THE INFLUENCE OF THE AXIAL LIGANDS OF A SERIES OF PLATINUM(IV) ANTICANCER COMPLEXES ON THEIR REDUCTION TO PLATINUM(II) AND REACTION WITH DNA

被引:161
作者
ELLIS, LT [1 ]
ER, HM [1 ]
HAMBLEY, TW [1 ]
机构
[1] UNIV SYDNEY,DEPT INORGAN CHEM,SYDNEY,NSW 2006,AUSTRALIA
关键词
D O I
10.1071/CH9950793
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
The electrochemical reduction and DNA binding have been studied for a series of platinum(IV) complexes with Cl-, OH-, and carboxylate anions as the axial ligands; [Pt(en)Cl-4], [Pt(en)Cl-2(OH)(2)], and [Pt(en)Cl-2 (OC(O)R)(2)], R = CH3, CH2CH3, CH2CH2CH3. Cathodic reduction potentials vary by more than 650 mV with the tetrachloro complex reduced most readily and the dihydroxo least readily. The binding of the complexes correlates with the reduction potentials with the more readily reduced complexes binding more readily to DNA. The influence of the reducing agent glutathione on platinum binding to DNA was found to depend on whether it was added before or after Pt/DNA incubation. The results are consistent with octahedral platinum(IV) binding monofunctionally to DNA, and molecular modelling studies have been used to confirm that this is sterically feasible. The crystal structure of [Pt(en)Cl-2(OC(O)CH3)(2)] has been determined by X-ray diffraction methods and refined to R = 0 . 028 (977 F). The crystals are monoclinic, space group C-2/c, a 15 . 569(6), b 8 . 104(1), c 13 . 188(1) Angstrom, beta 136 . 38(2)degrees.
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页码:793 / 806
页数:14
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