Atomistic Simulations of Acid-Base Equilibria

Chemical reactions in aqueous media represented a great challenge for computational chemistry since its early days. Among them, acid–base reactions are among the most important yet hard to describe chemical processes. Most difficulties lie in the description of the elusive nature of hydrated water ions, charge carriers formed within the solvent due to the excess or defect of hydrogen cations. The increasing computational power as well the rising of technological and methodological advancements have made it possible to investigate these species with unprecedented accuracy and resolution. However, an atomistic description of these species often faces significant limitations in discerning the main structure of these ions from the solvent itself. These charge carriers are stabilized by organized water clusters that actively participate in the structure of these ions. The continuous rearrangement of these structures does not allow to easily identify which atoms actively participate to the solvation process, resulting in severe limitations in the applicability of many computational approaches. In molecular dynamics simulations, breaking and forming covalent bonds such as those involved require crossing high energy barriers. This leads to kinetic bottlenecks that frustrate sampling and make some events rare in the typical simulation timescales. Enhanced sampling methods like Metadynamics can overcome this issue accelerating configurational space exploration along specific process descriptors named Collective Variables (CVs). This work proposes a paradigm shift in the definition of the CVs describing the dynamics of hydrated ionic species that are here identified as local anomalies in the proton density irrespective to any reference structure. These anomalies are revealed partitioning the entire volume in Voronoi-like polyhedra placed around every acid-base site and counting any variation in the number of hydrogen atoms within each partitioned volume. Two CVs have been derived starting from this fundamental definition allowing monitoring and accelerating reaction involving proton migrations. Firstly, these descriptors have been tested on acetic acid, ammonia and bicarbonate in aqueous solutions chosen as representative benchmark for an acid a base and an amphoteric species. Secondly, we applied this method in the study of tautomeric interconversions such as the neutral/zwitterionic and keto/enol equilibria of glycine and acetone respectively. Lastly, we have investigated the acid-base behavior of Bronsted acid sites in zeolites and how confinement effects influence their activities. Contrary to standard descriptors, the general applicability of our approach allowed to obtain the expected results although no a priori impositions were imposed on final products or reactive pathways. The absence of reference structures definition or reactivity constraints makes this approach highly versatile to explore any relevant thermodynamic state in a single run allowing studying complex systems characterized by competitive reactions and multiple reaction mechanisms