Β‐Ionic Conjugated Chlorin‐Type Photosensitizers Based on Porpholactone: Synthesis, Photophysical Properties, and Photodynamic Activity. Issue 1 (22nd December 2014)

• Record Type: Journal Article
• Authors: Ke, Xian‐Sheng; Tang, Juan; Chen, Juan‐Juan; Zhou, Zheng‐Yang; Zhang, Jun‐Long
• Is Part Of: ChemPlusChem. Volume 80:Issue 1(2015:Jan.)
• Page Start: 237
• Page End: 252
• Publication Date: 2014-12-22
• Subjects: apoptosis -- photodynamic therapy -- photosensitizers -- porphyrinoids -- reactive oxygen species; Chemistry -- Periodicals; 540.5
• DOI: 10.1002/cplu.201402356
• Languages: English
• ISSNs: 2192-6506

Abstract

Abstract: Porpholactones and their derivatives have attracted increasing attention for their promising application as photosensitizers. Reduction of the β‐lactone moiety in porpholactone to β‐hemiacetal, named porpholactol, allows the synthesis of chlorin‐type photosensitizers with enhanced near‐infrared absorption as well as β functionalization of water‐soluble conjugates. By employing β‐hydrophilic conjugates terminated by different ionic groups, such as neutral (ZnL1 ), anionic (ZnL2 ), zwitterionic (ZnL3 ), and cationic (ZnL4–6 ) groups, a series of photosensitizers (ZnL1–6 ) were synthesized and characterized, and their photophysical properties were studied, including magnetic circular dichroism measurement. The terminal ionic groups on β conjugates influence significantly the cellular uptake of ZnL1–6 in the order ZnL4–6 (positive charge)>ZnL1–3 (negative charge or neutral). Importantly, the photocytotoxicity of ZnL1–6 against cancer cells showed IC50 values down to the sub‐micromolar range and exhibited the same trend as their cellular uptake, clearly revealing the relationship of β‐ionic conjugates, cellular uptake, and intracellular photodynamic therapy (PDT) activity. Furthermore, using ZnL4 as an example, mechanistic studies, such as cell imaging experiments and Western blot analysis for the PDT process, indicate that ZnL4 exerts photodynamic activity through apoptosis, which is highly associated with lysosome disruption, mitochondria depolarization, and nuclei condensation. Abstract : It's terminal : Six tetrapentafluorophenylporpholactol zinc(II) complexes with β‐hydrophilic chains terminated by glucosyl (neutral, ZnL1 ), sulfonic (anionic, ZnL2 ), zwitterionic (ZnL3 ), and quaternary ammonium groups (cationic, ZnL4–6 ) were synthesized and characterized (see figure). The relationship of β‐ionic conjugates, cellular uptake, and intracellular photodynamic therapy activity was demonstrated and the mechanism of photoinduced cell death was studied.