Actinoperylone, a novel perylenequinone-type shunt product, from a deletion mutant of the actVA-ORF5 and ORF6 genes for actinorhodin biosynthesis in Streptomyces coelicolor A3(2)

A novel shunt product, actinoperylone, has been isolated from a deletion mutant of the actVA-ORF5 and ORF6 genes involved in the biosynthesis of a benzoisochromanequinone (BIQ) antibiotic actinorhodin (ACT) in Streptomyces coelicolor A3(2). Spectroscopic analysis revealed its perylenequinone-type skeleton with the four chiral centers, obviously derived from the dimerization of an ACT intermediate. The structure of actinoperylone indicates the essential role of ActVA-ORF5 in the oxygen introduction at C-6, which is common to the formation of BIQ chromophore. The present results also agree with the distribution of the actVA-ORF5 homologues in all known BIQ biosynthetic clusters in streptomycetes.     

Synthesis of nanometer-scale porphyrin wheels of variable size

Starting from 1,3-phenylene linked diporphyrin zinc(II) complex 2ZA, repeated stepwise Ag I-promoted coupling reactions provided linear oligomers from 2nZA up to 128ZA. Of these zigzag shaped porphyrin arrays, the Ag I-promoted intramolecular cyclization reaction of 2 nZA (n=5, 6, 8, 9, 12, and 16) under dilute conditions gave the corresponding cyclic porphyrin wheels C2nZA (n=5, 6, 8, 9, 12, and 16), whereas large arrays 2nZA (n=24, 32, and 48) did not provide cyclic porphyrin products. These large discrete porphyrin arrays and wheels were fully characterized by means of 1H NMR spectroscopy, MALDI-TOF mass spectrometry, UV/Vis absorption spectroscopy, GPC-HPLC analysis, and the scanning tunneling microscopy (STM) technique. The STM images of C12ZA and C18ZA reveal their large circular structures. In the cyclic structures of C2nZA in solution, however, the gradual decrease in fluorescence quantum yields and fluorescence lifetimes are observed, reflecting some conformational heterogeneities. Collectively, the present work provides an important contribution to the construction of fully covalently linked large cyclic arranged porphyrin arrays with ample electronic interactions as a model of light-harvesting antenna.     

Nagelamide J, a novel dimeric bromopyrrole alkaloid from a sponge Agelas species

A novel dimeric bromopyrrole alkaloid, nagelamide J (1), with antimicrobial activity has been isolated from an Okinawan marine sponge Agelas species, and the structure and stereochemistry were elucidated from spectroscopic data. Nagelamide J (1) is the first bromopyrrole alkaloid possessing a cyclopentane ring fused to an amino imidazole ring.     

A hexagonal prismatic porphyrin array: synthesis, STM detection, and efficient energy hopping in near-infrared region

A belt-shaped hexagonal cyclic porphyrin array 2 that comprises of six meso-meso, beta-beta, beta-beta triply linked diporphyrins 3 bridged by 1,3-phenylene spacers is prepared by oxidation from cyclic dodecameric array 1 consisting of six meso-meso directly linked diporphyrins 4 with DDQ and Sc(OTf)3. The absorption spectrum of 2 is similar to that of the constituent subunit 3 but shows a slight red-shift for the Q-bands in near-infrared (NIR) region, indicating the exciton coupling between the neighboring diporphyrin chromophores. Observed total exciton coupling energies in the absorption spectra were largely matched with the calculated values based on point-dipole exciton coupling approximation. It was found that the experimental exciton coupling strength (292 cm(-1)) of the Q-band in 2 is slightly larger than the calculated one (99 cm(-1)), indicating that the electronic communications are enhanced through 1,3-phenylene linkers in hexameric macromolecule. A rate of the excitation energy hopping (EEH) that occurs in 2 at the lowest excited singlet state in the near-infrared region has been determined to be (1.8 ps)(-1) on the basis of the pump-power dependent femtosecond transient absorption (TA) and the transient absorption anisotropy (TAA) decay measurements. The 2 times faster EEH rate of 2 than that of 1 (4.0 ps)(-1) mainly comes from involving through-bond energy transfer among diporphyrin subunits via 1,3-phenylene bridges as well as F?rster-type through-space EEH processes. STM measurement of 2 in the Cu(100) surface revealed that it takes several discrete conformations with respect to the relative orientation of neighboring diporphyrins. Collectively, an effective EEH in the NIR region is realized in 2 due largely to the intensified oscillator strength in the S(1) state (Q-band) and the close proximity held by 1,3-phenylene spacers.     

