1-Butyl-1-chloro-3-methyl-3H-2,1λ4-benzoxatellurole: crystal structure and Hirshfeld analysis

Two independent molecules comprise the asymmetric unit in the title benzoxatellurole compound, C12H17ClOTe. The molecules, with the same chirality at the methine C atom, are connected into a loosely associated dimer by Te...O interactions, leading to a {...Te—O}2 core. The resultant C2ClO2 donor set approximates a square pyramid with the lone pair of electrons projected to occupy a position trans to the n-butyl substituent. Interestingly, the TeIV atoms exhibit opposite chirality. The major difference between the independent molecules relates to the conformation of the five-membered chelate rings, which is an envelope with the O atom being the flap, in one molecule and is twisted about the O—C(methine) bond in the other. No directional intermolecular interactions are noted in the molecular packing beyond the aforementioned Te...O secondary bonding. The analysis of the Hirshfeld surface reveals the dominance of H...H contacts, i.e. contributing about 70% to the overall surface, and clearly differentiates the immediate crystalline environments of the two independent molecules in terms of both H...H and H...Cl/Cl...H contacts

Crystal structure of (E)-dichloro(1-chloro-3-methoxyprop-1-en-2-yl)(4-methoxyphenyl)-λ4-tellane, C11H13Cl3O2Te

C11H13Cl3O2Te, monoclinic, P21/c (no. 14), a = 11.0098(8) Å, b = 16.471(1) Å, c = 8.4975(7) Å, β = 99.421(7)°, V = 1520.17(19) Å3, Z = 4, Rgt(F) = 0.0306, wRref(F2) = 0.0852, T = 293(2) K

Crystallographic and docking (Cathepsins B, K, L and S) studies on bioactive halotelluroxetanes

The molecular structures of the halotelluroxetanes p-MeOC6H4Te(X)[C(=C(H)X′)C(CH2)nO], X=X′=Cl and n=6 (1) and X=Cl, X′=Br and n=5 (4), show similar binuclear aggregates sustained by {· · ·Te–O}2 cores comprising covalent Te–O and secondary Te· · ·O interactions. The resulting C2ClO2(lone-pair) sets define pseudo-octahedral geometries. In each structure, C–X· · ·π(arene) interactions lead to supramolecular layers. Literature studies have shown these and related compounds (i.e. 2: X=X′=Cl and n=5; 3: X=X′=Br and n=5) to inhibit Cathepsins B, K, L and S to varying extents. Molecular docking calculations have been conducted on ligands (i.e. cations derived by removal of the tellurium-bound X atoms) 1′–3′ (note 3′=4′) enabling correlations between affinity for sub-sites and inhibition. The common feature of all docked complexes was the formation of a Te–S covalent bond with cysteine residues, the relative stability of the ligands with an E-configuration and the formation of a C–O· · ·π interaction with the phenyl ring; for 1′ the Te–S covalent bond was weak, a result correlating with its low inhibition profile. At the next level differences are apparent, especially with respect to the interactions formed by the organic-ligand-bound halides. While these atoms do not form specific interactions in Cathepsins B and K, in Cathepsin L, these halides are involved in C–O· · ·X halogen bonds

Crystal structures and docking studies in cathepsin S of bioactive 1,3‐diphenyl‐4‐(trichloro‐λ4‐tellanyl)but‐2‐en‐1‐one derivatives

The molecular structures of three 1,3‐diphenyl‐4‐(trichloro‐lλ4‐tellanyl)but‐2‐en‐1‐one derivatives (1–3), show similar coordination geometries defined by methylene-C, three chloride and carbonyl-O atoms. In each case, the resulting CCl3O donor set defines a square-pyramid with the vacant space opposite the methylene-C atom occupied by a lone-pair of electrons. Each of the molecules dimerises in the crystal via weak intermolecular Te…Cl interactions so a distorted ψ-pentagonal-bipyramidal geometry ensues. Previous work has shown these compounds to inhibit cathepsin S to varying extents, with 2, having 2-methoxy substituents in the 2-position of rings, being particularly effective. Molecular docking calculations of cathepsin S with ligands 1'–3' (i.e. cations derived from 1–3 by removal of one of the tellurium-bound chloride atoms) showed the higher experimental second order inactivation rate of 2, compared with the other two ligands, is explained by the observation that the ligand occludes the entrance to the channel thereby blocking access to the catalytic Cys25 site and also because 2' occupies part of the crucial subsite S3 of the protein

Crystal structure of (E)-dichloro(1-chloro-3-methoxyprop-1-en-2-yl)(4-methoxyphenyl)-λ4-tellane, C11H13Cl3O2Te

C11H13Cl3O2Te, monoclinic, P21/c (no. 14), a = 11.0098(8) Å, b = 16.471(1) Å, c = 8.4975(7) Å, β = 99.421(7)°, V = 1520.17(19) Å3, Z = 4, Rgt(F) = 0.0306, wRref(F2) = 0.0852, T = 293(2) K

Structure-activity relationships of hypervalent organochalcogenanes as inhibitors of cysteine cathepsins V and S

A new series of organotelluranes were synthesized and investigated, and the structure-activity relationships in cysteine proteases inhibition were determinated. It was possible to identify the relevance of structural components linked to the reactivity of these compounds as inhibitors. For example, dibromo-organotelluranes showed to be more reactive than dichloro-organotelluranes towards cysteine cathepsins V and S. Besides, no remarkable enantio-selectivity was verified. In general the achiral organotelluranes were more reactive than the chiral congeners against cysteine cathepsins V and S. A reactivity order for organochalcogenanes and cysteine cathepsins was proposed after the comparison of the inhibitory potencies of organotelluranes with the related organoselenanes. (C) 2011 Elsevier Ltd. All rights reserved.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)CNPqCAPESCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)FAPESPFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP