Activation of acyl phosphate monoesters by lanthanide ions: Enhanced reactivity of benzoyl methyl phosphate

Acyl phosphate monoesters are intermediates in many biochemical acylation reactions, such as those involving aminoacyl adenylates. Benzoyl methyl phosphate, a typical aryl phosphate monoester, is slowly hydrolyzed in neutral solutions but reacts rapidly with amines. Since biochemical processes of acyl phosphate monoesters involve accelerated reactions with oxygen-centered nucleophiles, we sought catalysts for hydrolysis and methanolysis of benzoyl methyl phosphate to mimic the biochemical outcome. Lanthanide ions are particularly effective catalysts, accelerating reactions much more than comparable levels of magnesium ion. Detailed kinetic analysis of the hydrolysis reactions reveals formation of a 1 a complex, followed by rapid reaction wish a nucleophile. The hydroxide-dependent hydrolysis rate in the europium complex is about 10(5) times chat of free substrate with hydroxide. A mechanism that accounts for the data and observed behavior involves bidentate coordination of the metal ion by the acyl phosphate through phosphate and carbonyl oxygens, lowering the energy of the tetrahedral addition intermediate and the associated transition states. The dependence of the metal ion catalyzed process on the concentration of hydroxide ion is consistent with coordinated hydroxide acting as a nucleophile. The reaction of benzoyl methyl phosphate with methanol to form methyl benzoate and methyl phosphate is 30 000 times more rapid in the presence of 0.0001 M lanthanum triflate (in the absence of the metal ion k(obs) = 2.1 x 10(-7)s(-1), at 25 C). Thus, the combination of acyl phosphate esters and lanthanide salts appears to be a promising method for biomimetic acylation of hydroxyl groups.