Iron Catalysis of C(sp3)-H Azidation Using a Heteroarene Radical Cation Strategy.

The FeIII(phen)3 catalysis of the benzylic C(sp3)-H azidation of indoles has been investigated. The Fe(III) complex can selectively oxidize indoles to form arene radical cations, which are transformed into benzylic C(sp3) radical intermediates. This strategy exhibits a difference in reactivity between N-heteroarenes and benzene, which is difficult to achieve via direct hydrogen abstraction approaches. Various biorelevant azide precursors were constructed, highlighting the utility of this mild first-row transition-metal catalyst system.

Green-Light-Driven Fe(III)(btz)3 Photocatalysis in the Radical Cationic [4+2] Cycloaddition Reaction.

Green-light-driven FeIII(btz)3 photocatalysis for the radical cationic [4+2] cycloaddition of terminal styrenes and nucleophilic dienes has been investigated. The Fe-MIC (mesoionic carbene) complex forms a ligand-to-metal charge-transfer transition state with relatively high excited-state reduction potentials that can selectively oxidize terminal styrene derivatives. Unique multisubstituted cyclohexenes and structurally complex biorelevant cyclohexenes were constructed, highlighting the usefulness of this mild and practical first-row transition metal complex system.

Experimental and Theoretical Studies on the Mechanism of DDQ-Mediated Oxidative Cyclization of N-Aroylhydrazones.

The controversial single-electron-transfer process, frequently proposed in many 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ)-mediated reactions, was investigated experimentally and theoretically using the oxidative cyclization of aroylhydrazone with DDQ. DDQ-mediated oxadiazole formation involves several processes, including cyclization to form an oxadiazole ring and N-H bond cleavage, either by proton, hydride, or hydrogen atom transfer. The detailed mechanistic study using the M06-2X density functional theory, and the 6-31+G(d,p) basis set, suggests that the pathways involving radical ion pair (RIP) intermediates, which resulted from single-electron transfer (SET), were found to be energetically nearly identical to the pathway without the SET. The substituent-dependent reactivity of oxadiazole formation was consistent with the free energy profiles of both pathways, with or without the SET. This result indicates that in addition to the electron-transfer pathway, the nucleophilic addition/elimination pathway for DDQ should be considered as a possible mechanism of the oxidative transformation reaction using DDQ.

Comparative Study of the Effect of 5,6-Dihydroergosterol and 3-epi-5,6-dihydroergosterol on Chemokine Expression in Human Keratinocytes.

5,6-Dihydroergosterol-glucose is an organic synthetic derivative of spinasterol-glucose, which has potent anti-inflammatory activity. We previously synthesized alpha and beta anomers of DHE-glycosides and compared their inhibitory activity on CCL17 and CCL22 mRNA expression induced by TNF-α/IFN-γ in activated HaCaTs. Recently, we synthesized a new type of DHE-glycosides, 3-epi-5,6-dihydroergosterol(3-epi-DHE)-glycosides, and compared its inhibitory activity on mRNA expression levels of CCL17 and CCL22 in TNF-α/IFN-γ-induced HaCaT. DHE-Xly did not affect TNF-α/IFN-γ induced CCL17 and CCL22 mRNA expression in HaCaTs, however, 3-epi-DHE-Xly strongly inhibited TNF-α/IFN-γ induced CCL17 and CCL22 mRNA expression levels in human keratinocytes. These results provide important clues for development of chronic dermatitis treatment via inhibition of chemokine expression using DHE derivatives.

Multifunctional and Sustainable Fe-Iminopyridine Complexes for the Synthesis of Cyclic Carbonates.

The use of multifunctional and sustainable Fe catalysts for the formation of cyclic carbonates from epoxides and carbon dioxide at 80 °C and 3 bar pressure is presented. The optimal catalyst possesses a halide counteranion and a hydrogen bond donor to activate the epoxide for ring opening, affording a single-component, cocatalyst-free catalytic system.

