Design of unsymmetrical azo initiators to increase radical generation efficiency in low-density lipoproteins
Design of unsymmetrical azo initiators to increase radical generation efficiency in low-density lipoproteins
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DOI：
10.1080/10715760000301231
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发表时间：
2000-01-01
影响因子：
3.3
通讯作者：
Porter, NA
中科院分区：
文献类型：
--
作者：
Culbertson, SM;Porter, NA
脂质过氧化研究通常使用偶氮引发剂来产生缓慢、稳定的自由基来源，但缺乏能够在脂质区域有效产生自由基的引发剂在这些研究中产生了持续的问题。例如，使用对称亲脂性或对称亲水性偶氮引发剂的实验越来越多地表明，它们在低密度脂蛋白（LDL）中的引发机制依赖于α-生育酚的存在来介导过氧化。我们在这里报告的合成和研究的新的不对称偶氮化合物SA-1，SA-2，C-16，C-12，和C-8，在一个方便的温度范围内分解，提高自由基生成效率和进入脂质隔室。不对称引发剂在37 ℃甲醇中的分解半衰期（τ（1/2））范围为SA-1为121小时，SA-2为77小时，C-16、C-15和C-8系列约为25小时。用这些不对称引发剂孵育的LDL的琼脂糖凝胶电泳支持这样的结论，即引发剂与脂蛋白相关，而不破坏颗粒的完整性。与对称亲水引发剂C-0相比，非对称引发剂C-8能够提供增加的LDL过氧化，如通过胆固醇亚油酸酯氧化产物的形成和α-生育酚的消耗所监测的。发现亲脂性和亲水性隔室中自由基产生的效率通过使用自由基清除剂组合α-生育酚和尿酸来表示，但不通过使用N，N '-二苯基-对苯二胺（DPPD）和尿酸来表示。与广泛使用的对称偶氮引发剂相比，这些不对称引发剂在低密度脂蛋白中脂质过氧化的研究中提供了自由基产生、亲脂性进入和恒定自由基产生的优势。
Lipid peroxidation studies often employ the use of azo initiators to produce a slow, steady source of free radicals, but the lack of initiators capable of efficiently generating radicals in lipid regions has created persistent problems in these investigations. For example, experiments with symmetrical lipophilic or symmetical hydrophilic azo initiators increasingly suggest that their initiation mechanisms in low-density lipoproteins (LDL) rely upon the presence of alpha -tocopherol to mediate peroxidation. We report here the synthesis and study of the new unsymmetrical azo compounds SA-1, SA-2, C-16, C-12, and C-8 that decompose over a range of convenient temperatures and improve radical generation efficiency and access to lipid compartments. The half-life for decomposition (tau (1/2)) Of the unsymmetrical initiators at 37 degreesC in methanol covered a range of 121 hours for SA-1, 77 hows for SA-2, and approximate to 25 hours for the series C-16, C-15 and C-8. Agarose gel electrophoresis of LDL incubated with these unsymmetrical initiators supports the conclusion that the initiators associate with lipoprotein without disrupting integrity of the particle. The unsymmetical initiator C-8 when compared to symmetical hydrophilic initiator C-0 is capable of providing increased peroxidation of LDL, as monitored by formation of cholesteryl linoleate oxidation products and consumption of alpha -tocopherol. Efficiency of radical generation in lipophilic and hydrophilic compartments was found to be represented with the use of the radical scavenger combination alpha -tocopherol and uric acid, but not with the use of N,N'-Diphenyl-p-phenylenediamine (DPPD) and uric acid. These unsymmetrical initiators, when compared to the widely used symmetrical azo initiators, provide an advantage of free radical production, lipophilic access, and constant radical generation in the investigation of lipid peroxidation in low-density lipoproteins.