Phosphate diester binding
Phosphate diester hydrolysis
RAPID PHOSPHODIESTER HYDROLYSIS
POTENTIAL ANTICANCER DRUGS
ESTER CLEAVAGE PROPERTIES
The interaction of the antitumoural metallocene dihalides, titanocene dichloride (Cp2TiCl2) and Titanocene Y (bis-[(p-methoxybenzyl)cyclopentadienyl]titanium(IV) chloride), with bis(4-nitrophenyl) phosphate (BNPP), which is a widely used model for the phosphate diester linkages in DNA, has been studied. Cp2TiCl2 has been shown to promote the cleavage of the phosphate diester in weakly acidic solution. At pH 4, 37 degrees C, a 10(6)-fold rate acceleration over the uncatalysed reaction was observed under pseudo-first-order conditions, when freshly prepared solutions of Cp2TiCl2 were applied. The activity of aged solutions dropped significantly due to the formation of insoluble precipitates of hydrolysed Ti species. The precipitates isolated from aged solutions were shown to act as moderately active, heterogeneous catalysts for BNPP cleavage. By contrast, no hydrolysis of the phosphate diester could be observed in the presence of Titanocene Y. Implications for the mode of action of the apoptosis-inducing metallocene dihalides are discussed. (C) 2009 Elsevier Inc. All rights reserved.