Exploring the (Very Flat) Potential Energy Landscape of R−Br⋅⋅⋅π Interactions with Accurate CCSD(T) and SAPT Techniques

Abstract

Halogen bonds involving an aromatic moiety as an acceptor, otherwise known as R-X…π interactions, have increasingly been recognized as being important in materials and in protein-ligand complexes. These types of interactions have been the subject of many recent investigations, but little is known about the ways in which the strengths of R-X…π interactions vary as a function of the relative geometries of the interacting pairs. Here we use the accurate CCSD(T) and SAPT2+3δMP2 methods to investigate the potential energy landscapes for systems of HBr, HCCBr, and NCBr complexed with benzene. It is found that only the separation between the complexed molecules have a strong effect on interaction strength while other geometric parameters, such as tilting and shifting R-Br…π donor relative to the benzene plane, affect these interactions only mildly. Importantly, it is found that the C6v (T-shaped) configuration is not the global minimum for any of the dimers investigated.

Strength and Character of R–X···π Interactions Involving Aromatic Amino Acid Sidechains in Protein-Ligand Complexes Derived from Crystal Structures in the Protein Data Bank

“…R-X···π interactions are generally slightly weaker than their R-X···Y counterparts, with binding energies whose magnitudes are typically 10-25% lower [20,25,29]. The SAPT characteristics of R-X···π interactions are similar to those of R-X···Y interactions, however, the former tend to have larger relative contributions from dispersion, which is to be expected given the large size and polarizabilities of both halogens and phenyl groups [25,29].…”

“…The SAPT characteristics of R-X···π interactions are similar to those of R-X···Y interactions, however, the former tend to have larger relative contributions from dispersion, which is to be expected given the large size and polarizabilities of both halogens and phenyl groups [25,29]. The geometric properties of R-X···π interactions are inherently different than those of standard halogen bonds because of the diffuse nature of the region of negative potential in an aromatic system.…”

“…Thus, it is observed that a halogen bound to an electron withdrawing group will generally have a larger, more positive, σ-hole than one bound to an electropositive or electroneutral group. The size of a σ-hole correlates strongly with the strength of the halogen bonding, or R-X···π, interaction in which the halogen participates [24,25,34,35].…”

“…Traditionally, electronegative Lewis bases have been considered the primary halogen bond accepting group, as is true in hydrogen bonding [12][13][14][15][16]. More recently, π-bonding and aromatic moieties have been shown to be effective halogen bond acceptors, leading to a subclass of interactions, sometimes called R-X···π (or C-X···π) interactions [19][20][21][22][23][24][25].…”

“…In a recent computational study, utilizing the accurate CCSD(T)/aug-cc-pVQZ and SAPT2+3δMP2/aug-cc-pVTZ methods on model complexes involving a benzene R-X···π acceptor, the ways in which the strengths of R-X···π interaction depends on the relative orientation of the interacting pair that were investigated [25]. It was seen that the strength of an R-X···π interaction depends strongly on the distance between the halogen and the benzene ring, a distance that is described by both R(R-X···π) and the α angle (as defined in Figure 2, and first introduced by Glaser et al) [33], while being only mildly dependent on the R-X···π angle (θ).…”