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