Platinum(II) complexes of dipyridophenazine as metallointercalators for DNA and potent cytotoxic agents against carcinoma cell lines

The synthesis and spectroscopic characterization of a new class of DNA-inte rcalating platinum(II) complexes, [Pt(dppz)(tN(Lambda)C)]CF3SO3 (dppz = dip yrido[3,2-a:2',3'-c]phenazine, tN(Lambda)CH = 4-tert-butyl-2-phenylpyridine ) and [Pt(dppz)(L)(2)](CF3SO3)(2) (L = 1-methylimidazole (Meim-1) or 4-amin opyridine (NH(2)py-4)) are described. All the complexes are photoluminescen t in degassed acetonitrile at, room temperature. [Pt(dppz)(tN(Lambda)C)]CF3 SO3 shows a vibronic structured emission (lambda(max) = 477 nm) which is as signed to the intraligand transition (IL) of the C-deprotonated 4-tert-buty l-2-phenylpyridine ligand. Both [Pt(dppz)(Meim-1)(2)]-(CF3SO3)(2) and [Pt(d ppz) (NH(2)py-4)(2)]-(CF3SO3)(2) display a lower energy emission band with lambda(max) at 558 nm, which is originated from a (MLCT)-M-3 state [5d(Pt) -->pi*(dppz)]. The binding reactions of platinum(Il) complexes with double- stranded DNA (dsDNA) were studied by spectroscopic methods and the intrinsi c binding constants (K) are 1.1 x 10(4)-1.3 x 10(4) dm(3) mol(-1). The resu lts of gel electrophoresis and UV melting experiments revealed that they in teract strongly with DNA. In aerated aqueous Tris buffer solution, [Pt(dppz )(tN(Lambda)C)]CF3SO3 is nonemissive. Upon intercalation of [Pt(dppz)-(tN(L ambda)C)]CF3SO3 into calf thymus DNA (ctDNA), a low energy emission with la mbda(max) = 650 nm is developed and this is ascribed to exciplex formation between the excited state of [Pt(dppz)(tN(Lambda)C)](+) with the DNA base p airs. The cytotoxicity of [Pt(dppz)(tN(Lambda)C)]CF3SO3 was compared to tha t of cisplatin using human carcinoma KB-3-1 and its multidrug-resistant sub clone KB-V1 cell lines, which is 10 and 40 times more potent than cisplatin in the killing of KB-3-1 and KB-V1 cells. respectively.