Interactions of Metal−Metal-Bonded Antitumor Active Complexes with DNA Fragments and DNA

Abstract

This Account summarizes the DNA binding properties of anticancer active dinuclear Rh, Re, and Ru compounds. The combined results of NMR spectroscopy, X-ray crystallography, and various biochemical tools provide incontrovertible evidence that dinuclear complexes are favorably poised to bind to purine nucleobases, DNA fragments, and double-stranded DNA. Moreover, direct DNA photocleavage in vitro is effected by dirhodium compounds in the presence of electron acceptors in solution or directly attached to the dirhodium core. This research has provided valuable insight in the interactions of dinuclear compounds with DNA, knowledge that is an excellent backdrop for rational design of promising dinuclear drugs.

Glutathione binding to dirhodium tetraacetate: a spectroscopic, mass spectral and computational study of an anti-tumour compound

“…Dirhodium(II) tetraacetate (Rh2(OAc)4) is a bimetallic complex with four bridging acetate ligands bound in an octahedral geometry, with an empty axial site usually coordinated by solvent. This complex is capable of inhibiting DNA polymerase I and RNA polymerase, showing cytotoxic behaviour in vivo against L1210 tumours, Ehrlich ascites, and the sarcoma 180 and P388 tumour lines, as well as exhibiting DNA-binding in a manner similar to that of cisplatin 34,35,45,46 . However, because of the strong, sulfur-binding properties of dirhodium(II) carboxylates, intracellular thiols like glutathione may prevent these rhodium-based therapeutics from reaching their intended target unchanged, especially with the Rh axial bioactive site remaining available.…”

New ternary copper(II) complexes of l-alanine and heterocyclic bases: DNA binding and oxidative DNA cleavage activity

“…Substantial progress has been made during the past few decades to develop metal-based small molecules as DNA foot-printing as well as the therapeutic agents that are capable of binding and cleaving DNA under the physiological condition [1][2][3][4][5][6][7][8][9][10][11][12]. Metal complexes, in this context, with tunable coordination environments and versatile physicochemical properties offer scope for designing and developping highly sensitive diagnostic agents for medicinal applications as exemplified by the chemotherapeutic agents such as cis-platin and bleomycins [13][14][15].…”

μ-Oxamido binuclear copper (II) complexes: Synthesis, crystal structure, DNA interaction and antibacterial studies

“…Substantial progress has been made over the past couple of decades in the fundamental characterization of a variety of drug-DNA interactions [1][2][3][4][5][6][7][8][9][10]. The interaction of transition metal complexes with dioxygen in the presence of a reducing or oxidizing agent generates reactive oxygen species (ROS) that ultimately cleave DNA [7].…”