Role of Ring Ortho Substituents on the Configuration of Carotenoid Polyene Chains.

The 9-(Z)-configuration was exclusively obtained in the carotenoid polyene chain irrespective of olefination and disconnection methods for terminal ortho-unsubstituted benzene rings. The 2,6-dimethyl substituents in the terminal rings secure an all-(E)-polyene structure. The single molecular conductance of the pure 9-(Z)-carotene was measured for the first time to be 1.53 × 10-4 ± 6.37 × 10-5G0, whose value was 47% that of the all-(E)-carotene ((3.23 × 10-4) ± (1.23 × 10-4) G0).

Fe(II)/Fe(III)-Catalyzed Intramolecular Didehydro-Diels-Alder Reaction of Styrene-ynes.

The intramolecular didehydro-Diels-Alder reaction of styrene-ynes was catalyzed by Fe(II) and Fe(III) to produce various naphthalene derivatives under microwave heating conditions. Mechanistic calculations found that the Fe(II) catalyst activates the styrenyl diene in an inverse-electron-demand Diels-Alder reaction, and the consecutive dehydrogenation reaction can be promoted by either Fe(II)-catalyzed direct dehydrogenation or an Fe(III)-catalyzed rearomatization/dehydrogenation pathway.

Photoswitchable "Turn-on" Fluorescence Diarylethenes: Substituent Effects on Photochemical Properties and Electrochromism.

A series of "turn-on" fluorescence diarylethenes derived from 2,3-bis(2-methylbenzo[b]thiophen-3-yl)-5,6-dihydro-4H-thieno[2,3-b]thiopyran-4-one (1) with alkyl and acetyl substituents were synthesized. The photochemical and photophysical properties of these derivatives, including the photoreaction of crystalline 1, were thoroughly investigated to reveal substituent effects on their properties. The results indicated that alkyl substituents did not significantly affect the absorption and emission spectra of the diarylethenes. However, large absorption and emission wavelength shifts were observed for the diarylethene with an acetyl substituent due to extension of π-π conjugation. Significantly, all of the fluorescent ring-closed forms of the compounds isomerized to their ring-open forms in the presence of Cu(2+) in the dark. EPR results provide clear evidence for the formation of the compound 1 radical cation intermediate that might be generated in the reaction between c-1 and Cu(2+) . DFT calculations found that the ground-state activation energy for ring-opening of 1(.+) was approximately 9.2 kcal mol(-1) lower than that of 1 without Cu(2+) , such that a Cu(2+) -catalyzed oxidative cycloreversion reaction at room temperature might be possible.

The effect of a "push-pull" structure on the turn-on fluorescence of photochromic thio-ketone type diarylethenes.

a series of diarylethene compounds with a thiophene bridging unit have been synthesized to investigate the relationship between molecular structure and photochromic properties. In particular, the fluorescence properties related to compound 1 were investigated. The results showed that a six-membered ring carrying an electron-donating sulfur atom and an electron-withdrawing carbonyl group is necessary to form a "push-pull" system for the fluorescence of 1.

Isolation of a Mn(IV) acylperoxo complex and its monooxidation ability.

The first example of monooxygenation by a high-valent Mn(IV) complex with a peroxide is described. A key Mn(IV) acylperoxo intermediate, which uses m-chloroperoxybenzoic acid as the oxygen donor, is directly observed by electro-spray ionization mass spectrometry and resonance Raman spectroscopy.

A substituted 3,4-dihydropyrimidinone derivative (compound D22) prevents inflammation mediated neurotoxicity; role in microglial activation in BV-2 cells.

