Nuclear Quantum Effects Across Chemical Space

Nuclear quantum effects (NQEs) are important in many physical and chemical processes--particularly those involving lighter nuclei or occurring at low temperatures. Nevertheless, NQEs have been carefully quantified in few systems, such as water, and their importance is rarely considered. Here, using path-integral molecular dynamics, we critically examine NQEs for a range of molecular properties (e.g., density, thermal expansion coefficients, isothermal compressibility, static dielectric constant, and the heat of vaporization) across 87 molecular liquids. We discover substantial NQEs in this broad chemical space, with molar volumes exhibiting differences of up to 5% between classical and quantum treatments; similar magnitudes are revealed in equilibrium isotope effects from deuteration. Using machine learning, we identify that four molecular properties that are readily known or easily computed with classical simulations—density, molar mass, hydrogen density, and thermal expansion coefficient—are strong predictors of NQEs. Further data-driven analysis reveals how molecular factors, such as branching and heteroatom composition, influence intermolecular interactions and fluid stability and thereby affect observed NQEs. This work offers new insights into the relationship between NQEs and molecular chemistry and refines expectations for when rigorous treatment of NQEs is necessary.