Harnessing Electrophiles In Vivo: A Pilot Study in Swine Using a Hydrophobic Radiopaque Formulation of 2‑Propylpentanoyl Chloride

Manipulating biology through chemistry is older than the discipline of chemistry itself. Traditionally, selectivity of oral or intravenous drugs relied on preferential drug-receptor binding. A novel approach exploiting image-guided techniques to impart spatial selectivity opens up a wide range of new possibilities for study and manipulation of biology. Motivated initially by the poor prognosis for solid tumors such as liver cancer, we demonstrate the use of an extreme form of in vivo chemistry for targeted delivery of 2-propylpentanoyl chloride in a swine model. The ensuing reaction in tissue devitalizes it by multiple mechanisms with lasting effects and, critically, demonstrates very low systemic exposure compared to controls. This work points toward a new, powerful strategy for investigating the interface between chemistry and biology in vivo.