Hammett Structural Relationships Revealed in Chalcogen Bonded Co-crystals of Electron Rich Pyridines with 4′-Substituted Ebselen Derivatives

In this work, a detailed Hammett structure-structure correlation was applied to a range of chalcogen bonded co-crystals prepared by combining 4′-substituted derivatives of the selenium-based drug ebselen with three different 4-amino-substituted pyridine based chalcogen bond acceptors of differing basicities. This established that the N · · · Se chalcogen bond distance is well within the sum of the van der Waals radii of Se and N and is sensitive to the electronic nature of the substituent. Thus N · · · Se distances ranging from 2.2424(5)–2.4496(9) Å were observed with the shorter distances being observed in co-crystals of ebselen substituted with electron withdrawing groups. Associated with trends of the N · · · Se distance as a function of the 4′-substituent was lengthening of the internal Se−N bond distance consistent with a significant covalent contribution to N · · · Se chalcogen bonding in these derivatives. We define a covalency quotient for the chalcogen bond as the negative slope of the plot of the internal Se−N bond distance vs the external N · · · Se chalcogen bond distance. A value of 0.31 was obtained implying a significant covalent contribution to N · · · Se chalcogen bond. A similar result was obtained by an analysis of chalcogen bonded selenium containing molecules harvested from the Cambridge Crystallographic Database. The covalency quotient is extended to the general case for sigma-hole interactions including halogen bonding and hydrogen bonding, and we show that the covalent component of such interactions can be inferred from the lengthening of the donor bond. The degree of charge transfer in a smaller number of chalcogen bonded co-crystals of ebselen was established by measuring experimental electron density using high-resolution x-ray diffraction to more accurately measure the degree of electron transfer and hence covalency. This showed that in the most strongly bound systems, up to 1 electron worth of charge is transferred from the Lewis base to the Ch-bond donor, which again clearly points to significant covalent character.