Synthesis and photophysical properties of 1,2-diphenylindolizine derivatives: fluorescent blue-emitting materials for organic light-emitting device.

New blue-emitting materials based on 1,2-diphenylindolizine were designed and synthesized through a microwave-assisted Suzuki coupling reaction. The photophysical, electrochemical, and thermal properties of the 1,2-diphenylindolizine derivatives were investigated using UV-visible and fluorescence spectroscopy, cyclic voltammetry, thermogravimetric analysis, and differential scanning calorimetry. The 1,2-diphenylindolizine derivatives had band gaps of 3.1-3.4 eV and indicated proper emission of around 450 nm without significant difference between in solution and thin solid film. The indolizine derivatives show an enhanced thermal stability (∆Tm > 100 °C), compared with 1,2-diphenylindolizine. These results suggest the 1,2-diphenylindolizine derivatives are suitable for blue-emitting materials in organic light-emitting devices.

Small polyanion recognition of a triazolium cyclodextrin click cluster in water.

In order to detect small polyanions (sPAs), which play important roles in many biological systems, a triazolium cyclodextrin click cluster (5, hexakis{6-(3-methyl-4-hydroxymethyl-1H-1,2,3-triazolium-1-yl)-6-deoxy}-α-cyclodextrin iodide) was synthesized and characterized. The competition binding to 5 occupied by 5-carboxyfluorescein of inositol-1,4,5-trisphosphate (IP3), phytic acid, adenosine triphosphate (ATP), ethylenediaminetetraacetic acid (EDTA), glucose, and glucose-6-phosphate was evaluated by UV/vis titration in HEPES (10 mM, pH 7.4) : methanol (1 : 1, v/v). We obtained the binding constants of IP3 and phytic acid to 5 (1.4 × 10(6) and 1.9 × 10(6) M(-1), respectively); however, the binding constants of ATP and EDTA were significantly lower (2.1 × 10(5) and 4.5 × 10(4) M(-1), respectively). Moreover, glucose and glucose-6-phosphate did not show any detectable binding. In addition, the sPA recognition of the triazolium cyclodextrin click cluster in water was confirmed by fluorescence titration.

Synthesis, cytotoxicity, and phase-solubility study of cyclodextrin click clusters.

To explore the possibility of cyclodextrin click clusters (CCCs) as a new cyclodextrin-based excipient, we prepared three different CCCs; heptakis{6-(4-hydroxymethyl-1H-[1,2,3]triazol-1-yl)-6-deoxy}-ß-cyclodextrin (HT-ß-CD), heptakis{6-(4-hydroxymethyl-1H-[1,2,3]triazol-1-yl)-6-deoxy}{2,3-di-O-methyl}-ß-cyclodextrin (HT-ß-CD(OMe)2 ), and heptakis{6-(4-sulfonylmethyl-1H-[1,2,3]triazol-1-yl)-6-deoxy}-ß-cyclodextrin (ST-ß-CD). The CCCs were prepared using copper(I)-catalyzed azide-alkyne cycloaddition from 6-azido-6-deoxy-ß-CD and their water solubility, cytotoxicity, and drug-solubilizing effect were investigated. Water turbidity testing of the CCCs showed that the minimum water solubility of the CCCs is at least 20 times higher than that of ß-CD. An MTT cell viability assay performed on HeLa cells demonstrated a low cytotoxicity of the CCCs compared with 2,6-dimethyl-ß-cyclodextrin. HT-ß-CD(OMe)2 and ST-ß-CD did not demonstrate any cytotoxicity within the experimental concentration (∼5 mM) like 2-hydroxypropyl-ß-CD. A phase-solubility study of prednisolone with the CCCs suggested that CCCs showed increased solubility of prednisolone in the presence of increasing concentrations of the CCCs. The comparison between the conventional CD derivatives and CCCs on solubility, cytotoxicity, and binding property implies that CCCs are alternative cyclodextrin derivatives useful for overcoming the restrictions of conventional cyclodextrin chemistry.

6-Triazolyl-6-deoxy-ß-cyclodextrin derivatives: synthesis, cellular toxicity, and phase-solubility study.

