DNA Binding Modes of Novel Terpyridine Ruthenium(II) Complexes Containing a Chloroquine Analogue

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Arriola, Kyle B
Terpyridine Chloroquine Ruthenium DNA anticancer intercalation Binding; Inorganic Chemistry
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The discovery of cis-platin as a chemotherapeutic agent has pioneered the search for superior anticancer drugs within the domain of inorganic chemistry. Ruthenium complexes have had quite the spotlight in this search due to their chemical and biological properties; NAMI-A and KP1019, two ruthenium anticancer drugs, have made it to clinical trials. Ligands of the polypyridyl class are known to be good intercalators. Chloroquine, aside from its antimalarial qualities, has induced apoptosis in several tumor cell lines of glioma and when combined with ruthenium, has exhibited the induction of apoptosis upon multiple cell lines. The synthesis, spectroscopic characterization, and DNA binding interactions have been studied for novel ruthenium complexes of the general formula: [Ru(x-tpy)(Y)(L)], where x is the modification of the terpyridine ligand (x=hydrogen, phenyl, tolyl, methoxyphenyl), Y is either a -chloro or -aquo ligand, and L is the chloroquine analogue ligand. Absorption titration and competitive binding studies with ethidium bromide have produced binding constants within the magnitude of 10^5 and 10^4, respectively, suggesting that the complexes bind fairly strongly to CT-DNA. Thermal denaturation studies indicate that our complexes do intercalate with DNA, while other possible DNA binding modes inherent to our complexes (phosphodiester cleavage, minor groove binding, adduct formation) have not been determined with precision.