Andreas Heine

Structure and crystal packing of 4-aminobenzonitriles and 4-amino-3,5-dimethylbenzonitriles at various temperatures

The amino N atom in 4-aminobenzonitrile (ABN) and 4-(dimethylamino)benzonitrile (DMABN) has a pyramidal character, with values of 34 (3) and 11.9 (3) o , respectively, for the angle between the planes of the amino group and the phenyl ring. In 3,5-dimethyl-4-(dimethylamino)benzonitrile (MMD) at 173 K, the dimethylamino group is twisted over an angle of 59.3 (2) o with respect to the phenyl plane. In addition, the amino N(1) atom is not located in the plane of the phenyl ring, with an out-of-plane displacement of 0.117 (5) A

One Question, Multiple Answers: Biochemical and Biophysical Screening Methods Retrieve Deviating Fragment Hit Lists.

Fragment‐based lead discovery is gaining momentum in drug development. Typically, a hierarchical cascade of several screening techniques is consulted to identify fragment hits which are then analyzed by crystallography. Because crystal structures with bound fragments are essential for the subsequent hit‐to‐lead‐to‐drug optimization, the screening process should distinguish reliably between binders and non‐binders. We therefore investigated whether different screening methods would reveal similar collections of putative binders. First we used a biochemical assay to identify fragments that bind to endothiapepsin, a surrogate for disease‐relevant aspartic proteases. In a comprehensive screening approach, we then evaluated our 361‐entry library by using a reporter‐displacement assay, saturation‐transfer difference NMR, native mass spectrometry, thermophoresis, and a thermal shift assay. While the combined results of these screening methods retrieve 10 of the 11 crystal structures originally predicted by the biochemical assay, the mutual overlap of individual hit lists is surprisingly low, highlighting that each technique operates on different biophysical principles and conditions.

[Cu2R2BrLi(thf)3], R = Si(SiMe3)3–a complex containing five-coordinate silicon in a three-centre two-electron bond (thf = tetrahydrofuran)

The title compound is obtained from the reaction of (Me3Si)3SiLi(thf)3 with CuBr in n-hexane and structurally characterised by X-ray diffraction; in [Cu2R2BrLi(thf)3], R = Si(SiMe3)3 one silyl ligand is bridging a very short Cu–Cu bond, resulting in a three-centre two-electron bond, while the second is terminally bound to copper; the other copper atom is linked to a lithium atom via a Cu ⋯ Br ⋯ Li bridge.

Strukturuntersuchungen an den Produkten aus der Reaktion des Tris(trimethylsilyl)silyllithiums mit Aceton

Abstract The reaction of (Me 3 Si) 3 SiLi ( 1 ) with acetone has been clarified with the aid of crystal structure and 29 Si NMR investigations of H(Me 3 Si) 2 Si(Me 3 Si) 2 SiCMe 2 SiMe 3 ( 3 ) and (Me 3 Si) 3 Si(Me 3 Si) 2 SiCMe 2 SiMe 3 ( 4 ). The chemically but not crystallographically equivalent silicon atoms in 3 and 4 and the two crystallographically independent molecules of 4 all gave rise to separate signals in the solid state 29 Si-MAS NMR spectra. The 1 J ( 29 Si, 29 Si) couplings observed in solution facilitated the assignment of 29 Si resonances.

2,5-Dihydroborole und 1,3-dihydro-1,3-diborete aus 1,3-dienen und aus alkinen durch umsetzung mit dichlor(diisopropylamino)boran und alkalimetallen

Abstract The reactions of subvalent species generated by the reaction of dichloro(diisopropylamino)borane with sodium/potassium alloy with unsaturated aliphatic hydrocarbons, have yielded the following compounds: the 2,5-dihydroboroles I and II from 1,3-dienes; the 1,3-dihydrodiboretes III and IV from alkynes and the 1-bis(diisopropylamino)boryl-2-trimethylsilylethyne V from bis(trimethylsilyl)ethyne. The compounds have been characterized by elemental analyses and by mass and NMR (1H, 11B, 13C and in part 15N and 29Si) spectroscopy. An X-ray diffraction study has been performed on II.

