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

用于封装二亚硝基铁和二铁氢化酶仿生材料的聚碳酸酯胶束的开发

• 批准号: 1665258
• 负责人: Marcetta Darensbourg
• 金额: $ 45万
• 依托单位: Texas A&M University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-15 至 2020-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1665258&HistoricalAwards=false
• 关键词: Development; Polycarbonate; Micelles; Encapsulation; Dinitrosyl

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.

自然界经常将高活性分子包裹在一个环境中，以保护其免受不必要的反应的影响。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)，能够保护他们的药物“货物”，直到它们到达它们在人体内的目的地。本项目由化学部化学合成计划资助。德克萨斯农工大学的Marcetta Y.Darensburg教授和Donald J.Darensburg教授正在从丰富的二氧化碳气体中制备塑料胶束。由于胶束是可生物降解的，它们在活着的有机体中解体，并缓慢释放药物。要调查的特定系统之一涉及包埋一氧化氮(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医学等具有社会重要性的问题上所起作用的认识。Marcetta Darensburg教授和她的团队是科学和工程女性、为六年级女孩拓宽视野和化学奥林匹克等项目的领导者。这些活动惠及布赖恩/大学站社区的学童。唐纳德·达伦斯堡教授主要研究二氧化碳的利用及其对碳管理的影响。他为化学和化学工程专业的高级本科生开发关于绿色化学的课程和教材。这个项目专注于制备三嵌段，“ABA”，聚碳酸酯，加入水后，由于A段是亲水的，B段是疏水的，自组装成胶束。胶束的疏水内部负载了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连接结合。对聚合物进行了合成和充分表征。在生物可降解胶束的疏水区域内保护反应性NO释放药物可以调节和控制在生物/药物应用中的NO输送。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，并比较了二亚硝基铁络合物在溶液中和嵌入胶束中释放NO的能力。此外，通过氰化物与金属卟啉光敏剂连接的聚合物固定双铁配合物的合成正朝着作为制氢催化剂的发展方向发展，最初是在没有水的情况下。研究小组希望通过附着到(有机溶剂)可溶聚合物上来稳定脆弱的二铁或镍铁络合物，生成防止氧降解和聚集的贱金属和有机金属催化剂。

项目成果

Proton affinity studies of nickel N2S2 complexes and control of aggregation

• DOI: 10.1007/s00775-019-01671-4
• 发表时间: 2019-09-01
• 期刊: JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY
• 影响因子: 3
• 作者: Arnet, Nicholas A.;Bhuvanesh, Nattamai;Darensbourg, Marcetta Y.
• 通讯作者: Darensbourg, Marcetta Y.

Toward the Optimization of Dinitrosyl Iron Complexes as Therapeutics for Smooth Muscle Cells

优化二亚硝基铁配合物作为平滑肌细胞的治疗方法

• DOI: 10.1021/acs.molpharmaceut.9b00389
• 发表时间: 2019
• 期刊: Molecular Pharmaceutics
• 影响因子: 4.9
• 作者: Pectol, D. Chase;Khan, Sarosh;Chupik, Rachel B.;Elsabahy, Mahmoud;Wooley, Karen L.;Darensbourg, Marcetta Y.;Lim, Soon-Mi
• 通讯作者: Lim, Soon-Mi

Controlling O 2 Reactivity in Synthetic Analogues of [NiFeS]- and [NiFeSe]-Hydrogenase Active Sites

控制[NiFeS]-和[NiFeSe]-氢化酶活性位点的合成类似物中的O 2 反应性

• DOI: 10.1021/jacs.9b07448
• 发表时间: 2019
• 期刊: Journal of the American Chemical Society
• 影响因子: 15
• 作者: Yang, Xuemei;Elrod, Lindy C.;Le, Trung;Vega, Valeria S.;Naumann, Haley;Rezenom, Yohannes;Reibenspies, Joseph H.;Hall, Michael B.;Darensbourg, Marcetta Y.
• 通讯作者: Darensbourg, Marcetta Y.

Kinetic studies of thermal dissociation of carbon monoxide ligands from manganese tri- and tetra-carbonyl derivatives containing the bulky dipiperidylmethane ligand, CH2Pip2

• DOI: 10.1016/j.ica.2018.09.004
• 发表时间: 2019
• 期刊: Inorganica Chimica Acta
• 影响因子: 2.8
• 作者: T. M. Folsom;D. Darensbourg

Metal‐Templated, Tight Loop Conformation of a Cys‐X‐Cys Biomimetic Assembles a Dimanganese Complex

金属-Cys-X-Cys 仿生紧密环构象组装二锰络合物

• DOI: 10.1002/anie.201913259
• 发表时间: 2020
• 期刊: Angewandte Chemie International Edition
• 作者: Le, Trung;Nguyen, Hao;Perez, Lisa M.;Darensbourg, Donald J.;Darensbourg, Marcetta Y.
• 通讯作者: Darensbourg, Marcetta Y.