De novo generation of singlet oxygen and ammine ligands by photoactivation of a platinum anticancer complex.
Bottom Line: Worth the excitement: Highly reactive oxygen and nitrogen species are generated by photoactivation of the anticancer platinum(IV) complex trans,trans,trans-[Pt(N3 )2 (OH)2 (MA)(Py)] (MA=methylamine, Py=pyridine).Singlet oxygen is formed from the hydroxido ligands and not from dissolved oxygen, and ammine ligands are products from the conversion of azido ligands to nitrenes.Both processes can induce oxidation of guanine.
Affiliation: Department of Chemistry, University of Warwick, Coventry CV4 7AL (United Kingdom); Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190 (P.R. China).Show MeSH
Mentions: Since neither of the oxygen atoms in the released 1O2 originate from water, the most plausible source is the OH groups of 1. Furthermore, solvent substitution at PtIV is not likely to occur before its reduction to PtII. A possible photolysis mechanism is given in Schemeâ€…2. Upon irradiation with short-wavelength light, such as UVA, photodecomposition of 1 in the presence of 5â€²-GMP may occur through two pathways. In the first, two azidyl radicals (N3.) are lost and PtIV is reduced to PtII. The OH groups are protonated and thus are substituted by 5â€²-GMP to give product 1â€‰b. The second pathway is more complicated, but perhaps more likely. The integration of the HPLC peaks in Figureâ€…1â€‰C suggested that about 92â€‰% of the Pt species were produced through this pathway. Complex 1 loses one azide ligand (N3âˆ’) and the OH ligands donate one electron each to reduce the PtIV to PtII; they then rapidly recombine to generate oxygen gas, as singlet oxygen, through H2O2 formation.14 Then the binding of 5â€²-GMP to Pt produces 1â€‰a, which can be further transformed to 1â€‰e by loss of N2 gas from the N3 ligand, as in Schemeâ€…1. Alternately, if N2 is expelled from the N3 ligand before 5â€²-GMP binds, 1â€‰d is produced, which can also be transformed to 1â€‰e by reacting with 1O2 (Schemeâ€…1).
Affiliation: Department of Chemistry, University of Warwick, Coventry CV4 7AL (United Kingdom); Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190 (P.R. China).