Conformation-reactivity relationship for pyridoxal Schiff's bases. Rates of racemization and alpha-hydrogen exchange of the pyridoxal Schiff's bases of amino acids.

The role of stereoelectronic effects in controlling the reaction specificity of biological reactions involving pyridoxal phosphate-amino acid Schiff's bases was tested with nonenzymatic models. The rates of racemization and Halpha exchange of a series of pyridoxal-amino acid Schiff's bases were determined. The order of these rates does not parallel the predictions based solely on electronic or steric effect, but parallels the proportions of the reactive conformers (e.g., conformers with the Calpha--Halpha bond orthogonal to the pi system) estimated by CPK models. The special reactivity of the phenylalanine Schiff's base was consistent with a special conformation in which some type of pi--pi interaction increases the proportion of exchangeable conformers, thus further substantiating the role of conformation in governing the reactivity of the Calpha--Halpha bond. Furthermore, semiempirical calculations of the conformation about the Calpha00N bond were performed using the CAMSEA conformational analysis program. The results of conformational calculations are consistent with the results of conformational analysis by nuclear magnetic resonance. The order of reactivity of the the Calpha--Halpha bond of the SB dianion, pH 12.0, predicted by calculation based on stereoelectronic effects, though not quantatively parallel to the observed rate constants, is qualitatively in agreement with the experimental results.