Dinuclear complex-induced DNA melting

Dinuclear copper complexes have been designed for molecular recognition in order to selectively bind to two neighboring phosphate moieties in the backbone of double strand DNA. Associated biophysical, biochemical and cytotoxic effects on DNA were investigated in previous works, where atomic force microscopy (AFM) in ambient conditions turned out to be a particular valuable asset, since the complexes influence the macromechanical properties and configurations of the strands. To investigate and scrutinize these effects in more depth from a structural point of view, cutting-edge preparation methods and scanning force microscopy under ultra-high vacuum (UHV) conditions were employed to yield submolecular resolution images. DNA strand mechanics and interactions could be resolved on the single base pair level, including the amplified formation of melting bubbles. Even the interaction of singular complex molecules could be observed. To better assess the results, the appearance of treated DNA is also compared to the behavior of untreated DNA in UHV on different substrates. Finally, we present data from a statistical simulation reasoning about the nanomechanics of strand dissociation. This sort of quantitative experimental insights paralleled by statistical simulations impressively shade light on the rationale for strand dissociations of this novel DNA interaction process, that is an important nanomechanistic key and novel approach for the development of new chemotherapeutic agents.

Automated summary

Dinuclear copper complexes have been designed to selectively bind to neighboring phosphate moieties in DNA. Previous works have investigated the effects of these complexes on DNA through biophysical, biochemical, and cytotoxic analyses, with atomic force microscopy (AFM) being particularly valuable in assessing the macroscopic properties of the DNA strands. To gain a deeper understanding of these effects, cutting-edge preparation methods and scanning force microscopy under ultra-high vacuum (UHV) conditions were used to obtain submolecular resolution images. The mechanics and interactions of the DNA strands were analyzed at the single base pair level, including the formation of melting bubbles and the interaction of individual complex molecules.