Rate Acceleration by Stereopopulation Control: Models for Enzyme Action
01 Nov 1970-Proceedings of the National Academy of Sciences of the United States of America (National Academy of Sciences)-Vol. 67, Iss: 3, pp 1143-1147
TL;DR: The magnitude of the effect suggests that the contribution of substrate "freezing" to total rate enhancement by an enzyme can be considerably greater than previously supposed and may in fact be sufficient to complete the justification for enzyme catalysis.
Abstract: As a result of alkyl substitution in both aromatic ring and side chain, the rate constant for acid-catalyzed lactonization of hydrocoumaric acid is increased by factors as high as 1011 and, in comparison with the bimolecular esterification of phenol and acetic acid, by almost 1016. In the most favorable case studied, the half-life of the phenolic acid (imidazole buffer, pH 7, 30°C) is 6 sec, with 90% of the total rate being due to catalysis by the buffer species. The effect is attributed to a unique interlocking of methyl groups, which produces a severe conformational restriction of the side chain and increases greatly the population of the most productive conformer. This phenomenon is presented as a model for the conformational restraint imposed by an enzyme on its substrate. The magnitude of the effect suggests that the contribution of substrate „freezing” to total rate enhancement by an enzyme can be considerably greater than previously supposed and may in fact be sufficient to complete the justification for enzyme catalysis.
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TL;DR: It is pointed out that translational and (overall) rotational motions provide the important entropic driving force for enzymic and intramolecular rate accelerations and the chelate effect; internal rotations and unusually severe orientational requirements are generally of secondary importance.
Abstract: It is pointed out that translational and (overall) rotational motions provide the important entropic driving force for enzymic and intramolecular rate accelerations and the chelate effect; internal rotations and unusually severe orientational requirements are generally of secondary importance. The loss of translational and (overall) rotational entropy for 2 → 1 reactions in solution is ordinarily on the order of 45 entropy units (e.u.) (standard state 1 M, 25°C); the translational entropy is much larger than 8 e.u. (corresponding to 55 M). Low-frequency motions in products and transition states, about 17 e.u. for cyclopentadiene dimerization, partially compensate for this loss, but “effective concentrations” on the order of 108 M may be accounted for without the introduction of new chemical concepts or terms.
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TL;DR: The promise of advancing and integrating cutting edge conceptual, experimental, and computational tools brings mechanistic enzymology to a new era, one poised for novel fundamental insights into biological catalysis.
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TL;DR: This review comprehensively covers organic and transition metal-containing photoactivatable compounds (complexes) that absorb in the visible- and NIR-range to release various leaving groups and gasotransmitters (carbon monoxide, nitric oxide, and hydrogen sulfide).
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