Taming Fluorine: New Nanomaterials for Drug Synthesis
To develop new drugs, medicinal chemists synthesize large organic molecules. They custom-build these molecules using smaller chemical building blocks in a multistep process that entails a series of intermediate reactions. Despite decades of reaction development, however, medicinal chemists still face fundamental barriers. For example, adding fluorine to a target molecule can improve its therapeutic potential but actually making that addition is often difficult to achieve. Fluorine bonds are stable in large molecules, but when chemists integrate fluorine into the smaller building blocks necessary for organic synthesis, the resulting reagents tend to be gaseous, toxic, corrosive, or volatile.
Borrowing from materials science, Phillip J. Milner, Chemistry and Chemical Biology, is developing metal-organic frameworks—a class of porous, crystalline nanomaterials—that can stabilize volatile fluorine-containing reagents. In some cases, the nanomaterials will hold volatile molecules in vessel-like nanostructures that release the stored reagent in a controlled manner. In others, the nanomaterials will serve as crucibles, facilitating new chemical transformations within their pores. To name one possibility, sequestering a gaseous, fluorine-containing reagent in a metal-organic framework might allow chemists to handle it safely as a powder.
This research aims to open up new avenues in the synthesis of biologically active molecules and, more broadly, to demonstrate the unrealized potential of porous nanomaterials in medicine and human health. By taming the reactivity of fluorinated building blocks, this research could enable the preparation of previously inaccessible fluorinated compounds and their evaluation as next-generation medicines.
NIH Award Number: 1R35GM138165-01