Effective Monofunctional Azaphthalocyanine Photosensitizers for Photodynamic Therapy

Petr Zimcik; Miroslav Miletin; Veronika Novakova; Kamil Kopecky; Marcela Nejedla; Vendula Stara; Katerina Sedlackova

doi:10.1071/CH08392

RESEARCH ARTICLE

Effective Monofunctional Azaphthalocyanine Photosensitizers for Photodynamic Therapy

Petr Zimcik ^A ^B , Miroslav Miletin ^A , Veronika Novakova ^A , Kamil Kopecky ^A , Marcela Nejedla ^A , Vendula Stara ^A and Katerina Sedlackova ^A

+ Author Affiliations

- Author Affiliations

^A Department of Pharmaceutical Chemistry and Drug Control, Faculty of Pharmacy in Hradec Kralove, Charles University in Prague, Heyrovskeho 1203, Hradec Kralove, 50005, Czech Republic.

^B Corresponding author. Email: petr.zimcik@faf.cuni.cz

Australian Journal of Chemistry 62(5) 425-433 https://doi.org/10.1071/CH08392
Submitted: 16 September 2008 Accepted: 29 January 2009 Published: 15 May 2009

Abstract

In this work we present a rational design of the active part of third generation photosensitizers for photodynamic therapy based on phthalocyanine and an azaphthalocyanine core. The preferred zinc complexes of the AAAB type that contain bulky tert-butylsulfanyl substituents (A) and one carboxy group (B) have been synthesized by statistical condensation and fully characterized. The tetramerization was performed using magnesium(ii) butoxide followed by demetalation and insertion of Zn^II. Compound 1 synthesized from 4,5-bis(tert-butylsulfanyl)phthalonitrile (A) and 2,3-dicyanoquinoxaline-6-carboxylic acid (B) exerted very promising photophysical properties (Q-band absorption at 726 nm, ϵ = 140000 M^–1 cm^–1), which allowed strong absorption of light at long wavelengths where the penetration of the light through human tissues is deeper. The very high singlet oxygen quantum yield of 1 (Φ_Δ = 0.80) assures efficient photosensitization. As a result of bulky peripheral substituents, compound 1 shows good solubility in organic solvents with a low degree of aggregation, which makes it potentially viable for non-complicated modification. One carboxy group in the final structure of 1 allows simple binding to possible carriers. This compound is suitable for binding to targeting moieties to form the highly active part of a third-generation photosensitizer.

Acknowledgements

This work has been supported by Czech Science Foundation, grant No. 203/07/P445 and by Ministry of Education, Youth and Sports of the Czech Republic, research project No. MSM 0021620822.

References

Effective Monofunctional Azaphthalocyanine Photosensitizers for Photodynamic Therapy

Abstract

Acknowledgements

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