Immobilization of a flavin molecule onto poly(methacrylic acid)s and its application in aerobic oxidation catalysis: effect of polymer stereoregularity.

The isoalloxazine ring system, called flavin, was successfully immobilized on poly(methacrylic acid)s, PMAAs, with different tacticity via post-polymerization modification under suitable conditions. The resulting flavin-containing polymers showed catalytic activity for aerobic oxidation reactions, in which the polymer stereoregularity clearly influenced their catalytic activity.

Synthesis of D-π-A type benzothiazole-pyridinium salt composite and its application as photo-degradation agent for amyloid fibrils.

We have synthesized a cyan fluorescent benzothiazole-pyridinium salt composite based on D-π-A architecture. This salt was found to work as not only a two- and three-photon excitable fluorophore but also a degradation agent against amyloid fibrils under LED irradiation conditions.

Unexpected formation of poly-functionalized fulvenes by the reaction of a tetraaryl[5]cumulene with iodine.

Longer cumulenes have come to draw considerable attention due to their unique properties and reactivities, leading to various hydrocarbons. In this manuscript, we describe the reaction of tetrakis(p-methoxyphenyl)[5]cumulene with iodine to afford poly-functionalized fulvenes via unexpected migration of a terminal aryl ring under ambient conditions. The obtained iodinated fulvenes were utilized in Suzuki-Miyaura cross-coupling reactions affording penta- and fully-arylated fulvenes successfully.

Two- and three-photon excitable quaternized imidazo[1,2-a]pyridines as mitochondrial imaging and potent cancer therapy agents.

We have synthesized a series of quaternized imidazo[1,2-a]pyridines in three steps from commercially available reagents. These compounds exhibit blue fluorescence emission at around 425 nm with good quantum yields. In addition, one specific compound was found to work as not only a two- and three-photon excitable mitochondria imaging agent, but also a therapeutic agent upon continuous irradiation conditions.

Enzyme-like Regiodivergent Behavior of a Flavopeptide Catalyst in Aerobic Baeyer-Villiger Oxidation.

We recently developed a flavopeptide immobilized on polystyrene resin, Fl-Pep-PS, that could realize the first N5-unmodified neutral flavin (Fl)-catalyzed aerobic oxygenation reactions under non-enzymatic conditions. Although a key active species is assumed to be the corresponding 4a-hydroperoxyflavin (Fl4aOOH) from the unprecedented activity and unique chemoselectivity, further circumstantial support would be helpful to be sure since spectroscopic evidence is difficult to obtain due to the compound's insolubility. In this article, we report that the aerobic Baeyer-Villiger oxidation of a fused cyclobutanone, (±)-cis-bicyclo[3.2.0]hept-2-en-6-one (1), can be promoted with Fl-Pep-PS in a FMO-like chemoselectivity and regiodivergent manner via Fl-related catalytic intermediates, which delivers strong evidence of the involvement of Fl4aOOH as an active species in Fl-Pep-PS-catalyzed aerobic oxygenation reactions.

Target delivery and controlled release of the chemopreventive drug sulindac by using an advanced layered double hydroxide nanomatrix formulation system.

Target delivery and controlled release of the chemopreventive drug sulindac that possesses low water solubility present a great challenge for its pharmaceutical industry. Here, we offered an advanced nanomatrix formulation system of sulindac based on layered double hydroxide materials. The X-ray analysis and infrared spectroscopy confirmed the incorporation of sulindac into the gallery of the layered double hydroxides. The incorporation ratios of sulindac were recorded to be 45, 31 and 20 for coprecipitation, anion-exchange and reconstruction techniques, respectively. The scanning electron microscopy showed a nanomatrix-structure of ~50 nm. The release studies of sulindac-nanomatrix showed a 96% controlled release at the small intestine solution during 3 h(s), indicating an enhancement in the dissolution profile of sulindac after the matrix formation. The layered structure of the matrix supplied sulindac with a well-ordered structure and a relatively hydrophobic microenvironment that controlled the guest hydrolysis and reactivity during the release process. The laminar structure of layered double hydroxides offered a safe preservation for sulindac against photodecarboxylation, and enhanced the drug thermal stability from 190 to 230° C. The ionic electrostatic interaction of sulindac through its acidic group with layered double hydroxides demolished the gastrointestinal ulceration.

