The reaction of [Pt(hpip)Cl 2 ] (hpip ) homopiperazine ) 1,4-diazacycloheptane) with d(GpG) yields two apparently isomeric products, separable by HPLC. These have been characterized by a combination of 2D NMR and molecular mechanics modeling. NOESY correlations between the H8 protons show that both products are head-to-head isomers, and NOESY correlations between the d(GpG) dinucleotide and the diamine ligand show that the difference between the isomers lies in the orientation of the two and three carbon chains of the hpip ligand with respect to the heads (H8 protons) of the guanine bases. Molecular mechanics calculations yield total energies that are consistent with the observation of the two isomers in approximately equal amounts.

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A series of compounds designed to bind to GpA sequences of DNA has been prepared and characterised. Procedures have been developed for the syntheses of [ Pt{MeS(O)CH,CH,NH,}Cl~] 1 and (2S.SR)and (2S,SS)-[Pt{MeS(O)CH,CH,CH(CO,Me)NH,}CI,] 2a. 2b. The crystal structures of 1 and of the two diastereomers, 2a and 2b, have been determined. Crystals of 1 are orthorhombic, space group Pcab, a = 9.405(1), b = 10.847(1), c = 16.1 70(1) A, 2 = 8, R = 0.30 for 141 0 reflections. Crystals of 2a are orthorhombic, space group P2,2,2,, a = 9.738(1), b = 10.588(1), c = 11.090(1) A, Z = 4, R = 0.021 for 1382 reflections. Crystals of 2b are orthorhombic, space group P2,2,2,, a = 10.977(3), b = 13.738(9), c = 25.24(1) A, Z = 12, R = 0.078 for 1482 reflections. Energy minimisation calculations have been used to develop a force field for a series of dichloroplatinum( 11) sulfoxide complexes.

Using assays based on the inhibition of restriction enzyme cleavage of plasmid and synthetic DNA, the complex (2-amino-2-methyl-3-butanone oxime)dichloroplatinum(II), [PtCl2(ambo)], has been shown to have an increased tendency for binding to adenine-rich sequences when compared to cis[PtCl2(NH3)2] (cisplatin). [PtCl2(ambo)] was found to form substantially fewer interstrand adducts than does cisplatin. The in vitro cytotoxicity of [PtCl2(ambo)] against a human bladder cancer cell line was determined and found to be more than two orders of magnitude lower than that of cisplatin, yet it was also found to be equally effective at passing into cells and binding to isolated DNA.

Two complexes, namely, chloro[N-(2-aminoethyl)-N-(2-ammonioethyl)ethane-1,2-diamine]platinum(II) chloride {[PtCl(tren+H)]Cl2} and dichloro[4,7-diaza-1-azoniacyclononane]platinum(II) tetrachloroplatinate(II)–water (1/2) {[PtCl2(tacn+H)]2[PtCl4]·2H2O}, have been prepared and structurally characterized by single-crystal X-ray diffractometry as part of a study of the nature and strength of Pt···H(–N) interactions. Crystals of [PtCl(tren+H)]Cl2 are monoclinic, space group P21/c, a 8.293(2), b 14.396(6), c 11.305(3) Å, β 107.34(2)º, Z 4, and the structure has been refined to a residual of 0.042 based on 1631 reflections. Crystals of [PtCl2(tacn+H)]2[PtCl4]·2H2O are monoclinic, space group P21/a, a 12.834(4), b 8.206(4), c 13.116(8) Å, β 93.01(4)˚, Z 2, and the structure has been refined to a residual of 0.035 based on 1974 reflections. In [PtCl(tren+H)]2+, the protonated amine forms hydrogen bonds with chloride anions and no close contacts with the metal ion. In [PtCl2(tacn+H)]+, a short intramolecular contact is observed between the metal and the protonated amine and the results of molecular mechanics modelling are consistent with there being a Pt···H hydrogen bond. Molecular mechanics modelling of [PtCl(tren+H)]2+ and [PtCl2(dien+H)]+ shows that the protonated amines could readily form close contacts with the metal. It is concluded that there is evidence for the formation of Pt···H(–N) hydrogen bonds but these bonds are very weak, being similar or lower in energy than Cl···H(–NPt) hydrogen bonds.