Liver X receptors (LXRs) have been increasingly recognized as a potential therapeutic target to treat pathological conditions ranging from vascular and metabolic diseases, neurological degeneration, to cancers that are driven by lipid metabolism. Amidst intensifying efforts to discover ligands that act through LXRs to achieve the sought-after pharmacological outcomes, several lead compounds are already being tested in clinical trials for a variety of disease interventions. While more potent and selective LXR ligands continue to emerge from screening of small molecule libraries, rational design, and empirical medicinal chemistry approaches, challenges remain in minimizing undesirable effects of LXR activation on lipid metabolism. This review provides a summary of known endogenous, naturally occurring, and synthetic ligands. The review also offers considerations from a molecular modeling perspective with which to design more specific LXRβ ligands based on the interaction energies of ligands and the important amino acid residues in the LXRβ ligand binding domain.

Halogen bonds involving cationic halogen bond donors and anionic halogen bond acceptors have recently been recognized as being important in stabilizing the crystal structures of many salts. Theoretical characterization of these types of interactions, most importantly in terms of their directionality, has been limited. Here we generate high-quality symmetry adapted perturbation theory potential energy curves of a H ₃ N–CC–Br ⁺ ⋯Cl ⁻ model system in order to characterize halogen bonds involving charged species, in terms of contributions from electrostatics, exchange, induction, and dispersion, with special emphasis on analyzing contributions that are most responsible for the directionality of these interactions. It is found that, as in the case of neutral halogen bonds, exchange forces are important contributors to the directionality of charged halogen bonds, however, it is also found that induction effects, which contribute little to the stability and directionality of neutral halogen bonds, play a large role in the directionality of halogen bonds involving charged species. Potential energy curves based on the ωB97X-D/def2-TZVP/C-PCM method, which includes an implicit solvation model in order to mimic the effects of the crystal medium, are produced for both the H ₃ N–CC–Br ⁺ ⋯Cl ⁻ model system and for the 4-bromoanilinium⋯Cl ⁻ dimer, which is based on the real 4-bromoanilinium chloride salt, whose crystal structure has been determined experimentally. It is found that, within a crystal-like medium, charged halogen bond are significantly weaker than in the gas phase, having optimum interaction energies up to approximately −20 kcal mol ⁻¹ .

Here, we investigate the strengths of R–X···π interactions, involving both chlorine and bromine, in model systems derived from protein-ligand complexes found in the PDB. We find that the strengths of these interactions can vary significantly, with binding energies ranging from −2.01 to −3.60 kcal/mol. Symmetry adapted perturbation theory (SAPT) analysis shows that, as would be expected, dispersion plays the largest role in stabilizing these R–X···π interactions, generally accounting for about 50% to 80% of attraction. R–Br···π interactions are, for the most part, found to be stronger than R–Cl···π interactions, although the relative geometries of the interacting pair and the halogen’s chemical environment can also have a strong impact. The two factors that have the strongest impact on the strength of these R–X···π interactions is the distance between the halogen and the phenyl plane as well as the size of the halogen σ-hole.

In this paper, we focus on surface electrostatic potentials and a variety of statistically derived quantities defined in terms of the surface potentials. These have been shown earlier to be meaningful in describing features of these potentials and have been utilized to understand the interactive tendencies of molecules in condensed phases. Our current emphasis is on ionic salts and liquids instead of neutral molecules. Earlier work on ionic salts has been reviewed. Presently, our results are for a variety of singly charged cations and anions that can combine to form ionic solids or liquids. Our approach is computational, using the density functional B3PW91/6-31G(d,p) procedure for all calculations. We find consistently that the average positive and negative surface electrostatic potentials of the cations and anions decrease with the size of the ion, as has been noted earlier. A model using computed statistical quantities has allowed us to put the melting points of both ionic solids and liquids together, covering a range from 993 °C to 11 °C.