氧化应激与衰老、炎症等很多疾病息息相关。使用抗氧化剂来调节人体失衡的氧化还原系统是应对氧化应激的重要手段。然而传统的小分子抗氧化剂在使用过程中存在水溶性差、安全性不足、体内循环时间短等问题，往往难以用于临床。大分子抗氧化剂可以解决上述问题，因此我们选用多组分反应来制备大分子抗氧化剂。多组分反应具有条件温和、产物单一、原料广泛、操作简便等优点，近年来，通过多组分反应合成功能高分子成为高分子领域的重要方向之一。基于此，我们利用多组分反应开发了一系列具有独特的性质的抗氧化聚合物。首先，我们利用Ugi反应将抗氧化结构引入聚合物中合成了一系列抗氧化聚合物。评价这些聚合物的抗氧化活性，筛选出三种抗氧化能力最强的聚合物用于斑马鱼胚胎的氧化损伤防护。这三种聚合物在安全范围内能极大提高氧化损伤下斑马鱼胚胎的存活率。这一工作说明可以用Ugi反应合成抗氧化聚合物，其中的高效抗氧化聚合物可以用于活体防护。其次，我们用Ugi反应同时引入酚羟基与苯硼酸来制备功能化的聚合物，该聚合物与聚乙烯醇（Polyvinyl alcohol，PVA）在水溶液中混合，便可以形成自修复水凝胶。凝胶骨架中的酚羟基具有抗氧化能力，也具有抗菌能力，这为聚合物以及水凝胶增添了抗氧化性与抗菌性。这一工作充分说明Ugi反应底物适用范围广，可以为聚合物赋予多种功能。此外，Biginelli反应可以生成具有抗氧化活性的二氢嘧啶（Dihydropyrimidin，DHPM）。我们用Biginelli反应将苯硼酸引入聚合物中，该聚合物与PVA混合后得到可注射水凝胶。将其注射到小鼠皮下，在3天内表现出很好的生物安全性。这些结果说明，这种凝胶有望用作可注射药物载体或者生物填料。最后，我们通过Biginelli反应合成了大分子防晒剂。这种防晒剂可以清除自由基，也能有效避免小鼠皮肤被紫外线灼伤。其分子量大的特点避免了防晒剂透皮吸收的问题。此外，这种防晒剂对不会影响珊瑚的正常生长。这一工作通过Biginelli开发了一种大分子防晒剂，拓展了抗氧化聚合物的适用范围。总的来说，基于多组分反应的抗氧化聚合物有效解决了小分子抗氧化剂存在的一些问题。本文除了直接将抗氧化聚合物用于氧化损伤防护之外，还探索了其在水凝胶材料和防晒剂中的应用，充分说明用多组分反应开发功能高分子的优势。
Oxidative stress is associated with aging, inflammation, and many other diseases. Using antioxidants to regulate imbalanced redox system is an important way to deal with oxidative stress. However, traditional small-molecule antioxidants are often difficult to be used in clinical practice because of their poor water solubility, inadequate safety and short circulation time in vivo. Polymeric antioxidants can solve the above problems, so we choose multi-component reactions (MCRs) to prepare polymeric antioxidants. The MCRs have the advantages of mild conditions, single product, wide range of raw materials and easy operation, etc. In recent years, the synthesis of functional polymers by MCRs have become one of the important directions in the field of polymers. Based on this, we have developed a series of antioxidant polymers with unique properties using MCRs.Firstly, a series of antioxidant monomers were efficiently synthesized using the Ugi reaction to introduce antioxidant structures into polymers. The antioxidant activity of these polymers was evaluated and three polymers with the highest antioxidant capacity were selected for protection against oxidative damage in zebrafish embryos. These three polymers greatly improved the survival rate of zebrafish embryos under oxidative damage in a safe range. This work illustrates that antioxidant polymers can be synthesized using the Ugi reaction and that the highly efficient antioxidant polymers among them can be used for in vivo protection.Secondly, the Ugi reaction was used to introduce both phenolic hydroxyl groups and phenylboronic acid to produce a functionalised polymer, which was mixed with polyvinyl alcohol (PVA) in aqueous solution to form a self-healing hydrogel through the formation of borate ester bonds. The phenolic hydroxyl group in the gel backbone has both antioxidant and antibacterial properties, which add to the antioxidant and antibacterial properties of the polymer and the hydrogel. This work demonstrates that Ugi reactive substrates are versatile and can impart a wide range of functions to polymers.Moreover, the Biginelli reaction produces dihydropyrimidin (DHPM), which has antioxidant activity. We used the Biginelli reaction to introduce phenylboronic acid into a polymer which was mixed with PVA to give an injectable hydrogel. The gel was injected subcutaneously into mice and showed a good biosafety within 3 days. These results suggest that this gel is expected to be used as an injectable drug carrier or biofiller.Finally, we have synthesised a polymeric UV filter through the Biginelli reaction. This polymeric UV filter has antioxidant capacity and is also effective in avoiding UV burns on the skin of mice. Its large molecular weight avoids the problem of transdermal absorption. In addition, the polymeric UV filter does not affect the growth of corals. This work extends the applicability of antioxidant polymers by developing a polymeric UV filter through the Biginelli reaction.In general, the MCRs-based antioxidant polymers effectively solve some problems of small-molecule antioxidants. In this paper, in addition to the direct use of antioxidant polymers for oxidative damage protection, their applications in hydrogel materials and sunscreens are explored, illustrating the advantages of developing functional polymers with MCRs.
