A combinatorial approach for polymer design
A combinatorial approach for polymer design
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DOI：
10.1021/ja970389z
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发表时间：
1997-05-14
影响因子：
15
通讯作者：
Kohn, J
中科院分区：
文献类型：
--
作者：
Brocchini, S;James, K;Kohn, J
用于特殊应用的聚合物的设计，如医疗植入物，1，2压电3和光子材料，4或自组装系统5是具有挑战性的，因为这些材料必须满足多方面的要求。例如，组织工程领域的关键在于开发可降解支架，其通过仔细控制聚合物表面性质来促进细胞增殖和表达所需的生理行为。6在这里，我们报告了置换设计的单体系统的概念，以创建结构相关的聚合物库。为了获得材料特性以可预测和系统的方式变化的库，有必要使用精心设计的单体和聚合策略。这可以在严格交替的AB型共聚物中实现，其中第一单体（A）含有用于连接一系列侧链的反应性基团，而第二单体（B）允许聚合物主链结构的系统变化。n种不同的单体A与m种不同的单体B的共聚产生了一系列n× m结构相关的共聚物。这些库可用于（1）增加任何特定应用的可用聚合物候选材料的数量，以及（2）使聚合物结构、材料性质和性能之间的相关性研究系统化。作为该概念的第一个实施方案，由14种不同的酪氨酸衍生的二酚1和8种脂肪族二酸2制备112种多芳基化合物3的文库（图1）。这些聚合物基于天然代谢物，并且是可生物降解的，并且潜在地可用作医疗植入材料。7在酪氨酸衍生的二酚组1中，侧基R和亚甲基的数目（n）（0，1）变化，而在二酸组2中，聚合物主链通过Y处的结构变化而变化。在组合中，R和Y的变化提供了聚合物自由体积、蓬松度、柔性和疏水性的增量差异。我们发现，112种聚合物的库在玻璃化转变温度（Tg）、表面润湿性（通过空气-水接触角测量）和细胞反应（通过体外细胞增殖研究测量）方面表现出可预测的变化。另一方面，由于所有聚合物都是由非常相似的单体衍生而来，因此它们可以在相同的反应条件下制备，并具有重要的材料性质，如在有机溶剂中的溶解性、热加工性和无定形形态。在设置在水振荡器浴中的单独反应容器中进行0.2g规模（基于二酚1的量）的多达32个同时反应。由于所使用的单体在其各自的官能团处具有几乎相同的反应性，因此采用相同的反应条件，并且在相同的反应容器中进行和处理每次聚合。在从甲醇中沉淀两次后，获得约0.1- 0.2g的每种聚合物。该方法可用于聚合物库的自动化合成。反应规模提供了足够的聚合物来建立基本材料和生物性质的相关性。使用小于40 mg的每种聚合物的常规分析提供了分子量（GPC）、Tg（DSC）和空气-水接触角（座滴）。平均分子量范围为50 000至150 000 g/mol。多分散性范围为1.4至2.0。所有聚合物的分子量足够高，多分散性相似，可用于评价和比较其各自的材料和生物学特性。几种聚芳酯也在更大的...
The design of polymers for specialty applications such as medical implants, 1, 2 piezoelectric3 and photonic materials, 4 or self-assembling systems5 is challenging since such materials must meet multifaceted requirements. For example, the field of tissue engineering hinges on developing degradable scaffolds that promote cell proliferation and expression of desired physiologic behaviors through careful control of the polymer surface properties. 6 Here we report the concept of permutationally designed monomer systems to create libraries of structurally related polymers. To obtain libraries in which material properties vary in a predictable and systematic fashion, it is necessary to use carefully designed monomers and polymerization strategies. This can be achieved in strictly alternating AB type copolymers in which the first monomer (A) contains a reactive group for the attachment of a series of pendent chains, while the second monomer (B) allows for systematic variations in the polymer backbone structure. The copolymerization of n different monomers A with m different monomers B gives rise to an array of n× m structurally related copolymers. Such libraries can be used to (1) increase the number of available polymeric candidate materials for any specific application and (2) systematize the study of correlations between polymer structure, material properties, and performance. As a first implementation of this concept, a library of 112 polyarylates 3 was prepared from 14 distinct tyrosine-derived diphenols 1 and eight aliphatic diacids 2 (Figure 1). These polymers are based on natural metabolites and are biodegradable and potentially useful as medical implant materials. 7 In the set of tyrosine-derived diphenols 1, the pendent group R and the number of methylene groups (n) 0, 1) were varied, while in the set of diacids 2, the polymer backbone was varied via structural changes at Y. In combination, variations at R and Y provided incremental differences in polymer free volume, bulkiness, flexibility, and hydrophobicity. We found that the library of 112 polymers exhibited predictable changes in glass transition temperature (Tg), surface wettability (as measured by the air-water contact angle), and cellular response (as measured by in vitro cell proliferation studies). On the other hand, since all polymers were derived from very similar monomers, they could be prepared under identical reaction conditions and shared important material properties such as solubility in organic solvents, thermal processibility, and amorphous morphology. Up to 32 simultaneous reactions on a 0.2 g scale (based on the amount of diphenol 1) were conducted in separate reaction vessels set up in a water shaker bath. Since the monomers used had almost identical reactivities at their respective functional groups, the same reaction conditions were employed and each polymerization was conducted and worked up in the same reaction vessel. About 0.1-0.2 g of each polymer was obtained after two precipitations from methanol. This methodology can be used for the automated synthesis of polymer libraries. The reaction scale provided sufficient polymer to establish basic material and biological property correlations. Routine analysis using less than 40 mg of each polymer provided the molecular weight (GPC), Tg (DSC), and air-water contact angle (sessile drop). Molecular weight averages ranged from 50 000 to 150 000 g/mol. Polydispersities ranged from 1.4 to 2.0. All polymers were sufficiently high in molecular weight and similar in polydispersity for evaluation and comparison of their respective material and biological properties. Several of the polyarylates were also prepared on a larger …