This article describes novel conformationally ordered alpha/beta-hybrid peptides consisting of repeating l-proline-anthranilic acid building blocks. These oligomers adopt a compact, right-handed helical architecture determined by the intrinsic conformational preferences of the individual amino acid residues. The striking feature of these oligomers is their ability to display an unusual periodic pseudo beta-turn network of nine-membered hydrogen-bonded rings formed in the forward direction of the sequence by 1-->2 amino acid interactions both in solid-state and in solution. Conformational investigations of several of these oligomers by single-crystal X-ray diffraction, solution-state NMR, and ab initio MO theory suggest that the characteristic steric and dihedral angle restraints exerted by proline are essential for stabilizing the unusual pseudo beta-turn network found in these oligomers. Replacing proline by the conformationally flexible analogue alanine (Ala) or by the conformationally more constrained alpha-amino isobutyric acid (Aib) had an adverse effect on the stabilization of this structural architecture. These findings increase the potential to design novel secondary structure elements profiting from the steric and dihedral angle constraints of the amino acid constituents and help to augment the conformational space available for synthetic oligomer design with diverse backbone structures.

Understanding the crystalline structure of racemic carvedilol phosphate hemihydrate presents several challenges that were overcome using a combination of single-crystal X-ray diffraction, solid-state NMR (SSNMR), and other analytical techniques. Initial attempts to obtain a crystal structure were hampered by difficulties with twinning and problematic disorder in the final refinements. Multinuclear SSNMR analysis localized the disorder to portions of the molecule near the chiral center. As a result, single-enantiomer carvedilol phosphate was prepared and was found to crystallize in a phase that was isomorphous with the racemate, while SSNMR spectra of the single enantiomers did not contain the disorder observed in the racemate. The singlecrystal X-ray structure of the (R)-enantiomer was solved and used as a starting point to successfully progress the solution of the disordered racemic crystal structure. Thermal analysis and construction of a phase diagram, along with crystallographic and spectroscopic analysis, found the crystal structure of the racemate to be a solid solution of (R)-and (S)-enantiomers, with the conformation of the molecule adjusting to fit. The crystal structures show the stoichiometry of the both the racemate and (R)-enantiomer to be a hemihydrate. The phase isomorphically dehydrates below relative humidity values of 1% and above temperatures of 125 °C as assessed by water vapor sorption studies, powder X-ray diffraction, and SSNMR. Single-crystal diffraction detected significant changes in the unit cell dimensions as the phase dehydrated, which was related to the visual appearance of opacity in a single crystal of the (R)-enantiomer. The mechanism of water incorporation was further probed spectroscopically via exchange with deuterium, 17 O-, and 18 O-labeled water; the results suggest that dehydration and rehydration likely proceed via narrow tunnels in the crystal structure, combined with the formation of fissures in the crystal. 2 H SSNMR experiments showed that the water does not engage in solid-state jump motion even at higher temperatures.

N-Methyl and N-n-butyl-2-(2-boronophenyl)benzimidazoles are accessed from the corresponding mono-N-alkyl-ortho-phenylenediamines, either using a polyphosphoric acid-mediated cyclisation with ortho-bromobenzoic acid, or preferably using an Oxone-mediated cyclisation of the corresponding aldehyde, followed by a lithium-exchange and borylation sequence. The resulting boronic acids show unusual physical and chemical properties, as shown by 11B NMR and X-ray crystallography.