We report on the synthesis of 32-arm polysarcosine (PSar) star polymers initiated from a lysine dendrimer macroinitiator and describe faster rates of polymerisation compared to linear PSar equivalents. These polymerisations were monitored using in situ Fourier Transform Infrared spectroscopy (FTIR) to measure the disappearance of absorption bands related to the N-carboxyanhydride (NCA) monomer carbonyl groups. The star polymerisation rates were found to be faster than the linear equivalents irrespective of chain length and the effect was also observed in solvents with different dielectric constants. This effect was investigated further by synthesising star polymers as tetrablock homopolymers in one-pot reactions that revealed the polymerisation rate decreased with each additional block, confirming that chemical features in the dendrimer core were acting to catalyse the reaction. The increased rate was hypothesised to originate from hydrogen bonding between the lysine tert-butyloxycarbonyl (boc) protecting groups in the final generation of the lysine dendrimer and the NCA. Replacing the lysine –NHBoc group for a –NMeBoc resulted in a drop in reaction rate, confirming the hypothesis. However, the data also indicated to a lesser extent that some of the enhanced rate effect also likely originated from the dendrimer core lysine amides as well. This effect was corroborated by performing a density functional theory study on the mechanism of NCA ring opening, which revealed a high energy barrier for proton transfer in the zwitterion intermediate of the reacting NCA that is facilitated by a proton donor in close proximity. This is the first observation of this behaviour for PSar, a polymer that has found increasing popularity as a hydrophilic polymer in drug delivery systems and demonstrates the value of in situ reaction monitoring for NCA polymerisations.

中文翻译：

---

相邻氢键效应驱动的赖氨酸树枝状聚合物大分子引发剂的肌氨酸 N-羧酸酐聚合速率提高

我们报道了由赖氨酸树枝状大分子引发剂引发的 32 臂聚肌氨酸 (PSar) 星形聚合物的合成，并描述了与线性 PSar 等效物相比更快的聚合速率。使用原位傅立叶变换红外光谱（FTIR）监测这些聚合，以测量与N-羧酸酐（NCA）单体羰基相关的吸收带的消失。研究发现，无论链长如何，星形聚合速率都比线性聚合速率更快，并且在具有不同介电常数的溶剂中也观察到了这种效应。通过在一锅反应中将星形聚合物合成为四嵌段均聚物，进一步研究了这种效应，结果表明，每增加一个嵌段，聚合速率就会降低，从而证实了树枝状聚合物核心中的化学特征正在发挥催化反应的作用。假设增加的速率源自最终生成的赖氨酸树枝状聚合物和NCA中赖氨酸叔丁氧羰基(boc)保护基团之间的氢键。将赖氨酸 –NHBoc 基团替换为 –NMeBoc 导致反应速率下降，证实了这一假设。然而，数据还在较小程度上表明，一些增强的速率效应也可能源自树枝状聚合物核心赖氨酸酰胺。通过对 NCA 开环机制进行密度泛函理论研究证实了这种效应，该研究揭示了反应 NCA 的两性离子中间体中质子转移的高能垒，这是由附近的质子供体促进的。这是首次观察到 PSar 的这种行为，这种聚合物作为亲水性聚合物在药物输送系统中越来越受欢迎，并证明了原位反应监测对 NCA 聚合反应的价值。