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Biomedical subjects

M J Dewar

Publications and source records attributed to M J Dewar.

8 recordsLinked to original sources
PubMed1993

An AM1 molecular orbital study of alpha-D-glucopyranose and beta-maltose: evaluation and implications.

Chemical reactivity and other characteristics of alpha-D-glucopyranose and beta-maltose were evaluated within a semiempirical molecular orbital (AM1) framework. Theoretically generated structures compared well to those determined by X-ray crystallographic techniques. Calculations suggested that the secondary hydroxy functions (OH-2 and OH-3) of the mono- and di-saccharides were more acidic than the primary alcohol (OH-6), which is consistent with experimental findings. In addition, the enhanced reactivity of the OH-3 locus, which is observed upon OH-2 alkylation of the object sugars, was rationalized in terms of increased OH-3 acidity. The chemical behavior of the monomers examined may be insightful in explaining the reactivity of glucopyranose polymers.

Carbohydrate Conformation↗
PubMed1988

Mechanism of the chain extension step in the biosynthesis of fatty acids.

The chain extension step in the enzymatic synthesis of fatty acids by fatty acid synthase, involving a formal Claisen condensation of thio esters, has been clarified by theoretical calculations for model systems, using the modified neglect of diatomic overlap and Austin Model 1 parametric self-consistent field molecular orbital procedures. The reaction involves a free carbanion, formed by decarboxylation of a malonate ion. Formation of the carbanion and condensation with the fatty acid thio ester are not concerted. The decarboxylation is strongly endothermic. It is brought about by electrostatic interaction (field effect) with an ammonium ion derived from an adjacent lysine residue, the ions being far enough apart to inhibit proton transfer between them. Proton transfer would lead to an enol that is predicted not to be able to undergo the Claisen condensation. The formation of the ammonium ion is considered in terms of the pKa of the relevant groups. The bearing of this work on a recent interpretation of the activity and selectivity of enzyme reactions is discussed, and some misunderstandings concerning this interpretation are clarified.

Fatty Acid Synthases↗
PubMed1986

New ideas about enzyme reactions.

Since a proper substrate of an enzyme fits its active site closely, adsorption in the active site can occur only if all water is excluded from between them. Any subsequent reaction therefore takes place in the absence of solvent, i.e. as it would in the gas phase. The specificity and high rates of enzyme reactions can be explained immediately in terms of this analogy. Past experimental studies of enzyme mechanisms, based on analogy with reactions in solution, need to be reevaluated. Interpretation of enzyme reactions requires information concerning gas phase chemistry, which is usually lacking. The role of theoretical calculations in this connection is pointed out.

Enzyme Activation↗
PubMed1985

Alternative view of enzyme reactions.

Since adsorption of the substrate in the active site of an enzyme can occur only if all solvent is squeezed out from between them, any reaction between them takes place in the absence of any intervening solvent--i.e., as it would in the gas phase. Recent work has shown that ionic reactions in the gas phase often differ greatly from analogous processes in solution. Therefore, current interpretations of enzyme reactions in terms of solution chemistry are misguided. The large rates and specificity of enzyme reactions may be due simply to elimination of the solvent. The cleavage of peptides by chymotrypsin and carboxypeptidase A can be interpreted satisfactorily in this way.

Adsorption↗
PubMed1978

Some recent developments in quantum organic chemistry.

The present status of attempted to calculate chemical behaviour in organic chemistry in a quantitative manner is reviewed. Results given by a new semiempirical SCF MO method (MNDO) are reported. Specific topics discussed include the calculation of molecular vibration frequencies, entropies, specific heats, entropies of activation, kinetic isotope effects, and the mechanisms of several organic reactions, in particular the Diels-Alder reaction and the Cope rearrangment.

Chemistry, Organic↗