Investigating Benzimidazole-Based Fluorophores for Their Biological Activities

Howells, Chloe and Fletcher, Nick (2022) Investigating Benzimidazole-Based Fluorophores for Their Biological Activities. PhD thesis, Lancaster University.

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Abstract

This research thesis concerns the synthesis of novel mononuclear ruthenium(II) polypyridyl complexes with one ligand functionalised with benzimidazole groups, and the investigation into their ability to interact with DNA and various anions using different techniques, such as UV/Vis absorbance and emission, 1H-NMR and circular dichroism spectroscopies. Various complexes of the form [Ru(bpy/phen)2(L)]2+ {where bpy = 2,2´-bipyridine, phen = 1,10-phenanthroline, L = 4,4-bis(benzimidazol-2-yl)-2,2-bipyridine (bbib), 4,4’-bis(amidobenzimidazol-2-yl)-2,2’-bipyridine (bbaib), 4,4ʹ-bis(benzimidazole-2-yl-methyl)-2,2ʹ-bipyridine (bbimb), 4,4ʹ-bis(benzimidazole-2-yl-carbonyl)-2,2ʹbipyridine (bbimbo)} were synthesised in their racemic forms. Absorbance, fluorescence and 1H-NMR titrations studies were used to investigate the interaction between the complexes and dihydrogen phosphate, acetate, chloride and bromide anions. The results indicated that [Ru(bpy)(bbib)]2+, [Ru(phen)(bbib)]2+ [Ru(bpy)(bbaib)]2+, [Ru(phen)(bbaib)]2+, [Ru(bpy)(bbimb)]2+ and [Ru(bpy)(bbimbo)]2+ have high levels of interaction with dihydrogen phosphate and acetate in aqueous environments and no interaction with bromide and chloride. Stability constants calculated for [Ru(bpy)(bbib)]2+, [Ru(phen)(bbib)]2+ [Ru(bpy)(bbaib)]2+ and [Ru(phen)(bbaib)]2+ suggest a 2:1 guest:host stoichiometry for dihydrogen phosphate and a 1:1 guest:host stoichiometry with acetate. UV/Vis absorption, luminescence and circular dichroism (CD) titration studies with calf thymus DNA (ct-DNA) were used to analyse the binding between the racemic complexes and ct-DNA. The results were insufficient to confirm whether interaction occurs between [Ru(bpy)(bbib)]2+, [Ru(phen)(bbib)]2+ [Ru(bpy)(bbaib)]2+, [Ru(phen)(bbaib)]2+, [Ru(bpy)(bbimb)]2+ and [Ru(bpy)(bbimbo)]2+ and ct-DNA. CD Thermal denaturation studies indicated a decrease in stability of ct-DNA structure in the presence of [Ru(bpy)(bbib)]2+, [Ru(phen)(bbib)]2+ [Ru(bpy)(bbaib)]2+ and [Ru(phen)(bbaib)]2+. Equilibrium membrane dialysis studies were employed to determine whether enantioselective binding occurs between complex and ct-DNA. The results gave no indication that there are enantioselective interactions between [Ru(bpy)(bbib)]2+, [Ru(phen)(bbib)]2+ [Ru(bpy)(bbaib)]2+ and [Ru(phen)(bbaib)]2+ and ct-DNA. Viscosity studies with ct-DNA showed no change in relative viscosity of ctDNA with [Ru(bpy)(bbib)]2+, [Ru(phen)(bbib)]2+ [Ru(bpy)(bbaib)]2+ and [Ru(phen)(bbaib)]2+.