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

Abstract

Coordination of metal ions by the tetrapyrrolic macrocyclic 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.

Keywords:

• Photodynamic therapy
• photosensitizer
• metalloporphyrin
• singlet oxygen
• photooxidation

Acknowledgments

The authors are grateful to Ms. F. Sequeira for excellent technical assistance and to OMICSRU/RCF, projects SRUL02/13 and GM01/15, Kuwait University.

Disclosure statement

The authors report there are no competing interests to declare.

Data availability statement

Publicly available datasets were analyzed in this study. This data can be found here: https://osf.io/84whj/

Additional information

Funding

This research was supported by Kuwait University, Kuwait, under Grant MB01/18.