Complete Computational Exploration of Eight-Carbon Hydrocarbon Chemical Space

Hydrocarbons are the most fundamental class of chemical species, but even the chemical space of those with 8 carbon atoms or less has not been explored exhaustively. Here we report a full enumeration and computational exploration of this space. Density functional theory based geometry optimization and energy calculations have identified all stable molecules within this space, forming a new database called CHX8. A universal strain value has been proposed and assigned to each of these molecules, acting as a proxy for synthesizability and providing a clear guideline of how synthetically plausible these molecules could be. This paper explores the limits of the chemical space within CHX8, with a focus on trans-fused, unsaturated, and anti-Bredt ring systems. We show that, contrary to prevailing wisdom, most of these unconventional structures should be synthetically accessible, with relative strain energies less than that of cubane. It is expected that this data set will inspire the synthesis of many new molecules with applications in various areas of chemistry, biology and materials science. The resulting data set also provides a valuable resource for the development of general and robust machine learning models.