Two-directional elaboration of hydroxyacetone under thermodynamically controlled conditions: allylation or 2-propynylation and aldol reaction

Enolate generated from O-(tetrahydropyran-2-yl)hydroxyacetone under thermodynamically controlled conditions (1.3 equiv of NaH, THF, 0 degrees C to rt) was allylated at the carbon bearing the protected hydroxy group with very high regioselectively. When tert-BuOH, equivalent to the excessive portion of initially added NaH, was introduced into the mixture followed by addition of aldehyde, aldol reaction took place on the methyl group to give 1-substituted 4-hydroxy-(1E),6-heptadien-3-one in acceptable yields after acidic treatment of the mixture for dehydration and deprotection. Introducing a chiral auxiliary protecting group into hydroxyacetone led to asymmetric allylation though stereoselectivity was around 50% ee. Thus, the hidden aspect of the chemoselective nature of protected hydroxyacetone-derived enolate generated under thermodynamically controlled conditions has opened a new avenue for two-directional elaboration of hydroxyacetone that should be potentially useful in organic synthesis.     

Molecular aggregates of partially fluorinated quaternary ammonium salt gemini surfactants

The size and shape of novel partially fluorinated gemini surfactant 1,2-bis[dimethyl-(3-perfluoroalkyl-2-hydroxypropyl)ammonium]ethane bromide (CnFC3-2-C3CnF, where n=4, 6, and 8) were investigated in aqueous solution by means of light scattering and transmission electron microscopy (TEM). The sizes of these molecular aggregates changed with increasing carbon number of the alkyl chain and concentration. For example, the apparent hydrodynamic radius by dynamic light scattering was 18 nm at a concentration of cmcx5 for n=4, 115 nm at the cmcx15 for n=6, and 62 nm at the cmcx30 for n=8, at 298.2 K. The shapes of CnFC3-2-C3CnF aggregates drastically changed with the alkyl chain length; the aggregates were mainly in the form of large or irregular small aggregates (n=4), string-like aggregates (n=6), and vesicles (n=8). The bromide-ion activity was measured using a bromide-ion-selective electrode to determine the degree of counterion binding to the aggregates. The degree of counterion binding to aggregate was very small compared with that in the typical hydrogenated gemini surfactants. These results indicated that the small curvature of large aggregates was not influenced by an electrostatic repulsion between the cationic head groups in the case of the bulky molecular volume of fluorinated gemini surfactants.     

In Vitro Analyses of Spinach-Derived Opioid Peptides,Rubiscolins: Receptor Selectivity and Intracellular Activities through G Protein- and β-Arrestin-Mediated Pathways

Activated opioid receptors transmit internal signals through two major pathways: the G-protein-mediated pathway, which exerts analgesia, and the β-arrestin-mediated pathway, which leads to unfavorable side effects. Hence, G-protein-biased opioid agonists are preferable as opioid analgesics. Rubiscolins, the spinach-derived naturally occurring opioid peptides, are selective δ opioid receptor agonists, and their p.o. administration exhibits antinociceptive effects. Although the potency and effect of rubiscolins as G-protein-biased molecules are partially confirmed, their in vitro profiles remain unclear. We, therefore, evaluated the properties of rubiscolins, in detail, through several analyses, including the CellKey^TM assay, cADDis^® cAMP assay, and PathHunter^® β-arrestin recruitment assay, using cells stably expressing µ, δ, κ, or µ/δ heteromer opioid receptors. In the CellKey^TM assay, rubiscolins showed selective agonistic effects for δ opioid receptor and little agonistic or antagonistic effects for µ and κ opioid receptors. Furthermore, rubiscolins were found to be G-protein-biased δ opioid receptor agonists based on the results obtained in cADDis^® cAMP and PathHunter^® β-arrestin recruitment assays. Finally, we found, for the first time, that they are also partially agonistic for the µ/δ dimers. In conclusion, rubiscolins could serve as attractive seeds, as δ opioid receptor-specific agonists, for the development of novel opioid analgesics with reduced side effects.     

