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.

项目概要尽管反应已经发展了数十年，但药物化学家在合成反应时仍然经常面临合成障碍。制备具有潜在治疗价值的分子，例如用C-H键取代C-F键。可以提高靶分子的代谢稳定性、膜通透性和生物活性，但这取代通常不可能在实验室中实现，这是因为氟化。否则，简单的构建块或试剂通常会使它们呈气态、有毒、腐蚀性或不稳定。这个“试剂问题”不仅限于有机氟化学，它阻碍了这一领域的重大进展因此，拟议研究的总体目标是“驯服”氟化建筑的反应性。具体来说，所提出的方法可以阻止并使其用于构建复杂的氟化分子。多学科项目旨在采用不溶性多孔材料，这些材料通常充当“宿主” 材料科学中的“客体”分子，用于控制氟化剂的反应性。异质物种将充当“纳米容器”，能够可控地释放储存的试剂或作为促进其孔隙内新转变的“纳米反应器”该提案的中心假设。金属有机框架是一类相对较新的多孔晶体材料，由有机物构成 “连接体”和无机“二级建筑单元”是实现这一目标的理想平台，因为它们该研究目标是 PI 更广泛的研究计划的一部分，旨在解锁金属有机框架在有机合成、医学和结构生物学中的应用潜力。 PI 还在探索利用电力作为一种低成本工具来合成复杂分子该行政补充文件将支持购买粉末 X 射线衍射仪 (PXRD)，以作为母提案的一部分，促进 MOF 的表征是最重要的。确定纳米晶体材料原子尺度结构的方法，但实施起来仍然具有挑战性通常，必须使用同步加速器 X 射线源来收集数据，这会导致此次购买将允许样品制备和数据采集之间的显着延迟（> 6 周）。在康奈尔大学只需几分钟而不是几周即可获取 PXRD 数据。

项目成果

期刊论文数量（19）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Handling fluorinated gases as solid reagents using metal-organic frameworks.

使用金属有机框架将氟化气体作为固体试剂处理。

DOI：
发表时间：
2023-09-29
期刊：
影响因子：
0
作者：
Keasler, Kaitlyn T;Zick, Mary E;Stacy, Emily E;Kim, Jaehwan;Lee, Jung;Aeindartehran, Lida;Runčevski, Tomče;Milner, Phillip J
通讯作者：
Milner, Phillip J

Reactive Chlorine Capture by Dichlorination of Alkene Linkers in Metal-Organic Frameworks.

通过金属有机框架中烯烃连接体的二氯化捕获活性氯。

DOI：
发表时间：
2022-12-07
期刊：
影响因子：
9.5
作者：
Azbell, Tyler J;Mandel, Ruth M;Lee, Jung;Milner, Phillip J
通讯作者：
Milner, Phillip J

Investigation of ion-electrode interactions of linear polyimides and alkali metal ions for next generation alternative-ion batteries.

研究下一代替代离子电池的线性聚酰亚胺和碱金属离子的离子电极相互作用。

DOI：
发表时间：
2022-08-17
期刊：
影响因子：
8.4
作者：
Gannett, Cara N;Kim, Jaehwan;Tirtariyadi, Dave;Milner, Phillip J;Abruña, Héctor D
通讯作者：
Abruña, Héctor D

Electroreductive Radical Borylation of Unactivated (Hetero)Aryl Chlorides Without Light by Using Cumulene-Based Redox Mediators.

使用基于积烯的氧化还原介体，在无光的情况下对未活化的（杂）芳基氯进行电还原自由基硼化。

DOI：
发表时间：
2023-10-02
期刊：
影响因子：
0
作者：
Lai, Yihuan;Halder, Arjun;Kim, Jaehwan;Hicks, Thomas J;Milner, Phillip J
通讯作者：
Milner, Phillip J

Biocompatible metal-organic frameworks for the storage and therapeutic delivery of hydrogen sulfide.

用于储存和治疗递送硫化氢的生物相容性金属有机框架。

DOI：
发表时间：
2021-04-30
期刊：
影响因子：
8.4
作者：
Chen, Faith E;Mandel, Ruth M;Woods, Joshua J;Lee, Jung;Kim, Jaehwan;Hsu, Jesse H;Fuentes;Wilson, Justin J;Milner, Phillip J
通讯作者：
Milner, Phillip J