Anticancer Activity, DNA Binding, and Photodynamic Properties of a N∧C∧N-Coordinated Pt(II) Complex

In the effort to discover new targets and improve the therapeutic efficacy of metal-containing anticancer compounds, transition metal complexes that can elicit cytotoxicity when irradiated with light of a proper wavelength and, then, candidates as potential photosensitizers for photodynamic therapy are actively being investigated. In this work, the cytotoxicity in the dark and the photophysical properties of the complex Pt(N boolean AND C boolean AND N)Cl, where the N boolean AND C boolean AND N ligand is 2,6-dipyrido-4-methyl-benzene chloride, are investigated in detail by means of a series of theoretical levels, that is density functional theory and its time-dependent extension together with molecular dynamics (MD) simulations. In the dark, cytotoxicity has been explored by simulating the steps of the mechanism of action of classical Pt(II) complexes. The suitability of the investigated complex to act as a photosensitizer has been verified by calculating spectroscopic properties for both the unperturbed complex and its aquated and guanine-bound forms. Furthermore, using MD simulation outcomes as a starting point, the photophysical properties of DNA-intercalated and -bound complexes have been evaluated with the goal of establishing how intercalation and binding affect sensitization activity.

Automated summary

This study investigates the cytotoxicity and photophysical properties of a platinum complex containing a 2,6-dipyrido-4-methyl-benzene chloride ligand through density functional theory and molecular dynamics simulations. The complex is found suitable as a photosensitizer for photodynamic therapy, with evaluations on how DNA intercalation and binding affect sensitization activity.