Thanh N. Truong

Kinetics of Enol Formation from Reaction of OH with Propene

Kinetics of enol generation from propene has been predicted in an effort to understand the presence of enols in flames. A potential energy surface for reaction of OH with propene was computed by CCSD(T)/cc-pVDZ//B3LYP/cc-pVTZ calculations. Rate constants of different product channels and branching ratios were then calculated using the Master Equation formulation (J. Phys. Chem. A 2006, 110, 10528). Of the two enol products, ethenol is dominant over propenol, and its pathway is also the dominant pathway for the OH + propene addition reactions to form bimolecular products. In the temperature range considered, hydrogen abstraction dominated propene + OH consumption by a branching ratio of more than 90%. Calculated rate constants of enol formation were included in the Utah Surrogate Mechanism to model the enol profile in a cyclohexane premixed flame. The extended model shows consistency with experimental data and gives 5% contribution of ethenol formation from OH + propene reaction, the rest coming from ethene + OH.

Heterogeneous CO2 Evolution from Oxidation of Aromatic Carbon-Based Materials

Carbon dioxide is one of the main gaseous products in oxidation of carbonaceous materials via both homogeneous and heterogeneous reactions. However, the mechanisms of heterogeneous CO(2) evolution during oxidation of aromatic carbon-based materials are not known in detail. Using density functional theory, a new oxidation mechanism of aromatic hydrocarbons with atomic oxygen was suggested to consist of four main steps, namely, (1) adsorption of oxygen atom, (2) insertion of O atom into the ring, (3) rearrangement to form a five-membered ring and four-membered ring lactone group, and (4) desorption of CO(2). Using naphthoxy radical as a model system, the proposed reaction pathway can explain how some of the experimentally observed CO(2) is formed.

Kinetics of the C–C Bond Beta Scission Reactions in Alkyl Radical Reaction Class

Kinetics of the β-scission in alkyl radical reaction class was studied using the reaction class transition state theory (RC-TST) combined with the linear energy relationship (LER) and the barrier height grouping (BHG) approach. All necessary parameters were derived from first-principle density functional calculations for a representative set of 21 reactions. Different error analyses and comparisons with available literature data were made. Direct comparison with available experimental data indicates that the RC-TST/LER, where only reaction energy is needed, can predict rate constants for any reaction in this reaction class with excellent accuracy. Specifically for this reaction class, the RC-TST/LER method has less than 60% systematic errors on average in the predicted rate constants when compared to explicit rate calculations.

Determination of structural requirements of influenza neuraminidase type A inhibitors and binding interaction analysis with the active site of A/H1N1 by 3D-QSAR CoMFA and CoMSIA modeling

As a basis for predicting structural features that may lead to the design of more potent and selective inhibitors of influenza neuraminidase type A, three-dimensional quantitative structure–activity relation (3D-QSAR) studies were performed on a set of sixty one known neuraminidase type A inhibitors. The studies include Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA). Atom and centroid/atom based alignment and docked conformation-based alignments were used to develop different CoMFA models. A homology modelled A/H1N1 with one of the most active neuraminidase inhibitors (Relenza) inside the active site structure was used for docking purposes. The resulted docking based conformers of the inhibitors were used for developing the CoMFA model. The model developed by considering the docked conformation-based alignment was found to perform better than that developed by atom and centroid/atom based alignments with excellent predictive r2. The CoMFA model generated using docked conformer-based alignment served as alignment strategy for CoMSIA. The CoMSIA model with a combination of steric, electrostatic and acceptor fields yielded the highest cross-validated r2. CoMFA steric, electrostatic and CoMSIA donor contour maps were mapped in the active site of A/H1N1. These 3D-QSAR studies revealed indispensable structural features of different chemical classes of molecules which could be exploited for the structural modifications of these lead molecules in order to achieve improved neuraminidase type A inhibitory activity.

Explicitly Solvated Ligand Contribution to Continuum Solvation Models for Binding Free Energies: Selectivity of Theophylline Binding to an RNA Aptamer

To provide more accurate computational estimates of binding free energies in solution from molecular dynamics (MD) simulations, a separate solvation contribution for the binding ligand is determined from a linear response treatment. We use explicit water coordinates for this term and combine with MM-PBSA (molecular mechanics, Poisson-Boltzmann, and surface area contributions) in a new approach (MM-PB/LRA-SA). To assess this method, application to the binding between theophylline and its derivatives to an RNA aptamer was performed and compared with experimental binding affinities. Explicitly solvated MD trajectories were generated with the same parameter set used in the previous work by Gouda et al., who compared the relative binding of these molecules by both the MM-PBSA and thermodynamic integration methods. Substituting the linear response term for the ligand in the MM-PB/LRA-SA approach led to an improvement upon MM-PBSA when compared with experimental and thermodynamic integration results at approximately twice the computational cost. The balance between accuracy and computational expense achieved using this method suggests potential advantages in applying it in the virtual drug-screening process.

Top-hits for A/H1N1 Identified by Virtual Screening Using Ensemble-based Docking.

A list of 27 promising antiviral drugs are proposed for use against the H1N1pdm strain. Since the binding site of the H1N1pdm neuraminidase is similar to that of the bird flu H(5)N1, an effective means to quickly identify top candidates for use against H1N1pdm is to use known bird-flu drugs and the 27 compounds from the NCI diversity set which bind best to H(5)N1 neuraminidase. These compounds serve as viable candidates for docking against the H1N1pdm neuraminidase, using ensembles extracted from molecular dynamics simulations of the H1N1pdm system. The ranking order of these top candidates was found to be different from the previously published results for H(5)N1. The results indicated that the Oseltamivir (Tamiflu) and Peramivir drugs have higher ranking than Zanamivir (Relenza). However, six drug candidates were found to bind more effectively to H1N1pdm neuraminidase than Tamiflu. Detailed hydrogen bond network analysis for these six candidates is also provided.

Effects of amine organic groups as lattice in ZSM-5 on the hydrolysis of dimethyl ether

The effects of doping amine to ZSM-5 on its catalytic activity for hydrolysis of dimethyl ether (DME) have been studied theoretically using Density Functional Theory with the embedded cluster ONIOM(M06/6-31G(d,p):UFF) model. Doping by amine to ZSM-5 yields two new active centers, namely the protonated Z[NH2] and non-protonated Z[NH] amine sites in addition to the normal Brønsted acid Z[OH] site. The reaction has two possible stepwise and concerted channels. The stepwise channel consists of two elementary steps; (i) the demethylation followed by (ii) the hydrolysis while the concerted channel involves in the demethylation and hydrolysis in a single step. We found that the reaction favors to proceed via the concerted channel at all three active centers. The results predict that the Z[OH] shows the best catalytic performance for the studied reaction. The Z[NH2] is not catalytically active due to the activation barriers are extremely high for both stepwise and concerted pathways. The demethylation step is energetically favorable over the Z[NH] site, however, the product methylamonium surface intermediate is too stable to be further converted to methanol.