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Erxleben, A,Claffey, J,Tacke, M
2010
April
Journal Of Inorganic Biochemistry
Binding and hydrolysis studies of antitumoural titanocene dichloride and Titanocene Y with phosphate diesters
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Titanocene dichloride Titanocene Y Phosphate diester binding Phosphate diester hydrolysis Antitumour activity RAPID PHOSPHODIESTER HYDROLYSIS POTENTIAL ANTICANCER DRUGS ESTER CLEAVAGE PROPERTIES RAY CRYSTAL-STRUCTURES DOUBLE-STRANDED DNA SUBSTITUTED TITANOCENES LANTHANIDE COMPLEXES COPPER(II) COMPLEXES ANTIPROLIFERATIVE ACTIVITY METALLOCENE DICHLORIDES
104
390
396
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.
DOI 10.1016/j.jinorgbio.2009.11.010
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