Hydrolysis of a Phosphate Diester Doubly Coordinated to a Dinuclear Cobalt(III) Complex: A Novel Mechanism

Abstract

Metal ions play enormously important roles in both enzymic and nonenzymic"] hydrolysis of phosphate diesters including DNA and RNA. Some enzymes such as 3'4' exonuclease from the Klenow fragment of DNA polymerase I, ['] ['] are activated by two or more metal ions. Functional models of phosphoesterases with two metal atoms in the active site may provide mechanistic insights into the role of the metal ions in the enzymes. We have shown that dinuclear copper(I1) complexes, in which both Cu atoms reversibly coordinate the two phosphoryl oxygens of a bridging phosphate diester simultaneously, can be highly reactive for cleaving the ester."] Here we report on the hydrolysis of a phosphate diester that is doubly coordinated to a dinuclear cobalt(1n) complex. Since this complex does not undergo rapid substitution. it is possible to examine the effect of the dinuclear complex alone on the hydrolysis of the coordinated phosphate diester.The perchlorate salts of the dinuclear cobalt(n1) complex cations 1 and 2['01 with bridging dimethyl phosphate and bridging methyl p-nitrophenyl phosphate ligands, respectively, were synthesized by treating [([9]aneN,),Co,(OH),](NO,), ([9]aneN3 = 1,4,7-triazacyclononane) (25 mM) with the sodium salt of the phosphate diester (25 mM) in aqueous HCIO, (1 M). ["] 31P N M R spectroscopy is a useful method for characterizing the bridging phosphate diester in 1 and 2.[L01 Monodentate coordination of dimethyl phosphate to mononuclear Co"' complexes results in a downfield shift of the phosphorus signal by about 7ppm.["] The phosphorus signals of the bridging phosphates in 1 and 2 are shifted about 14 ppm downfield relative to the signals of the corresponding free phosphates. Over the years many interesting dinuclear metal complexes structurally related to 1 and 2 that contain bridging carboxylate" 'I rather than bridging phosphate groups have been reported. Many structures of substitutionally labile dinuclear metal complexes with bridging phosphate diesters have also been reported. [9, 13] Figure 1 shows the crystal structure of trication l. [14] This is the first structure of a complex in which a phosphate diester ligand bridges two substitutionally inert metal centers.The distance between the two cobalt(iI1) centers in 1 (2.9 A) is somewhat shorter than intermetallic distances in dinuclear phosphodiesterases (ca. 4 A)[2, but comparable to that recently reported for a purple acid phosphatase (ca. 3.1 A).[7d1 The distances between the phosphorus and the bridging oxygen atoms (PI -05, PI -06 3.230(7) A) are slightly shorter than the P -0 van der Waals distance (3.3 A).

Catalytic hydrolysis of DNA by metal ions and complexes

“…The reader is referred to a review by Chin and co-workers [63], who has quantitatively described the role of various dinuclear complexes in the hydrolysis of DNA and RNA. Interestingly, dinuclear Co(III) complexes have shown incredible rate enhancements over their mononuclear analogs [64]. Considerable cooperativity seems to exist between the two metal ions in double Lewis acid activation of phosphodiester bond cleavage.…”

An Altered Mechanism of Hydrolysis for a Metal-Complexed Phosphate Diester

“…1,2 We have measured kinetic isotope effects (KIEs) which show that this rate acceleration is accompanied by a change in mechanism as compared to uncomplexed phosphate diesters.…”

A química dos ésteres de fosfato

“…O complexo 9, que apresenta um diéster de fosfato coordenado a um centro dinuclear de Co 3+ , foi empregado no estudo da labilidade isotópica de 18 O para mostrar que a ponte óxido atua como um nucleófilo bastante eficiente na hidrólise de fosfato 63 . A ativação do ácido de Lewis, em combinação com a ativação da ponte hidróxido, provoca um aumento de, aproximadamente, 11 ordens de magnitude na hidrólise do diéster de fosfato no complexo 9 64 .…”