Limits...
De novo generation of singlet oxygen and ammine ligands by photoactivation of a platinum anticancer complex.

Zhao Y, Farrer NJ, Li H, Butler JS, McQuitty RJ, Habtemariam A, Wang F, Sadler PJ - Angew. Chem. Int. Ed. Engl. (2013)

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.

View Article: PubMed Central - PubMed

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
Possible mechanisms for the photoreaction of 1 with 5′-GMP upon irradiation with UVA. Species in square brackets are unstable intermediates. Charges are omitted for clarity. Species percentages are average HPLC integrations for four experiments with UVA irradiation (Figure 1 C).
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4230391&req=5

sch2: Possible mechanisms for the photoreaction of 1 with 5′-GMP upon irradiation with UVA. Species in square brackets are unstable intermediates. Charges are omitted for clarity. Species percentages are average HPLC integrations for four experiments with UVA irradiation (Figure 1 C).

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 Scheme 2. Upon irradiation with short-wavelength light, such as UVA, photodecomposition of 1 in the presence of 5′-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 5′-GMP to give product 1 b. The second pathway is more complicated, but perhaps more likely. The integration of the HPLC peaks in Figure 1 C suggested that about 92 % of the Pt species were produced through this pathway. Complex 1 loses one azide ligand (N3−) 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 5′-GMP to Pt produces 1 a, which can be further transformed to 1 e by loss of N2 gas from the N3 ligand, as in Scheme 1. Alternately, if N2 is expelled from the N3 ligand before 5′-GMP binds, 1 d is produced, which can also be transformed to 1 e by reacting with 1O2 (Scheme 1).


De novo generation of singlet oxygen and ammine ligands by photoactivation of a platinum anticancer complex.

Zhao Y, Farrer NJ, Li H, Butler JS, McQuitty RJ, Habtemariam A, Wang F, Sadler PJ - Angew. Chem. Int. Ed. Engl. (2013)

Possible mechanisms for the photoreaction of 1 with 5′-GMP upon irradiation with UVA. Species in square brackets are unstable intermediates. Charges are omitted for clarity. Species percentages are average HPLC integrations for four experiments with UVA irradiation (Figure 1 C).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4230391&req=5

sch2: Possible mechanisms for the photoreaction of 1 with 5′-GMP upon irradiation with UVA. Species in square brackets are unstable intermediates. Charges are omitted for clarity. Species percentages are average HPLC integrations for four experiments with UVA irradiation (Figure 1 C).
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 Scheme 2. Upon irradiation with short-wavelength light, such as UVA, photodecomposition of 1 in the presence of 5′-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 5′-GMP to give product 1 b. The second pathway is more complicated, but perhaps more likely. The integration of the HPLC peaks in Figure 1 C suggested that about 92 % of the Pt species were produced through this pathway. Complex 1 loses one azide ligand (N3−) 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 5′-GMP to Pt produces 1 a, which can be further transformed to 1 e by loss of N2 gas from the N3 ligand, as in Scheme 1. Alternately, if N2 is expelled from the N3 ligand before 5′-GMP binds, 1 d is produced, which can also be transformed to 1 e by reacting with 1O2 (Scheme 1).

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.

View Article: PubMed Central - PubMed

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