Margaret A. Eastman

3D conductive nanocomposite scaffold for bone tissue engineering

Bone healing can be significantly expedited by applying electrical stimuli in the injured region. Therefore, a three-dimensional (3D) ceramic conductive tissue engineering scaffold for large bone defects that can locally deliver the electrical stimuli is highly desired. In the present study, 3D conductive scaffolds were prepared by employing a biocompatible conductive polymer, ie, poly(3,4-ethylenedioxythiophene) poly(4-styrene sulfonate) (PEDOT:PSS), in the optimized nanocomposite of gelatin and bioactive glass. For in vitro analysis, adult human mesenchymal stem cells were seeded in the scaffolds. Material characterizations using hydrogen-1 nuclear magnetic resonance, in vitro degradation, as well as thermal and mechanical analysis showed that incorporation of PEDOT:PSS increased the physiochemical stability of the composite, resulting in improved mechanical properties and biodegradation resistance. The outcomes indicate that PEDOT:PSS and polypeptide chains have close interaction, most likely by forming salt bridges between arginine side chains and sulfonate groups. The morphology of the scaffolds and cultured human mesenchymal stem cells were observed and analyzed via scanning electron microscope, micro-computed tomography, and confocal fluorescent microscope. Increasing the concentration of the conductive polymer in the scaffold enhanced the cell viability, indicating the improved microstructure of the scaffolds or boosted electrical signaling among cells. These results show that these conductive scaffolds are not only structurally more favorable for bone tissue engineering, but also can be a step forward in combining the tissue engineering techniques with the method of enhancing the bone healing by electrical stimuli.

Structural characterization of Eu2O3–MgO–Na2O–Al2O3–SiO2 glasses with varying Eu2O3 content: Raman and NMR studies

Abstract Raman, 27Al and 29Si NMR spectroscopies are used to investigate the structure of [0.15Na2O–0.12MgO–0.03Al2O3–0.70SiO2](100−x): [Eu2O3]x glasses with varying Eu2O3 content (x=0, 0.73, 1.26, 3.90, 5.26 and 8.11 mol%). Spectral changes in the Raman envelope at (900–1240) cm−1 indicate that the number of silica tetrahedra with more than one non-bridging oxygen (NBO) per tetrahedron and the number of silica tetrahedra with one NBO associated with Eu increase with increasing rare-earth concentration. 29Si MAS NMR spectra show a single broad peak with maxima at frequencies attributable to a predominance of Q3 species. Quantitative 27Al and 29Si NMR spectroscopies show that aluminum and silicon species become less observable as Eu2O3 content increases, presumably due to interactions with paramagnetic europium. The 27Al NMR spectra reveal the presence of only tetrahedrally coordinated Al sites, with a gradual increase in the structural disorder associated with these sites as the concentration of Eu2O3 increases. This is in agreement with the appearance of the broad Raman band at 790 cm−1 attributed to Al–O stretching vibrations with Al in fourfold coordination.

Heteroarotinoids with Anti-Cancer Activity Against Ovarian Cancer Cells

The Flex-Het compound 10a (SHetA2-NSC 721689) {[4-nitrophenylamino][(2,2,4,4-tetramethylthiochroman-6-yl)amino]methane-1-thione]} has shown promise in preclinical testing as an anti-cancer agent without evidence of toxicity, skin irritancy, or teratogenicity. One objective of this study was to synthesize a series of heteroarotinoids structurally related to SHetA2 and to measure the effect of structural alterations on the cytotoxicity activities of the compounds on A2780 ovarian cancer cells. Alterations included comparisons of activity of an NO2 end group versus a CO2Et end group, a thiourea linker versus a urea linker, and a distorted, thiochroman ring unit versus a planar quinoline ring unit. Cytotoxicity assays demonstrated the thiourea linker compounds to be similar in potency to the urea linker counterparts, the NO2 substitutions were slightly more potent than the CO2Et substitutions, and replacement of the thiochroman group with a planar quinoline fused ring system markedly reduced activity. The mechanism of cytotoxicity through apoptosis was confirmed for the compounds. The optimal combination of structural features for enhancing potency consisted of a urea linker, a NO2 substitution, and a flexible thiochroman unit. Extensive H-bonding in the more active urea derivative was confirmed by X-ray and NMR analyses. This is the first example in which the biological activity of flexible, thiochroman units is compared to that of fused aryl units in a heteroarotinoid molecule.

