XTB Nano-Reactor for Essential Organic Reactions

In the present study, we have explored the capability of an efficient GFN2-xTB meta-dynamics nano-reactor protocol for essential organic transformations in March's Advanced Organic Chemistry. Specifically, we have examined nucleophilic substitution and the related elimination in detail, and we have validated the protocol for electrophilic aromatic substitution, radical substitution, addition to C═C bond, addition to C═O bond, rearrangement, oxidation, and reduction. For an efficient and realistic nano-reaction, we propose the use of a reactive catalyst, a carefully tuned explicit solvation environment, and, if necessary, multiple simulation temperatures. A limitation of the nano-reactor in its current form is the lack of exchange of chemical species between the (simulated) reaction region and the (non-simulated) environment. Another issue is the use of a constant spin multiplicity that prohibits spin crossover that may occur in the real world. One may also need to adjust the size of the spherical wall potential for reactions that necessitate tighter confinement of the reactants. In a case study, we have examined the hydrothermal liquefaction of some lignin models. The nano-reactions account for key products observed in previous experiments, and they enable us to observe mechanisms that may not be trivially conceived. While there is room for development, with our standardized computational settings the nano-reactor protocol already provides an essentially black-box and efficient approach to examine details of a reaction and to provide hints for tuning real-world reaction conditions.