Development of Polycarbonate Micelles for Encapsulation of Dinitrosyl Iron and Diiron Hydrogenase Biomimetics

大自然经常将高活性分子封装在一个环境中，以保护其免受不必要的反应。这项研究的目标是制备类似的由塑料制成的封装装置（胶束），并能够保护它们的药物“货物”，直到它们到达人体的目的地。本项目由化学学部化学合成项目资助。德克萨斯农机大学的Marcetta Y. Darensbourg教授和Donald J. Darensbourg教授正在从丰富的气体二氧化碳中制备塑料胶束。由于胶束是可生物降解的，它们在生物体中分解并缓慢释放它们的药物。要研究的一个特定系统涉及捕获一氧化氮（NO）释放药物。一氧化氮与血管调节和免疫功能有关。这项工作的更广泛的影响是提高学生对化学家在诸如医学等重要社会问题中所起作用的认识。Marcetta Darensbourg教授和她的团队是“女性参与科学与工程”、“六年级女生拓宽视野”和“化学奥林匹克”等项目的领导者。这些活动延伸到布莱恩/大学城社区的学童。Donald Darensbourg教授主要研究二氧化碳利用及其对碳管理的影响。他为化学和化学工程的高级本科生开发绿色化学课程和教育材料。本项目的重点是制备三嵌段“ABA”聚碳酸酯，这种聚碳酸酯在加水后自组装成胶束，因为A嵌段是亲水的，B嵌段是疏水的。胶束的疏水内部装载了具有药物潜力的分子有效载荷，通过非共价范德华相互作用或共价附着结合。进行了聚合物的合成和全面表征。在生物可降解胶束的疏水区域内保护活性NO释放药物可以调节和控制NO在生物/制药应用中的传递。化学分析和细胞研究（细胞毒性和细胞摄取）验证了这一假设，并比较了二硝基铁配合物在溶液和嵌入胶束中的NO释放能力。此外，由氰化物连接到金属卟啉光敏剂的聚合物固定化双铁配合物的合成，最初是在没有水的情况下，面向作为产氢催化剂的发展。研究小组通过附着在（有机溶剂）可溶性聚合物上，生成贱金属，有机金属催化剂，防止氧降解和聚集，寻找易碎的二铁或镍铁配合物的稳定性。

Nature often encapsulates highly reactive molecules within an environment that offers protection from unwanted reactions. The goal of this research is to prepare similar encapsulation devices (micelles) that are made from plastics and are capable of protecting their pharmaceutical drug "cargoes" until they reach their destination in the human body. This project is funded by the Chemical Synthesis Program of the Chemistry Division. Professors Marcetta Y. Darensbourg and Donald J. Darensbourg of Texas A&M University are preparing the plastic micelles from the abundant gas, carbon dioxide. Since the micelles are biodegradable, they fall apart in living organisms and slowly release their drug cargo. One of the specific systems to be investigated involves entrapping nitric oxide (NO)-releasing drugs. Nitric oxide is implicated in vasoregulation and immune function. The broader impact of this work is to heighten students' awareness of the roles chemists play in issues of societal importance, like medicine. Professor Marcetta Darensbourg and her group are leaders in programs such as Women in Science and Engineering, Broadening Horizons for 6th Grade Girls, and the Chemistry Olympiad. These activities reach out to school children in the Bryan/College Station communities. Professor Donald Darensbourg focuses on carbon dioxide utilization and its impacts on carbon management. He develops courses and education materials on Green Chemistry for advanced undergraduates in chemistry and chemical engineering.This project focuses on the preparation of triblock, "ABA", polycarbonates that, on addition of water, self-assemble into micelles as the A blocks are hydrophilic and the B blocks are hydrophobic. The hydrophobic interiors of the micelles are loaded with molecular payloads of pharmaceutical potential, binding either by non-covalent van der Waals interactions or by covalent attachment. Syntheses and full characterization of the polymers are conducted. The protection of reactive NO-release drugs within the hydrophobic region of a biodegradable micelle may tune and control NO delivery in biological/pharmaceutical applications. Chemical assays and cell studies (cytotoxicity and cell uptake) test this assumption and compare dinitrosyl iron complexes of NO release ability in solution and imbedded within the micelles. Further, the synthesis of polymer immobilized diiron complexes, linked by cyanide to metallo-porphyrin photosensitizers are oriented towards development as hydrogen production catalysts, initially in the absence of water. The research team looks for the stabilization of the fragile diiron or nickel-iron complexes by attachment to (organic solvent) soluble polymers, generating base metal, organometallic catalysts protected from oxygen degradation and aggregation.