Structures of quinoxaline antibiotics

The crystal structures of three quinoxaline antibiotics-echinomycin 2QN, triostin C and the C222(1) form of triostin A--have been determined, and the structure of the P2(1)2(1)2(1) form of triostin A has been re-refined against our previously reported data. The molecular conformations are compared with those deduced from NMR data and those reported for two complexes of triostin A with oligonucleotides. Although the depsipeptide ring conformations are basically similar, the effective twofold molecular symmetry is violated by the folding of one of the quinoxaline chromophores in echinomycin 2QN and by a rotation of one of the ester planes with the formation of an intramolecular hydrogen bond in triostin C. In the oligonucleotide complexes of triostin A the chirality of the disulfide bridge is inverted. The alanine NH groups are involved in intermolecular hydrogen bonds in all four structures, and (except in echinomycin 2QN) the stacking of the chromophores in the crystal emulates the intercalation involved in DNA complex formation. In echinomycin 2QN, the antibiotic molecules are hydrogen bonded to form a helix along the crystallographic 6(5) screw axes, with a channel of disordered solvent running through the middle of the helix. Crystal data: (1), echinomycin 2QN, C53H66N10O12S2.2.5(C3H6O).2.5(H2O), M(r) = 1289.5, hexagonal, P6(5), a = b = 22.196(15), c = 24.64 (2) A, V = 10,513 (13) A3, Z = 6, Dx = 1.222 Mg m-3, lambda (Cu K alpha) = 1.5418 A, mu = 1.275 mm-1, T = 193 K, R = 9.0% for 4828 I > 2 sigma (I) and 11.8% for all 7102 unique reflections; (2), triostin C, C54H70N12O12S2.0.67(CHCl3).0.67(H2O), M(r) = 1234.2, orthorhombic, P2(1)2(1)2(1), a = 16.054 (8), b = 17.128 (9), c = 22.706 (12) A, V = 6244 (6) A3, Z = 4, Dx = 1.313 Mg m-3, lambda (Mo K alpha) = 0.71073 A, mu = 0.239 mm-1, T = 188 K, R = 7.7% for 4678 I > 2 sigma (I) and 14.0% for all 7260 unique reflections; (3), triostin A, C50H62N12O12S2.2(C7H14O2), M(r) = 1347.6, orthorhombic, P2(1)2(1)2(1), a = 20.94 (2), b = 18.53 (2), c = 18.80 (2) A, V = 7292 (13) A3, Z = 4, Dx = 1.228 Mg m-3, lambda (Cu K alpha) = 1.5418 A, mu = 1.245 mm-1, T = 293 K, R = 6.8% for 2116 I > 2 sigma (I) and 9.3% for all 2928 unique reflections; (4), triostin A, C50H62N12O12S2.HCl.2(C3H7NO), M(r) = 1269.9, monoclinic, C222(1), a = 10.622 (10), b = 17.035 (17), c = 35.21 (3) A, V = 6371 (10) A3, Z = 4, Dx = 1.324 Mg m-3, lambda (Mo K alpha) = 0.71073 A, mu = 0.199 mm-1, T = 153 K, R = 7.5% for 2164 I > 2 sigma (I) and 13.2% for all 3402 unique reflections. Extensive use was made of restraints on the geometrical and displacement parameters in the successful anisotropic refinement of these structures against weak data.

Synthesis and X-Ray crystal structure of a tricyclic lead-nitrogen-boron heterocycle

1,3,5,7-Tetra-t-butyl-4,8-Biphenyl-1,3,5,7-tetra-aza-2,6-diplumba-4,8-diboratricyclo[4.2.0.02,5]octane-1,5-diium-2,6-diide(1)hasbeen obtained from PhB(NButLi)2 and PbCl4in hexane or from PbCl2 intetrahydrofuran and structurally characterised by X-ray diffraction.

Reaktionen der Enthalogenierungsprodukte von Dichlor(diisopropylamino)boran mit Olefinen in n-Hexan

Reactions of vinyltrimethylsilane, propene, 3,3-dimethyl-1-butene, 1-butene, 3-methyl-1-butene, 1-pentene, 4,4-dimethyl-1-pentene, cyclopentene, cyclohexene and cyclooctene with dichloro(diisopropylamino)borane and Na/K-alloy in n-hexane yield the 1,2-diboretanes I-VII, IX, XI and the 1,2,3-triborolanes VIII, X, XII. By-products XIV and XVI–XVIII were found in the mass-spectra. In reaction to VII the 1,2,3,4-tetrakis(diisopropylamino)tetraborane(6) (XIX) was isolated as by-product. Vinyl-3-cyclohexene reacts under the same conditions to give the triborolane (XIII). The compounds I–XIII, XV and XIX were characterized by elemental analyses and spectroscopic data (MS; NMR: 1H, 13C, 11B, 29Si), X, XII, XIII and XIX also by X-ray structure analyses.

Neue Cyclophosphazene mit Metallen der III. Hauptgruppe als Ringbausteine / New Cyclophosphazenes with Metals of Main Group III as Building Blocks

Abstract Acylic silylated phosphazenes of the type HN(PR2NSiMe3)2 (1) react quantitatively with molecules MMe3 (M = Al, Ga, In) under ring formation and CH4 evolution. The ring compounds N(PPh2NSiMe3)2AlMe2 (2 a) and N(PPh2NSiMe3)2InMe2 (4 a) have been investiga ted by X-ray structure determination. 2a and 4a crystallize in the space groups P 1̄ and P 31, respectively; they show different conformations regarding the cyclohexane framework. NMR spectroscopy of the nuclei in the chelating phosphazene ligand indicates decreasing Lewis acidity of the metal containing fragments in the series AlMe2 ≥ GaMe2 > InMe2.

New Insights into Human 17β-Hydroxysteroid Dehydrogenase Type 14: First Crystal Structures in Complex with a Steroidal Ligand and with a Potent Nonsteroidal Inhibitor

17β-HSD14 is a SDR enzyme able to oxidize estradiol and 5-androstenediol using NAD(+). We determined the crystal structure of this human enzyme as the holo form and as ternary complexes with estrone and with the first potent, nonsteroidal inhibitor. The structures reveal a conical, rather large and lipophilic binding site and are the starting point for structure-based inhibitor design. The two natural variants (S205 and T205) were characterized and adopt a similar structure.