Design of ruthenium polypyridyl complexes for DNA sensing and attachment

The properties of ruthenium complexes, such as the tunability of their photochemical activity, and high kinetic stability, mean they are used across a wide range of applications, including catalysis and dye-sensitized solar cells. Ruthenium polypyridyl complexes can also be synthesised to produce luminescence upon binding to DNA, so they have been extensively investigated for use as therapeutics and diagnostics. As small changes in structure can affect DNA binding properties, it would be of use to have a wide variety of ruthenium complexes to screen against. It is also of interest to be able to attach these ruthenium complexes to larger macromolecules, such as nanosheets, as this could increase sensitivity to DNA. Thus this work proposed the synthesis of a ruthenium complex with DNA binding capability, which contains a ligand that can be used for further attachment, or functionalisation via a simple mechanism. Two complexes were synthesised that contain a ‘light switch’ ligand that can intercalate into DNA, dppz, and a ligand available for further attachment, epip or bip; the parent complexes, complex 2 ([Ru(bpy)(dppz)(bip)]2+) and complex 4 ([Ru(bpy)(dppz)(epip)]2+) (where bip = 2-(4-bromophenyl)imidazo[4,5-f]-1,10phenanthroline, epip = 2-(4-ethynylphenyl)-1H-imidazo[4,5-f][1,10]-phenanthroline, dppz = dipyrido[3,2-a:2’,3’-c]phenazine, bpy = 2,2’-bipyridine). These were then used in the Sonogashira cross coupling reaction and the copper catalysed alkyne/azide cycloaddition (CuAAC) click reaction to synthesise a library of nine complexes, complexes 2a-2d and 4a-4c, 4f-4g. Both attachment reactions worked well across the different functional groups tested, with only the azide sulfone functional group degrading during the CuAAC click reaction, meant to yield complex 4d. The synthesis of complex 4e was unsuccessful due to impure nature of the pyrene azide being used. A dinuclear complex was synthesised via Glaser coupling of complex 4. Overall thirteen novel complexes were synthesised, including an earlier parent complex design that was not used for further functionalisation, complex 1. DNA binding was investigated for all the complexes through luminescence DNA titrations, which gave the site size and the binding constants of the complexes and the DNA binding mode was investigated by viscosity testing. Most of the complexes binding constants to DNA lay in the range of 105 M−1, with the exceptions of complex 1a, complex 1b (geometric isomers of complex 1) and complex 4g which showed binding constants of 2.1 × 106 M−1, 1.4 × 107 M−1 and 1.0 × 106 M−1 respectively. However of these higher binding complexes, only complex 1a and complex 4g showed classical intercalation. No simple conclusions could be drawn on any correlation between the type of functional group added during CuAAC or Sonogashira reactions to the attachment ligand and binding strength, however the largest improvement in binding was seen with the addition of a simple aliphatic chain and chains containing amines.