Towards binuclear metal complexes as probes for DNA : a study of bis-phenanthroline ruthenium (II) dipyrido[3,2-d:2\u273\u27-f]quinoxaline and its derivatives

THESIS 7332The synthesis of the novel ligand methyldipyrido [3,2-f:2\u27,3\u27-h]quinoxaline-2-carboxylate (mdpqc), with an electrophilic site for the attachment of a flexible tail, is presented. The synthesis, purification and characterisation of five dpq based mononuclear ruthenium complexes is described - [Ru(phen)2(dpq)]2+, [Ru(phen)2(Medpq)]2+ [Ru(phen)2(Me2 dpq)]2+ [Ru(phen)2(mdpqc)]2+ and [Ru(phen)2 (dpqa)]2+. [Ru(phen)2(mdpqc)]2+ was found to decompose to [Ru(phen)2(dpq)]2+ in an aqueous environment. Although the synthesis of the targeted bridging ligand was not accomplished, the central aim of synthesising a ligand with the potential for the selective synthesis of both homonuclear and heteronuclear metal complexes was still achieved through the synthesis of 2- dipyrido[3,2-f:2\u27,3\u27-h]quinoxaline acid amino-pentylamide. The presence of the free amino group provides the potential for the future selective synthesis of both homonuclear and heteronuclear complexes. The ground state pKaS for the mono-protonation of the [Ru(phen)2 (Rdpq)]2+ family were determined. The electron donating methyl groups increase the electron density available for protonation and so the order of basicity was determined to be [Ru(phen)2(Me2 dpq)]2+ (pKa = -1.9) > [Ru(phen)2(Medpq)]2+ (pKa = -2.3) > [Ru(phen)2(dpq)]2+ (pKa = -2.7). The photophysical properties of the [Ru(phen)2(Rdpq)]2+ family in DMSO, MeCN, MeOH, EtOH, H2O and pH 7 tris buffer were established. The trend in ? deg (and (?deg) of the [Ru(phen)2(Rdpq)]2+ family in organic solvents correlates well with the solvent polarity parameter ?*, DMSO > MeCN > MeOH > EtOH. There is a decrease in ? deg on going from [Ru(phen)2(dpq)]2+ to [Ru(phen)2 (Medpq)]2+ to [Ru(phen)2 (Me2 dpq)]2+ due to the increase in Knr. he trend in ? deg in water is [Ru(phen)2(Me2 dpq)]2+ > [Ru(phen)2 (Medpq)]2+ > [Ru(phen)2(dpq)]2+. The increased steric hindrance of the successive methyl groups is proposed to inhibit the deactivation by hydrogen bonding interactions with solvent water molecules. The emitting 3MLCT excited state of the [Ru(phen)2(Rdpq)]2+ family in solution is deactivated by internal conversion to the thermally accessible metal centred (3MC) state. In degassed MeCN, Eact exhibits the following trend [Ru(phen)2(dpq)]2+ (28 kJmoK-1) > [Ru(phen)2(Medpq)]2+ (25 kJmol-1) > [Ru(phen)2(Me2 dpq)]2+ (21 kJmol-1). [Ru(phen)2(dpqa)]2+ exhibits luminescence in organic solutions but does not emit in an aqueous environment. This is first example of this effect being activated by a single substitution - [Ru(phen)2 (Medpq)]2+ luminescent in an aqueous environment while [Ru(phen)2(dpqa)]2+ is not. Binding of the rac [Ru(phen)2(Rdpq)]2+ family to salmon sperm DNA was investigated. At P/D values of 100, a general broadening of the MLCT band and some hypochromicity is observed in the absorption spectra of [Ru(phen)2(Rdpq)]2+. The excited state lifetimes and luminescence intensities are substantially increased when [Ru(phen)2(Rdpq)]2+ interacts with DNA. Analysis of the binding data suggests that the strength of binding decreases on increasing the number of methyl substituents - the values of Kapp are 4.1 x 10 6 M-1 (? 0.2 x 10 5 M -1) for [Ru(phen)2(dpq)] 2+, 2.6 x 10 6 M-1 ( ? 2 X 10 5 M-1) for [Ru(phen)2(Medpq)]2+ and 1.3 x 10 6 M-1 (? 2 x 10 5 M -1) for [Ru(phen)2(Me2dpq)]2+. Binding of the ? and ? enantiomers of [Ru(phen)2(dpq)]2+ (provided by Dr. Janice Aldrich- Wright) to salmon sperm DNA, [poly(dA-dT).poly(dA-dT)] and [poly(dG-dC).poly(dG-dC)] was studied. Both emission intensity and excited state lifetime are significantly increased when either enantiomer is bound to DNA or the polynucleotides. Analysis of the spectroscopic data demonstrated little enantioselectivity between the ? and ? enantiomers of [Ru(phen)2 (dpq)]2+ on binding DNA (Kapp ~ 10 6 M-1). Examination of the binding of rac-[Ru(phen)2(dpqa)]2+ to salmon sperm DNA illustrates the profound effect changing the methyl group to an amide has. This is the first example of the ?light switch? effect being activated by a single substitution - binding to DNA enhances the emission intensity of [Ru(phen)2(Medpq)]2+ while ?switches on? the luminescence of [Ru(phen)2(dpqa)]2+