Synthesis, thermal properties and cell-compatibility of photocrosslinked cinnamoyl-modified hydroxypropyl cellulose.

Biocompatibility of cinnamoyl-modified carbohydrate materials is not well-known, while they are attracting attention as a photoreactive material. In order to investigate biocompatible properties of cinnamoyl-modified carbohydrate, hydroxypropyl cellulose (HPC) was reacted with cinnamoyl chloride to yield cinnamoyl-modified HPC (HPC-C) for a cell proliferation test. HPC-Cs with three different degrees of substitution (DS) were prepared by changing a feed ratio of cinnamoyl chloride to HPC. The DS of the products ranged from 1.3 to 3.0 per one hydroxylpropyl anhydroglucose unit. Thermal analysis using DSC and TGA showed that the HPC-C with higher DS has a glass transition temperature and higher thermal stability. Ultraviolet (UV) light was irradiated on the HPC-C thin films, and changes in the UV-vis spectrum of the films were examined. In the course of UV irradiation, the absorbance at 280 nm was reduced. Fibroblast cells were cultured on the photocrosslinked HPC-C films, and cell growth was examined. The cell proliferation test revealed that the photocrosslinked HPC-C films have good compatibility with fibroblast cells.

Combined Theoretical and Experimental Studies of Nickel-Catalyzed Cross-Coupling of Methoxyarenes with Arylboronic Esters via C-O Bond Cleavage.

Nickel(0)-catalyzed cross-coupling of methoxyarenes through C-O bond activation has been the subject of considerable research because of their favorable features compared with those of the cross-coupling of aryl halides, such as atom economy and efficiency. In 2008, we have reported nickel/PCy3-catalyzed cross-coupling of methoxyarenes with arylboronic esters in which the addition of a stoichiometric base such as CsF is essential for the reaction to proceed. Recently, we have also found that the scope of the substrate in the Suzuki-Miyaura-type cross-coupling of methoxyarenes can be greatly expanded by using 1,3-dicyclohexylimidazol-2-ylidene (ICy) as the ligand. Interestingly, a stoichiometric amount of external base is not required for the nickel/ICy-catalyzed cross-coupling. For the mechanism and origin of the effect of the external base to be elucidated, density functional theory calculations are conducted. In the nickel/PCy3-catalyzed reactions, the activation energy for the oxidative addition of the C(aryl)-OMe bond is too high to occur under the catalytic conditions. However, the oxidative addition process becomes energetically feasible when CsF and an arylboronic ester interact with a Ni(PCy3)2/methoxyarene fragment to form a quaternary complex. In the nickel/ICy-catalyzed reactions, the oxidative addition of the C(aryl)-OMe bond can proceed more easily without the aid of CsF because the nickel-ligand bonds are stronger and therefore stabilize the transition state. The subsequent transmetalation from an Ar-Ni-OMe intermediate is determined to proceed through a pathway with lower energies than those required for ß-hydrogen elimination. The overall driving force of the reaction is the reductive elimination to form the carbon-carbon bond.

Stereocomplexation, Thermal and Mechanical Properties of Conetworks Composed of Star-Shaped l-Lactide, d-Lactide and ε-Caprolactone Oligomers Utilizing Sugar Alcohols as Core Molecules.

It is important to develop tailor-made biodegradable/biocompatible polymer networks usable for biomaterials whose thermal and mechanical properties are easily controlled by changing the composition. We synthesized sugar-alcohol-based polymer networks (SPN-mscLAO/3CLO, m = 4, 5 or 6) by the crosslinking reactions of erythritol, xylitol or sorbitol-based m-armed star-shaped l-lactide and d-lactide oligomers (HmSLLAO and HmSDLAO), a glycerol-based 3-armed star-shaped ε-caprolactone oligomer (H3SCLO) and hexamethylene diisocyanate (HDI) at the weight ratios of HmSLLAO/HmSDLAO = 1/1 and (HmSLLAO + HmSDLAO)/H3CLO = 100/0, 75/25, 50/50, 25/75 or 0/100). The influence of the arm number on the crystallization behavior, thermal and mechanical properties of SPN-mscLAO/3CLOs were systematically investigated by comparing with those of sugar-alcohol-based homochiral polymer network (SPN-mLLAO, m = 4, 5 or 6) prepared by the reaction of HmSLLAO and HDI. Stereocomplex (sc) crystallites are dominantly formed for SPN-mscLAO/3CLOs 100/0⁻25/75, whereas SPN-mLLAOs were amorphous. The higher order of melting temperature of sc-crystals for SPN-mscLAO/3CLOs 100/0⁻25/75 was m = 5 > m = 6 > m = 4. The sc-crystallinities of SPN-4scLAO/3CLOs 100/0⁻50/50 were significantly lower than those of SPN-mscLAO/3CLOs 100/0⁻50/50 (m = 5 and 6). The larger order of the sc-spherulite size at crystallization temperature of 110 °C was m = 5 > m = 6 > m = 4 for SPN-mscLAO/3CLO 100/0. The size and number of sc-spherulites decreased with increasing crystallization temperature over the range of 110⁻140 °C and with increasing CLO fraction. Among all the networks, SPN-5scLAO/3CLOs 75/25 and 50/50 exhibited the highest and second highest tensile toughnesses (21.4 and 20.3 MJ·m-3), respectively.

