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A J Mulholland

Publications and source records attributed to A J Mulholland.

5 recordsLinked to original sources
PubMed2000

Wave propagation in 0-3/3-3 connectivity composites with complex microstructure.

This work presents a study of the properties of particulate composites. The whole range of particle volume fraction (0-1) and ideal 0-3, 3-3 and intermediate 0-3/3-3 connectivities are analysed. Two different approaches to produce a realistic model of the complex microstructure of the composites are considered. The first one is based on a random location of mono-dispersed particles in the matrix; while the second incorporates a size distribution of the particles based on experimental measurements. Different particle shapes are also considered. A commercial finite element package was used to study the propagation of acoustic plane waves through the composite materials. Due to the complexity of the problem, and as a first step, a two-dimensional model was adopted. The results obtained for the velocity of sound propagation from the finite element technique are compared with those from other theoretical approaches and with experimental data. The study validates the use of this technique to model acoustic wave propagation in 0-3/3-3 connectivity composites. In addition, the finite element calculations, along with the detailed description of the microstructure of the composite, provide valuable information about the micromechanics of the sample and the influence of the microstructure on macroscopic properties.

Acoustics↗
PubMed1997

Acetyl-CoA enolization in citrate synthase: a quantum mechanical/molecular mechanical (QM/MM) study.

Citrate synthase forms citrate by deprotonation of acetyl-CoA followed by nucleophilic attack of this substrate on oxaloacetate, and subsequent hydrolysis. The rapid reaction rate is puzzling because of the instability of the postulated nucleophilic intermediate, the enolate of acetyl-CoA. As alternatives, the enol of acetyl-CoA, or an enolic intermediate sharing a proton with His-274 in a "low-barrier" hydrogen bond have been suggested. Similar problems of intermediate instability have been noted in other enzymic carbon acid deprotonation reactions. Quantum mechanical/molecular mechanical calculations of the pathway of acetyl-CoA enolization within citrate synthase support the identification of Asp-375 as the catalytic base. His-274, the proposed general acid, is found to be neutral. The acetyl-CoA enolate is more stable at the active site than the enol, and is stabilized by hydrogen bonds from His-274 and a water molecule. The conditions for formation of a low-barrier hydrogen bond do not appear to be met, and the calculated hydrogen bond stabilization in the reaction is less than the gas-phase energy, due to interactions with Asp-375 at the active site. The enolate character of the intermediate is apparently necessary for the condensation reaction to proceed efficiently.

Acetyl Coenzyme A↗
PubMedDate not supplied

Combined quantum mechanical and molecular mechanical reaction pathway calculation for aromatic hydroxylation by p-hydroxybenzoate-3-hydroxylase.

The reaction pathway for the aromatic 3-hydroxylation of p-hydroxybenzoate by the reactive C4a-hydroperoxyflavin cofactor intermediate in p-hydroxybenzoate hydroxylase (PHBH) has been investigated by a combined quantum mechanical and molecular mechanical (QM/MM) method. A structural model for the C4a-hydroperoxyflavin intermediate in the PHBH reaction cycle was built on the basis of the crystal structure coordinates of the enzyme-substrate complex. A reaction pathway for the subsequent hydroxylation step was calculated by imposing a reaction coordinate that involves cleavage of the peroxide oxygen-oxygen bond and formation of the carbon-oxygen bond between the C3 atom of the substrate and the distal oxygen of the peroxide moiety of the cofactor. The geometric changes and the Mulliken charge distributions along the calculated reaction pathway are in line with an electrophilic aromatic substitution type of mechanism. The energy barrier of the calculated reaction is considerably lower when the substrate hydroxyl moiety is deprotonated, in comparison with the barrier found with a protonated hydroxyl moiety. This effect of the protonation state of the substrate on the calculated energy barrier supports experimental observations that deprotonation is required for hydroxylation of the substrate. A notable event in the calculated reaction pathway is a lengthening of the peroxide oxygen-oxygen bond at an intermediate stage. Further analysis of the reaction pathway indicates that this oxygen-oxygen bond elongation is accompanied by an increase in electrophilic reactivity on the distal oxygen of the peroxide moiety, which may assist the C-O bond formation in the reaction of the C4a-hydroperoxyflavin intermediate with the substrate. Analysis of the effect of individual active site residues on the reaction reveals a specific transition state stabilization by the backbone carbonyl moiety of Pro293. The crystal water 717 appears to drive the hydroxylation step through a stabilizing hydrogen bond interaction to the proximal oxygen of the C4a-hydroperoxyflavin intermediate, which increases in strength as the hydroperoxyflavin cofactor converts to the anionic (deprotonated) hydroxyflavin.

4-Hydroxybenzoate-3-Monooxygenase↗