Exploring arylglyoxals as the arginine reactivity probes. A mechanistic investigation using the buffer and substituent effects

Abstract

The modification of arginine side chain by the α-dicarbonyl reagents was submitted to a mechanistic investigation. The reactivity of 4-substituted phenylglyoxals toward N α-acetylarginine was found to be dependent on the substituent as well as buffer effects. Borate formed a complex with the glyoxal-hydrates to cause an activation of the electron-rich glyoxals and an inactivation of the electron-deficient glyoxals. The ϱ value in the Hammett correlation in this buffer was found to be −1.0. Bicarbonate also complexed with the glyoxal-hydrates, to increase their reactivity irrespective of the substituent effects. The Hammett correlation in this buffer gave the ϱ value of +1.0. On the basis of these and related observations, the mechanism in arginine modification has been formulated as a sequential process involving the intermolecular attack of guanidine at the α-dicarbonyl, the pH-dependent deprotonation of the resulting monocarbinolamine, and the intramolecular bond formation within this intermediate as the rate-determining step in the overall reaction.