Synthesis of 1,2-Bis(2-aryl-1H-indol-3-yl)ethynes via 5-exo-Digonal Double Cyclization Reactions of 1,4-Bis(2-isocyanophenyl)buta-1,3-diyne with Aryl Grignard Reagents.

New π-conjugated 1,2-bis(2-aryl-1H-indol-3-yl)ethynes 1a-j having various substituents on the two aryl groups were efficiently synthesized via unusual 5-exo-digonal double isocyanide-acetylene cyclization reactions of 1,4-bis(2-isocyanophenyl)buta-1,3-diyne 3 and aryl Grignard reagents (R-MgBr, R = C6H5 (1a), 4-H3CC6H4 (1b), 2-H3CC6H4 (1c), 3-MeOC6H4 (1d), 3-(CH3)2NC6H4 (1e), 4-F3CC6H4 (1f), 4-FC6H4 (1g), 3-FC6H4 (1h), 4-PhOC6H4 (1i), and 2-Naph (1j)) in 19-85% yields. The UV-vis spectra were rationalized in detail using time-dependent DFT and single point calculations. The fluorescence emission peaks for 1a-j were observed at around 450 nm. Especially for 1f and 1j, those spectra displayed broad emission bands and relatively large Stokes shifts (3977-4503 cm-1), indicating the contribution of an intramolecular charge transfer. The absolute quantum yields (0.50-0.62) of 1a-j were higher than those of parent 8 (0.19) and 2-phenyl-1H-indole (0.11). The electrochemical features for 1a-j were investigated by cyclic voltammetry. The frontier molecular orbital levels for 1a-j were estimated based on the combination of oxidation potentials, UV-vis, and DFT calculated data. The structural property of 1,2-bis(2-phenyl-1H-indol-3-yl)ethyne 1a was characterized by several spectroscopic methods and finally determined by X-ray analysis of a single crystal of 1a recrystallized from ethyl acetate. The structural features of 1a-j were also supported by DFT calculations.

Photocrosslinkable Trehalose Derivatives Carrying Mesogenic Groups: Synthesis, Characterization, and in Vitro Evaluation for Fibroblast Attachment.

A photocrosslinkable trehalose derivative carrying mesogenic groups was synthesized by esterification reactions. The derivative (TC-HBPHA) was synthesized by the reaction of partially cinnamoyl-modified trehalose (TC4) with 4-(4-hexyloxybenzoyloxy)phenoxy-6-oxohexanoic acid (HBPHA) as a mesogenic unit. TC-HBPHA showed a nematic liquid crystalline mesophase at a temperature range from 150 °C to 175 °C in the heating process under observation with a polarized optical microscope. The dimerization of the cinnamoyl groups of TC-HBPHA by ultraviolet (UV) light irradiation was monitored by ultraviolet-visible (UV-Vis) spectroscopy and Fourier transform infrared (FT-IR) spectroscopy. The photocrosslinked film was obtained after the UV irradiation of TC-HBPHA, and it kept the liquid crystalline mesophase at almost the same temperature range. Fibroblast cells cultured on the photocrosslinked TC-HBPHA proliferated as well as on the polystyrene culture plate, indicating that the film has no toxicity. Interestingly, some cells on photocrosslinked TC-HBPHA had a spindle shape and aligned characteristically.

Stereocomplexation in Copolymer Networks Incorporating Enantiomeric Glycerol-Based 3-Armed Lactide Oligomers and a 2-Armed ɛ-Caprolactone Oligomer.

