Form Hydrogen-bonded Dimers Research Articles

Structural characterization of a 3-hydroxychromone dye trehalose conjugate for fluorescent labelling of mycobacteria

3-Hydroxychromone (3HC) dye trehalose conjugates have previously been exploited as environment-sensitive fluorescent labels to detect mycobacteria by fluorescence microscopy. We have studied the 3HC dye 2-(6-(diethylamino)benzofuran-2-yl)-3-hydroxy-4H-chromen-4-one (3HC-2) trehalose conjugate 3HC-2-Tre by X-ray crystallography, spectroscopic methods augmented by DFT calculations and conducted preliminary labelling experiments with Mycobacterium abscessus, a non-tuberculous mycobacterium and opportunistic pathogen. In the crystal structure of 3HC-2-Tre ⋅ 3.14 H2O, the 3HC-2-Tre molecules exhibit an intramolecular OH⋅⋅⋅O hydrogen bond between the 5-hydroxy group of trehalose and the chromone carbonyl oxygen atom, and form hydrogen-bonded dimers via the trehalose units with approximate local C2 symmetry. The chromophore adopts an s-cis conformation of the chromone and benzofuran systems about its central CC bond, as previously encountered in the crystal structure of the free dye 3HC-2, and the trehalose moieties approximately retain the shape as found in the crystal structures of anhydrous trehalose and the dihydrate. Absorption spectra of 3HC-2-Tre acquired in four different solvents revealed small positive solvatochromy. Fluorescence microscopy detected M. abscessus cells treated with 3HC-2-Tre in the GFP channel.

On the structures of free-base lepidine and some mineral acid salts

The crystal and molecular structures of free-base lepidine (4-methylquinoline, 1) and the mineral acid salts lepidinium chloride (2), nitrate (3) and dihydrogen phosphate (4) are reported. Compound 1 was studied by differential scanning calorimetry and in situ capillary cryocrystallography. In the crystal structures, the molecules of free-base lepidine in 1 and the lepidinium cations in 2–4 are face-to-face π⋅⋅⋅π-stacked. The quinoline nitrogen atom is not involved in directional intermolecular interactions such as weak hydrogen bonds in 1. In the salts 2–4, proton transfer to the quinoline nitrogen atom and N−H⋅⋅⋅Cl (in 2) and N−H⋅⋅⋅O (in 3 and 4) hydrogen bonding is observed. Hirshfeld surface analysis reveals that lepidinium salts 2 and 3 form hydrogen-bonded dimers in the crystal and confirms that the packing of 4 is dominated by hydrogen-bonded dihydrogen phosphate anion chains.

Polymorphism of Oligomers of a Peptide from β-Amyloid

This contribution reports solution-phase structural studies of oligomers of a family of peptides derived from the β-amyloid peptide (Aβ). We had previously reported the X-ray crystallographic structures of the oligomers and oligomer assemblies formed in the solid state by a macrocyclic β-sheet peptide containing the Aβ15–23 nonapeptide. In the current study, we set out to determine its assembly in aqueous solution. In the solid state, macrocyclic β-sheet peptide 1 assembles to form hydrogen-bonded dimers that further assemble in a sandwich-like fashion to form tetramers through hydrophobic interactions between the faces bearing V18 and F20. In aqueous solution, macrocyclic β-sheet peptide 1 and homologue 2a form hydrogen-bonded dimers that assemble to form tetramers through hydrophobic interactions between the faces bearing L17, F19, and A21. In the solid state, the hydrogen-bonded dimers are antiparallel, and the β-strands are fully aligned, with residues 17–23 of one of the macrocycles aligned with residues 23–17 of the other. In solution, residues 17–23 of the hydrogen-bonded dimers are shifted out of alignment by two residues toward the C-termini. The two hydrogen-bonded dimers are nearly orthogonal in the solid state, while in solution the dimers are only slightly rotated. The differing morphology of the solution-state and solid-state tetramers is significant, because it may provide a glimpse into some of the structural bases for polymorphism among Aβ oligomers in Alzheimer’s disease.

Synthesis and structure of trans-(+)-(3 S,4 S)-3-amino-4-ferrocenyl-1- p-methoxyphenylazetidin-2-one

trans-(+)-(3 S,4 S)-3-Amino-4-ferrocenyl-1- p-methoxyphenylazetidin-2-one ( I) was obtained with >99% e.e. applying lithium chiral ester enolate-imine condensation strategy. The X-ray structure was determined in order to establish unambigously both absolute and relative configurations at the stereogenic centers C11 and C12. The final value of the freely refined Flack parameter, x=−0.007(11), confirmed the S configuration at both stereogenic centers C11 and C12. The azetidin-2-one ring and the methoxyphenyl moiety revealed a static disorder with the two slightly different, but clearly resolved conformations with the partial population factors close to 0.5 (conformations A and B). The ferrocene subunit and the atom C11 which is attached directly to the cyclopentadiene of the ferrocene moiety, on the other hand, reveal unique crystallographic positions throughout the structure. The crystal structure determination confirmed the trans-arrangement of the substituents with respect to the bond C11–C12 (torsion angle C6–C11–C12–N2 is 121.5(15)° in conformation A and C6–C11–C12A–N2A is 125(6)° in conformation B). The non-bonded interactions governing crystal packing are present only between the molecules of the identical conformation. Consequently, two separated crystal packing conceptions are present in the structure, and none of the non-covalent interactions was observed between them. Hydrogen bonding patterns between those two packings are rather different: while molecules of the conformation A form hydrogen-bonded dimers via N2–H2B⋯O1 bond, those of the conformation B form endless double chains via N2A–H2A3⋯O2A and N2A–H2A2⋯O1A bonds.