Syntheses, crystal and solution structures, ligand-exchange, and ligand-coupling reactions of mixed pentaarylantimony compounds

All possible combinations of mixed pentaarylantimony compounds bearing p-methylphenyl and p-trifluoromethylphenyl groups were synthesized; ArnTol5-nSb (n=0-5: Ar=p-CF3C6H4, Tol=p-CH3C6H4): Tol5Sb (1), ArTol4Sb (2), Ar2Tol3Sb (3), Ar3Tol2Sb (4), Ar4TolSb (5), and Ar5Sb (6). Compounds 2-5 are the first well-characterized examples of mixed acyclic pentaarylantimony species. The structures of 2-6 were determined by X-ray crystallography to feature trigonal-bipyramidal (TBP) geometry with the more electronegative p-trifluoromethylphenyl substituents selectively occupying the apical positions. Consideration of the chemical shifts of the ipso carbons of the aryl and tolyl groups suggested that the solution structures of 1-6 were also TBP, although their pseudorotation could not be frozen even at -80 degrees C. Ligand-exchange reactions (LERs) took place between 1 and 6 at approximately 60 degrees C in [D6]benzene and all six species 1-6 were found in the equilibrium mixture. The relative stabilities of 1-6 were determined quantitatively by comparison of the observed molar ratios of 1-6 in equilibrium with calculated statistical molar ratios, and Ar2Tol3Sb (3) was found to be the most stable. The ligand-coupling reactions (LCRs) of 2-5 in solution were greatly accelerated by adding Cu(acac)2 or Li+TFPB- (TFPB: [3,5-(CF3)2 C6H3]4 B), whereby the rate becomes comparable to the LER. The use of flash vacuum thermolysis (FVT) allowed the LCR to occur with very little ligand-exchange; the exception ArTol4Sb had very fast ligand-exchange. The selectivities of the LCRs were calculated from the yield of the biaryls synthesized by using FVT. These results were highly consistent with reactions catalyzed in solution, in which bitolyl was not obtained at all. The experimental results suggested that the LCR of pentaarylantimony compounds proceeds in the manner of apical-apical coupling.     

Metachromins R--T, new sesquiterpenoids from marine sponge Spongia sp

Three new sesquiterpenoids, metachromins R--T (1--3), have been isolated from an Okinawan marine sponge Spongia sp. The structures and stereochemistry of 1--3 were elucidated on the basis of the spectroscopic data. Metachromins S (2) and T (3) showed modest cytotoxicity.     

Electric quadrupole model on the formation of molecular chirality dependent domain shapes of lipid monolayers at the air-water interface

Shapes and orientational deformation of a lipid monolayer domain have been analyzed taking into account the surface pressure, line tension, and electrostatic energy due to the spontaneous polarization and electric quadrupole density generated from the domain. The electrostatic energy due to the generation of spontaneous polarization and electric quadrupole density contributes to the formation of orientational deformation as the Frank elastic energy and spontaneous splay, respectively. Since the orientational configuration of the electric quadrupole density and in-plane spontaneous polarization is dependent on the molecular chirality, and the positive splay deformation of electric quadrupole density is induced by the spontaneous splay, the bending direction of in-plane spontaneous polarization depends on the chirality of constituent lipids. The electrostatic energy due to the in-plane spontaneous polarization is dependent on the orientational deformation of in-plane spontaneous polarization, and bends the domain shape towards the bending direction of the in-plane spontaneous polarization. It has been demonstrated that the chiral dependence of the domain shapes of lipid monolayers originated from the chiral dependence of orientational structure due to the electric quadrupole density.     

