Degradation of bidentate-coordinated platinum(II)-based DNA intercalators by reduced L-glutathione.

We have examined the interaction of [(5,6-dimethyl-1,10-phenanthroline)(1S,2S-diaminocyclohexane)platinum(II)] (2+) (1, 56MESS), [(5-methyl-1,10-phenanthroline)(1S,2S-diaminocyclohexane)platinum(II)] (2+) (2, 5MESS), [(5,6-dimethyl-1,10-phenanthroline)(1R,2R-diaminocyclohexane)platinum(II)] (2+) (3, 56MERR), and [(5,6-dimethyl-1,10-phenanthroline)(ethylenediamine)platinum(II)] (2+) (4, 56MEEN) with reduced L-glutathione and L-methionine. Both thiols degrade all four complexes, mainly by displacing the ancillary ligand and forming a doubly bridged dinuclear complex. The degradation half-life of all the complexes with methionine is >7 days, indicating that these reactions are not biologically relevant.

Encapsulation of platinum(II)-based DNA intercalators within cucurbit[6,7,8]urils.

The partial encapsulation of platinum(II)-based DNA intercalators of the type [Pt(5-Cl-phen)(ancillary ligand)](2+), where 5-Cl-phen is 5-chloro-1,10-phenanthroline and the ancillary ligand is ethylenediamine, (1S,2S)-diaminocyclohexane (S,S-dach) or (1R,2R)-diaminocyclohexane, within cucurbit[n]uril (CB[n], where n is 6, 7 or 8) has been examined by (1)H and (195)Pt NMR and mass spectrometry. For CB[7], the molecule encapsulates over the ancillary ligand of all metal complexes, whether this is ethylenediamine or diaminocyclohexane. For CB[8], encapsulation occurs over the sides of the 5-Cl-phen ligand at low [Pt(5-Cl-phen)(S,S-dach)](2+) (5CLSS) to CB[8] ratios (i.

DNA intercalators in cancer therapy: organic and inorganic drugs and their spectroscopic tools of analysis.

Since the discovery of the DNA intercalation process by Lerman in 1961 thousands of organic, inorganic octahedral (particularly ruthenium(II) and rhodium(III)) and square-planar (particularly platinum(II)) compounds have been developed as potential anticancer agents and diagnostic agents. The design and synthesis of new drugs is focused on bis-intercalators which have two intercalating groups linked via a variety of ligands, and synergistic drugs, which combine the anticancer properties of intercalation with other functionalities, such as covalent binding or boron-cages (for radiation therapy). Advances in spectroscopic techniques mean that the process of DNA intercalation can be examined in far greater detail than ever before, yielding important information on structure-activity relationships.

The effect of ancillary ligand chirality and phenanthroline functional group substitution on the cytotoxicity of platinum(II)-based metallointercalators.

Fifteen platinum(II)-based metallointercalators have been synthesised that utilise substituted 1,10-phenanthroline (phen) ligands, including 5-chloro-1,10-phenanthroline (5-Cl-phen), 5-methyl-1,10-phenanthroline (5-CH3-phen), 5-amino-1,10-phenanthroline (5-NH2-phen), 5-nitro-1,10-phenanthroline (5-NO2-phen) and dipyrido[3,2-d:2',3'-f]quinoxaline (dpq), and achiral ethylenediamine (en) and the chiral ancillary ligands 1S,2S-diaminocyclohexane (S,S-dach) and 1R,2R-diaminocyclohexane (R,R-dach). Their cytotoxicity in the L1210 murine leukaemia cell line was determined using growth inhibition assays. The most cytotoxic metal complexes are those that contain S,S-dach ancillary ligands and 5-CH3-phen intercalating ligands.