Dipyridophenazine complexes of ruthenium show an outstandingly sensitive luminescence response to the water activity in their surroundings, which together with a rigid, chiral architecture make them versatile for probing biomolecular assemblies. The project aims to achieve a comprehensive mechanistic and structural understanding of the selectivity in the interactions of such probes with nucleic acids, lipid membranes and amyloid fibrils with regard to thermodynamics, binding kinetics and excited state quenching. This knowledge will be used to pursue rational design of novel probes and drug leads with the ultimate goal of developing sensitive diagnostic agents and antibiotics. The studies will be a concerted effort combining three levels of increasing complexity: 1) Fundamental relations will be studied with rapidly equilibrating mononuclear complexes, for which high resolution X-ray data will provide a firm structural basis for the interpretation of the thermodynamics and photophysics. 2) The mechanism of the unprecedented AT selectivity of threading intercalating binuclear complexes, in particular those comprising the newly developed unsymmetrical dppzip bridging ligand, will be studied with respect to biologically relevant DNA sequences as well as to complex structure and stereochemistry. 3) Mechanisms behind intracellular localization and photoactivated cell uptake will be studied, and binding to new targets such as amyloid fibrils will be characterized.
Professor at Chemical and Biological Engineering, Physical Chemistry
Funding years 2013–2015