title: La(3+)-Catalyzed methanolysis of hydroxypropyl-p-nitrophenyl phosphate as a model for the RNA transesterification reaction.
abstract: The methanolysis of hydroxypropyl-p-nitrophenyl phosphate (HPNPP, 1) promoted by La(OTf)(3) under buffered conditions was studied in methanol as a function of pH at 25 degrees C. (31)P NMR studies at -90 degrees C indicate that there are at least three La/1 complexes formed at pH approximately 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 [La(3+)] at 4.5 < pH < 10.5 indicate there are two general pH regimes. In the low pH regime between 4.5 and 7.6, the plots of k(obs) versus [La(3+)] exhibit saturation behavior with very strong 1:1 binding, with a plateau rate constant that depends on [OCH(3)(-)]. The catalytically productive species is shown to be a 2:2 complex of La(3+) 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 pH regime from 7.9 to 10.5, 1:1, 2:2, and 2:1 La(3+)/1 complexes are formed with the La(3+) coordinated in the form of [La(3+)(OCH(3)(-))](1,2). Throughout this pH regime at high [La(3+)], a saturation complex, (La(3+)OCH(3)(-))(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 pH 8.0.
authors.affiliation: Department of Chemistry, Queen's University, Kingston, Ontario, Canada, K7L 3N6.
authors.forename: Josephine S W
authors.initials: JS
authors.lastname: Tsang
authors.forename: Alexei A
authors.initials: AA
authors.lastname: Neverov
authors.forename: R S
authors.initials: RS
authors.lastname: Brown
mesh_terms: D002384:Catalysis; D002412:Cations; D004951:Esterification; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D007811:Lanthanum / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D000432:Methanol / Q000737:chemistry; D010755:Organophosphates; D009943:Organophosphorus Compounds / Q000737:chemistry*; D010758:Phosphorus; D011522:Protons; D012313:RNA / Q000737:chemistry* / Q000378:metabolism
chemical_list: C436487:2-(hydroxypropyl)-4-nitrophenyl phosphate; D002412:Cations; D010755:Organophosphates; D009943:Organophosphorus Compounds; D011522:Protons; D010758:Phosphorus; D012313:RNA; D007811:Lanthanum; D000432:Methanol