Metal-based photoactivated chemotherapy (PACT) against cancer can provide temporal and spatial control to reduce off-target side effects and battle inherent and acquired resistances. PACT candidates can destroy cancer cells through their metal core and/or released ligand species. Studying their underlying photophysical and photochemical mechanisms of action remains challenging.
Peter J. Sadler, University of Warwick, UK, Bayden R. Wood, Monash University, Clayton, Australia, and colleagues have studied the potent diazido Pt(IV) PACT prodrug trans,trans,trans-[Pt(N3)2(OH)2(py)2] (py = pyridine). The team used infrared (IR) spectroscopy to follow the metal and ligand vibrations upon light activation, combined with transient electronic absorption and UV/Vis spectroscopy, mass spectrometry (MS), and theoretical calculations.
The results provide insights into the unusual reactivity of this prodrug: The team was able to identify trans-[Pt(N3)(py)2(OH/H2O)] as an intermediate and trans-[Pt(py)2(OH/H2O)2] as the final product upon light activation of the prodrug. These findings could help to understand the chemical and biological mechanism of the complexes anticancer activity. They also demonstrate the potential of vibrational spectroscopic techniques to study such metal complexes.
- Spectroscopic Studies on Photoinduced Reactions of the Anticancer Prodrug, trans,trans,trans-[Pt(N3)2(OH)2(py)2],
Robbin R. Vernooij, Tanmaya Joshi, Michael D. Horbury, Bim Graham, Ekaterina I. Izgorodina, Vasilios G. Stavros, Peter J. Sadler, Leone Spiccia, Bayden R. Wood,
Chem. Eur. J. 2018.