Phosphate diester hydrolysis in biological relevant compounds by dinuclear metal complexes

Abstract

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.