APPLICATIONS OF PHOTOCATALYSIS TO ORGANIC REACTION DEVELOPMENT AND PROXIMITY LABELING

Abstract

I. Organic Reaction Development. The development and application of novel catalytic methods for the assembly of organic molecules represents a major ongoing endeavor in the chemical sciences. New methods for molecule construction promise to enable advances in diverse corners of society, accelerating the production of new medicines, biotechnologies, materials, and consumer products. To expedite organic synthesis, visible-light driven catalysis has emerged as a promising approach to procure value-added products from readily accessible feedstocks. The selective delivery of photonic energy enables the controlled generation and manipulation of reactive intermediates, permitting broad access to previously elusive transformations. The combination of photocatalysis with transition metal catalysis, termed metallaphotoredox, has rapidly enabled the assembly of C(sp3)-enriched molecular scaffolds from highly abundant precursors, including alkyl chlorides (Chapter 2), carboxylic acids (Chapter 3), and alcohols (Chapters 3 & 4). II. Proximity Labeling. Protein-protein interactions mediate essential cellular functions, and their dysregulation forms the basis of disease, including many types of cancer. Deconvolution of biomolecular interaction networks in cancer-relevant cellular systems can provide a mechanistic understanding of critical aspects of tumorigenesis, immune evasion, and therapeutic intervention. In Chapter 5, photocatalytic microenvironment mapping (µMap) and quantitative chemoproteomics are leveraged to interrogate protein interaction landscapes that undergo perturbation due to oncogenic signaling or drug treatment. Photo-proximity labeling is applied to investigate the microenvironment of cell surface immunoreceptors (Chapter 5.IV) and the mechanism-of-action of small-molecule glues (Chapter 5.V).