R44GM131452

PROJECT SUMMARYThe underlying technology developed in this project is photoredox catalysis, an active research area with growing academic and industrial interest. The impact of photoredox catalysis is expected to exceed palladium catalysis, the Nobel-prize-winning chemistry that fueled the golden age of drug discovery. Photoredox catalysis uses light to activate chemical reactions, as opposed to heat in conventional processes. Unique single-electron radical chemistry is accessed through light absorption enabling new reactivities and unprecedented process efficiencies e.g. synthesis of drug candidates in fewer steps. Of additional industrial interest, it also permits the use of low-cost and structurally diverse raw materials in drug development and manufacturing that are otherwise unreactive in conventional processes. From a public health perspective, photoredox catalysis has the potential to substantially lower the cost of therapeutics and improve overall human health by enabling accelerated drug development and reduced drug manufacturing costs.Completing this NIH SBIR Phase II project will result in the commercialization of high performance organic photoredox catalyst (PC) products. PCs are the key enabler of photoredox catalysis. However, PCs predominantly used today are based on iridium and ruthenium, two rare and expensive precious metals that do not scale beyond Randamp;D usage, posing serious cost and supply issues for industrial use. Organic PCs provide the solution. Made from abundant elements, they are sustainable and can easily scale to meet industrial demand. Notably, the organic PCs of interest here were designed by quantum simulations to possess critical properties resolving many limitations of earlier generations. In many applications, they were shown to match and in some cases exceed the performance of precious metal PCs. The organic PCs developed here provide the scalable solution for photoredox catalysis required for drug development and manufacturing.Specifically, this project integrates three main components pivotal to enabling industrial application of photoredox catalysis, namely i) organic PCs, ii) photochemical reactions, and iii) photoreactor technology. For organic PCs (Aims 1 and 2), a number of PC candidates will be synthesized with expanded ranges of reactivities capable of accommodating many industrial reaction conditions. For photochemical reactions (Aims 3 and 4), novel and medicinally important reactions (with extended substrate scope) with stated customer interest will be developed using various classes of organic PCs. Finally, for photoreactor integration (Aim 5), commercially available photoreactor designs and associated reaction conditions will be identified that maximize the performance of organic PCs.PROJECT NARRATIVE Photoredox catalysis, a subset of photochemistry, promises access to novel drug architectures via efficient synthetic routes, reduced drug development time, and improved process safety. In this NIH SBIR Phase II proposal, organic photoredox catalyst technology -- the key enabler of photoredox catalysis -- will be broadly developed. This project will increase the public’s access to life-enhancing and -saving therapeutics enabled by accelerated drug development and lower drug manufacturing costs.