Zinc(II) Sulfanyltribenzoporphyrazines with Bulky Peripheral Substituents—Synthesis, Photophysical Characterization, and Potential Photocytotoxicity

Abstract

The study’s aim was to synthesize new unsymmetrical sulfanyl zinc(II) porphyrazines and subject them to physicochemical and electrochemical characterization and also an initial acute toxicity assessment. The procedure was initiated from a commercially available dimercaptomaleonitrile disodium salt and o-phthalonitrile using Linstead’s macrocyclization reaction conditions, which led to magnesium(II) tribenzoporphyrazine with 4-(3,5-dibutoxycarbonylphenoxy)butylthio substituents. The obtained macrocycle was demetallated with trifluoroacetic acid and subsequently remetallated with zinc(II) acetate toward the zinc(II) porphyrazine derivative. The zinc(II) tribenzoporphyrazine with 4-(3,5-dibutoxycarbonylphenoxy)butylthio substituents was then subjected to the reduction reaction with LiAlH4, yielding zinc(II) tribenzoporphyrazine with 4-[3,5-di(hydroxymethyl)phenoxy]butylthio substituents. The new zinc(II) tribenzoporphyrazines were characterized by UV-Vis spectroscopy, various NMR techniques (1HNMR, 13CNMR, 1H-1H COSY, 1H-13C HSQC, and 1H-13C HMBC), and mass spectrometry. In the UV-Vis spectra, both macrocycles revealed characteristic Soret and Q-bands, whose positions were dependent on the solvent used for the measurements. Zinc(II) tribenzoporphyrazines were studied using electrochemical and photochemical methods, including the singlet oxygen generation assessment. Both zinc(II) porphyrazines revealed high singlet oxygen generation quantum yield values of up to 0.59 in DMSO, which indicates their potential photosensitizing potential for photodynamic therapy. In addition, new derivatives were subjected to a Microtox® bioluminescence assay.