Three-Dimensional Extrusion Printing of Porous Scaffolds Using Storable Ceramic Inks.

In this study, we describe the additive manufacturing of porous three-dimensionally (3D) printed ceramic scaffolds prepared with hydroxyapatite (HA), ß-tricalcium phosphate (ß-TCP), or the combination of both with an extrusion-based process. The scaffolds were printed using a novel ceramic-based ink with reproducible printability and storability properties. After sintering at 1200°C, the scaffolds were characterized in terms of structure, mechanical properties, and dissolution in aqueous medium. Microcomputed tomography and scanning electron microscopy analyses revealed that the structure of the scaffolds, and more specifically, pore size, porosity, and isotropic dimensions were not significantly affected by the sintering process, resulting in scaffolds that closely replicate the original dimensions of the 3D model design. The mechanical properties of the sintered scaffolds were in the range of human trabecular bone for all compositions. All ceramic bioinks showed consistent printability over a span of 14 days, demonstrating the short-term storability of the formulations. Finally, the mass loss did not vary among the evaluated compositions over a period of 28 days except in the case of ß-TCP scaffolds, in which the structural integrity was significantly affected after 28 days of incubation in phosphate-buffered saline. In conclusion, this study demonstrates the development of storable ceramic inks for the 3D printing of scaffolds of HA, ß-TCP, and mixtures thereof with high fidelity and low shrinkage following sintering that could potentially be used for bone tissue engineering in load-bearing applications.

Bisphosphine-functionalized cyclic decapeptides based on the natural product Gramicidin S: a potential scaffold for transition-metal coordination.

The natural product Gramicidin S is a promising scaffold for novel oligopeptide-based bisphosphine ligands, combining the advantageous rigid chiral backbone with the close proximity of phosphine substituents. The required unnatural, phosphine-containing, amino acid building blocks were synthesized by means of a novel protocol that involves the enantioselective alkylation of a chiral nickel Schiff base template. Three Ni complexes were prepared with different alkyl chains between the phosphine group and the alpha-carbon atom of the incorporated glycine; the absolute stereochemistry of two of them was determined by single-crystal X-ray structure analysis. By detaching the template, enantiopure L-phosphine amino acids resulted enabling the solid-phase, stepwise construction of a linear sequence of the phosphine-modified oligopeptides. On cyclization three bisphosphine-substituted Gramicidin S analogues resulted, differing only in the size and shape of the linkage between the phosphine groups and the oligopeptides backbone. Their crystal structures suggest these species to have potential as chelating ligands.

2,9-Dimethyl-6H,13H-5:12,7:14-dimethano-dibenzo[d,i][1,3,6,8]tetraazecine.

In the title structure, C(18)H(20)N(4), the aromatic rings are almost orthogonal [81.6 (2)°]. The mol-ecule has symmetry 2 since it is situated on a crystallographic twofold axis. There are only weak inter-molecular inter-actions present in the structure, notably C-H⋯π-electron ring inter-actions. The (1)H and (13)C NMR spectra are in accordance with the X-ray structure analysis.

Bis{(E)-3-[(diethyl-methyl-ammonio)meth-yl]-N-[3-(N,N-dimethyl-sulfamo-yl)-1-methyl-pyridin-4-yl-idene]-4-methoxy-anilinium} tetra-iodide penta-hydrate.

The title compound, 2C(21)H(34)N(4)O(3)S(2+)·4I(-)·5H(2)O, was prepared exclusively as the E isomer by methyl-ation of the corresponding N-phenyl-pyridin-4-amine. There are two symmetry-independent mol-ecules in the asymmetric unit with no significant differences in bond lengths and angles. The aromatic rings are not coplanar with the pyridin-4-imine groups, as indicated by the C-N-C-C torsion angles of 47.7 (7) and 132.6 (5)°.

7-hydroxy-5-methoxy-6,8-dimethylflavanone: a natural flavonoid.

The title flavonoid [systematic name: (2S)-7-hydroxy-5-methoxy-6,8-dimethyl-2-phenyl-3,4-dihydrochromen-4(2H)-one], C18H18O4, displays statistical conformational disorder, with three conformations of the molecule involving three orientations of the phenyl ring and two orientations of the fused heterocyclic ring. The conformational disorder is correlated with the isomerization equilibrium between the flavanone and chalcone forms. The conformational behaviour has a potential impact on the biological activity of this class of compounds. Moreover, pi stacking interactions at van der Waals distances are present between the aromatic rings of chroman-4-one groups of symmetry-related molecules. Apart from these pi-pi interactions, molecules are linked by strong O-H...O hydrogen bonds between hydroxy and carbonyl groups.

Benznidazole.

THE CONFORMATION OF THE TITLE COMPOUND [SYSTEMATIC NAME: N-benzyl-2-(2-nitro-imidazol-1-yl)acetamide], C(12)H(12)N(4)O(3), can be described in terms of the relative orientation of three planar fragments, the imidazol group (A), benzyl group (B), and the acetamide fragment (C), with corresponding dihedral angles: A/C = 88.17 (4), B/C = 67.12 (5) and A/B = 21.11 (4)°. The crystal packing is enhanced by a network of strong inter-molecular N-H⋯O hydrogen bonds.

Characterization of beta-lapachone and methylated beta-cyclodextrin solid-state systems.

The purpose of this research was to explore the utility of beta cyclodextrin (betaCD) and beta cyclodextrin derivatives (hydroxypropyl-beta-cyclodextrin [HPbetaCD], sulfobutylether-beta-CD [SBbetaCD], and a randomly methylated-beta-CD [RMbetaCD]) to form inclusion complexes with the antitumoral drug, beta-lapachone (betaLAP), in order to overcome the problem of its poor water solubility. RMbetaCD presented the highest efficiency for betaLAP solubilization and was selected to develop solid-state binary systems. Differential scanning calorimetry (DSC), X-ray powder diffractometry (XRPD), Fourier transform infrared (FTIR) and optical and scanning electron microscopy results suggest the formation of inclusion complexes by both freeze-drying and kneading techniques with a dramatic improvement in drug dissolution efficiency at 20-minute dissolution efficiency (DE(20-minute) 67.15% and 88.22%, respectively) against the drug (DE(20-minute) 27.11%) or the betaCD/drug physical mixture (DE(20-minute) 27.22%). However, the kneading method gives a highly crystalline material that together with the adequate drug dissolution profile make it the best procedure in obtaining inclusion complexes of RMbetaCD/betaLAP convenient for different applications of betaLAP.