A novel synthetic 3,4-dihydropyrimidinone derivative, compound D22 (ethyl 6-methyl-4-(3-phenoxyphenyl)-2-thioxo-3,4-dihydropyrimidine-5-carboxylate), was found to exert anti-inflammatory properties in lipopolysaccharide-stimulated microglial BV-2 cells. Compound D22 reduced the pro-inflammatory factors such as nitric oxide, prostaglandin E(2), tumor necrosis factor-α and interleukin-1ß. Moreover, it suppressed the expressions of inducible NO synthase and cyclooxygenase-2. Compound D22 inhibited the activation of mitogen-activated protein kinases. When compound D22-conditioned media from BV-2 cells were applied to N2a cells, neuronal cell death was inhibited via suppression of caspase-3 activation and regulation of Bcl-2 and Bax proteins expression. These results suggest that compound D22 may be useful for treating neurodegenerative diseases related with neuroinflammation.

Photoswitchable fluorescent diarylethene in a turn-on mode for live cell imaging.

A new diarylethene-derived photochromic compound, with little cytotoxicity, plasma membrane-permeability, and efficient photoswitchability in cells upon alternative UV and visible light irradiation, was synthesized and applied to live cell imaging.

Anti-neuroinflammatory activity of 1,5-benzodiazepine derivatives.

A series of 2,3-dihydro-1,5-benzodiazepines were synthesized and evaluated for anti-inflammatory effects in microglia cells. Among the 1,5-benzodiazepines tested, compound 3e strongly inhibited LPS-induced nitric oxide (NO) production, with an IC(50) value of 7.0microM in the microglia cells. Also, compound 3e significantly inhibited the enzymatic activity of inducible NO synthase (iNOS) without changes in iNOS protein expression or NO scavenging activity. This result suggests that compound 3e showed anti-neuroinflammatory effects by suppressing iNOS enzyme activity.

Photochromic optical memory based on non-destructive IR read-out.

The photochromic material 1-(2,5-dimethylthien-1,1-dioxide-3-yl)-2-(2,5-dimethylthien-3-yl)hexafluorocyclopentene (DMTFO2) undergoes reversible photocyclization and ring opening reactions upon alternate irradiation with UV and visible light, respectively. Upon photocyclization, the closed-ring isomer of DMTFO2 showed a strong IR absorption band at 1532 cm(-1) which was not observed for the open-ring isomer. To understand the IR spectra of DMTFO2, theoretical calculations were carried out using Gaussian 03 program at the B3LYP/6-31G(d) level. We also demonstrated non-destructive readout of photochromic recording by IR spectral difference between the open- and closed-ring isomers of DMTFO2 in film. We found that DMTFO2 exhibited a higher contrast ratio of IR image between open- and closed-ring isomer compared with previously reported 1,2-bis(2,5-dimethylthien-3-yl)perfluorocyclopentene (DMTF6) because of the increased photoconversion yield as well as higher vibrational transition intensity. These findings along with its high fatigue resistance indicate that DMTFO2 could be an excellent candidate for photon-mode RW (re-writable) memory devices based on photochromic recording and non-destructive IR read-out.

Superparamagnetic iron oxide nanoparticles with photoswitchable fluorescence.

The incorporation of superparamagnetic iron oxide nanoparticles with sulfur-oxidized diarylethene molecules resulted in a novel multifunctional nanosystem, in which the fluorescent performance and flocculation and dispersion are reversibly switched by light irradiation and external magnetic field, respectively.

Fatigue-resistant photochromic dithienylethenes by controlling the oxidation state.

High fatigue-resistant photochromic dithienylethenes were synthesized by controlling the oxidation state of 1,2-bis(2-methyl-1-benzothiophene-3-yl)perfluorocyclopentene (BTF6) and 1,2-bis(2,5-dimethylthien-3-yl)perfluorocyclopentene (DMTF6).

Highly fluorescent photochromic diarylethene in the closed-ring form.

A highly fluorescent diarylethene in the closed-ring form was synthesized by the oxidation of 1,2-bis(2-methyl-1-benzothiophene-3-yl)perfluorocyclopentene (BTF6).