Spectroscopic Studies on Photoinduced Reactions of the Anticancer Prodrug, trans,trans,trans ‐[Pt(N ₃ ) ₂ (OH) ₂ (py) ₂ ]

The photodecomposition mechanism of trans,trans,trans-[Pt(N3)2(OH)2(py)2] (1, py = pyridine), an anticancer prodrug candidate, was probed using complementary Attenuated Total Reflection Fourier Transform Infrared (ATR-FTIR), transient electronic absorption and UV-Vis spectroscopy. Data fitting using Principal Component Analysis (PCA) and multi-curve resolution alternating least squares, suggests the formation of a trans-[Pt(N3)(py)2(OH/H2O)] intermediate and trans [Pt(py)2(OH/H2O)2] as the final product upon 420 nm irradiation of 1 in water. Rapid disappearance of the hydroxido ligand stretching vibration upon irradiation is correlated with a -10 cm-1 shift to the anti-symmetric azido vibration, suggesting a possible second intermediate. Experimental proof of subsequent dissociation of azido ligands from platinum is presented, where at least one hydroxyl radical is formed in the reduction of Pt(IV) to Pt(II). Additionally, the photoinduced reaction of 1 with 5'-guanosine monophosphate was studied, and the identity of key photoproducts was assigned with the help of ATR FTIR spectroscopy, mass spectrometry and DFT calculations. The identification of marker bands for photoproducts, e.g. trans-[Pt(N3)(py)2(5'-GMP)] and trans-[Pt(py)2(5'-GMP)2], will aid elucidation of the chemical and biological mechanism of anticancer action of 1. In general, these studies demonstrate the potential of vibrational spectroscopic techniques as promising tools for studying such metal complexes.