Demonstration of Prominent Cu(II)-Promoted Leaving Group Stabilization of the Cleavage of a Homologous Set of Phosphate Mono-, Di-, and Triesters in Methanol

Abstract

A series of phosphate mono-, di-, and triesters with a common leaving group (LG) (2'-(2-phenoxy)-1,10-phenanthroline) was prepared, and the kinetics of decomposition of their Cu(II) complexes was studied in methanol at 25 degrees C under (s)(s)pH-controlled conditions. The Cu(II) complexes of 2-[2'-phenanthrolyl]phenyl phosphate (Cu(II):6), 2-[2'-phenanthrolyl]phenyl methyl phosphate (Cu(II):7), and 2-[2'-phenanthrolyl]phenyl dimethyl phosphate (Cu(II):8) are tightly bound, having dissociation constants Kd < or = 3 x 10(-7) M, with the Cu(II) being in contact with the departing phenoxide. The (s)(s)pH/rate profile for cleavage of Cu(II):6 has a low (s)(s)pH plateau (k(o) = 6.3 x 10(-3) s(-1)), followed by a bell-shaped maximum (kcat(max) = 14.7 +/- 0.4 s(-1)) dependent on two ionizations with (s)(s)pKa(2) and (s)(s)pKa(3) = 7.8 +/- 0.1 and 11.8 +/- 0.2. The (s)(s)pH/rate profile for cleavage of Cu(II):7 has a broad plateau from (s)(s)pH 3 to (s)(s)pH 10 followed by a descending wing at higher (s)(s)pH with a gradient of -2. The (s)(s)pH/rate profile for cleavage of Cu(II):8 is sigmoidal with two plateaus (k1 = (2.0 +/- 0.2) x 10(-5) s(-1), k2 = (1.2 +/- 0.2) x 10(-6) s(-1)), connected by an ionization with a (s)(s)pKa of 6.03. Activation parameters are given for the reactions in the plateau regions: all three species show similar DeltaH(double dagger) terms of 21.4-21.6 kcal/mol, with major differences in the DeltaS(double dagger) terms, which vary from 18 to 2.3 to -7.4 cal/(mol x K) passing from the mono- to di- to triester. Detailed analyses of the kinetics indicate that the reactions involve spontaneous solvent-mediated cleavage of the Cu(II)-coordinated phosphate dianion [Cu(II):6b]0 and phosphate diester monoanion [Cu(II):7b]+ and, for the triester, complexes containing Cu(II) and Cu(II):(-)OCH3 designated as [Cu(II):8a]2+ and [Cu(II):8b]+. Reactions where methoxide is the active nucleophile are not observed. Comparisons of the rates of the decomposition of these species at their (s)(s)pH maxima in the neutral (s)(s)pH region with the estimated rates of the background reactions indicate that leaving group assistance provided by the coordinated Cu(II) accelerates the cleavage of the phosphate mono-, di-, and triesters by 10(14) to 10(15), 10(14), and 10(5). Detailed Hyperquad 2000 analysis of titration data indicates that phenoxide 9- is bound 23 kcal/mol stronger than the phosphate triester 8. It is the realization of part of this energy in the emerging products resulting from P-O(LG) cleavage that provides the driving force for the catalyzed reactions.