All Graphene atoms first-and second-nearest neighbors to the SV and DV and all the molecules of the first methanol layer were included in the SPRINT definition, hence subject to the metadynamics bias. Three indipendent metadynamics simulations reveal functionalization of the undercoordinated C u1 atom by a methoxy group (see Fig. ). The analysis of the metadynamics bias suggests a free-energy bar- In the case of the DV, the same methoxy group functionalization of BLG is observed, but associated to a much higher barrier, the bias being about 250 kJ/mol. The strong barrier decrease in presence of a SV, compared to the pristine Graphene as well as to the DV cases, could be tentatively attributed to the presence of the under-coordinated C u1 atom. To elucidate the effect of high pressure on this transition, we simulated the same reaction under ambient pressure using metadynamics with the SPRINT collective variable. Four inde-pendent metadynamics simulations (see Fig. in the Supporting Information) reveal that, under ambient conditions, SV-BLG methanol functionalization proceeds through methanol reorientation and approach toward the BLG, followed by methanol dissociation and singlevacancy functionalization with both hydrogen and methoxy groups. The reorientation of the methanol pointing its oxygen toward the BLG SV, does not occur under high-pressure conditions, since the methanol is already in proximity of the graphene surface (see density profiles in Fig. ).