Reactant Discovery with an <i>Ab Initio</i> Nanoreactor: Exploration of Astrophysical N-Heterocycle Precursors and Formation Pathways

The incorporation of nitrogen atoms into cyclic compounds is essential for terrestrial life; nitrogen-containing (N-)heterocycles make up DNA and RNA nucleobases, several amino acids, B vitamins, porphyrins, and other components of biomolecules. The discovery of these molecules on meteorites with non-terrestrial isotopic abundances supports the hypothesis of exogenous delivery of prebiotic material to early Earth; however, there has been no detection of these species in interstellar environments, indicating that there is a need for greater knowledge of their astrochemical formation and destruction pathways. Here, we present results of simulations of gas-phase pyrrole and pyridine formation from an <i>ab initio</i> nanoreactor, a first-principles molecular dynamics simulation method that accelerates reaction discovery by applying non-equilibrium forces that are agnostic to individual reaction coordinates. Using the nanoreactor in a retrosynthetic mode, starting with the N-heterocycle of interest and a radical leaving group, then considering the discovered reaction pathways in reverse, a rich landscape of N-heterocycle-forming reactivity can be found. Several of these reaction pathways, when mapped to their corresponding minimum energy paths, correspond to novel barrierless formation pathways for pyridine and pyrrole, starting from both detected and hypothesized astrochemical precursors. This study demonstrates how first-principles reaction discovery can build mechanistic knowledge in astrochemical environments as well as in early Earth models such as Titan's atmosphere where N-heterocycles have been tentatively detected.