Synthesis, stereochemical, and conformational studies of selected 3,7-diheterabicyclo[3.3.1]nonan-9-ols: X-ray diffraction analyses of 7-benzyl-9-phenyl-3-oxa-7-azabicyclo[3.3.1]nonan-9-ol and 7-benzyl-9-(4-N, N′-dimethylaminophenyl)-3-thia-7-azabicyclo[3.3.1]nonan-9-ol, a rare stable chair-boat form with trigonal nitrogen

A systematic study of 1,2-additions to 3,7-diheterabicyclo[3.3.1]nonan-9-ones (3,7-DHBCN-9-ONES) by symmetrically substituted aryl Grignard reagents in anhydrous THF or ether has been conducted. 1,2-Additions of aryl Grignard reagents to the carbonyl group at C-9 in 7-benzyl-3-oxa-7-azabicyclo[3.3.1]nonan-9-one and 7-benzyl-3-thia-7-azabicyclo[3.3.1]nonan-9-one resulted in the formation of tertiary alcohols with the aryl group “syn” to the oxygen or sulfur atoms in the respective rings. The X-ray analyses demonstrated that the solid, bicyclic, oxygen-containing alcohol was in chair–chair form while the solid, bicyclic, sulfur-containing alcohol existed in chair–boat form. A tentative mechanism is that the Grignard reagent may coordinate with the oxygen atom and / or sulfur atom in a boat conformer of the bicyclic system prior to the attack from the “oxygen or sulfur sides.”

Magnetic resonance tells microbiology where to go; bacterial teichoic acid protects liquid water at sub-zero temperatures

Numerous chemical additives lower the freezing point of water, but life at sub-zero temperatures is sustained by a limited number of biological cryoprotectants. Antifreeze proteins in fish, plants, and insects provide protection to a few degrees below freezing. Microbes have been found to survive at even lower temperatures, although, with a few exceptions, antifreeze proteins are missing. Survival has been attributed to external factors, such as high salt concentration (brine veins) and adhesion to particulates or ice crystal defects. Teichoic acid is a phosphodiester polymer ubiquitous in Gram positive bacteria, composing 50% of the mass of the bacterial cell wall and excreted into the extracellular space of biofilm communities. We have found that when bound to the peptidoglycan cell wall (wall teichoic acid) or as a free molecule (lipoteichoic acid), teichoic acid is surrounded by liquid water at temperatures significantly below freezing. Using solid-state NMR, we are unable to collect 31P CPMAS spectra for frozen solutions of lipoteichoic acid at temperatures above -60 °C. For wall teichoic acid in D2O, signals are not seen above -30 °C. These results can be explained by the presence of liquid water, which permits rapid molecular motion to remove 1H/31P dipolar coupling. 2H quadrupole echo NMR spectroscopy reveals that both liquid and solid water are present. We suggest that teichoic acids could provide a shell of liquid water around biofilms and planktonic bacteria, removing the need for brine veins to prevent bacterial freezing.

Synthesis and conformational studies of tertiary alcohols derived from tetrahydro-4H-pyran-4-one and tetrahydrothiopyran-4-one

Abstract A series of derivatives of tetrahydro-4 H-pyran-4-one and tetrahydrothiopyran-4-one have been prepared by condensation with aryl Grignard reagents. IR spectra, 1 H and 13 C NMR spectral analyses, and elemental analyses support the structures. A single-crystal X-ray diffraction analysis of 4-(3,5-dimethylphenyl)tetrahydrothiopyran-4-ol [a = 9.729(10), b = 12.846(2), c = 9.970(10) Åi; space group Pna2(1)] confirmed the aryl group is located in a pseudo equatorial position, and the heterocyclic ring is slightly flattened near the sulfur end of the molecule.

Solid-state NMR and X-ray diffractional analysis of conformational effects in σ-symmetric bicyclo[2.2.1]hept-2-ene diester and monoesters

Abstract Solid state NMR and X-ray crystallographic analysis have proven that dissymmetrization by enzymatic asymmetric hydrolysis of meso bicyclo[2.2.1]hept-2-ene(norbornene) diesters does not induce significant electron distortion of the olefinic bond.