Effect of the nature of the chelated metal on the photodynamic activity of metalloporphyrins.

Abbas, Ghadeer

Alibrahim, Fatemah

Kankouni, Rawan

Al-Belushi, Sara

Al-Mutairi, Dalal A

Tovmasyan, Artak

Batinic-Haberle, Ines

Benov, Ludmil

2024-01-01T22:40:20Z

2024-01-01T22:40:20Z

2023-11

Coordination of metal ions by the tetrapyrrole ring of porphyrin-based photosensitizers (PSs) affects their photophysical properties and consequently, their photodynamic activity. Diamagnetic metals increase the singlet oxygen quantum yield while paramagnetic metals have the opposite effect. Since singlet oxygen is considered the main cell-damaging species in photodynamic therapy (PDT), the nature of the chelated cation would directly affect PDT efficacy. This expectation, however, is not always supported by experimental results and numerous exceptions have been reported. Understanding the effect of the chelated metal is hindered because different chelators were used. The aim of this work was to investigate the effect of the nature of chelated cation on the photophysical and photodynamic properties of metalloporphyrins, using the same tetrapyrrole core as a chelator of Ag(II), Cu(II), Fe(III), In(III), Mn(III), or Zn(II). Results demonstrated that with the exception of Ag(II), all paramagnetic metalloporphyrins were inefficient as generators of singlet oxygen and did not act as PSs. In contrast, the coordination of diamagnetic ions produced highly efficient PSs. The unexpected photodynamic activity of the Ag(II)-containing porphyrin was attributed to reduction of the chelated Ag(II) to Ag(I) or to demetallation of the complex caused by cellular reductants and/or by exposure to light. Our results indicate that in biological systems, where PSs localize to various organelles and are subjected to the action of enzymes, reactive metabolites, and reducing or oxidizing agents, their physicochemical and photosensitizing properties change. Consequently, the photophysical properties alone cannot predict the anticancer efficacy of a PS.

1071-5762

1029-2470

https://hdl.handle.net/10161/29600

eng

Informa UK Limited

Free radical research

10.1080/10715762.2023.2288997

https://creativecommons.org/licenses/by-nc/4.0

Photodynamic therapy

metalloporphyrin

photooxidation

photosensitizer

singlet oxygen

Effect of the nature of the chelated metal on the photodynamic activity of metalloporphyrins.

Journal article

1

18

Duke

School of Medicine

Clinical Science Departments

Radiation Oncology

Published