Premium
β‐Ionic Conjugated Chlorin‐Type Photosensitizers Based on Porpholactone: Synthesis, Photophysical Properties, and Photodynamic Activity
Author(s) -
Ke XianSheng,
Tang Juan,
Chen JuanJuan,
Zhou ZhengYang,
Zhang JunLong
Publication year - 2015
Publication title -
chempluschem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.801
H-Index - 61
ISSN - 2192-6506
DOI - 10.1002/cplu.201402356
Subject(s) - chemistry , chlorin , photodynamic therapy , photosensitizer , photochemistry , stereochemistry , combinatorial chemistry , organic chemistry
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 ( ZnL 1 ), anionic ( ZnL 2 ), zwitterionic ( ZnL 3 ), and cationic ( ZnL 4–6 ) groups, a series of photosensitizers ( ZnL 1–6 ) 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 ZnL 1–6 in the order ZnL 4–6 (positive charge)> ZnL 1–3 (negative charge or neutral). Importantly, the photocytotoxicity of ZnL 1–6 against cancer cells showed IC 50 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 ZnL 4 as an example, mechanistic studies, such as cell imaging experiments and Western blot analysis for the PDT process, indicate that ZnL 4 exerts photodynamic activity through apoptosis, which is highly associated with lysosome disruption, mitochondria depolarization, and nuclei condensation.