Mechanism and Transition State Structure of Aryl Methylphosphonate Esters Doubly Coordinated to a Dinuclear Cobalt(III) Center

Abstract

Reactivities of five phosphonate esters each coordinated to a dinuclear Co(III) complex were investigated ([Co 2 (tacn) 2 (OH) 2 {O 2 P(Me)OAr}] 3+ ; tacn = 1,4,7-triazacyclononane; substituent = m-F, p-NO 2 (1a); p-NO 2 (1b); m-NO 2 (1c); p-Cl (1d); unsubstituted (1e)). Hydrolysis of the phosphonate esters in 1a to 1e is specific base catalysed and takes place by intramolecular oxide attack on the bridging phosphonate. These data define a Brønsted β lg of −1.12, considerably more negative than that of the hydrolysis of the uncomplexed phosphonates (−0.69). For 1b, the kinetic isotope effects in the leaving group are 18 k lg = 1.0228 and 15 k = 1.0014, at the non-bridging phosphoryl oxygens 18 k non-bridge = 0.9954, and at the nucleophilic oxygen 18 k nuc = 1.0105. The KIEs and the β lg data point to a transition state for the alkaline hydrolysis of 1b that is similar to that of a phosphate monoester complex with the same leaving group, rather than the isoelectronic diester complex. The data from these model systems parallel the observation that in protein phosphatase-1, which has an active site that resembles the structures of these complexes, the catalysed hydrolysis of aryl methylphosphonates and aryl phosphates are much more similar to one another than the uncomplexed hydrolysis reactions of the two substrates.

On the question of stepwise vs. concerted cleavage of RNA models promoted by a synthetic dinuclear Zn(ii) complex in methanol: implementation of a noncleavable phosphonate probe

“…The hydrolysis of O-aryl methylphosphonates is subject to base catalysis with a reported b LG of -0.69, 20 and their hydrolysis, when doubly coordinated to an exchange inert dinuclear Co(III) complex, is proposed to be concerted on the basis of kinetic isotope effect data ( 18 k nuc and 18 k lg ). 20 In that instance a b LG of -1.12 was reported which is larger than that determined here for the 4promoted methanolysis of 8a-f and 6a (b LG = -0.80). It is difficult to determine if the respective Brønsted slopes determined here and in ref.…”

“…It is difficult to determine if the respective Brønsted slopes determined here and in ref. 20 indicate a different degree of P-OAr bond cleavage in consideration of the fact that neither is normalized by a known b EQ value in water or methanol nor are the effects of substitution of a P-CH 3 for P-Ph group known.…”

Why nature really chose phosphate

“…Thus, there exist enzymes catalyzing phopshoryl transfer that can function at both high and low pH, enzymes that utilize direct attack by water or alternately employ an enzyme-derived nucleophile, as well as enzymes that employ metal ions in catalysis, and others that do not. Phosphoryl transfer has also become the focus of much effort in the design of artificial catalysts, many of which draw their inspiration from known enzyme structures (Aguilar-Pérez et al 2006; Feng et al 2009; Williams, 2004a) as well as in artificial enzyme design (e.g. Alcolombri et al 2011).…”

Kinetic Isotope Effects for RNA Cleavage by 2′-O- Transphosphorylation: Nucleophilic Activation by Specific Base

“…A great advantage in interpreting KIEs for reactions involving RNA is the extensive experimental and conceptual framework derived from analyses of the KIEs of phosphodiester reactions9; 10; 11; 14; 16; 46; 47; 48; 49. Extensive studies of nucleophile, leaving group and non-bridging oxygen KIEs by Cleland and by Hengge demonstrate that these effects fall in the range of 0.93 – 1.07 ( k 16 / k 18 ) and provide important information on extents of bond formation and cleavage6; 11.…”