meso-Thiophenium Porphyrins and Their Zn(II) Complexes: A New Category of Cationic Photosensitizers

Abstract

A new category of cationic meso-thiophenium porphyrins are introduced as possible alternatives to the popular meso-pyridinium porphyrins. Combinations of cationic porphyrins bearing meso-2-methylthiophenium and meso-4-hydroxyphenyl moieties T 2 (OH) 2 M (A 2 B 2 type) and T(OH) 3 M (AB 3 type) along with their zinc(II) complexes T 2 (OH) 2 MZn and T(OH) 3 MZn, are reported. The increase in the number of thienyl groups attached to the meso-positions of the porphyrin derivatives (A 2 B 2 frame) has been shown to impart longer fluorescence lifetimes and stronger photocytotoxicity toward A549 lung cancer cells, as evident with T 2 (OH) 2 M and its corresponding diamagnetic metal complex T 2 (OH) 2 MZn. The photoactivated T 2 (OH) 2 MZn imparts an early stage reactive oxygen species (ROS) upregulation and antioxidant depletion in A549 cells and contributes to the strongest oxidative stress-induced cell death mechanism in the series. The DFT calculations of the singlet−triplet energy gap (ΔE) of all the four hydrophilic thiophenium porphyrin derivatives establish the potential applicability of these cationic photosensitizers as PDT agents.

Application of TD-DFT Theory to Studying Porphyrinoid-Based Photosensitizers for Photodynamic Therapy: A Review

“…The theoretical studies of various porphyrinoids done in Russo’s group indicate that the PBE0PBE and B3LYP functionals are the most suitable for reproducing the singlet–triplet energy gaps, and both have an average error of 0.1 eV [ 137 ]. B3LYP with both 6-31G and 6-31G(d,p) gives S 0 –T 1 energy gaps in agreement with experimental results for porphyrin, chlorin, porphyrazine, and zinc porphyrins bearing meso -4-methylthiophenium groups [ 107 , 138 ].…”

Combinations of meso-(4-carboxyphenyl) and meso-(4- hydroxyphenyl) porphyrins as anti-HIV-1 agents

“…25,35 Along similar lines, porphyrin derivatives bearing meso-4-(hydroxyphenyl) moieties have been particularly useful. 4,[36][37][38][39][40][41] S N 2 reaction at the -OH function with synthetic constructs bearing speci c functional units enables the attachment of biologically potent molecules to the porphyrin unit, de ning therapeutic outcomes. 36,[38][39][40]42,43 Derivatives of meso-(4-hydroxyphenyl)porphyrins standalone, [44][45][46] or in combination with different electron-donating or electron-withdrawing group 4,41 including fullerenes 47 or conjugated with nanoparticles [48][49][50] have shown enhanced photobiological outcomes in PDT.…”

Complexes of Zn(ii) with a mixed tryptanthrin derivative and curcumin chelating ligands as new promising anticancer agents

“…[12][13][14][15] Indeed, there has been an increasing interest in Zn(II) and its complexes because of their roles in biological functions, versatility in fluorescence imaging, use in photodynamic therapy, use as a photon fluorescent probe, and antitumor activity. In particular, Zn(II) bis(thiosemicarbazonato) probes, 16,17 Zn(II) phthalocyanine photodynamic drugs, [18][19][20][21][22][23][24][25][26][27][28][29][30][31] Zn(II)-2,2′-dipicolylamine derivatives, 32-39 benzo[d] imidazole Zn(II) complexes, 40,41 and Zn(II) terpyridine-phenanthroline complexes 42,43 have gained popularity. However, to date, reports on the clinical use of Zn(II) anticancer complexes with fluorescent probes, apoptosis-inducing activity, and photodynamic therapeutic effects are limited.…”