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Research has been conducted on the dinuclear platinum(II) complexes. The reactions of these complexes with 9-ethylguanine have been monitored in aqueous solution via (super)1 NMR spectroscopy and the results are described.

The synthesis, characterization and three single-crystal X-ray structures, as well as the cytotoxic study of the three new azole-bridged dinuclear platinum(II) complexes are reported. A cytotoxicity assay of these dinuclear platinum(II) compounds on human tumor cell lines was performed and the implications of each complex is discussed in the context of a structure-activity relationship.

We describe a 1.2 Å X-ray structure of a double-stranded B-DNA dodecamer (the Dickerson Dodecamer, DDD, [d(CGCGAATTCGCG)]2) associated with a cytotoxic platinum(lI) complex, [{trans-Pt- (NH3)2(NH2(CH2)6(NH3+)}2-μ-{ trans-Pt(NH3)2(NH2(CH2)6NH2)2}] (TriplatinNC). TriplatinNC is a multifunctional DNA ligand, with three cationic Pt(ll) centers, and directional hydrogen bonding functionalities, linked by flexible hydrophobic segments, but without the potential for covalent interaction. TriplatinNC does not intercalate nor does it bind in either groove. Instead, it binds to phosphate oxygen atoms and thus associates with the backbone. The three square-planar tetra-am(m)ine Pt(ll) coordination units form bidentate N-O-N complexes with OP atoms, in a motif we call the Phosphate Clamp. The geometry is conserved among the 8 observed phosphate clamps in this structure. The interaction appears to prefer 02P over 01 P atoms (frequency of interaction is 02P > 01P, base and sugar oxygens > N). The high repetition and geometric regularity of the motif suggests that this type of Pt(ll) center can be developed as a modular nucleic acid binding device with general utility. TriplatinNC extends along the phosphate backbone, in a mode of binding we call ‘Backbone Tracking’ and spans the minor groove in a mode of binding we call ‘Groove Spanning’. Electrostatic forces appear to induce modest DNA bending into the major groove. This bending may be related to the direct coordination of a sodium cation by a DNA base, with unprecedented inner-shell (direct) coordination of penta-hydrated sodium at the 06 atom of a guanine. [ABSTRACT FROM AUTHOR]

Four new isomeric azine-bridged complexes ([(cis-Pt(NH(3))(2)Cl)(2)(mu-pzn)]Cl(2) (1a) (pzn = pyrazine) and its corresponding nitrate salt (1b), [(cis-Pt(NH(3))(2)Cl)(2)(mu-pmn)]Cl(2) (2) (pmn = pyrimidine), and [(cis-Pt(NH(3))(2)Cl)(2)(mu-pdn)](NO(3))(2) (3) (pdn = pyridazine) have been newly synthesized as potential anticancer compounds. These complexes have been characterized by (1)H and (195)Pt NMR spectroscopy, and also the X-ray crystal structure of 1b has been determined. The reactions of 1a, 2, and 3 with guanosine-5'-monophosphate (GMP) have been monitored and kinetically investigated in D(2)O solutions at 310 K using (1)H NMR spectroscopy. Both 1a and 2 react with 2 equiv of GMP to form 1:2 complexes. The reactions involve a stepwise direct substitution of chloride ligands by GMP, with similar reaction rates for both complexes. On the other hand, the reaction of 3 with GMP results in the cleavage of one of the Pt-N(pyridazine) bonds to form an N7,O6-platinated polymer. The reaction products have been separated and have been characterized by (1)H and (195)Pt NMR spectroscopy. A cytotoxicity assay of the azine-bridged complexes (1a, 1b, 2, and 3) has been performed on human tumor cell lines and two L1210 murine leukemia cell lines (one sensitive to and one resistant to cisplatin). In general, the complexes show lower cytotoxicity than cisplatin for the human tumor cell lines except for the IGROV cell line. Their cytotoxicity for the mouse cell lines is comparable to or higher than that of cisplatin. Furthermore, these complexes appeared to largely or partly overcome the cross-resistance to cisplatin. Implications of these findings are discussed in the context of a structure-activity relationship for this class of compounds.