Separation of polar and resonance substituent effects in the reaction of benzaldehydes with hydrocyanic acid. A correlation between .rho.r/.rho.req ratios and central atom rehybridization

Transition-state structure in the yeast alcohol dehydrogenase reaction: the magnitude of solvent and .alpha.-secondary hydrogen isotope effects

“…In addition, detection of a closer correlation between the deduced charge distribution and bond hybridization at C-l of substrate in the transition state of the horse liver alcohol dehydrogenase reaction could provide the necessary information to distinguish a concerted hydride transfer mechanism from the uncoupled radical reaction illustrated in Scheme III. 3 In a recent study, Young & McMahon (1979) report secondary isotope effects and substituent effects for the addition of HCN to substituted benzaldehydes. The magnitude of p* (which reflects the resonance interaction of substituents with the reacting center) and secondary isotope effects support similar transition-state structures for reaction in both water and 60% acetonitrile-40% water.…”

Nonperfect Synchronization of Reaction Center Rehybridization in the Transition State of the Hydride Transfer Catalyzed by Dihydrofolate Reductase

“…A particularly interesting quantity is the magnitude of a 2° KIE relative to the corresponding equilibrium isotope effect (2° EIE), which is the ratio of the isotopically unsubstituted equilibrium constant to the isotopically substituted one. − For an atom transfer reaction, where the 2° isotopic atom is bonded to the donor (or the acceptor atom), the 2° KIEs are often considered to be mainly a consequence of the change in the hybridization state of donor or acceptor in proceeding from the reactant to the transition state. , Such hybridization changes have important effects on bending and stretching frequencies between the reactant and the transition state. ,− On the basis of this relationship between hybridization and KIEs, an empirical criterion has been widely used to infer the location of the transition state by comparing the 2° KIE for deuterium substitution to the 2° EIE. Thus a 2° KIE that is close to the 2° EIE is taken as an indication that the rehybridization of the reaction center bonded to the deuterium has already been accomplished at the transition state, yielding a late transition state that resembles the product. ,,− ,− The same criterion was also used to suggest that a small 2° KIE (close to unity) results from an early transition state (i.e., one resembling the reactant), and the fractional position of a 2° KIE between unity and the relevant 2° EIE ([2° KIE − 1]/[2° EIE − 1]) represents the fractional location of the transition state between reactant and product. ,,− However, this criterion seems to be oversimplified by neglecting factors other than the structural change from the reactant to the transition state that can significantly contribute to 2° KIEs. ,, Simply comparing the magnitude of the 2° KIE to that of the 2° EIE without considering such factors may lead to an incorrect characterization of the transition state structure.…”

“…Thus a 2°KIE that is close to the 2°EIE is taken as an indication that the rehybridization of the reaction center bonded to the deuterium has already been accomplished at the transition state, yielding a late transition state that resembles the product. 1,9,[13][14][15][16][22][23][24][25][26][27][28][29] The same criterion was also used to suggest that a small 2°KIE (close to unity) results from an early transition state (i.e., one resembling the reactant), and the fractional position of a 2°KIE between unity and the relevant 2°EIE ([2°KIE -1]/[2°EIE -1]) represents the fractional location of the transition state between reactant and product. 9,16,[22][23][24][25][26][27][28][29][30] However, this criterion seems to be oversimplified by neglecting factors other than the structural change from the reactant to the transition state that can significantly contribute to 2°KIEs.…”

Synthesis of the Adrenergic Bronchodilators (R)-Terbutaline and (R)-Salbutamol from (R)-Cyanohydrins1

“…Since addition of more enzyme does not increase the conversion, the equilibrium concentration of the reaction obviously is reached in these cases. From donor-substituted benzaldehydes it is known that the equilibrium concentration of the HCN addition is not completely on the product side …”