The Moschitto lab utilizes synthetic organic methodology to drive projects in drug discovery.  Our interdisciplinary research integrates diverse synthetic methodologies—including photocatalysis, organocatalysis, and organometallic chemistry—with assay development and medicinal chemistry.  Over the past decade, there has been a resurgence in the use of covalent inhibitors. The formation of a covalent bond results in complete and prolonged target inhibition leading to a lower dosage needed to obtain a similar effect to that of a reversible inhibitor.  Given the lessened need for noncovalent interactions, covalent inhibitors can also bind effectively in shallow binding sites, thus expanding the scope of druggable targets. Overall, covalent inhibitors do not require continual administration, reducing the necessity of hospital visits, the cost of the treatment, and potential side effects.  On the methodology front, our work focuses on controlling the reactivity of sulfinates, thiols, and sulfones to forge new carbon–carbon and carbon–sulfur bonds using environmentally friendly and accessible approaches. We also develop methods for synthesizing protected sulfinate reagents and libraries, and for enabling late-stage sulfonylation reactions. From a medicinal chemistry perspective, we explore the application of covalent inhibitors in drug discovery and chemical biology, with a particular emphasis on screening and deploying sulfonyl fluorides and other covalent warheads. Ultimately, our goal is to harness these synthetic strategies to discover lead covalent inhibitors and complex small molecules targeting understudied proteins.