Accurate Determination of Isotope Effects on the Dynamics of H-Bond Breaking and Making in Liquid Water

Isotopic substitution of light hydrogen atoms with heavier deuterium atoms in liquid water renders the resulting liquid, heavy water (D₂O), poisonous to most organisms when it replaces a critical fraction of water in living organisms. The mechanisms through which heavy water disrupts biological function are challenging to disentangle experimentally. Isotopic substitution has long been known to affect the H-bond dynamics of liquid water, but experiments have yet to quantify the extent of the differences in the time scales of H-bond breaking and making processes between H₂O and D₂O. In this work, we analyze H-bond dynamics through extensive coupled cluster-quality path integral simulations of H₂O and D₂O under ambient conditions that grant access to unambiguous molecular analyses. We find substantial isotope substitution effects on the rates of H-bond formation and breaking, and H-bond lifetimes, with dynamics in D₂O ∼25% slower than in H₂O. The toxicity of D₂O can thus be ascribed, at least in part, to the effect of slowed H-bond dynamics on biochemical reactions.