Photostability is considered a key asset for photosensitizers (PS) used in medical applications as well as for those used in energy conversion devices. In light-mediated medical treatments, which are based on PS-induced harm to diseased tissues, the photoinduced cycle of singlet oxygen generation has always been considered to correlate with PS efficiency. However, recent evidence points to the fundamental role of contact-dependent reactions, which usually cause PS photobleaching. Therefore, it seems reasonable to challenge the paradigm of photostability versus PS efficiency in medical applications. We have prepared a series of Mg(II) porphyrazines (MgPzs) having similar singlet oxygen quantum yields and side groups with different electron-withdrawing strengths that fine-tune their redox properties. A detailed investigation of the photobleaching mechanism of these porphyrazines revealed that it is independent of singlet oxygen, occurring mainly via photoinduced electron abstraction of surrounding electron rich molecules (solvents or lipids), as revealed by the formation of an air-stable radical anion intermediate. When incorporated into phospholipid membranes, photobleaching of MgPzs correlates with the degree of lipid unsaturation, indicating that it is caused by an electron abstraction from the lipid double bond. Interestingly, upon comparing the efficiency of membrane photodamage between two of these MgPzs (with the highest and the lowest photobleaching efficiencies), we found that the higher the rate of PS photobleaching the faster the leakage induced in the membranes. Our results therefore indicate that photobleaching is a necessary step toward inflicting irreversible biological damage. We propose that the design of more efficient PS for medical applications should contemplate contact-dependent reactions as well as strategies for PS regeneration.
Abstract:The presented setup for singlet oxygen luminescence detection in cell suspensions outperforms the current setups by more than one order-of-magnitude gain in sensitivity. This not only allows precise determination of the singlet oxygen lifetime in cells but also reveals a previously unnoticeable behaviour of the singlet oxygen luminescence during low dose illumination.Counts, 1000/div.
Systematic in vitro studies on singlet oxygen luminescence kinetics have been carried out reconciling recently published contradictory results reported for sub-cellular singlet oxygen kinetics obtained with two different approaches: single cell -and cell ensemble measurements. The singlet oxygen luminescence kinetics in two cell lines were investigated after incubation with three different photosensitizers. In each case a strong dependency of the singlet oxygen luminescence kinetics from the applied illumination already at very low doses was observed. Analysis of the obtained results allows judging the usability of the two approaches for detailed investigation of sub-cellular singlet oxygen kinetics. Intrinsically existing detection limits as well as local heating during the measurement will be discussed.
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