Water-soluble platinum(II) complexes of diamine chelating ligands bearing amino-acid type substituents: the effect of the linked amino acid and the diamine chelate ring size on antitumor activity, and interactions with 5'-GMP and DNA.

Six new Pt(II) complexes are described having the general formula PtCl(2)(LL), in which LL is a chelating diamine ligand bearing an amino acid as substituent. The amino acids chosen are l-alanine and its methyl ester, and l-phenylalanine. The compounds have been characterized using analytical and spectroscopic methods. The influence on the biological properties of the size of the chelate ring and the structure of the amino acid substituent has been studied. The effect of the presence of a carboxylic or carboxylate group on the amino acid C-terminus has also been determined. It is demonstrated by circular dichroism (CD) that the effect on the secondary structure of DNA induced by the six complexes differ from each other. In all cases, the interaction takes place at the N7 position of the purine bases, as shown by NMR monitoring. The general behavior of these platinum complexes, with one exception, is to uncoil the DNA from the B form to the C form. The interactions with 5'-GMP and DNA have been compared with their expected antitumour activity. The complexes with l-alanine and l-phenylalanine exhibit cytotoxic activity in HeLa and HL-60 cell lines, in a dose- and time-dependent manner. No cytotoxic activity of the methyl ester derivatives have been determined because of their low solubility in aqueous solution.

Platinum complexes of diaminocarboxylic acids and their ethyl ester derivatives: the effect of the chelate ring size on antitumor activity and interactions with GMP and DNA.

A number of new Pt(II) complexes is described having the general formula PtCl(2)(LL), where LL is a chelating diamine ligand. Ligands LL were chosen as D,L-2,3-diaminopropionic acid and its ethyl ester, and D,L-2,4-diaminobutyric acid and its ethyl ester. The compounds were characterized using analytical and spectroscopic methods. The influence of the size of the chelate ring and its functionalization on the biological properties was studied. It was demonstrated by circular dichroism (CD) that the effects on the secondary structure of DNA induced by the four complexes are different. The interaction takes place at the N7 position of the purine bases, as shown by NMR studies. The platinum complexes of 2,3-diaminopropionic acid and 2,4-diaminobutyric acid are able to form intrastrand adducts with DNA and to distort the double helix by changing the base stacking. The ethyl ester derivatives uncoil the DNA from the B form to the C form. The interactions with 5'-GMP and DNA were compared with their antitumor activity. The platinum complexes of diaminocarboxylic acids exhibit cytotoxic activity in the A431, HeLa, and HL-60 cell lines in a dose- and time-dependent manner.

A trinuclear Pt(II) compound with short Pt-Pt-Pt contacts. An analysis of the influence of pi-pi stacking interactions on the strength and length of the Pt-Pt bond.

In this work we report the first example of a trinuclear Pt(II) complex with Pt-Pt-Pt bonds that are not facilitated by direct intervention of bridging ligands but are partially held by the attractive pi-pi stacking interaction between the phenyl units of the 4,4'-dimethyl-2,2'-bipyridyl ligands. The effect of the pi-pi stacking interactions on the strength and length of the Pt-Pt bond has been discussed using reduced models of the interacting moieties in which the aromatic rings have been removed. The nature of the Pt-Pt bonds has been studied through energy decomposition and atoms-in-molecules analyses. The results indicate that the relatively strong (about 40 kcal mol(-1)) Pt-Pt metallic bond has similar covalent and ionic contributions.