The reactions of enantiomeric glycerol-based 3-armed lactide oligomers (H3DLAO and H3LLAO) and a diethylene glycol-based 2-armed ɛ-caprolactone oligomer (H2CLO) with hexamethylene diisocyanate (HDI) produced polyesterurethane copolymer networks (PEU-3scLAO/2CLOs 100/0, 75/25, 50/50, 25/75 and 0/100) with different feed ratios of stereocomplex (sc) lactide oligomer (H3scLAO = H3DLAO + H3LLAO, H3DLAO/H3LLAO = 1/1) and H2CLO. Thermal and mechanical properties of the copolymer networks were compared with those of a simple homochiral (hc) network (PEU-3DLAO) produced by the reaction of H3DLAO and HDI. X-ray diffraction and differential scanning calorimetric analyses revealed that sc crystallites are formed without any hc crystallization for PEU-3scLAO/2CLOs, and that PEU-3DLAO is amorphous. The melting temperatures of sc crystallites for PEU-3scLAO/2CLOs were much higher than that of hc crystallites of H3DLAO. The polarized optical microscopic analysis revealed that the nucleation efficiency is enhanced with increasing feed of H3scLAO fraction, whereas the spherulite growth rate is accelerated with increasing feed H2CLO fraction over 100/0-50/50 networks. PEU-3scLAO/2CLO 100/0 (i.e., PEU-3scLAO) exhibited a higher tensile strength and modulus than PEU-3DLAO. The elongation at break and tensile toughness for PEU-3scLAO/2CLOs increased with an increasing feed amount of H2CLO.

Chiroptical properties of 1,3-diphenylallene-anchored tetrathiafulvalene and its polymer synthesis.

A novel tetrathiafulvalene dimer, bridged by a chiral 1,3-diphenylallene framework, has been prepared as an optically active compound having strong chiroptical properties. Although a chiral allene bearing strong electron-donating group(s) often undergoes slow photoracemization even in daylight, the present allene is totally configurationally stable under ordinary conditions. Each isomer possesses pronounced chiroptical properties in its ECD spectra reflecting the chiral allene framework. Moreover, the elongation of the chiral main chain was also carried out by direct C-H activation of the TTF unit, and the chiroptical properties of the resulting polymer were also investigated.

Preparation of photocrosslinked fish elastin polypeptide/microfibrillated cellulose composite gels with elastic properties for biomaterial applications.

Photocrosslinked hydrogels reinforced by microfibrillated cellulose (MFC) were prepared from a methacrylate-functionalized fish elastin polypeptide and MFC dispersed in dimethylsulfoxide (DMSO). First, a water-soluble elastin peptide with a molecular weight of ca. 500 g/mol from the fish bulbus arteriosus was polymerized by N,N'-dicyclohexylcarbodiimide (DCC), a condensation reagent, and then modified with 2-isocyanatoethyl methacrylate (MOI) to yield a photocrosslinkable fish elastin polypeptide. The product was dissolved in DMSO and irradiated with UV light in the presence of a radical photoinitiator. We obtained hydrogels successfully by substitution of DMSO with water. The composite gel with MFC was prepared by UV irradiation of the photocrosslinkable elastin polypeptide mixed with dispersed MFC in DMSO, followed by substitution of DMSO with water. The tensile test of the composite gels revealed that the addition of MFC improved the tensile properties, and the shape of the stress-strain curve of the composite gel became more similar to the typical shape of an elastic material with an increase of MFC content. The rheology measurement showed that the elastic modulus of the composite gel increased with an increase of MFC content. The cell proliferation test on the composite gel showed no toxicity.

Structures and reaction mechanisms of the two related enzymes, PurN and PurU.

The crystal structures of glycinamide ribonucleotide transformylases (PurNs) from Aquifex aeolicus (Aa), Geobacillus kaustophilus (Gk) and Symbiobacterium toebii (St), and of formyltetrahydrofolate hydrolase (PurU) from Thermus thermophilus (Tt) were determined. The monomer structures of the determined PurN and PurU were very similar to the known structure of PurN, but oligomeric states were different; AaPurN and StPurN formed dimers, GkPurN formed monomer and PurU formed tetramer in the crystals. PurU had a regulatory ACT domain in its N-terminal side. So far several structures of PurUs have been determined, yet, the mechanisms of the catalysis and the regulation of PurU have not been elucidated. We, therefore, modelled ligand-bound structures of PurN and PurU, and performed molecular dynamics simulations to elucidate the reaction mechanisms. The evolutionary relationship of the two enzymes is discussed based on the comparisons of the structures and the catalytic mechanisms.

Organogelation behavior and thermal properties of supramolecular polymer network composed of carboxy- and pyridyl-terminated 4-arm star-shaped ε-caprolactone oligomers.

