Phosphate diester hydrolysis in biological relevant compounds by dinuclear metal complexes

The dinuclear Ni2+ and Zn2+ complexes of 1,1'-[(1H-pyrazole-3,5-diyl)bismethylene]-bis(octahydro-1H-1,4,7-triazonine) induce phosphate diester hydrolysis in biological relevant substrates such as thymidine 5'-monophosphate 4-nitrophenylester (TMPNP), guanosine (2'-3') cyclic phosphate ((2'-3')cGMP), guanylyl (2'-5') guanosine ((2'-5')GpG), adenylyl (3'-5') adenosine ((3'-5')ApA), and (2'-deoxy)adenylyl (3'-5') (2'-deoxy)adenosine ((3'-5')dApdA). Quantitative measurements of the hydrolysis of TMPNP indicate a Michaelis-Menten mechanism in which the substrate is bound by the dinuclear complex and is hydrolyzed by an intramolecular attack of a coordinated OH- group. Qualitative HPLC measurements of the hydrolysis of the dinucleotide show that in the case of (2'-5')GpG a cyclic phosphate is formed which then hydrolyses to 2'-GMP and 3'-GMP. The hydrolysis of (2'-3)cGMP also gave, induced by the dinuclear Zn2+ complex, 2'-GMP and 3'-GMP. (C) 2004 Elsevier B.V. All rights reserved.