Tunable Interaction Strength and Nature of the S···Br Halogen Bonds in [(Thione)Br₂] Systems

The strength and nature of the S···Br and Br···Br interactions were systematically tuned by altering the electron donor properties of the thione group. Three new halogen-bonded compounds, [(<i>N</i>-methylbenzothiazole-2-thione)­Br₂]·0.5CH₂Cl₂ (<b>1</b>), [(2­(3<i>H</i>)-benzothiazolethione)­Br₂] (<b>2</b>), and [(2-benzimidazolethione)­Br]·[Br₃] (<b>3</b>), were synthesized and studied structurally by using X-ray crystallography and computationally by using charge density analysis based on QTAIM calculations. Analysis of the interaction strength indicated a formation of surprisingly strong S···Br halogen bonds in <b>1</b> (−104 kJ mol^–1, and <i>R</i>_BrS = 0.64) and <b>2</b> (−116 kJ mol^–1, and <i>R</i>_BrS = 0.63) with a substantial covalent contribution. The strong electron donor character of the thione ligand in <b>3</b> induced a heterolytic cleavage of the dibromine molecule and a change in the S···Br interaction nature to form a covalent bond with a high interaction energy (−147 kJ mol^–1, and <i>R</i>_BrS = 0.60)

Tunable Interaction Strength and Nature of the S···Br Halogen Bonds in [(Thione)Br₂] Systems

The strength and nature of the S···Br and Br···Br interactions were systematically tuned by altering the electron donor properties of the thione group. Three new halogen-bonded compounds, [(<i>N</i>-methylbenzothiazole-2-thione)­Br₂]·0.5CH₂Cl₂ (<b>1</b>), [(2­(3<i>H</i>)-benzothiazolethione)­Br₂] (<b>2</b>), and [(2-benzimidazolethione)­Br]·[Br₃] (<b>3</b>), were synthesized and studied structurally by using X-ray crystallography and computationally by using charge density analysis based on QTAIM calculations. Analysis of the interaction strength indicated a formation of surprisingly strong S···Br halogen bonds in <b>1</b> (−104 kJ mol^–1, and <i>R</i>_BrS = 0.64) and <b>2</b> (−116 kJ mol^–1, and <i>R</i>_BrS = 0.63) with a substantial covalent contribution. The strong electron donor character of the thione ligand in <b>3</b> induced a heterolytic cleavage of the dibromine molecule and a change in the S···Br interaction nature to form a covalent bond with a high interaction energy (−147 kJ mol^–1, and <i>R</i>_BrS = 0.60)

Role of C–H···Au and Aurophilic Supramolecular Interactions in Gold–Thione Complexes

The role of noncovalent gold–hydrogen and aurophilic interactions in the formation of extended molecular systems of gold complexes was studied. Three new gold compounds with a heterocyclic thione ligand <i>N</i>-methylbenzothiazole-2-thione (mbtt), namely, [AuCl­(mbtt)] (<b>1</b>), [AuBr­(mbtt)] (<b>2</b>), and [Au­(mbtt)₂]­[AuI₂]_1–<i>n</i>[I₃]_<i>n</i> (<b>3</b>), were synthesized and characterized. The halide ligand had a considerable effect on the complex structures and thus to noncovalent contacts. Intermolecular C–H···Au and aurophilic Au···Au contacts were the dominant noncovalent interactions in structures <b>1</b>–<b>3</b> determining the supramolecular arrays of the gold complexes. In <b>1</b> and <b>2</b>, unusual intermolecular C–H···Au gold–hydrogen contacts linked the adjacent mononuclear molecules to a chain structure, while in <b>3</b> the change in the ligand coordination induced the formation of an intermolecular aurophilic interaction. Au···I, π–π, halogen–halogen, and hydrogen bonding interactions supported further the supramolecular array of <b>3</b>. The interactions were analyzed with theoretical calculations using the Quantum Theory of Atoms in Molecules (QTAIM). The results thus obtained were consistent with the experimental data clarifying both the nature and the role of noncovalent interactions in structures <b>1</b>–<b>3</b>

