La3+-catalyzed methanolysis of hydroxypropyl-p-nitrophenyl phosphate as a model for the RNA transesterification reaction

The methanolysis of hydroxypropyl-rho-nitrophenyl phosphate (HPNPP, 1) promoted by La(OTf)(3) under buffered conditions was studied in methanol as a function of (s)(s)pH at 25 degreesC. P-31 NMR studies at -90 degreesC indicate that there are at least three La/1 complexes formed at (s)(s)pH approximate to 5.3 of 1:1, 2:2, and 1:2 stoichiometry. Kinetic studies of the observed pseudo-first-order rate constants for the methanolysis of 1 as a function of [La3+] at 4.5 < (s)(s)pH < 10.5 indicate there are two general (s)(s)pH regimes. In the low (s)(s)pH regime between 4.5 and 7.6, the plots of k(obs) versus [La3+] exhibit saturation behavior with very strong 1:1 binding, with a plateau rate constant that depends on [OCH3-]. The catalytically productive species is shown to be a 2:2 complex of La3+ and 1, where the phosphate is proposed to be doubly activated, thereby promoting the methoxide reaction by some 4.6 x 10(10)-fold. In the high (s)(s)pH regime from 7.9 to 10.5, 1:1, S 2:2, and 2:1 La3+/l complexes are formed with the La3+ coordinated in the form of [La3+(OCH3-)](1,2). Throughout this (s)(s)pH regime at high [La3+], a saturation complex, (La3+OCH3-)(2)/1 is formed that spontaneously decomposes with a rate constant of (5-10) x 10(-3) S-1, leading to an acceleration of 10(9)-fold at (s)(s)pH 8.0.