Sabine Foro

Oxidation‐Triggered Ring‐Opening Metathesis Polymerization

Eight new N-Hoveyda-type complexes were synthesized in yields of 67-92 % through reaction of [RuCl2 (NHC)(Ind)(py)] (NHC=1,3-bis(2,4,6-trimethylphenylimidazolin)-2-ylidene (SIMes) or 1,3-bis(2,6-diisopropylphenylimidazolin)-2-ylidene (SIPr), Ind=3-phenylindenylid-1-ene, py=pyridine) with various 1- or 1,2-substituted ferrocene compounds with vinyl and amine or imine substituents. The redox potentials of the respective complexes were determined; in all complexes an iron-centered oxidation reaction occurs at potentials close to E=+0.5 V. The crystal structures of the reduced and of the respective oxidized Hoveyda-type complexes were determined and show that the oxidation of the ferrocene unit has little effect on the ruthenium environment. Two of the eight new complexes were found to be switchable catalysts, in that the reduced form is inactive in the ring-opening metathesis polymerization of cis-cyclooctene (COE), whereas the oxidized complexes produce polyCOE. The other complexes are not switchable catalysts and are either inactive or active in both reduced and oxidized states.

A mononuclear diketone-based oxido-vanadium(IV) complex: structure, DNA and BSA binding, molecular docking and anticancer activities against MCF-7, HPG-2, and HT-29 cell lines

A mononuclear oxido-vanadium(IV) complex, [VO(L)2], has been prepared from the reaction of dibenzoylmethane (HL) and VO(acac)2 in a 2 : 1 molar ratio, and fully characterized using elemental analyses, molar conductivity, FT-IR, and electronic spectroscopy. The structure of this compound was also confirmed by single crystal X-ray diffraction. It was found that in the title complex, the metal coordination geometry is described as a distorted square pyramid. DNA binding activities of this complex were investigated using electronic absorption titration, competitive fluorescence titration and cyclic voltammetry studies. The obtained results showed groove binding of the complex to salmon sperm DNA accompanied with a partial insertion of the ligand between the base stacks of the DNA with a binding constant of 2.3 × 103 M−1. In addition, the interaction of the complex with bovine serum albumin (BSA) was studied using electronic absorption and fluorescence spectroscopies at different temperatures indicating a good affinity of the complex for BSA. These experimental results were confirmed by the results of molecular docking. Finally, the in vitro cytotoxicity properties of the synthesized complex against MCF-7, HPG-2 and HT-29 cell lines were evaluated and compared with those of the ligand (HL). It was found that complexation improved the anticancer activity significantly. IC50 values for the V(IV) complex against MCF-7, HPG-2 and HT-29 cell lines were obtained as 7.8, 13.5 and 16.1 μM, respectively.

Magnetooptical and structural investigations of five dimeric cobalt(II) complexes mimicking metalloenzyme active sites.

Four novel cobalt(II) complexes mimicking metalloenzyme active sites, novel C(14)H(22)Cl(12)Co(2)O(13)·2C(3)H(8)O (1), C(28)H(36)Cl(24)Co(4)O(28)·4C(4)H(8)O(2) (2), C(16)H(22)Cl(12)Co(2)O(13)·C(2)HCl(3)O(2) (3), C(16)H(22)Cl(12)Co(2)O(13) (4), and one known C(40)H(78)Cl(8)Co(2)O(17) (5) are composed of the same core of two high-spin cobalt(II) centers triply bridged by water and two trichloroacetato (1-4) or two pivalate (5) groups but differ in terminal ligands. The crystal structures of new compounds 1-4 belong to the space groups P ̅1, P2(1)/c, P ̅1, and Pbcn, respectively. All five investigated complexes contain Co atoms in distorted octahedral coordination. The complexes were characterized by magnetic susceptibility and magnetization measurements and by variable-temperature variable-field magnetic circular dichroism spectroscopy. Experimental data were analyzed in the frame of the theoretical model, which includes an unquenched orbital moment of the Co(II) ions. All investigated compounds are antiferromagnetically coupled with exchange constants in the range -1.5 to -2.1 cm(-1). However, there is a significant difference between the crystal-field-splitting parameters.

Improved Synthesis of ADAM10 Inhibitor GI254023X

Background: The metalloproteinases ADAM10 and ADAM17 are involved in various diseases: neurodegeneration, cancer and inflammation. Objective: The inhibition of these proteases is a promising target in the treatment of inflammation and cancer. Methods and Results: In this study, we present an improved synthesis of the ADAM10 reference inhibitor GI254023X with a higher overall yield, enhanced detection ability and increased acid stability, providing easier handling. Conclusion: This upscaled synthesis, free of diastereomeric intermediates, ensures single-batch identity, thus warranting its reproducibility in further biological investigations.