Heptakis{6-(4-hydroxymethyl-1H-[1,2,3]triazol-1-yl)-6-deoxy}-ß-cyclodextrin (HTßCD) and heptakis{6-(4-sulfonylmethyl-1H-[1,2,3]triazol-1-yl)-6-deoxy}-ß-cyclodextrin (STßCD) were prepared using copper(I)-catalyzed azide-alkyne cycloaddition between 6-azido-6-deoxy-ß-CD and one of two alkynes, propargyl alcohol, and sodium propargyl sulfonate, respectively. The structures of HTßCD and STßCD were characterized by NMR techniques. NMR interpretations and computer modeling suggested that the limited freedom of rotation of the triazole moieties keeps HTßCD and STßCD rigid and compact. Water solubility tests of HTßCD and STßCD showed that the minimum water solubility of HTßCD and STßCD is at least 20times higher than that of ß-CD. MTT assay showed that HTßCD and STßCD did not influence the cell viability under 1mM. A phase-solubility study of prednisolone with the CD derivatives showed increased solubility of prednisolone in the presence of increasing concentrations of HTßCD and STßCD.

Antibody functionalization with a dual reactive hydrazide/click crosslinker.

A water-soluble, dual reactive hydrazide/click crosslinker (ethynyl hydrazide, EH) was synthesized and characterized. A model antibody, human immunoglobulin G (hIgG), was ethynylated by conventional oxidation/hydrazide reactions with the hydrazide moiety of EH. The terminal alkyne conjugated to the glycan of hIgG was easily functionalized by quantitative and bioorthogonal Cu(I)-catalyzed azide-alkyne cycloaddition. The potential of the hydrazide/click crosslinker as a reagent to functionalize antibodies was demonstrated with fluorophore labeling and antibody immobilization.

Small molecular weight PEGylation of diosgenin in an in vivo animal study for diabetic auditory impairment treatment.

Diosgenin was modified to control its in vivo bioavailability by conjugating a hydrophilic unit, tetraethylene glycol. The diosgenin-tetraethylene glycol conjugate (TE) was orally administered in streptozotocin induced diabetic mice for this auditory protection study. The bioactivity improvement of TE for in vivo diabetic auditory impairment treatment was clearly observed in three different auditory tests and compared with that of diosgenin. The improvement in in vivo efficacy suggests that the small molecular weight PEGylation of diosgenin is a synthetically robust and systematically applicable strategy to reform the poor pharmacokinetics of a hydrophobic aglycone.

Solid-supported monolayers and bilayers of amphiphilic beta-cyclodextrins.

This paper describes the adsorption and spreading of beta-cyclodextrin (CD) vesicles on hydrophobic and hydrophilic substrates, which involves a transition from bilayer vesicles to planar molecular monolayers or bilayers. On substrates that are patterned with self-assembled monolayers by microcontact printing (muCP), the CD vesicles preferentially adsorb on hydrophobic areas instead of hydrophilic (nonionic) areas, and on cationic areas instead of hydrophilic (nonionic) areas. Supported monolayers of amphiphilic cyclodextrins CD1 and CD2 were obtained by adsorption of CD vesicles to hydrophobic substrates, and supported bilayers of amphiphilic cyclodextrins CD1 and CD2 were prepared by adsorption of CD vesicles on cationic substrates. Contact angle goniometry, atomic force microscopy and confocal fluorescence microscopy (CFM) were used to analyze the supported CD layers. The fluidity of the supported CD layers was verified using fluorescence recovery after photobleaching experiments. The supported layers function as a supramolecular platform that can bind suitable guest molecules through inclusion in the CD host cavities. Additionally, the CD host layers were patterned with fluorescent guest molecules by supramolecular muCP on the supported CD layers. The host-guest interactions were investigated with CFM and fluorescence resonance energy transfer experiments.

Intravesicular and intervesicular interaction by orthogonal multivalent host-guest and metal-ligand complexation.

Host vesicles composed of amphiphilic beta-cyclodextrin CD1 recognize metal-coordination complexes of the adamantyl-functionalized ethylenediamine ligand L via hydrophobic inclusion in the beta-cyclodextrin cavities at the vesicle surface. In the case of Cu(II) and L, the resulting coordination complex was exclusively CuL(2), and the interaction with the host vesicles was intravesicular, unless the concentration of metal complex and vesicles was high (>0.1 mM). In the case of Ni(II) and L, a mixture was formed consisting of mainly NiL and NiL(2), the interaction with the host vesicles was effectively intervesicular, and addition of the guest-metal complex resulted in aggregation of the vesicles into dense, multilamellar clusters even in dilute solution [1 microM Ni(II)]. The metal-L complex could be eliminated by a strong chelator such as EDTA, and the intervesicular interaction could be suppressed by a competitor such as unmodified beta-cyclodextrin. The result from this investigation is that the strongest metal-coordination complex [Cu(II) with L] binds exclusively intravesicularly, whereas the weakest metal-coordination complex [Ni(II) with L] binds predominantly intervesicularly and is the strongest interfacial binder. These experimental observations are confirmed by a thermodynamic model that describes multivalent orthogonal interactions at interfaces.

