Department of Chemistry, Renmin University of China, Beijing 100872.
J Phys Chem B. 2010 Nov 4;114(43):13904-10. doi: 10.1021/jp106734p.
We report a novel molecular dyad as an antioxidant, retinylisoflavonoid, with a retinal analogue C(22)-aldehyde and the isoflavonoid daidzein covalently linked. Its physicochemical properties, pK(a) (pK(a1) = 8.45, pK(a2) = 11.42), oxidation potential (1.03 V vs NHE), and Log(10) partition (Log P = 1.96), as well as the Trolox equivalent antioxidant capacity (TEAC = 0.4), have been characterized. Spectroscopic and quantum chemical investigations have revealed the following unique structural characters: (i) Either free in solution or included in liposomal membranes, the C(22)-aldehyde moiety of retinylisoflavonoid is coplanar with the B-ring of daidzein owing to the strong intramolecular hydrogen bonding C(14')=O···HO-B4'. Accordingly, the C(22)-aldehyde moiety extends its π-conjugation significantly to the B-ring. (ii) The inherent amphiphilicity of retinylisoflavonoid allows the C(22)-aldehyde moiety embedded in the lipid phase of the liposomes, whereas the daidzein counterpart stays at the membrane surface, in effect facilitating interior-to-surface radical communication. As the result, the antilipooxidation activity of retinylisoflavonoid is improved significantly in protecting membrane lipids compared to the parent compounds alone or in combination, and importantly, the performance is more prominent under higher-level oxidative stress. This work provides an advanced case study of new antioxidant development based on optimized electronic and molecular structures.
我们报告了一种新型的分子偶联物作为抗氧化剂，即视黄基异黄酮，它通过共价键连接了视黄醛类似物 C(22)-醛和异黄酮大豆黄素。其物理化学性质，pKa（pKa1 = 8.45，pKa2 = 11.42），氧化电位（1.03 V 相对于 NHE）和 Log（10）分配（Log P = 1.96），以及 Trolox 等效抗氧化能力（TEAC = 0.4）已经得到了表征。光谱和量子化学研究揭示了以下独特的结构特征：（i）无论是在溶液中游离还是包含在脂质体膜中，由于强烈的分子内氢键 C(14')=O···HO-B4'，视黄基异黄酮的 C(22)-醛部分与大豆黄素的 B 环共面。因此，C(22)-醛部分显著扩展了其到 B 环的π共轭。（ii）视黄基异黄酮的固有两亲性允许 C(22)-醛部分嵌入脂质体的脂质相中，而大豆黄素的对应部分留在膜表面，有效地促进了内部到表面的自由基通讯。因此，与母体化合物单独或组合相比，视黄基异黄酮在保护膜脂方面的抗脂质过氧化活性显著提高，并且在更高水平的氧化应激下，性能更为突出。这项工作提供了一个基于优化的电子和分子结构的新型抗氧化剂开发的先进案例研究。