5-(4-Methoxyphenyl)-4-methylthiazole-2(3H)-thione

The mol­ecules of the title compound, C11H11NOS2, form hydrogen-bonded dimers in the solid state. The amide H atom serves as hydrogen-bond donor and the thio­carbonyl S atom of a neighbouring mol­ecule serves as acceptor. The p-methoxy­phenyl substituent is tilted by 7.3 (5)° from the thia­zole-2(3H)-thione plane.

The twinned crystal structure of rac-(R,R)-N,N'-oxalyldivalinol.

The title compound, rac-(R,R)-N,N'-bis(1-hydroxy-3-methyl-2-butyl)oxalamide, C 12 H 24 N 2 O 4 , crystallizes as a non-merohedral twin in the triclinic space group P1. The twin is generated by a twofold rotation about c*. The terminal hydroxy groups of molecules related by an inversion center form hydrogen-bonded dimers. This hydrogen-bonding pattern is further extended into a one-dimensional chain by N-H...O hydrogen bonds.

Anion–anion dimerization in tetrabutylammonium hydrogensulfate

The hydrogen­sulfate ions of the title compound, C16H36N+·HSO4−, form hydrogen-bonded dimers.

Structural characteristics of isoxazol-3-ol and isothiazol-3-ol, carboxy group bioisosteres examined by X-ray crystallography and ab initio calculations

Low-temperature single-crystal structure determinations have been carried out on isoxazol-3-ol, 5-methyl-isoxazol-3-ol, isothiazol-3-ol and 5-methylisothiazol-3-ol, the heterocyclic ring systems used as carboxy group bioisosteres in numerous neuroactive analogues of 4-aminobutyric acid (GABA) and glutamic acid. All compounds form hydrogen-bonded dimers in the solid state. The OH · · · N hydrogen bonds are shorter in isoxazol-3-ols than in isothiazol-3-ols. The excess molecular van der Waals volume of the sulfur-containing ring systems as compared to the corresponding isoxazol-3-ols amounts to about 15%. The sulfur substitution significantly affects the position of the 5-substituents in relation to the heterocyclic ring. Such effects may contribute to the observed differences in pharmacological effects of the structurally related isoxazol-3-ol and isothiazol-3-ol amino acids. The geometries of the compounds have been optimized by ab initio calculations at the HF/6-31G* level, and in some cases also at the MP2/6-311G** level. The gas-phase calculations are in agreement with the experimental data, especially when correction for the effects of hydrogen bonding is made, as estimated using a complex between isoxazol-3-ol and formic acid. Calculated dipole moments of isoxazol-3-ols and isothiazol-3-ols are similar. Isoxazol-3-ol is more acidic than isothiazol-3-ol by 1.7 pKa unit as determined by 13C NMR titration, and the differences in acidity are believed to be one of the major factors causing the differences in the biological actions of isoxazol-3-ol amino acids and the corresponding isothiazol-3-ol analogues.

Syn- and anti-Conformation in oxodipyrromethenes: crystal and molecular structure of 3,4-dimethyl-2,2′-pyrromethen-5(1H)-one and its N-methyl derivative

The structure of two oxodipyrromethenes have been determined from three-dimensional diffractometer data. One is 3,4-dimethyl-2,2′-pyrromethen-5(1H)-one, C11H12N2O (I), which crystallizes in the monoclinic space group P21/n with a= 13.597(1), b= 5.809(1), c= 12.558(1)Å, β= 101.29(1)°, Z= 4. The second is a derivative of this compound in which one of the pyrrole nitrogen atoms is methylated. This is 1′,3,4-trimethyl-2,2′-pyrromethen-5(1H)-one, C12H14N2O, (II). It also crystallizes in P21/n with a= 7.122(1), b= 22.873(1), c= 7.012(1)Å, β= 104.64(2)°, Z= 4. Both structures were solved by direct methods and refined by full-matrix least squares. The isomers obtained both had the Z-configuration, but in (I), the nitrogen atoms are syn, while in (II), they are anti. Both compounds show relatively small deviation from planarity, but (II) shows larger deviations than (I). Both form hydrogen-bonded dimers between the lactam oxygen atom and pyrrole nitrogen atoms. A comparison of the structures in the solid state and in solution indicates the difference in energy between a planar and twisted conformation is small.