Expression of a supramolecular complex at a multivalent interface.

The multivalent binding of a supramolecular complex at a multivalent host surface by combining the orthogonal beta-cyclodextrin (CD) host-guest and metal ion-ethylenediamine coordination motifs is described. As a heterotropic, divalent linker, an adamantyl-functionalized ethylenediamine derivative was used. This was complexed with Cu(II) or Ni(II). The binding of the complexes to a CD self-assembled monolayer (SAM) was studied as a function of pH by means of surface plasmon resonance (SPR) spectroscopy. A heterotropic, multivalent binding model at interfaces was used to quantify the multivalent enhancement at the surface. The Cu(II) complex showed divalent binding to the CD surface with an enhancement factor higher than 100 relative to the formation of the corresponding divalent complex in solution. Similar behavior was observed for the Ni(II) system. Although the Ni(II) system could potentially be trivalent, only divalent binding was observed at the CD SAMs, which was confirmed by desorption experiments.

Dynamic multivalent recognition of cyclodextrin vesicles.

Cyclodextrin bilayer vesicles have dynamic membranes that recognize guest molecules through efficient multivalent host-guest interaction reminiscent of multivalent binding of a ligand with receptors in a biological membrane.

Bilayer vesicles of amphiphilic cyclodextrins: host membranes that recognize guest molecules.

A family of amphiphilic cyclodextrins (6, 7) has been prepared through 6-S-alkylation (alkyl=n-dodecyl and n-hexadecyl) of the primary side and 2-O-PEGylation of the secondary side of alpha-, beta-, and gamma-cyclodextrins (PEG=poly(ethylene glycol)). These cyclodextrins form nonionic bilayer vesicles in aqueous solution. The bilayer vesicles were characterized by transmission electron microscopy, dynamic light scattering, dye encapsulation, and capillary electrophoresis. The molecular packing of the amphiphilic cyclodextrins was investigated by using small-angle X-ray diffraction of bilayers deposited on glass and pressure-area isotherms obtained from Langmuir monolayers on the air-water interface. The bilayer thickness is dependent on the chain length, whereas the average molecular surface area scales with the cyclodextrin ring size. The alkyl chains of the cyclodextrins in the bilayer are deeply interdigitated. Molecular recognition of a hydrophobic anion (adamantane carboxylate) by the cyclodextrin vesicles was investigated by using capillary electrophoresis, thereby exploiting the increase in electrophoretic mobility that occurs when the hydrophobic anions bind to the nonionic cyclodextrin vesicles. It was found that in spite of the presence of oligo(ethylene glycol) substituents, the beta-cyclodextrin vesicles retain their characteristic affinity for adamantane carboxylate (association constant K(a)=7.1 x 10(3) M(-1)), whereas gamma-cyclodextrin vesicles have less affinity (K(a)=3.2 x 10(3) M(-1)), and alpha-cyclodextrin or non-cyclodextrin, nonionic vesicles have very little affinity (K(a) approximately 100 M(-1)). Specific binding of the adamantane carboxylate to beta-cyclodextrin vesicles was also evident in competition experiments with beta-cyclodextrin in solution. Hence, the cyclodextrin vesicles can function as host bilayer membranes that recognize small guest molecules by specific noncovalent interaction.

Versatile formation of [2]catenane and [2]pseudorotaxane structures; threading and noncovalent stoppering by a self-assembled macrocycle.

A self-assembled dimeric macrocycle between 4,4'-bis(4-pyridylmethoxy)biphenyl (L) and (en)Pd(NO(3))(2) was constructed, and its interactions with cyclodextrins of different cavity size resulted in the formation of [2]catenane and [2]pseudorotaxane systems, respectively. The structures were identified by 1D and 2D NMR spectroscopy and cold spray ionization mass (CSI-MS) spectrometry.