Carboxy-terminated 4-arm star-shaped ε-caprolactone oligomers (Tetra-SA-CLO, Tetra-PA-CLO, and Tetra-TCPA-CLO) were synthesized by the reactions of hydroxy-terminated 4-arm star-shaped ε-caprolactone oligomers (Tetra-OH-CLO) having the degree of polymerization per one oligocaprolactone chain, n=3 and 5 with succinic anhydride, phthalic anhydride, and 2,3,4,5-tetrachlorophthalic anhydride, respectively. As a pyridyl-terminated analog, nicotinate-functionalized 4-arm star-shaped ε-caprolactone oligomer (Tetra-NA-CLO) was synthesized by the esterification reaction of Tetra-OH-CLO with nicotinic acid. All mixtures of the carboxy- and pyridyl-terminated analogs became thermoreversible organogels in N,N-dimethylformamide and nitromethane at around 15°C. The (1)H NMR and FT-IR analyses of the mixtures revealed the formation of hydrogen-bonded polymer network. The glass transition and cold crystallization temperatures of the mixtures were higher than the values estimated from those of the single components.

Nickel-catalyzed Suzuki-Miyaura reaction of aryl fluorides.

Two protocols for the nickel-catalyzed cross-coupling of aryl fluorides with aryl boronic esters have been developed. The first employs metal fluoride cocatalysts, such as ZrF(4) and TiF(4), which enable Suzuki-Miyaura reactions of aryl fluorides bearing electron-withdrawing (ketones, esters, and CF(3)), aryl and alkenyl groups as well as those comprising fused aromatic rings, such as fluoronaphthalenes and fluoroquinolines. The second protocol employs aryl fluorides bearing ortho-directing groups, which facilitate the difficult C-F bond activation process via cyclometalation. N-heterocycles, such as pyridines, quinolines, pyrazoles, and oxazolines, can successfully promote cross-coupling with an array of organoboronic esters. A study into the substituent effects with respect to both coupling components has provided fundamental insights into the mechanism of the nickel-catalyzed cross-coupling of aryl fluorides.

Nickel-catalyzed reductive cleavage of aryl-oxygen bonds in alkoxy- and pivaloxyarenes using hydrosilanes as a mild reducing agent.

A nickel-catalyzed reductive deoxygenation of aryl alkyl ethers and aryl pivalates has been developed. Hydrosilanes serve as a mild reducing agent. The present protocol allows the use of a pivalate group as a robust and traceless steering group in arene functionalization reactions.

Nickel-catalyzed amination of aryl pivalates by the cleavage of aryl C-O bonds.

Catalytic amination: The title reaction demonstrates the use of aryl carboxylates as suitable electrophilic coupling substrates in catalytic amination reactions. N-heterocyclic carbene ligands and NaOtBu promote the amination of aryl pivalates through the cleavage of normally unreactive aryl carbon-oxygen bonds (see scheme; cod=cyclooctadiene).

Nickel-catalyzed cross-coupling reaction of alkenyl methyl ethers with aryl boronic esters.

The Ni(0)-catalyzed cross-coupling of alkenyl methyl ethers with boronic esters is described. Several types of alkenyl methyl ethers can be coupled with a wide range of boronic esters to give the stilbene derivatives.

Novel pyromellitic diimide-based macrocycle with a linear pi-electronic system and bis(phenylethynyl)pyromellitic diimide: syntheses, structures, photophysical properties, and redox characteristics.

We report the syntheses, structures, photophysical properties, and redox characteristics of the [2 + 2] pyromellitic diimide-based macrocycle with a linear pi-electronic system 2 as well as the 3,6-bis(phenylethynyl)pyromellitic diimide derivative 3. The interesting solid state structural properties of the clathrates of 3 with pi-donors are also reported. The macrocycle 2 was synthesized by the direct cyclocondensation followed by the Sonogashira coupling reaction. X-ray crystallographic studies showed that the phenylacetylene moieties in 2 formed the intramolecular benzene dimer structures, and the bis(phenylethynyl)pyromellitic diimide moieties in both 2 and 3 were stacked in a parallel and slanted arrangement. Theoretical calculations for 2' and 3 suggested the existence of electrostatic interactions between the bis(phenylethynyl)pyromellitic diimide moieties. The UV/vis spectral measurements and TDDFT calculations of 2, 2', and/or 3 were performed to understand their electronic transitions. The fluorescence spectral measurements showed that 2 and 3 have visible fluorescence properties and 2 displays an excimer fluorescence at ca. 590 nm. The cyclic voltammetry measurements revealed that the electrostatic repulsion between the diimide moieties in 2 is greater than that in 1 according to the extension of the pi-electronic systems. X-ray crystallography of the clathrates of 3 with various pi-donors demonstrated the formation of the segregated donor-acceptor structures, indicating the strong aggregation ability of the bis(phenylethynyl)pyromellitic diimide moiety.

