Exocyclically metallated tetrapyridinoporphyrazine as a potential photosensitizer for photodynamic therapy

Abstract

Synthesis and biological evaluations of a potential dual chemotherapeutic photosensitizer for photodynamic therapy based on the first exocyclically platinated tetrapyridinoporphyrazine.

Studying the cellular distribution of highly phototoxic platinated metalloporphyrins using isotope labelling

“…Together these two effects improve the PI by almost a factor of five. These results can be attributed to the higher singlet oxygen quantum yield (determined as described in 11 ) of tPt-Zn4PyP compared to tPt-H24PyP (Table S3) and are in line with previous reports about other (metallo)porphyrin containing photosensitizers. 6a, 6b, 6d However, the zinc complexes cPt-Zn4PyP and dPt-Zn4PyP are less phototoxic than their corresponding metal-free porphyrins cPt-H24PyP and dPt-H24PyP.…”

Highly Phototoxic Transplatin‐Modified Distyryl‐BODIPY Photosensitizers for Photodynamic Therapy

“…The data for imidazole‐substituted BODIPYs 2 and 2‐tPt 3 and anisole‐substituted BODIPYs 3 and 3‐tPt shows that the conjugation of photosensitizers with transplatin increases the photocytotoxicity and therefore the PIs, as reported previously by our group [14,40–41] . Interestingly, the increase in phototoxicity after platination speaks against the expectations, as the decrease in singlet oxygen yields (see Table 2) after the platination would suggest a lower potency of the photosensitizers.…”

“…The compound displayed a phototoxicity in the micromolar range even though it did not show any singlet oxygen generation. This phenomenon has been observed for a transplatin‐phthalocyanine conjugate before [41] . In order to clarify this issue, BODIPY 4‐tPt was irradiated with light in the presence of the hydroxyl radical sensor aminophenyl fluorescein [57] .…”

“…Singlet oxygen quantum yields: The singlet oxygen quantum yields ( Φ Δ ) were determined analogously to a method reported by our group [41] but with the following divergences: the photosensitizers were dissolved in CD 3 OD (1 M DCl in CD 3 OD for 4(H + ) 3 ) and two different concentrations were prepared for each photosensitizer, while the maximum absorption intensities were kept under 1.0. Excitation was performed using a high‐power‐LED light source (690 nm, FC5‐LED‐WL, Prizmatix Ltd., Israel) of which the light intensity at the position of the cuvette was measured to be 12.3 mW/cm 2 .…”

“…Coordination of photosensitizers to the trans ‐(NH 3 ) 2 Pt(Cl) unit (synthesized by chloride abstraction from transplatin) has been shown by our group to be highly beneficial for photosensitizer performance in vitro . For tetrapyridyl‐porphyrin, [14] its Zn(II)‐containing analogue, [40] and a Zn(II)‐containing tetrapyridinoporphyrazine, [41] it has been shown that the phototoxic index increases significantly after coordination of one trans ‐bis(ammine)platinum‐monochloride to each of the pyridyl substituents, and this effect is larger for the trans ‐complex than for the one derived from cisplatin. The lower dark toxicity of the trans ‐conjugates compared to the cis ‐conjugates can be explained by the much lower toxicity of transplatin itself, [42] as the complex mostly dissociates in the cell, leaving behind relatively innocuous mono‐activated transplatin.…”