Kagan J, Wang T P, Kagan I A, Tuveson R W, Wang G R, Lam J
Department of Chemistry, University of Illinois, Chicago 60680.
Photochem Photobiol. 1992 Jan;55(1):63-73. doi: 10.1111/j.1751-1097.1992.tb04210.x.
The natural product 2-chloro-3,11-tridecadiene-5,7,9-triyn-1-ol (1) photosensitized the inactivation of Escherichia coli in the presence of near-ultraviolet light (320-400 nm; NUV) under both aerobic and anaerobic conditions. A series of E. coli strains differing in DNA repair capabilities and catalase proficiency exhibited indistinguishable inactivation kinetics following treatment with the chemical plus NUV. The presence of carotenoids did afford some protection to E. coli against inactivation under aerobic conditions, consistent with the involvement of singlet oxygen. The photosensitized hemolysis of human erythrocytes occurred more rapidly in the absence than in the presence of oxygen. Aerobically, the onset of hemolysis was partially inhibited by NaN3 and by 2,6-di-t-butyl-4-methylphenol (BHT) but not by superoxide dismutase (SOD). The aerobic lipid peroxidation observed in the membranes of erythrocyte ghosts was completely inhibited by BHT, and partially by NaN3, but not by SOD. These results suggest that either lipid peroxidation of the membrane is not the main cause of photohemolysis or that BHT has insufficient access to intact erythrocyte lipids to protect them. Aerobically, crosslinking of membrane proteins was also observed; it was not affected by SOD, but was partially inhibited by BHT and NaN3. The anaerobic photosensitized hemolysis of erythrocytes was more rapid; a radical mechanism was suggested since BHT inhibited the hemolysis to a greater extent than under aerobic conditions. Neither lipid peroxidation nor protein crosslinking was observed under conditions believed to be anaerobic. A light-dependent electron transfer to cytochrome c was obtained under argon but not under oxygen. Although induced mutations were not observed in the experiments with E. coli, 1 was capable of damaging both supercoiled pBR322 and Haemophilus influenzae transforming DNA in a manner that seemed to be equivalent under aerobic and anaerobic conditions. In conclusion, 1 can behave as typical photodynamic molecule under aerobic conditions but, in contrast to most photodynamic molecules, it is also phototoxic under anaerobic conditions. The extent to which the radical reactions detected under anaerobic reactions compete with the photodynamic processes when oxygen is present is not known.
天然产物2-氯-3,11-十三碳二烯-5,7,9-三炔-1-醇（1）在有氧和无氧条件下，于近紫外光（320 - 400 nm；NUV）存在时能使大肠杆菌失活。一系列DNA修复能力和过氧化氢酶活性不同的大肠杆菌菌株，在用该化合物加NUV处理后表现出难以区分的失活动力学。类胡萝卜素的存在确实在有氧条件下为大肠杆菌提供了一定程度的保护，使其免受失活影响，这与单线态氧的参与一致。人红细胞的光敏溶血在无氧条件下比有氧条件下发生得更快。在有氧条件下，NaN₃和2,6-二叔丁基-4-甲基苯酚（BHT）能部分抑制溶血的起始，但超氧化物歧化酶（SOD）则不能。红细胞膜上观察到的有氧脂质过氧化被BHT完全抑制，被NaN₃部分抑制，但不受SOD影响。这些结果表明，要么膜的脂质过氧化不是光溶血的主要原因，要么BHT无法充分接触完整的红细胞脂质以保护它们。在有氧条件下，还观察到膜蛋白的交联；它不受SOD影响，但被BHT和NaN₃部分抑制。红细胞的厌氧光敏溶血更快；由于BHT在厌氧条件下比有氧条件下对溶血的抑制作用更大，因此提示存在自由基机制。在被认为是厌氧的条件下，未观察到脂质过氧化和蛋白质交联。在氩气环境下而非氧气环境下获得了光依赖的向细胞色素c的电子转移。尽管在大肠杆菌实验中未观察到诱导突变，但1能够以在有氧和无氧条件下似乎等效的方式损伤超螺旋pBR322和流感嗜血杆菌转化DNA。总之，1在有氧条件下可表现为典型的光动力分子，但与大多数光动力分子不同的是，它在厌氧条件下也具有光毒性。当存在氧气时，在厌氧反应中检测到的自由基反应与光动力过程竞争的程度尚不清楚。