Enantiopure anthrylene-ethynylene cyclic tetramer and racemization via rotation of anthracene unit about acetylenic axes.

Four anthracene and four acetylene units are used to construct a chiral pi-conjugate macrocycle, the chirality of which is due to the restricted rotation about acetylenic axes. Enantiomers were readily resolved by chiral HPLC and racemized slowly even at 70 degrees C.

Structures and inclusion properties of racemic and enantiopure dimethyl and diphenyl 9,9'-bianthryl-2,2'-dicarboxylates.

The authors prepared the dimethyl and diphenyl esters of 9,9'-bianthryl-2,2'-dicarboxylic acid in racemic and enantiopure (M) forms. The enantiopure dimethyl ester forms inclusion compounds with various organic compounds such as benzene, methanol, phenol, and aniline whereas the racemic form does this only with benzene. No guest molecules are included by the racemic and enantiopure diphenyl esters. These effects of substituents and homochirality on the inclusion properties are discussed on the basis of X-ray structures of some inclusion and guest-free compounds.

Synthesis, structural, spectral, and photoswitchable properties of cis- and trans-2,2,2',2'-tetramethyl-1,1'-indanylindanes.

As versatile synthetic intermediates for new photoswitchable molecules with a tetramethylindanylindane (stiff-stilbene) core, the cis and trans isomers of 5,16-dibromo-2,2,13',13'-tetramethylindanylindanes 2 were synthesized by the Barton-Kellogg coupling. The bromine atoms of trans-2 could be readily replaced with alkyl (sp3), aryl (sp2), and ethynyl (sp) groups. The cis isomers of the parent tetramethylindanylindane 1 and its bromo derivative 2 were isolated, and their structural and photophysical properties were examined for the first time. Clean and efficient trans-cis and cis-trans photochemical isomerization processes were observed in 1.

Synthesis and structural and photoswitchable properties of novel chiral host molecules: axis chiral 2,2'-dihydroxy-1,1'-binaphthyl-appended stiff-stilbene.

Novel photoswitchable chiral hosts having an axis chiral 2,2'-dihydroxy-1,1'-binaphthyl (BINOL)-appended stiff-stilbene, trans-(R,R)- and -(S,S)-1, were synthesized by palladium-catalyzed Suzuki-Miyaura coupling and low-valence titanium-catalyzed McMurry coupling as key steps, and they were fully characterized by various NMR spectral techniques. The enantiomers of trans-1 showed almost complete mirror images in the CD spectra, where two split Cotton effects (exciton coupling) were observed in the beta-transitions of the naphthyl chromophore at 222 and 235 nm, but no Cotton effect was observed in the stiff-stilbene chromophore at 365 nm. The structures of (R)-10 and trans-(R,R)-1 were confirmed by X-ray structural analysis. The optimized structure of cis-1 by MO calculations has a wide chiral cavity of 7-8 A in diameter, whereas trans-1 cannot form an intramolecular cavity based on the X-ray data. Irradiation of (R,R)-trans-1 with black light (lambda = 365 nm) in CH3CN or benzene at 23 degrees C led to the conversion to the corresponding cis-isomer, as was monitored by 1H NMR, UV-vis, and CD spectra. At the photostationary state, the cis-1/trans-1 ratio was 86/14 in benzene or 75/25 in CH3CN. On the other hand, irradiation of the cis-1/trans-1 (75/25) mixture in CH3CN with an ultra-high-pressure Hg lamp at 23 degrees C (lambda = 410 nm) led to the photostationary state, where the cis-1/trans-1 ratio was estimated to be 9/91 on the basis of the 1H NMR spectra. The cis-trans and trans-cis interconversions could be repeated 10 times without decomposition of the C=C double bond. Thus, a new type of photoswitchable molecule has been developed, and trans-1 and cis-1 were quite durable under irradiation conditions. The guest binding properties of the BINOL moieties of trans- and cis-(R,R)-1 with F-, Cl-, and H2PO4- were examined by 1H NMR titration in CDCl3. Similar interaction with F- and Cl- was observed in trans-1 (host/guest = 1/1, Kassoc = (1.0 +/- 0.13) x 103 for F- and (4.6 +/- 0.72) x 102 M-1 for Cl-) and cis-1 (host/guest = 1/1, Kassoc = (1.0 +/- 0.13) x 103 for F- and (5.9 +/- 0.69) x 10 M-1 for Cl-), but H2PO4- interacted differently: the cis-isomer formed the 1/1 complex (Kassoc = (9.38 +/- 2.67) x 10 M-1), whereas multistep equilibrium was expected for the trans-isomer.