Synthesis of Optically Active Polyguanidines by Polyaddition Reaction of Biscarbodiimides with Chiral Diamines.

Herein, we present the first study on the polyaddition reaction of biscarbodiimides with chiral diamines, which focuses on a definite case using optically active trans-4a,8a-decahydroquinoxaline and 1,4-phenylenebis(arylcarbodiimide)s, which readily react with each other under ambient and catalyst-free conditions. The specific reactivity allows for facile access to not only the corresponding chiral polyguanidines under balanced stoichiometry but also their oligomeric analogues under imbalanced stoichiometry via a step-by-step procedure. Spectroscopic, chromatographic, and computational characterization of the novel molecular chains containing arrayed guanidines have revealed their structural, optical, and conformational properties as well as the mechanism of polymerization assisted by molecular association. Their potential use as asymmetric catalysts is also described.

Two-photon excitable boron complex based on tridentate imidazo[1,5-a]pyridine ligand for heavy-atom-free mitochondria-targeted photodynamic therapy.

We have synthesized a cyan fluorescent boron complex based on a tridentate imidazo[1,5-a]pyridine ligand. The boron complex was found to have potential applications as not only a chiroptical material but also a heavy-atom-free mitochondria-targeted photosensitizer for cancer treatment.

Design of temperature-responsive polymers with enhanced hysteresis: alpha,alpha-disubstituted vinyl polymers.

Three temperature-responsive polymers which are alpha,alpha-disubstituted vinyl polymers having two amphiphilic groups (ethylamide or ethylester) per monomeric unit were designed. Two of these polymers showed unusually large hysteresis in their phase transition temperatures between a heating and a cooling process. This hysteresis resulted from the extremely slow kinetics of the dissolution process of the aggregated polymer chains in the cooling process due to intra- and interchain interactions including hydrogen bonding and hydrophobic interaction. The high density of the amphiphilic substituents on the polymer chain due to the alpha,alpha-disubstituted structure enhanced these intra- and interchain interactions. The large hysteresis was also observed in the volume change of a corresponding hydrogel. These new classes of temperature-responsive polymers are interesting materials because their large hystereses can be regarded as erasable memory function.

Nanocomposite formulation system of lipid-regulating drugs based on layered double hydroxide: synthesis, characterization and drug release properties.

PURPOSE: To design a nanocomposite formulation system of lipid-regulating drugs with versatile approaches using layered double hydroxide (LDH) material. METHODS: The co-precipitation technique has been used to prepare the selected drugs [bezafibrate (BZF) and clofibric acid (CF)]-LDH nanocomposites. The nanocomposite materials (BZF-LDH and CF-LDH) were characterized by X-ray powder diffraction, infrared spectroscopy, thermogravimetric analysis, and scanning electron microscopy. The in vitro study was investigated in simulated gastrointestinal solutions at 36.8°C. RESULTS: X-ray measurement and spectroscopic analysis indicated the formation of fully monophase drug-nanocomposites. The nanocomposites' gallery heights were calculated to be 23.5 and 16.3 Å for BZF and CF, respectively. The new gallery heights indicated that BZF and CF drugs have been stacked into LDH as a monolayer with a staggered inter-digitated arrangement. The size of the nanocomposites described by SEM microscopy was ∼ 0.1 µm. The nanocomposite formulation has improved the drugs properties (thermal stability, dissolution, and controlled release) beside the achievement of drug target delivery. CONCLUSIONS: Nanocomposites composed of lipid-regulating drugs (BZF and CF) with LDH were successfully synthesized as a new formulation system of this drug category. The LDH nanocomposite formulation system has improved the drugs release properties.

An uncommon use of irradiated flavins: Brønsted acid catalysis.

We present that thioacetalization of aldehydes can be induced by blue light irradiation in the presence of a catalytic amount of riboflavin tetraacetate (RFTA) under aerobic conditions. Several control experiments have suggested that the reaction is more likely to be catalyzed by acidic species generated in situ upon light irradiation. We have proposed that single electron transfer from a thiol (RSH) to the excited state of RFTA can take place to give a one-electron oxidized thiol (RSH+˙) and the one-electron reduced RFTA (RFTA-˙), which can be trapped by molecular oxygen to be stabilized as Brønsted acids including the protonated RFTA-˙ (RFTAH˙). Finally, we have demonstrated that such acidic species can be prepared in advance as a solution and used as Brønsted acid catalysts for not only thioacetalization but also Mannich-type reactions.

