Department of Chemistry, University of Wisconsin-Madison , 1101 University Avenue, Madison, Wisconsin 53706, United States.
Biomacromolecules. 2012 Feb 13;13(2):323-31. doi: 10.1021/bm2013058. Epub 2011 Dec 29.
Nylon-3 polymers contain β-amino-acid-derived subunits and can be viewed as higher homologues of poly(α-amino acids). This structural relationship raises the possibility that nylon-3 polymers offer a platform for development of new materials with a variety of biological activities, a prospect that has recently begun to receive experimental support. Nylon-3 homo- and copolymers can be prepared via anionic ring-opening polymerization of β-lactams, and use of an N-acyl-β-lactam as coinitiator in the polymerization reaction allows placement of a specific functional group, borne by the N-acyl-β-lactam, at the N-terminus of each polymer chain. Controlling the unit at the C-termini of nylon-3 polymer chains, however, has been problematic. Here we describe a strategy for specifying C-terminal functionality that is based on the polymerization mechanism. After the anionic ring-opening polymerization is complete, we introduce a new β-lactam, approximately 1 equiv relative to the expected number of polymer chains. Because the polymer chains bear a reactive imide group at their C-termini, this new β-lactam should become attached at this position. If the terminating β-lactam bears a distinctive functional group, that functionality should be affixed to most or all C-termini in the reaction mixture. We use the new technique to compare the impact of N- and C-terminal placement of a critical hydrophobic fragment on the biological activity profile of nylon-3 copolymers. The synthetic advance described here should prove to be generally useful for tailoring the properties of nylon-3 materials.
尼龙-3 聚合物含有 β-氨基酸衍生的亚基，可以被视为聚（α-氨基酸）的更高同系物。这种结构关系提出了这样一种可能性，即尼龙-3 聚合物为开发具有各种生物活性的新材料提供了一个平台，这一前景最近开始得到实验支持。尼龙-3 均聚物和共聚物可以通过β-内酰胺的阴离子开环聚合来制备，并且在聚合反应中使用 N-酰基-β-内酰胺作为共引发剂可以将特定的官能团（由 N-酰基-β-内酰胺承载）置于每个聚合物链的 N-末端。然而，控制尼龙-3 聚合物链的 C-末端单元一直是一个问题。在这里，我们描述了一种基于聚合机制的指定 C-末端官能团的策略。在阴离子开环聚合完成后，我们引入一种新的β-内酰胺，相对于预期的聚合物链数约为 1 当量。由于聚合物链在其 C-末端带有反应性酰亚胺基团，因此这种新的β-内酰胺应该在此位置连接。如果终止β-内酰胺带有独特的官能团，那么该官能团应该附着在反应混合物中大多数或所有 C-末端。我们使用新技术比较了 N-和 C-末端放置关键疏水性片段对尼龙-3 共聚物生物活性谱的影响。这里描述的合成进展应该被证明对定制尼龙-3 材料的性能普遍有用。
