Computational Analysis of the Behavior of BODIPY Decorated Monofunctional Platinum(II) Complexes in the Dark and under Light Irradiation

Abstract

Dual-action drugs are occupying an important place in the scientific landscape of cancer research owing to the possibility to combine different therapeutic strategies into a single molecule. In the present work, the behavior of two BODIPY-appended monofunctional Pt­(II) complexes, one mononuclear and one binuclear, recently synthesized and tested for their cytotoxicity have been explored both in the dark and under light irradiation. Quantum mechanical DFT calculations have been used to carry out the exploration of the key steps, aquation and guanine attack, of the mechanism of action of Pt­(II) complexes in the dark. Due to the presence of the BODIPY chromophore and the potential capability of the two investigated complexes to work as photosensitizers in PDT, time dependent DFT has been employed to calculate their photophysical properties and to inspect how the sensitizing properties of BODIPY are affected by the presence of the platinum “heavy atom”. Furthermore, also the eventual influence on of the photophysical properties due to the displacement of chlorido ligands by water and of water by guanine has been taken into consideration.

G-quadruplex DNA selective targeting for anticancer therapy: a computational study of a novel PtII monofunctional complex activated by adaptive binding

“…Formation of the aquated product, which from now on will be named Pt1 wat , is endergonic by 4.4 kcal mol −1 . The comparison of the range of higher values 43,44 previously calculated with those experimentally estimated for the cisplatin aquation barrier further confirms that the carbon atom at the trans position to the chlorido leaving ligand is efficacious in favouring the dissociation 45,46 and activation by aquation to occur very quickly.…”

Predicting 195Pt NMR Chemical Shifts in Water‐Soluble Inorganic/Organometallic Complexes with a Fast and Simple Protocol Combining Semiempirical Modeling and Machine Learning

“…Another remarkable usage area of Pt compounds is pharmaceutics, where water‐soluble Pt complexes with simple organic ligands gave rise to the new generation of anticancer drugs [18–24] . Investigation on biological activity and mechanism of action by use of DFT is still on high demand for rational design of novel platinum‐based antitumor drugs [25–53] …”