A Versatile Polymer Platform for Biomedical Applications

项目总结/摘要 合成聚合物和生物系统的合并有着重要的历史，但许多 选择用于目标应用的材料是由于它们的商业可用性 或者容易进入。这些材料很少引出所有的功能，这将是可取的， 如可降解性、生物相容性和对聚合物结构和组成的控制。这 该计划采取了一种自上而下的方法来开发一种高度通用的聚合物平台， 由化学创新驱动，以整合所需的设计功能和灵活性 for interfacing接口with biology生物.这是通过从钌的强大化学性质开始实现的- 基于烯烃复分解，并将其与底物定向化学反应的能力相结合。 通过这种通用策略，已经设计出了令人难以置信的稳健连接反应， 将活性聚合物直接与其他大分子结合，从而无需 通过传统的点击化学。这将导致高度简化的生物缀合策略， 同时也提供了有效去除钌的机会。这一概念也使 设计全新的单体家族，使聚合物具有响应性化学反应， 用于可编程靶向、降解和货物释放的骨架。通过改变 结构，降解动力学的微调可以优化，也可以重新设计，以保持 生物相容性最后，这一战略将解决一个长期存在的挑战， 合成聚合物与生命系统的相互作用：建筑学。一项趋同战略将是 开发用于控制合成聚合物中支化的位置和程度 系统.这将导致在聚合物的结构-性能关系的解剖 这是目前现代技术无法实现的拓扑结构。所有这些方法结合起来 将导致一个真正的“药物化学”的方法来设计聚合物的结构， 在构建、设计和优化过程中始终牢记特定的最终目标。

Project Summary/Abstract The merger of synthetic polymers and biological systems has a significant history, but many of the materials chosen for targeted applications are selected due to their commercial availability or ease of access. These materials rarely elicit all of the features that would be desirable such as degradability, biocompatibility, and control over polymer architecture and composition. This program takes a ground-up approach to developing a highly versatile polymer platform that is driven by chemical innovation in order to incorporate the design features and flexibility needed for interfacing with biology. This is achieved by starting with the robust chemistry of ruthenium- based olefin metathesis and merging it with the power of substrate-directed chemical reactions. With this general strategy, incredibly robust ligation reactions have been designed to rapidly conjugate living polymers directly to other macromolecules, thereby removing the need to go through traditional click chemistry. This will lead to highly simplifying bioconjugation strategies, while also presenting opportunities for efficient ruthenium removal. This concept also enables the design of entirely new monomer families that give polymers with responsive chemistry in the backbone for programmable targeting, degradation, and cargo release. By changing the structure, fine tuning of degradation kinetics can be optimized and also redesigned to maintain biocompatibility. Lastly, this strategy will tackle a longstanding challenge in understanding the interaction of synthetic polymers with living system: architecture. A convergent strategy will be developed to give control of both the location and degree of branching in synthetic polymer systems. This will lead to the dissection of structure-property relationships in the polymer topology that is currently inaccessible with modern techniques. All of these methods combined will lead to a truly “medicinal chemistry” approach to polymer design where structures can be built, designed, and optimized with the specific end goals in mind.