Interaction forces between poly(amidoamine) (PAMAM) dendrimers adsorbed on gold surfaces

Interaction forces between two gold surfaces with adsorbed poly(amidoamine) (PAMAM) dendrimers (generations G3.0 and G5.0) have been investigated using colloidal probe atomic force microscopy (AFM). In the absence of dendrimers or at their low concentrations, an attractive force derived from the van der Waals interaction was observed. On the other hand, this attractive interaction changed to repulsion with increasing dendrimer concentration. The origin of the repulsion can be attributed to either an electric double layer interaction or a steric effect of the adsorbed dendrimers, depending on the concentration of dendrimer. The steric hindrance was also influenced by the generation of the dendrimer; the force-detectable distance in the presence of PAMAM G5.0 dendrimer was slightly longer than that in the presence of G3.0 dendrimer. In order to estimate the occupied area of each dendrimer adsorbed on gold, quartz crystal microbalance (QCM) measurement was also carried out.     

Gelatin methacrylate as a promising hydrogel for 3D microscale organization and proliferation of dielectrophoretically patterned cells

Establishing the 3D microscale organization of cells has numerous practical applications, such as in determining cell fate (e.g., proliferation, migration, differentiation, and apoptosis) and in making functional tissue constructs. One approach to spatially pattern cells is by dielectrophoresis (DEP). DEP has characteristics that are important for cell manipulation, such as high accuracy, speed, scalability, and the ability to handle both adherent and non-adherent cells. However, widespread application of this method is largely restricted because there is a limited number of suitable hydrogels for cell encapsulation. To date, polyethylene glycol-diacrylate (PEG-DA) and agarose have been used extensively for dielectric patterning of cells. In this study, we propose gelatin methacrylate (GelMA) as a promising hydrogel for use in cell dielectropatterning because of its biocompatibility and low viscosity. Compared to PEG hydrogels, GelMA hydrogels showed superior performance when making cell patterns for myoblast (C2C12) and endothelial (HUVEC) cells as well as in maintaining cell viability and growth. We also developed a simple and robust protocol for co-culture of these cells. Combined application of the GelMA hydrogels and the DEP technique is suitable for creating highly complex microscale tissues with important applications in fundamental cell biology and regenerative medicine in a rapid, accurate, and scalable manner.     

Star-shaped trimeric quaternary ammonium bromide surfactants: adsorption and aggregation properties

Novel star-shaped trimeric surfactants consisting of three quaternary ammonium surfactants linked to a tris(2-aminoethyl)amine core were synthesized. Each ammonium had two methyls and a straight alkyl chain of 8, 10, 12, or 14 carbons. The adsorption and aggregation properties of these tris(N-alkyl-N,N-dimethyl-2-ammoniumethyl)amine bromides (3C(n)trisQ, in which n represents alkyl chain carbon number) were characterized by equilibrium and dynamic surface tension, rheology, small-angle neutron scattering (SANS), and cryogenic transmission electron microscopy (cryo-TEM) techniques. 3C(n)trisQ showed critical micelle concentrations (CMC) 1 order of magnitude lower than that of the corresponding gemini surfactants with an ethylene spacer and the corresponding monomeric surfactants. The logarithm of the CMC decreased linearly with increasing hydrocarbon chain length for 3C(n)trisQ. The slope of the line, which is well-known as Klevens equation, was larger than those of the monomeric and gemini surfactants; however, considering the total carbon number in the chains, the slope was shallower than the monomeric and was close to the gemini. Through the results such as surface tensions at the CMC (32-34 mN m(-1)) and the parameters of standard free energy, CMC/C(20) and pC(20), it was found that 3C(n)trisQ could adsorb densely at the air/water interface despite the strong electrostatic repulsion between multiple quaternary ammonium headgroups. Moreover, dynamic surface tension measurements showed that the kinetics of adsorption for 3C(n)trisQ to the air/water interface was slow because of their bulky structures. Furthermore, the results of rheology, SANS, and cryo-TEM determined that 3C(n)trisQ with n = 10 and 12 formed ellipsoidal micelles at low concentrations in solution and the structures transformed to threadlike micelles with very few branches for n = 12 as the concentration increased, but for n = 14 threadlike micelles formed at relatively low concentrations.     

Self-assembling porphyrins and phthalocyanines for photoinduced charge separation and charge transport

Large π-conjugated compounds are promising building blocks for organic thin-film electronics such as organic light-emitting diodes, organic field-effect transistors, and organic photovoltaics. Utilization of porphyrins and phthalocyanines for this purpose is highly fascinating because of their excellent electric, photophysical, and electrochemical properties as well as intense self-assembling abilities arising from π-π stacking interactions. This paper focuses on fundamental aspects of self-assembled structures that have been obtained from porphyrin and phthalocyanine building blocks and more complex composites for photoinduced charge separation and charge transport toward the potential applications to organic thin-film electronics.