Taming Fluorine: Metal-Organic Frameworks for the Heterogeneous Delivery of Fluorinated Building Blocks

驯服氟：用于氟化构件异质输送的金属有机框架

基本信息

批准号：
10798398
负责人：
Phillip John Milner
金额：
$ 24.37万
依托单位：
CORNELL UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-08-01 至 2025-07-31
项目状态：
未结题

项目摘要

Project Summary Despite decades of reaction development, medicinal chemists still frequently face synthetic barriers when preparing molecules with potential therapeutic value. For example, the substitution of C–H bonds for C–F bonds in a target molecule can improve its metabolic stability, membrane permeability, and biological activity, but this substitution is often impossible to realize in the laboratory. This obstacle arises because the fluorination of otherwise simple building blocks or reagents generally renders them gaseous, toxic, corrosive, or unstable. While this “reagent problem” is not limited to organofluorine chemistry, it has prevented significant advances in this area. Therefore, the overall objective of the proposed research is to “tame” the reactivity of fluorinated building blocks and enable their use for the construction of complex fluorinated molecules. Specifically, the proposed multidisciplinary program aims to employ insoluble porous materials, which commonly serve as “hosts” for “guest” molecules in materials science, to control the reactivity of fluorinating agents. The resulting heterogeneous species will function as “nanovessels” capable of controllably releasing the stored reagents or as “nanoreactors” that facilitate new transformations within their pores. The central hypothesis of this proposal is that metal–organic frameworks, a relatively new class of porous, crystalline materials constructed from organic “linkers” and inorganic “secondary building units,” are the ideal platform to achieve this objective due to their unparalleled structural tunability. This research aim is part of the PI’s broader research program to unlock the potential of metal–organic frameworks for applications in organic synthesis, medicine, and structural biology. The PI is also exploring the use of electricity as a low-cost tool to enable the synthesis of complex molecules This administrative supplement will support the purchase of a powder X-ray diffractometer (PXRD) to facilitate the characterization of MOFs prepared as part of the parent proposal. PXRD is the most important method for determining the atomic-scale structures of nano-crystalline materials but remains challenging to carry out at Cornell University. Typically, synchrotron X-ray sources must be used to collect data, which results in significant delays (>6 weeks) between sample preparation and data acquisition. This purchase would allow for the acquisition of PXRD data in minutes instead of weeks at Cornell University.

项目摘要尽管有数十年的反应发展，但当药物化学家在制备具有潜在治疗价值的分子。例如，C – H键代替C – F键在目标分子中可以改善其代谢稳定性，膜渗透性和生物活性，但这是在实验室中通常无法实现替代。出现此障碍是因为否则，简单的构件或试剂通常会使它们气体，有毒，腐蚀性或不稳定。尽管这种“试剂问题”不仅限于有机氟化化学，因此阻止了这一点的重大进展区域。因此，拟议的研究的总体目标是“驯服”氟化建筑的反应性块并使它们用于构建复杂的氟化分子。具体而言，提议多学科计划旨在使员工不溶性多孔材料，这些材料通常用作“主机” 材料科学中的“来宾”分子，以控制荧光剂的反应性。结果异质物种将充当能够控制释放的储存试剂或作为“纳米反应器”，促进了毛孔内的新转变。该提议的中心假设是金属 - 有机框架，是一种相对新的多孔，结晶材料，由有机构建 “接头”和无机“二级建筑单元”是实现此目标的理想平台无与伦比的结构可可匹配性。该研究目的是PI更广泛的研究计划的一部分，以解锁该计划金属 - 有机框架在有机合成，医学和结构生物学中应用的潜力。 PI还正在探索用电作为低成本工具，以使复杂分子合成这种管理补充剂将支持购买粉末X射线衍射仪（PXRD）促进作为父母建议的一部分制备的MOF的表征。 PXRD是最重要的确定纳米晶体材料的原子尺度结构的方法，但仍然挑战在康奈尔大学出去。通常，必须使用同步X射线源来收集数据，这导致样本制备和数据采集之间有明显的延迟（> 6周）。这次购买将允许康奈尔大学（Cornell University）在几分钟而不是几周内收购PXRD数据。