Versatile Coordination Modes in Silver-Imidazolecarbaldehyde Oxime Complexes: Structural and Computational Analysis

Silver imidazolecarbaldehyde oxime complexes [Ag­(1-methyl-1<i>H</i>-imidazole-2-carbaldehyde oxime)₂]­[NO₃] (<b>1</b>), [Ag­(1-methyl-1<i>H</i>-imidazole-2-carbaldehyde oxime)₂]­[ClO₃] (<b>2</b>), [Ag­(1<i>H</i>-5-methylimidazole-4-carbaldehyde oxime)]₂­[NO₃]₂ (<b>3</b>), [Ag­(1<i>H</i>-imidazole-2-carbaldehyde oxime)]_<i>n</i>­[NO₃]_<i>n</i> (<b>4</b>), [Ag­(1<i>H</i>-4-methylimidazole-5-carbaldehyde oxime)]_<i>n</i>­[ClO₃]<i>_n</i> (<b>5</b>), and [Ag­(<i>N</i>-hydroxy-1-methyl-1<i>H</i>-imidazole-2-carboximidamide)₂]₂­[CF₃SO₃]₂ (<b>6</b>) were structurally and computationally analyzed. Weak intramolecular interactions were found to play the main role in determining the most favorable structure of the free ligands, therefore controlling the final coordination mode, and the nuclearity of the complexes. Further information on the nature of the intra- and intermolecular interactions were provided utilizing computational density functional theory calculations and topological charge density analysis according to the Quantum Theory of Atoms in Molecules. The efficient control of the structure of the complexes also results in a better control of the material properties

Synthesis and Biological Evaluation of Second-Generation Tropanol-Based Androgen Receptor Modulators

To circumvent antiandrogen resistance in prostate cancer, antiandrogens effective for both the androgen receptor (AR) and AR mutants are required. The AR antagonists in this study originate from previous findings, which showed that subtle differences in substitution pattern lead to a conformational change that alters the ligand activity, rendering an agonist to an antagonist. We have identified small yet potent tropanol-based ligands possessing significant antiandrogenic activity with both wild-type AR and the two most common AR ligand binding domain (LBD) mutants

Modulation of Vitamin D Receptor Activity by the Corepressor Hairless: Differential Effects of Hairless Isoforms

The vitamin D receptor (VDR) and its corepressor Hairless (HR) are thought to regulate key steps in the hair cycle because mutations in VDR or HR cause alopecia in humans and mice. Many mammalian cells express two major HR isoforms due to alternative splicing of exon 17. HR isoform-a encodes an 1189-amino acid protein (full-length HR), and isoform-b encodes an 1134-amino acid protein (HRΔ1072-1126). We demonstrated that both HR isoforms are expressed in primary human keratinocytes and in the human keratinocyte cell line HaCaT. In transfected COS-7 cells, the full-length HR repressed VDR-mediated transactivation. In contrast, HRΔ1072-1126 failed to suppress and even stimulated VDR-mediated transactivation. In coimmunoprecipitation, both HR isoforms interacted with the VDR, but only the full-length HR interacted with histone deacetylase 1 (HDAC1). Alanine mutagenesis of two conserved glutamic acids residues (E1100A/E1101A) encoded by exon 17 completely eliminated HR corepressor activity and interactions with HDAC1. When the two HR isoforms were coexpressed in COS-7 cells, the corepressor activity of the full-length HR was not antagonized by the HRΔ1072-1126 isoform. When transfected into HaCaT cells, the full-length HR inhibited endogenous CYP24A1 basal gene expression as well as 1,25-dihydroxyvitamin D3-stimulated CYP24A1 expression. HRΔ1072-1126 failed to suppress basal or 1,25-dihydroxyvitamin D3-stimulated CYP24A1 gene expression. In conclusion, we have demonstrated that both HR isoforms are expressed in keratinocytes and that the HRΔ1072-1126 isoform lacks corepressor activity and is unable to bind HDACs. HRΔ1072-1126 may function as a coactivator in some settings by inhibiting HDAC recruitment to the VDR transcriptional complex