Efficient Use of Photons in Photoredox/Enamine Dual Catalysis with a Peptide-Bridged Flavin-Amine Hybrid.

An isoalloxazine (flavin) ring system and a secondary amine have been integrated through a short peptide linker with the aim of using photons as efficiently as possible in photoredox/enamine dual catalysis. We herein report a peptide-bridged flavin-amine hybrid that can catalyze α-oxyamination of aldehydes with TEMPO under weak blue light irradiation to achieve an extremely high quantum yield of reaction (Φ = 0.80).

Nanocomposites of 2-arylpropionic acid drugs based on Mg-Al layered double hydroxide for dissolution enhancement.

Naproxen (NP) and flurpibrofen (FB) as non-steroidal anti-inflammatory drugs (NSAIDs) of 2-arylpropionic acid derivatives have been used as host organic drugs to be intercalated into layered double hydroxide (LDH) applying reconstruction and co-precipitation techniques. The obtained NP-LDH and FB-LDH nanocomposites were characterized by X-ray powder diffraction, infrared and thermogravimetric analyses. From drug loading, thermal analysis and X-ray measurements we can decide that coprecipitaion technique is better than reconstruction technique to obtain intercalated monophase nanocomposites. In acidic medium LDH dissolved and the intercalated drug starts to release in a molecular form which is suitable for adsorption. The drug solubility has been investigated before and after intercalation. It has been found that LDH improves the drug solubility and its dissolution rate.

Design of peptide-containing N5-unmodified neutral flavins that catalyze aerobic oxygenations.

Simulation of the monooxygenation function of flavoenzyme (Fl-Enz) has been long-studied with N5-modified cationic flavins (FlEt+ ), but never with N5-unmodified neutral flavins (Fl) despite the fact that Fl is genuinely equal to the active center of Fl-Enz. This is because of the greater lability of 4a-hydroperoxy adduct of Fl, FlOOH , compared to those of FlEt+ , FlEtOOH , and Fl-Enz, FlOOH-Enz. In this study, Fl incorporated into a short peptide, flavopeptide (Fl-Pep), was designed by a rational top-down approach using a computational method, which could stabilize the corresponding 4a-hydroperoxy adduct (FlOOH-Pep) through intramolecular hydrogen bonds. We report catalytic chemoselective sulfoxidation as well as Baeyer-Villiger oxidation by means of Fl-Pep under light-shielding and aerobic conditions, which are the first Fl-Enz-mimetic aerobic oxygenation reactions catalyzed by Fl under non-enzymatic conditions.

Facile Preparation of Flavinium Organocatalysts.

We developed a safe, simple, inexpensive, and environmentally benign method for preparing N(5)-ethylated flavinium organocatalysts without using hazardous reagents or inert conditions as previously required. 5-Ethyl-3-methyllumiflavinium cation was prepared from its reduced form by NaNO2 -free aerobic oxidation, which was subsequently extracted onto commercial cation-exchange resins under NaClO4 -free conditions. The resulting resin-immobilized flavinium salts were found to be effective organocatalysts for aerobic oxidation reactions.

Design of a multifunctional nanohybrid system of the phytohormone gibberellic acid using an inorganic layered double-hydroxide material.

To offer a multifunctional and applicable system of the high-value biotechnological phytohormone gibberellic acid (GA), a nanohybrid system of GA using the inorganic Mg-Al layered double-hydroxide material (LDH) was formulated. The ion-exchange technique of LDH was applied to synthesize the GA-LDH hybrid. The hybrid structure of GA-LDH was confirmed by different spectroscopic techniques. The nanohybrid size was described by SEM to be ∼0.1 µm. The GA-LDH nanohybrid structure was the key parameter that controlled GA properties. The layered molecular structure of LDH limited the interaction of GA molecules in two-dimensional directions. Accordingly, GA molecules did not crystallize and were released in an amorphous form suitable for dissolution. At various simulated soil solutions, the nanohybrids showed a sustained release process following Higuchi kinetics. The biodegradation process of the intercalated GA showed an extended period of soil preservation as well as a slow rate of degradation.