N-(2-Chlorobenzoyl)benzenesulfonamide

In the crystal structure of the title compound, C13H10ClNO3S, the conformation of the N—H bond in the C—SO2—NH—C(O) segment is anti to the C=O bond. The dihedral angle between the two benzene rings is 87.5 (1)°. The crystal structure features inversion-related dimers linked by pairs of N—H⋯O(S) hydrogen bonds.

N-Benzoyl-2-chloro-benzene-sulfonamide.

In the crystal structure of the title compound, C13H10ClNO3S, the conformation of the of the N—H bond in the C—SO2—NH—C(O) segment is anti to the C=O bond. The dihedral angle between the two benzene rings is 73.3 (1)°. In the crystal, inversion dimers linked by pairs of N—H⋯O hydrogen bonds occur.

Triptycene‐Based Chiral and meso‐N‐Heterocyclic Carbene Ligands and Metal Complexes

Based on 1-amino-4-hydroxy-triptycene, new saturated and unsaturated triptycene-NHC (N-heterocyclic carbene) ligands were synthesized from glyoxal-derived diimines. The respective carbenes were converted into metal complexes [(NHC)MX] (M=Cu, Ag, Au; X=Cl, Br) and [(NHC)MCl(cod)] (M=Rh, Ir; cod=1,5-cyclooctadiene) in good yields. The new azolium salts and metal complexes suffer from limited solubility in common organic solvents. Consequently, the introduction of solubilizing groups (such as 2-ethylhexyl or 1-hexyl by O-alkylation) is essential to render the complexes soluble. The triptycene unit infers special steric properties onto the metal complexes that enable the steric shielding of selected areas close to the metal center. Next, chiral and meso-triptycene based N-heterocyclic carbene ligands were prepared. The key step in the synthesis of the chiral ligand is the Buchwald-Hartwig amination of 1-bromo-4-butoxy-triptycene with (1S,2S)-1,2-diphenyl-1,2-diaminoethane, followed by cyclization to the azolinium salt with HC(OEt)3 . The analogous reaction with meso-1,2-diphenyl-1,2-diaminoethane provides the respective meso-azolinium salt. Both the chiral and meso-azolinium salts were converted into metal complexes including [(NHC)AuCl], [(NHC)RhCl(cod)], [(NHC)IrCl(cod)], and [(NHC)PdCl(allyl)]. An in situ prepared chiral copper complex was tested in the enantioselective borylation of α,β-unsaturated esters and found to give an excellent enantiomeric ratio (er close to 90:10).

N-(2,5-Dimethyl-phen-yl)benzene-sulfonamide.

In the crystal structure of the title compound, C14H15NO2S, the N—H bond is trans to one of the S=O double bonds, similar to what is observed in N-(2-methylphenyl)benzenesulfonamide and other aryl sulfonamides. The two aromatic rings enclose a dihedral angle of 44.9 (1)°. The molecules are connected by intermolecular N—H⋯O hydrogen bonds into chains running along the a axis. An intermolecular C—H⋯O hydrogen bond is also present.

N-Benzoyl-4-chloro-benzene-sulfonamide.

The asymmetric unit of the title compound, C13H10ClNO3S, contains two independent molecules. The molecules have C—S—N—C torsion angles of −70.0 (2) and 61.3 (2)° for molecules 1 and 2, respectively. The dihedral angles between the sulfonyl benzene rings and the –SO2—NH—C—O segments are 72.0 (1) and 77.3 (1)° for molecules 1 and 2, respectively, and the dihedral angles between the sulfonyl and the benzoyl benzene rings are 62.8 (1) and 78.6 (1)°, respectively. In the crystal, molecules 1 and 2 are linked by pairs of N—H⋯O hydrogen bonds, forming inversion dimers.

N-(3-Chloro­phen­yl)benzene­sulfonamide

In the crystal structure of the title compound, C12H10ClNO2S, the N—H bond is trans to one of the S=O bonds. The two aromatic rings form a dihedral angle of 65.4 (1)°, compared with a value of 49.1 (1)° in N-(2-chlorophenyl)-benzenesulfonamide. The molecules are connected by intermolecular N—H⋯O hydrogen bonds into chains running along the b axis.