Within organic molecules, constitutional isomers, which are molecules with equivalent molecular formulas (e.g. ethanol and dimethyl ether for C 2 H 6 O) but varying connectivity, are conceptually similar to polymorphs due to being structural variants of a given composition. Thus, we define our new synthesizability descriptor as E min , the zero-kelvin enthalpy difference between a molecule and its most stable (i.e., lowest energy) constitutional isomer as computed with quantum chemistry (electronic energy with zero-point correction). We hypothesize that molecules with low E min values tend to be more synthesizable, just as how low E hull values are necessary for inorganic crystalline materials to be synthesizable. Unlike some other synthesizability scores, E min is 1) a quantity that is simple to interpret 2) is first-principles based, and 3) does not conceptually rely on databases, making it better-suited for predicting on unexplored chemical space.