Title:
|
Developing benzothiazole functionalised ruthenium(II) polypyridyl complexes as tuneable DNA binders
|
The aim of this research is to develop a range of new ruthenium(II) polypyridyl complexes to be analysed
spectroscopically in the presence of calf thymus-DNA to determine their relative binding affinities to the
polynucleotide, thus determining the best criteria for a detection tool for DNA. Reactions of selected
functional groups on one ligand of ruthenium(II) precursor complexes lead to the synthesis of six
benzothiazole containing complexes; [Ru(bpY)2(B16)]2+,, [Ru(bpy)2(P5)]2+, [Ru(phen)2(B16)]2+, [Ru
(phenh(P5)]2+, [Ru(Me2bpY)2(B16)]2+ and [Ru(Me2bpy)2(P5)]2+ and four "control" complexes; [Ru
(bpy)2(B2)]2+, [Ru(bpy)2(P2)] 2+, [Ru(phen)2(B2)]2+ and [Ru(phen)2(P2)]2+ bearing methyl groups.
Investigation established a two-step interaction occurring between the complexes and polynucleotides,
which have varying effects on the luminescence of the complexes, as a result samples were equilibrated
for 24 hours before steady state measurements were recorded in the presence of DNA. Denaturation
studies of DNA in the presence of each complex did not show a significant change in the melting
temperature to free DNA. UV / Vis absorption spectrometry of the complexes showed variation in the
absorption attributed to the benzothiazole functionalised ligand and each complex became more
luminescent with increasing concentrations of DNA. The circular dichroism spectra of ct-DNA and
increasing concentrations of each complex indicate that the double helical shape of the DNA is not
affected as the complexes interact. From equilibrium dialysis studies with each complex it can be
tentatively assigned that the ∆-enantiomer is associating most favourably with DNA. There are no
significant alterations between the spectra of the methyl functionalised "control" complexes and those
with increasing concentrations of DNA.
Selecting the promising DNA detecting complex, [Ru(phen)2(B16)]2+ and repeating the spectroscopic
studies with AT and GC rich oligos, showed the complex has a clear preference for AT rich DNA,
highlighting that the preferred mode of binding at equilibrium is potentially within the minor groove of the DNA double helix.
|