Computational Modeling of Human Paraoxonase 1: Preparation of Protein Models, Binding Studies, and Mechanistic Insights.

The enzyme human paraoxonase 1 (huPON1) has demonstrated significant potential for use as a bioscavenger for treatment of exposure to organophosphorus (OP) nerve agents. Herein we report the development of protein models for the human isoform derived from a crystal structure of a chimeric version of the protein (pdb ID: 1V04) and a homology model derived from the related enzyme diisopropylfluorophosphatase (pdb ID: 1XHR). From these structural models, binding modes for OP substrates are predicted, and these poses are found to orient substrates in proximity to residues known to modulate specificity of the enzyme.

Combustion pathways of the alkylated heteroaromatics: bond dissociation enthalpies and alkyl group fragmentations.

The bond dissociation enthalpies (BDEs) of the alkyl groups of the alkyl-substituted heterocycles have been studied and compiled using DFT methodology, with the intent of modeling the larger heterocyclic functionalities found in coal. DFT results were calibrated against CBS-QB3 calculations, and qualitative trends were reproduced between these methods. Loss of hydrogen at the benzylic position provided the most favorable route to radical formation, for both the azabenzenes and five-membered heterocycles.

Kinetic barriers of H-atom transfer reactions in alkyl, allylic, and oxoallylic radicals as calculated by composite ab initio methods.

Composite ab initio and density functional theory (DFT) methods were used to explore internal hydrogen-atom transfers in a variety of primary, secondary, and tertiary alkyl and functionalized radicals with implications for combustion environments. The composite ab initio method G3MP2B3 was found to achieve the most reasonable balance between accuracy and economy in modeling the energetics of these reactions. Increased alkyl substitution reduced barriers to isomerization by about 10 and 20 kJ mol(-1) for secondary and tertiary radical formation, respectively, relative to primary radical reactions and was relatively insensitive to the transition-state ring size (extent of H-atom internal shift).

Theoretical determinations of the ambient conformational distribution and unimolecular decomposition of n-propylperoxy radical.

The conformational distribution and unimolecular decomposition pathways for the n-propylperoxy radical have been generated at the CBS-QB3, B3LYP/6-31+G and mPW1K/6-31+G levels of theory. At each of the theoretical levels, the 298 K Boltzmann distributions and rotational profiles indicate that all five unique rotamers of the n-propylperoxy radical can be expected to be present in significant concentrations at thermal equilibrium. At the CBS-QB3 level, the 298 K distribution of rotamers is predicted to be 28.

Observation of the A-X electronic transition of the 1-C3H7O2 and 2-C3H7O2 radicals using cavity ringdown spectroscopy.

Cavity ringdown spectra of the A-X electronic transition of the 1-propyl and 2-propyl peroxy radicals are reported. Spectroscopic assignments are facilitated by implementing several production mechanisms, either isomer-specific or not. Assignments of specific spectral lines to particular conformers of a given isomer are suggested.

Non-aqueous solvation of n-octanol and ethanol: spectroscopic and computational studies.

Raman spectroscopy was used to examine the interactions of the free O-H bonds in n-octanol and ethanol with the organic solvents carbon tetrachloride (CCl(4)), cyclohexane, and benzene. These spectra reveal that the solvents CCl(4) and cyclohexane have a small effect on the free O-H peak of alcohols, whereas benzene as a solvent significantly red-shifts the free O-H band. Calculated spectra were generated via MP2/6-31G* calculations and the B3LYP/6-31+G**//MP2/6-31G*-derived Boltzmann populations of each ethanol complex and are consistent with the experimental results.