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.     

Effect of Interventions for Improving Lumbar Motor Control on Low Back Pain in Sedentary Office Workers: A Randomized Controlled Trials

Objective: To clarify the effect of intervention with dynamic motor control exercise (DMCE) for the lumbar region on low back pain in sedentary office workers (SOWs). Methods: The participants comprised 32 SOWs with low back pain who were randomly categorized into two groups: the DMCE group and the normal trunk exercise (NTE) group. Both groups performed each exercise for three days per week for 8 weeks. The primary endpoints were evaluated for the lumbar and hip flexion angles during trunk forward bending, effect of low back pain on activities of daily living (using the Oswestry Disability Index), and intensity of low back pain (using the Visual Analog Scale) pre- and post-intervention. The extent of changes was calculated by subtracting the pre-intervention value from the post-intervention value and was compared between the two groups using an unpaired t-test. Results: The extent of changes in the lumbar flexion and hip flexion angles at 10° of trunk forward bending were significantly greater in the DMCE group than in the NTE group, and no significant differences were noted between the two groups at other angles of trunk forward bending. The extent of changes in the Oswestry Disability Index and the Visual Analog Scale scores were significantly greater in the DMCE group than in the NTE group. Conclusion: DMCE is effective in improving motor control in the lumbar region and hip joints, thereby ameliorating low back pain in SOWs.     

Ion–ion interactions of LiPF6 and LiBF4 in propylene carbonate solutions

Self-diffusion coefficients of Li⁺ D_Li⁺, PF₆⁻ D_PF6⁻ and solvent propylene carbonate (PC) D_PC in LiPF₆−PC solutions were determined at 298 K by the pulse gradient spin echo (PGSE) NMR technique over the salt concentration range of 0.1–3.0 M (M = mol dm^– 3). The order of the diffusion coefficients was found to be D_Li⁺ < D_PF6⁻ < D_PC over the concentration range examined, and they were monotonically decreased with increasing the salt concentration. Haven ratio Λ/Λ_NMR, where Λ and Λ_NMR represent the ionic conductivity measured electrochemically and that estimated via the Nernst-Einstein equation using the diffusion coefficient, respectively, was evaluated as the measure of the ion–ion interaction in the LiPF₆–PC solutions. Though Λ/Λ_NMR values for LiPF₆-solutions decrease with increasing the salt concentration, they were greater than those for LiBF₄–PC solutions over the whole concentration range examined, which indicates that the ion pair formation ability of PF₆^– ion is weaker than that of the BF₄^– ion. The smaller value of the ionic conductivity for the highly concentrated LiPF₆–PC solution (above 2.0 M) than that of the LiBF₄-solutions can be attributed to the more rapidly increased viscosity relative to the LiBF₄-solution. Classic molecular dynamics (MD) simulations for the respective LiPF₆ and LiBF₄-solution of 0.5 and 1.0 M were also carried out based on the effective pair potentials. Diffusion coefficients, ionic conductivity and Haven ratio for these solutions were calculated from MD trajectories, and they qualitatively agree with those evaluated by experiments. Pair correlation functions g_LiO(r) (for Li⁺–O (PC) pair) and g_LiPF6(r) (for Li⁺–PF₆^– pair) or g_LiBF4(r) (for Li⁺–BF₄^– pair) revealed that the lithium ion weakly forms the contact ion pairs with PF₆^–, whilst strongly with BF₄^–, which supports the present experimental results. Moreover, the simulation results show that both anions in the contact ion pairs predominantly take the monodentate form, which is in contrast to the multidentate coordination predicted by ab initio calculation in gas phase.