Quantum Dot Photoactivation of Pt(IV) Anticancer Agents: Evidence of an Electron Transfer Mechanism Driven by Electronic Coupling

Herein we elucidate the mechanism of photoreduction of the Pt­(IV) complex <i>cis,cis,trans-</i>[Pt­(NH₃)₂(Cl)₂(O₂CCH₂CH₂CO₂H)₂] (<b>1</b>) into Pt­(II) species (among which is cisplatin) by quantum dots (QDs), a process which holds potential for photodynamic therapy. Density functional theory (DFT) and time-dependent density functional theory (TDDFT) methodologies, integrated by selected experiments, were employed to study the interaction and the light-induced electron transfer (ET) process occurring between two QD models and <b>1</b>. Direct adsorption of the complex on the nanomaterial surface results in large electronic coupling between the LUMO (lowest unoccupied molecular orbital) of the excited QD* and the LUMO+1 of <b>1</b>, providing the driving force to the light-induced release of the succinate ligands from the Pt derivative. As confirmed by photolysis experiments performed a posteriori, DFT highlights that QD photoactivation of <b>1</b> can favor the formation of preferred Pt­(II) photoproducts, paving the way for the design of novel hybrid Pt­(IV)–semiconductor systems where photochemical processes can be finely tuned