The fellowship of the Grignard: 21th century computational tools for hundred years-old chemistry

This perspective begins with the discovery of the Grignard reaction by a graduate student in the last years of the 19th century, before describing why it has remained largely unexplained for more than a century. From the summary of what has been achieved, focusing on the computational aspects, it is now clear that further studies of the chemistry of any chemical species that is highly sensitive to solvents, such as Group I and II elements, require a holistic approach that includes the solute andthe solvent together. Ab initio molecular dynamics, which meets these requirements, has produced some results, but it hits hard limits due to its relatively heavy computational costs. In these days, it is becoming clear that data-driven methods, including machine learning potentials and simulations driven by quantitative on-the-fly calculation of relevant observables, have the potential to better and more completely explore the very large chemical space associated with the presence of a large number of species in solution. These methodologies have the chance to give the keys to enter into the challenging and still poorly explored world of chemical species whose behaviour and reactivity are strongly influenced by the solvent and the experimental conditions.