Ruthenation of Duplex and Single‐Stranded d(CGGCCG) by Organometallic Anticancer Complexes

Abstract

We have studied the interaction of the organometallic anticancer ruthenium(II) complexes [(eta(6)-p-cymene)Ru(en)Cl][PF(6)] (1) and [(eta(6)-biphenyl)Ru(en)Cl][PF(6)] (2) (en=ethylenediamine) with the single-stranded (ss) DNA hexamer d(CGGCCG) (I) and the duplex d(CGGCCG)(2) (II) by HPLC, ESI-MS, and one- and two-dimensional (1)H and (15)N NMR spectroscopy. For ss-DNA, all three G's are readily ruthenated with [(eta(6)-arene)Ru(en)](2+), but for duplex DNA there is preferential ruthenation of G3 and G6, and no binding to G2 was detected. For monoruthenated duplexes, N7 ruthenation of G is accompanied by strong hydrogen bonding between G-O6 and en-NH for the p-cymene adducts. Intercalation of the non-coordinated phenyl ring between G3 and C4 or G6 and C5 was detected in the biphenyl adducts of mono- and diruthenated duplexes, together with weakening of the G-O6NH-en hydrogen bonding. The arene ligand plays a major role in distorting the duplex either through steric interactions (p-cymene) or through intercalation (biphenyl).

The in vitro antitumor activity of arene-ruthenium(II) curcuminoid complexes improves when decreasing curcumin polarity

“…Reactions between (η 6 -arene)Ru(ethylenediamine) species and DNA [16][17][18], serum proteins, peptides and amino acids [19][20], suggest that DNA is the favored target in living cells, specifically through metal binding at guanine N-7 [21]. DNA intercalation by these Ru II complexes is also feasible, both by arene pendant flat moieties [22], and by an aromatic substituent in the chelating ligand [23].…”

Using coordination chemistry to design new medicines

“…The circular dichroism data also suggest that intercalation and/or minor groove binding to calf thymus DNA are involved in the binding of the bip and anthracene derivatives, but not the cym complex [82]. These data have been also confirmed by NMR studies [83]. More recent studies [84] have revealed unique modes of binding of the anticancer complex [( 6 -bip)Ru(en)Cl] + to the 14-mer DNA duplex III:…”

Medicinal Applications of Metal Complexes Binding to Biological Macromolecules

“…b) The aza-pyridine compounds, in which different isomers show significantly different cytostatic activity. [92][93][94] c) The organometallic half-sandwich compounds of formula [Ru(sandwich)(diamine)Cl], in which the amine ligand is an important factor for the activity; [95][96][97] also here hydrogen bonding plays an importance role.…”