ChemInform Abstract: Phosphoryl Transfer to Anionic Oxygen Nucleophiles. Nature of the Transition State and Electrostatic Repulsion.

Abstract

Bimolecular phosphoryl transfer to anionic oxygen nucleophiles from phosphorylated pyridine monoanions is observed in aqueous solution at 25 OC and ionic strength 1.5. The dependence on ionic strength of several reactions suggests that screening of charge repulsion with an increase in ionic strength from 0 to 1.5 causes only - 5-fold increases in rate for these reactions between monoanions. Comparisons with reactions of neutral substrates suggest that the electrostatic repulsion which remains at ionic strength 1.5 causes a decrease in rate of - 10-fold or less. The small values of p,,, = 0.3 and the large negative values of PI, = -( 1 .O-0.8) for reactions of phosphorylated pyridines with anionic oxygen nucleophiles, and the small value of p,,, = 0.10 for the reverse reaction of substituted pyridines with acetyl phosphate dianion, suggest that there is little bond formation to the oxygen nucleophile and much bond cleavage to the pyridine leaving group in the dissociative, metaphosphate-like transition state of a concerted displacement reaction. The absence of an effect of Mg2+ binding on the value of p = 1.05-1.1 for the formation of phosphorylated pyridines shows that there is no significant charge/dipole interaction between Mg% and the substituent on the pyridine and that the effect of Mgz+ binding is less than the effect of protonation. The values of p,,, for phosphoryl transfer to nitrogen nucleophiles are not significantly different with oxygen and nitrogen leaving groups of the same pK,. Phosphoryl transfer to anionic oxygen nucleophiles is an im- portant biochemical reaction that usually involves a magnesium ion. Examples include the phosphorylation of AMPZ-, ADP3-, acetate ion, and 3-phosphoglycerate ionz Despite the biochemical importance of phosphoryl transfer to anionic nucleophiles, the transition state for the nonenzymatic reaction has not been characterized. One reason that these reactions have seldom been examined may be a widely held belief that electrostatic repulsion is large in phosphoryl transfer to anionic oxygen nucleophiles; in fact, the possibility has been raised that enzymes can catalyze phosphoryl transfer by overcoming electrostatic repulsion.z4 However, the arguments that have been presented to support a large effect of electrostatic repulsion on the rate of phosphoryl transfer are