Sequential Halogen Bonding with Ditopic Donors: σ-Hole Evolutions upon Halogen Bond Formation

The halogen bonding ability of ditopic halogen bond donors can be assessed from the maximum value of the molecular surface electrostatic potential, called σ-hole, at the two halogen atoms. We show here that in N,N′-diodo-dimethylhydantoin (DIH), the halogen bonding (XB) ability of the two nitrogen-bound iodine atoms does not parallel the calculated σ-hole amplitude. The cocrystallization of DIH with a series of para-substituted pyridines, noted Py-R (R = pyrrolidinyl, NMe2, Me, H, CO2Me, CF3, CN), affords bis-adducts DIH·(Py-R)2 with the more electron-rich pyridines, while mono-adducts DIH·(Py-R) are favored with the more electron-poor pyridines (R = CO2Me, CF3, CN). Analysis of the structural characteristics of these mono- and bis-adducts, combined with theoretical calculations, demonstrates that the formation of a first N–I···N′Py-R XB deeply modifies the XB ability (and associated σ-hole) of the second uncoordinated iodine atom. Under these conditions, the latter might associate through I···O XB to the carbonyl oxygen atom of a neighboring mono-adduct in the crystal rather than to a second pyridine. These studies show that when working with polytopic XB donors, one should always consider the deactivation of the remaining halogen atoms following sequential XB formation.