Unusual DNA binding modes for metal anticancer complexes

Abstract

DNA is believed to be the primary target for many metal-based drugs. For example, platinum-based anticancer drugs can form specific lesions on DNA that induce apoptosis. New platinum drugs can be designed that have novel modes of interaction with DNA, such as the trinuclear platinum complex BBR3464. Also it is possible to design inert platinum(IV) pro-drugs which are non-toxic in the dark, but lethal when irradiated with certain wavelengths of light. This gives rise to novel DNA lesions which are not as readily repaired as those induced by cisplatin, and provides the basis for a new type of photoactivated chemotherapy. Finally, newly emerging ruthenium(II) organometallic complexes not only bind to DNA coordinatively, but also by H-bonding and hydrophobic interactions triggered by the introduction of extended arene rings into their versatile structures. Intriguingly osmium (the heavier congener of ruthenium) reacts differently with DNA but can also give rise to highly cytotoxic organometallic complexes.

Parity-dependent hairpin configurations of repetitive DNA sequence promote slippage associated with DNA expansion

“…3D). Similar binding modes between metal ions and bases have been observed for Pt and cytosine crosslinked interaction in cisplatin-DNA complex structure (21). This implies that it could be possible to control the slippage process of dTGGAA repeats by metal ions in a manner similar to that proposed for controlling ribozyme activity (22).…”

Influence of pyridine versus piperidine ligands on the chemical, DNA binding and cytotoxic properties of light activated trans,trans,trans-[Pt(N3)2(OH)2(NH3)(L)]

“…Calculation of the lowest-lying triplet geometry can be highly informative [31][32][33] about the photochemistry of metal complexes. Such a state is generally populated in d 6 -metal complexes upon excitation and subsequent intersystem-crossing. [5] As already observed for other Pt IV -azides derivatives, the lowest-lying geometry of 5 is highly distorted (see supporting information).…”

“…[6,7] Thus, in addition studying the cytotoxic effects on cancer cell lines we have also characterized the interactions between DNA and the photoactivated Pt IV diazides in order to investigate similarities and differences in binding that might explain some of the biological effects of these compounds.…”

[(η6-p-cymene)Ru(H2O)3]2+ binding capability of aminohydroxamates — A solution and solid state study

“…Earlier studies mostly dealt with the design, synthesis, characterization and biological test of these [(η 6 -arene)Ru(XY)Z] type (arene = benzene(derivative), XY = chelating, Z = monodentate ligand) complexes. [6][7][8][9][10] Recent years research focusing on their solution behaviour or the interaction with various high [11][12][13][14][15][16][17] or low molecular mass [18][19][20][21][22][23][24][25][26][27][28][29] biomolecules is also in progress.…”