Factors Impacting sigma-and p-Hole Regions as Revealed by the Electrostatic Potential and Its Source Function Reconstruction: The Case of 4,4'-Bipyridine Derivatives

Positive electrostatic potential (V) values are often associated with sigma- and p-holes, regionsof lower electron density which can interact with electron-rich sites to form noncovalent interactions.Factors impacting sigma- and p-holes may thus be monitored in terms of the shape and values of theresulting V. Further precious insights into such factors are obtained through a rigorous decompositionof the V values in atomic or atomic group contributions, a task here achieved by extending theBader-Gatti source function (SF) for the electron density to V. In this article, this general methodologyis applied to a series of 4,4'-bipyridine derivatives containing atoms from Groups VI (S, Se) and VII(Cl, Br), and the pentafluorophenyl group acting as a p-hole. As these molecules are characterizedby a certain degree of conformational freedom due to the possibility of rotation around the twoC-Ch bonds, from two to four conformational motifs could be identified for each structure throughconformational search. On this basis, the impact of chemical and conformational features on sigma- andp-hole regions could be systematically evaluated by computing the V values on electron densityisosurfaces (VS) and by comparing and dissecting in atomic/atomic group contributions the VSmaxima (VS,max) values calculated for different molecular patterns. The results of this study confirmthat both chemical and conformational features may seriously impact sigma- and p-hole regions andprovide a clear analysis and a rationale of why and how this influence is realized. Hence, the proposedmethodology might offer precious clues for designing changes in the sigma- and p-hole regions, aimed ataffecting their potential involvement in noncovalent interactions in a desired way.