Extended Lithium Release from Metal-Organic Frameworks for Therapeutic Applications

用于治疗应用的金属有机框架的延长锂释放

• 批准号: 10307514
• 负责人: Adam Jaffe
• 金额: $ 3.43万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-01-01 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10307514
• 关键词: Address; Adsorption; Binding; Biological; Bipolar Disorder; Cations; Collaborations; Crystallization; Dangerousness; Development; Faculty; Gases; Health; Hybrids; Industrialization; Ions; Kinetics; Lithium; Lithium Carbonate; Major Depressive Disorder; Measurement; Mentorship; Metals; Methods; Modification; Monitor; Mood Disorders; Moods; NMR Spectroscopy; Patients; Physiological; Positioning Attribute; Powder dose form; Property; Protons; Research; Research Personnel; Roentgen Rays; Salts; Site; Spectrum Analysis; Structure; Students; Suicide; Techniques; Therapeutic; Thermodynamics; Training; Vertebral column; Work; X ray diffraction analysis; absorption; career; controlled release; crystallinity; effective therapy; functional group; improved; insight; interest; nervous system disorder; responsible research conduct; side effect; small molecule; solid state nuclear magnetic resonance; suicidal risk; supportive environment; uptake; vibration

Project Summary/Abstract Lithium salts have been used to treat severe bipolar disorder and major depression for decades, especially in instances with high suicide risk, and lithium remains their most effective treatment today. Despite its efficacy, lithium's therapeutic window is narrow, since it is difficult to maintain an effective concentration in the body without incurring severely detrimental side effects. This proposal aims to use metal-organic frameworks, a crystalline and porous class of hybrid organic-inorganic materials, for the slow and extended release of lithium as a therapeutic treatment for mood disorders. Metal-organic frameworks, as robust, tunable, and structurally well-defined materials, offer the advantages of facile modification and characterization. Through judicious choice of metals nodes, organic linkers, and guest species it will be possible to tune the thermodynamics and kinetics of Li+ uptake and release. Strategies for lithium interaction will include appending small organic molecules to open metal coordination sites, incorporating lithium-binding functional groups onto the backbones of organic linkers, and post-synthetically exchanging lithium for framework cations while maintaining crystallinity. Potential frameworks of interest will be synthesized using standard organic and inorganic synthesis methods and then subjected to a diverse toolbox of characterization techniques including: powder and single-crystal X-ray diffraction, gas sorption measurements, solution and solid-state NMR spectroscopy, and multiple forms of elemental analysis. Lithium uptake and release will be monitored via solution-state isotherms and kinetic measurements as well as by crystallographic and spectroscopy analysis of the frameworks in their (de)lithiated states. Promising materials will be iteratively improved and subjected to simulated biological conditions for the release of lithium. If successful, this project will position metal-organic frameworks as a versatile platform for addressing the important health challenge of treating severe neurological disorders with lithium. This research will take place in a supportive environment centered within a lab group that has a wealth of expertise in the synthesis and characterization of porous materials. The research will be assisted by a host of long-standing industrial, academic, and national lab collaborations. In addition to significant training in experimental techniques, this project will include guidance toward an academic faculty career, training in responsible conduct of research, professional development through interaction with scientific colleagues, and opportunities for mentorship of other students and researchers.

项目概要/摘要 几十年来，锂盐一直被用来治疗严重的双相情感障碍和重度抑郁症，特别是在 自杀风险很高的情况下，锂仍然是当今最有效的治疗方法。尽管有其功效， 锂的治疗窗很窄，因为很难在体内维持有效浓度 不会产生严重有害的副作用。该提案旨在使用金属有机框架， 结晶和多孔类有机-无机杂化材料，用于缓慢和延长锂的释放 作为情绪障碍的治疗方法。金属有机框架，坚固、可调且结构合理 明确的材料具有易于修饰和表征的优点。通过明智的选择 金属节点、有机连接体和客体物种的热力学和动力学的调整将成为可能 Li+的吸收和释放。锂相互作用的策略包括将有机小分子添加到 开放金属配位位点，将锂结合官能团整合到有机物的主链上 连接体，并在合成后将锂交换为框架阳离子，同时保持结晶度。潜在的 将使用标准有机和无机合成方法合成感兴趣的框架，然后 采用多种表征技术工具箱，包括：粉末和单晶 X 射线 衍射、气体吸附测量、溶液和固态核磁共振光谱以及多种形式的 元素分析。将通过溶液状态等温线和动力学监测锂的吸收和释放 测量以及（脱）锂框架的晶体学和光谱分析 州。有前景的材料将被迭代改进并置于模拟生物条件下 锂的释放。如果成功，该项目将把金属有机框架定位为多功能平台 解决用锂治疗严重神经系统疾病的重要健康挑战。这项研究 将在一个以实验室小组为中心的支持性环境中进行，该实验室小组在该领域拥有丰富的专业知识 多孔材料的合成与表征。该研究将得到一系列长期研究的协助 工业、学术和国家实验室合作。除了实验技术方面的大量培训外， 该项目将包括对学术教师职业的指导、负责任的研究行为的培训、 通过与科学同事的互动以及接受其他人的指导的机会来实现专业发展 学生和研究人员。