to 5-hydroxymethylfurfural in acidic ionic liquid: A quantum mechanical study.

Isomerization and transformation of glucose and fructose to 5‐hydroxymethylfurfural (HMF) in both ionic liquids (ILs) and water has been studied by the reference interaction site model self‐consistent field spatial electron density distribution (RISM‐SCF‐SEDD) method coupled with ab initio electronic structure theory, namely coupled cluster single, double, and perturbative triple excitation (CCSD(T)). Glucose isomerization to fructose has been investigated via cyclic and open chain mechanisms. In water, the calculations support the cyclic mechanism of glucose isomerization; with the predicted activation free energy is 23.8 kcal mol−1 at experimental condition. Conversely, open ring mechanism is more favorable in ILs with the energy barrier is 32.4 kcal mol−1. Moreover, the transformation of fructose into HMF via cyclic mechanism is reasonable; the calculated activation barriers are 16.0 and 21.5 kcal mol−1 in aqueous and ILs solutions, respectively. The solvent effects of ILs could be explained by the decomposition of free energies and radial distribution functions of solute‐solvent that are produced by RISM‐SCF‐SEDD.

Computational Studies of HIV-1 Integrase and its Inhibitors

Integration of the genome of the human immunodeficiency virus (HIV) into that of the host genome is catalyzed by HIV integrase (IN) and is an essential step in HIV-1 life cycle. Therefore, drug discovery efforts have been undertaken to identify selective IN inhibitors with the goal of improving the outcome of AIDS therapy using Highly Active Anti Retroviral Therapy (HAART). As computational technology has grown rapidly and is increasingly being used worldwide to accelerate the drug discovery processes, the aim of this review is to summarize the applications of the computer-aided drug design (CADD) techniques to HIV-1 IN and its inhibitors. The following applications are emphasized, including two- and three-dimensional quantitative structure activity relationships (2D/3D-QSAR), pharmacophore modeling, database searching, molecular docking, molecular dynamics simulations, and de novo methodologies.

Theoretical studies on the molecular basis of HIV-1RT/NNRTIs interactions

Molecular dynamics simulations (MD) of the human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT) complexed with the four non-nucleoside reverse transcriptase inhibitors (NNRTIs): efavirenz (EFV), emivirine (EMV), etravirine (ETV) and nevirapine (NVP), were performed to examine the structures, binding free energies and the importance of water molecules in the binding site. The binding free energy, calculated using molecular mechanics Poisson-Boltzmann surface area (MM-PBSA), was found to decrease in the following order: EFV ∼ ETV > EMV > NVP. The decrease in stability of the HIV-1 RT/NNRTI complexes is in good agreement with the experimentally derived half maximal inhibitory concentration (IC50) values. The interaction energy of the protein-inhibitor complexes was found to be essentially associated with the cluster of seven hydrophobic residues, L100, V106, Y181, Y188, F227, W229 and P236, and two basic residues, K101 and K103. Moreover, these residues are considered to be the most frequently detected mutated amino acids during treatment by various NNRTIs and therefore, those most likely to have been selected in the population for resistance.

Understanding the roles of novel electron donors in Ziegler–Natta catalyzed propylene polymerization

Roles of a novel dibenzoyl sulfide donor in Ziegler–Natta (ZN) catalyzed propylene polymerization were examined using DFT calculations. The adsorption mode for dibenzoyl sulfide and diisobutyl phthalate electron donors on the MgCl2(110) surface is the chelate coordination mode, similar to malonate electron donors. The dibenzoyl sulfide/diisobutyl phthalate donor provides regio- and stereo-selectivity to the ZN catalyst. Factors that control the isotacticity and activity of the ZN catalyst are steric repulsion and π-complex stabilization by electron donors. The steric repulsion signifies intrinsic activation energy and π-complex formation energy for π-complex stabilization. The two factors are combined in the apparent activation energy and dibenzoyl sulfide gives the lowest apparent activation energy. Therefore, dibenzoyl sulfide shows the best catalytic enhancement as compared to diisobutyl phthalate and di-n-butyl-2-cyclopentyl malonate, which is in good agreement with the results obtained from the experiments.