Conformational Properties of Aromatic Amides Bearing Imidazole Ring and Acid-Induced Trans-Cis Amide Switching.

Aromatic amides bearing secondary amide bond exist in trans conformation both in the crystal and in solution, whereas the conformation of the N-methylated derivatives is cis in the crystal and predominantly cis in various solvents. The cis conformational preference of N-alkylated benzanilide provides access to aromatic foldamers such as oligo(N-alkyl-p-benzamide)s, which adopt dynamic helical structures. Here, the conformational properties of imidazole-substituted amide in the crystal and in solution were examined. Imidazole-substituted amides 2a and 4a existed mainly in the cis conformation in solution. The ratio of the cis conformer of N-methyl-N-(1-methyl-1H-imidazol-4-yl)benzamide (4a) was smaller than that of N,1-dimethyl-N-phenyl-1H-imidazole-2-carboxamide (2a) or N-methylbenzanilide, but the introduction of a substituent strongly affected the conformer ratio. Compounds 6a and 7a bearing an electron-withdrawing group on the imidazole ring existed predominantly in trans form. On the other hand, the introduction of an electron-withdrawing group on the phenyl ring or a bulky substituent on the amide nitrogen of 4a increased the ratio of cis conformer. Further, the major conformer of N-alkylated N-imidazolylamides was switched from cis to trans by the addition of acid. These results suggest that imidazole-substituted amides might be applicable as conformational switches in aromatic foldamers to enable environment-dependent structural change.

Conformational Properties of Aromatic Oligoamides Bearing Pyrrole Rings.

N-Alkylbenzanilides generally exist in cis conformation both in the crystalline state and in various solvents, and this cis conformational preference can be utilized to construct dynamic helical oligoamides. Here, we synthesized the pyrrole-containing amides 2-5 and their oligomers 6-8 and examined their conformations in the crystalline state and in solution. All the N-methylated amides showed cis conformational preference in solution, but the ratio of the cis isomer was decreased when the amide bond was attached at the 4-position of the pyrrole ring, probably because the destabilization of the trans conformer due to electronic repulsion between the pyrrole π electrons and the amide carbonyl lone-pair electrons is reduced due to the small torsion angle between the 5-membered N-pyrrole and the amide bond. In the crystalline state, N-methylated amides showed cis structure, except for compound 5, and cis conformational preference was observed for the pyrrole amides. The CD spectra of oligoamides 15-18 bearing chiral N-substituents were consistent with the presence of dynamic and well-defined chiral foldamers, which were structurally distinct from N-alkylated poly( p-benzamide)s 1.

Structural elucidation of foldamers with no long range conformational order.

The synthesis and structural investigation of aromatic-aliphatic oligoamide foldamers reveals a zig-zag tape conformation with local conformational variability that precludes long range order.

Folding of a linear array of α-amino acids within a helical aromatic oligoamide frame.

Control of the spatial organization of proteinogenic side chains is critical for the development of protein mimics with selective recognition properties toward target protein surfaces. We present a novel methodology for producing a linear array of proteinogenic residues based on the incorporation of α-amino acids into sequences of rigid, helically folded oligoamides of 8-amino-2-quinolinecarboxylic acid (Q). When L-leucine (L) was alternated with dimer Q2, the resulting sequence adopted a right-handed helical conformation, as deduced in solution from the CD spectra of L-(LQ2)n (n = 2, 4) and in the solid state from X-ray crystallographic analysis of (±)-(LQ2)4. Each LQ2 segment spanned just one helix turn (pitch of 3.5 Å), and consequently, the four leucine side chains of (LQ2)4 formed a linear array. In solution, NMR analysis showed that both L-(LQ2)2 and L-(LQ2)4 exist as a mixture of two slowly equilibrating folded conformers, the proportion of which strongly varies with the solvent.

Synthesis of soluble aromatic multilayered tetra(m-phenylurea) and analysis of its helical conformation in various solvents.

Aromatic N,N'-dimethylated urea exists in (cis, cis) form, both in the crystal and in solution, and this structure can be utilized to construct intramolecular aromatic multilayered oligomers. These structures show helical conformation with all-R or all-S axis chirality, when the benzene rings are connected at the meta positions. To investigate the dynamic conformational behavior of such aromatic multilayered ureas in various solvents, we synthesized tetra(m-phenylurea) 3 bearing two chiral N-2-(methoxyethoxyethoxy)propyl groups and six N-methoxyethoxyethyl groups. The high solubility of compound 3 enabled its analysis in various solvents, including water. The CD spectra of compound 3 showed broad electronic absorption with high temperature-dependency, owing to the induction of handedness, in acetonitrile, chloroform, and methanol. In water, the CD signals of compound 3 indicated the presence of similar helical structure, but temperature-dependency was not observed.

Identification of absolute helical structures of aromatic multilayered oligo(m-phenylurea)s in solution.

The oligomeric aromatic ureas bearing N,N'-dimethylated urea bonds such as 3 have aromatic multilayered structure, based on the (cis,cis)-urea structure, and also have dynamic helical structure (all-R or all-S axis chirality) when the benzene rings are connected at the meta positions. The absolute helical structure of oligo(m-phenylurea)s were identified by the empirical and theoretical studies on the CD and vibrational CD (VCD) spectra. Thus, each enantiomer of the oligo(m-phenylurea)s 4 bearing a chiral N-2-(methoxyethoxyethoxy)propyl group were synthesized. Intense dispersion-type CD spectra of 4 were observed, which indicated the induction of handedness in the helical structure. In the VCD spectra of 4 in the film state, the signals due to the carbonyl and aromatic ring vibrations were seen with negative and positive values for compounds 4a and 4b, respectively. The calculations of both CD and VCD spectra of oligo(m-phenylurea)s 3 without any chiral N-substituent gave the same assignment about the axis chirality of 4. Thus, the absolute configurations of 4a and 4b are all-R and all-S structures, respectively.

Practical rapid, minimally invasive, reliable nonendoscopic method to obtain Helicobacter pylori for culture.

BACKGROUND: Helicobacter pylori culture typically requires endoscopy. AIM: To develop a minimally invasive rapid and reliable method to obtain H. pylori cultures. METHODS: An extendable oro-gastric brush, contained within a plastic over-tube, was constructed (Baylor Brush, US Endoscopy). After topical oral anesthesia, the 5-mm diameter brush assembly was swallowed. The brush was extended in the stomach and the mucosa was brushed three or four times. The brush was then retracted into the protective sleeve and withdrawn from the patient. The brush was either cultured directly or placed in cysteine transport medium with 20% glycerol which was then sampled immediately or after freezing at -70 degrees C. RESULTS: Twenty-five adult H. pylori-infected subjects (13 male, 12 female) were studied. Helicobacter pylori recovery rate was 100% (11 of 11) when cultured immediately or after storage in transport medium at -70 degrees C for 1 or 2 weeks or after storage at 4 degrees C for 24 hours (four of four) or 72 hours (four of four) before being cultured. Freezing on dry ice and air shipment did not reduce recovery. CONCLUSION: Rapid, reliable, nonendoscopic culture of gastric mucus is a practical method to obtain culture of H. pylori for clinical or research purposes. The method is amenable to being performed in a doctor's office or in the field.