Unusually large hysteresis of temperature-responsive poly(N-ethyl-2-propionamidoacrylamide) studied by microcalorimetry and FT-IR.

We reported here the full characterization of the hysteresis of the phase transition behavior of an aqueous solution of poly(N-ethyl-2-propionamidoacrylamide) (PNEPA), which has a unique alpha,alpha-disubstituted structure, by using microcalorimetry and FT-IR. Phase transition temperatures near the thermodynamic equilibrium were determined by extrapolating the scanning rate of the microcalorimetry to zero. The calculated hysteresis from the phase transition temperature was unusually very large (approximately 8 degrees C). FT-IR analysis indicated that the large hysteresis of PNEPA resulted from a coupling of intra-/intermonomeric unit hydrogen bonds, which is known to occur in a beta-sheet of proteins but has never been reported in temperature-responsive polymers. The effects of the molecular weight and polymer concentration on the hysteresis were studied by using fractionated PNEPAs and it was found that a low molecular weight and a low concentration enhanced the hysteresis.

"Threading" of beta-sheet peptides via radical polymerization.

A nonamer peptide containing a diene group in the center of the sequence was synthesized. When the peptide forms an antiparallel beta-sheet, the diene groups align ca. 5 A apart on the beta-sheet. The diene groups successfully photopolymerized without distorting the beta-sheet structure. The obtained beta-sheet showed high stability against acid denaturation and addition of 1,1,1,3,3,3-hexafluoroisopropanol.

Soluble-insoluble-soluble transitions of aqueous poly(N-vinylacetamide-co-acrylic acid) solutions.

Several poly(N-vinylacetamide-co-acrylic acid)s with various copolymer compositions have been synthesized, and their unique phase-transition behavior in aqueous salt (Na2SO4 or NaCl) solutions was investigated. Copolymers containing more than 51 mol % N-vinylacetamide (NVA) show reentrant soluble-insoluble-soluble transitions with increasing temperature. The soluble-insoluble transition temperature (T(p1)) increased linearly with increasing NVA content, whereas the insoluble-soluble transition temperature (T(p2)) was almost constant irrespective of the NVA content. Potentiometric titration of the copolymer solutions suggested that the acrylic acid (AA) carboxyl groups form hydrogen bonds with the NVA amide groups even under soluble conditions. Dehydration of the NVA amides and their consequent hydrogen bonding with the AA carboxyl groups during the soluble-insoluble transition process was indicated by FTIR measurements. Addition of salt (Na2SO4 or NaCl) to the aqueous media reduces the solvent quality and enhances the intra- and interchain interactions of the copolymers. Thus, T(p1) was observed to decrease and T(p2) was observed to increase with increasing salt concentration. However, the addition of urea to the media reverses the concentration dependence of T(p1) and T(p2) by disturbing the intra- and interchain interactions of the copolymers.

DNA sensor with a dipyridophenazine complex of osmium(lI) as an electrochemical probe.

Application of a dipyrido[3,2-a:2',3'-c]phenazine (DPPZ)-type metal complex as an DNA electrochemical probe was studied. The introduction of electron-donating groups (NH2) was effective for controlling the redox potential and binding affinities of the DPPZ-type osmium complex. The [Os(DA-bpy)2DPPZ]2+ complex (DA-bpy; 4,4'-diamino-2,2'-bipyridine) had a lower half-wave potential (E 1/2) of 147 mV (vs Ag/AgCl) and higher binding affinity with DNA (binding constant, K = 3.1 x 10(7) M(-1)) than those of other complexes. With a single-stranded DNA immobilized gold electrode, the hybridization signal (deltaI) of the [Os(DA-bpy)2DPPZ]2+ complex was linear in the concentration range of 1.0 pg mL(-1) - 0.12 microg mL(-1) for the targeted DNA with a regression coefficient of 0.999. The detection limit was 0. 1 pg mL(-1). The 400-bp yAL3 gene was also detected with good sensitivity and selectivity using the [Os(DA-bpy)2DPPZ]2+ complex.