Mechanistic Insights into Metallodrug-DNA Interactions Through Inelastic Neutron Scattering in TOSCA

Cancer is a growing health problem worldwide, and thus the development of effective chemotherapeutic approaches is crucial for improving human health. Much effort has been put into the design of metal-based drugs, particularly Pt(II) and Pd(II) polyamine chelates acting through unconventional interactions with DNA. This work aims to investigate how differences in the structure and coordination pattern of potential anticancer Pt/Pd-complexes determine their effect on cancer cells. Two types of compounds will be probed – with and without Cl hydrolysable ligands, the former able to bind covalently to the target, while the latter interacts electrostatically with negatively charged groups of biomolecules via phosphate-clamps (an unconventional drug mode of action). This INS experiment will monitor drug-prompted structural changes in the DNA.