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.

项目摘要/摘要 数十年来，锂盐一直用于治疗严重的躁郁症和重度抑郁症，尤其是在 自杀风险和锂的实例仍然是当今最有效的治疗方法。尽管有功效 锂的治疗窗口很狭窄，因为很难保持体内有效浓度 没有产生严重有害的副作用。该建议旨在使用金属有机框架，一个 晶体和多孔的杂化有机无机材料，用于缓慢而扩展的锂 作为情绪障碍的治疗疗法。金属有机框架，可稳固，可调和结构上 定义明确的材料，提供便利修改和表征的优势。通过明智的选择 金属节点，有机连接器和来宾物种可以调整热力学和动力学 Li+摄取和释放。锂相互作用的策略将包括将小有机分子附加到 开放的金属协调位点，将锂结合官能团纳入有机骨架上 连接器，并在保持结晶度的同时，在三个三角交换锂阳离子。潜在的 感兴趣的框架将使用标准有机和无机合成方法合成，然后 受到各种特征技术工具箱的影响，包括：粉末和单晶X射线 衍射，吸气测量，溶液和固态NMR光谱以及多种形式的 元素分析。锂吸收和释放将通过溶液状态等温线和动力学监测 测量以及通过晶体的晶体学和光谱分析（de）的框架分析 国家。有希望的材料将迭代改善并受到模拟生物条件的影响 锂的释放。如果成功，该项目将将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 将在一个以实验室组为中心的支持环境中进行，该实验室具有丰富的专业知识 多孔材料的合成和表征。这项研究将由许多长期存在的协助 工业，学术和国家实验室合作。除了实验技术的重大培训外， 该项目将包括有关学术职业的指导，负责任的研究培训， 通过与科学同事的互动和其他指导的机会，专业发展 学生和研究人员。