De Novo Generation of Singlet Oxygen and Ammine Ligands by Photoactivation of a Platinum Anticancer Complex

Induction of immunogenic cell death in cancer cells by a photoactivated platinum(iv) prodrug

“…Moreover, photo-reduction of 1 results in the release not only of Pt II species, but also of other photo-products including azidyl and hydroxyl radicals, nitrenes, and singlet oxygen. 8,9 These photoreduction products can modulate biochemical pathways in tumor cells which are not involved in the MoA of cisplatin and its direct derivatives, thus pointing to a novel MoA for 1. 9 One possibility of how the photoreduction products of 1 might act by an MoA different from that involving DNA damage (and typical for cisplatin and its direct derivatives) is that irradiated 1 could induce an immunogenic form of cell death (ICD).…”

“…It has also been shown 15,[18][19][20] that ICD-associated immunogenicity can be evoked through reactive oxygen species (ROS). Thus, it was reasonable to assume that the photoactivated 1, which generates ROS and RNS, 8,9 could induce, besides apoptosis, also ICD. Therefore, we investigated whether photoactivated 1 can induce ICD in vitro, which could synergistically enhance its anticancer efficiency, thus corroborating the immunomodulating capability of chemotherapy based on this photoactivatable Pt IV prodrug.…”

Investigating the influence of relativistic effects on absorption spectra for platinum complexes with light-activated activity against cancer cells

“…In several studies, TD-DFT has been used with great insight to explain the experimentally observed photochemistry of platinum complexes used in PACT. [10][11][12][13][14][15][16][17] In one case, several DFT functionals were also benchmarked against complete active space second-order perturbation theory (CASPT2) and it was concluded that range-separated functionals reproduce both experiment and CASPT2 results best. 18 Surprisingly, none of these investigations have focused on the importance of relativistic effects, in particular concerning explicit inclusion of spin-orbit coupling.…”

“…They are further the simplest among a number of related complexes which subsequently have shown similar photoactivity. [11][12][13][14][15][16][17][33][34][35][36][37][38] Their exact mechanism of photo-activation is not known in detail. However, the UV-vis spectra in combination with TD-DFT calculations 10,30 have shown that both trans-and cis-Pt complexes display ligand-to-metal chargetransfer (LMCT) excitations.…”

Solvent-dependent structural dynamics of an azido-platinum complex revealed by linear and nonlinear infrared spectroscopy

“…11,14 However, the structural evolution and ligand exchange dynamics of platinum(IV) prodrugs, which are important to their photoactivity, are not yet fully understood. 12,13,15 Moreover, the behaviors of these antitumor prodrugs in protic and aprotic solvents are much less understood. A better understanding of the structure and dynamics of these platinum-based prodrug complexes will contribute to illustrating their interactions with the key active biological molecules in cancer cells.…”