Novel cyclopropyl diketones and 14-membered macrolides from the soil fungus Hamigera avellanea BCC 17816

Two novel cyclopropyl diketones, hamavellone A (1) and B (2), and two new 14-membered nonaketide macrolactones, hamigeromycin A (3) and B (4), together with six known compounds, 89-250904-F1 (radicicol analogue A, 5), pseurotin A (6), emodin (7), ω-hydroxyemodin (8), and emodin bianthrones (9 and 10) were isolated from the soil fungus Hamigera avellanea BCC 17816. The structures of the new compounds were defined by analysis of NMR and MS data. The absolute stereochemistry of 3 was addressed by chemical correlation to 5. Hamavellone B (2) exhibited antimalarial activity with an IC₅₀ of 5.2 μg/mL, whereas it also showed comparable cytotoxicity.     

Synthesis of all-conjugated diblock copolymers by quasi-living polymerization and observation of their microphase separation

We designed and synthesized the all-conjugated diblock copolymers poly(3-hexylthiophene-block-3-(2-ethylhexyl)thiophene)s (P(3HT-b-3EHT)s) via a modified Grignard metathesis (GRIM), a type of quasi-living polymerization, and studied their microphase-separated structures. The P(3HT-b-3EHT)s synthesized had well-controlled molecular weights and very narrow polydispersity indices (PDIs), which demonstrates the usefulness of GRIM polymerization for the synthesis of semiconducting block copolymers. P(3HT-b-3EHT)s self-organized to form clear microphase-separated patterns upon thermal treatment, as observed by AFM. Interestingly, the enhancement of the interchain interaction of the P3HT segments compared with the P3HT homopolymer was clearly observed from the UV-vis spectra, despite the fact that the amount of crystalline P3HT fraction was reduced to 83% of the total polymer amount in P(3HT-b-3EHT). It is suggested that the relatively unconstrained, amorphous segments of P3EHT can enhance the crystallization of P3HT segments to form an ordered self-organized nanostructure.     

Artificial DNA made exclusively of nonnatural C-nucleosides with four types of nonnatural bases

We describe a new class of DNA-like oligomers made exclusively of nonnatural, stable C-nucleosides. The nucleosides comprise four types of nonnatural bases attached to a deoxyribose through an acetylene bond with the beta-configuration. The artificial DNA forms right-handed duplexes and triplexes with the complementary artificial DNA. The hybridization occurs spontaneously and sequence-selectively, and the resulting duplexes have thermal stabilities very close to those of natural duplexes. The artificial DNA might be applied to a future extracellular genetic system with information storage and amplifiable abilities.     

Effect of a tridentate ligand on the structure, electronic structure, and reactivity of the copper(I) nitrite complex: role of the conserved three-histidine ligand environment of the type-2 copper site in copper-containing nitrite reductases

It is postulated that the copper(I) nitrite complex is a key reaction intermediate of copper containing nitrite reductases (Cu-NiRs), which catalyze the reduction of nitrite to nitric oxide (NO) gas in bacterial denitrification. To investigate the structure-function relationship of Cu-NiR, we prepared five new copper(I) nitrite complexes with sterically hindered tris(4-imidazolyl)carbinols [Et-TIC = tris(1-methyl-2-ethyl-4-imidazolyl)carbinol and iPr-TIC = tris(1-methyl-2-isopropyl-4-imidazolyl)carbinol] or tris(1-pyrazolyl)methanes [Me-TPM = tris(3,5-dimethyl-1-pyrazolyl)methane; Et-TPM = tris(3,5-diethyl-1-pyrazolyl)methane; and iPr-TPM = tris(3,5-diisopropyl-1-pyrazolyl)methane]. The X-ray crystal structures of all of these copper(I) nitrite complexes were mononuclear eta(1)-N-bound nitrite complexes with a distorted tetrahedral geometry. The electronic structures of the complexes were investigated by absorption, magnetic circular dichroism (MCD), NMR, and vibrational spectroscopy. All of these complexes are good functional models of Cu-NiR that form NO and copper(II) acetate complexes well from reactions with acetic acid under anaerobic conditions. A comparison of the reactivity of these complexes, including previously reported (iPr-TACN)Cu(NO2) [iPr-TACN = 1,4,7-triisopropyl-1,4,7-triazacyclononane], clearly shows the drastic effects of the tridentate ligand on Cu-NiR activity. The copper(I) nitrite complex with the Et-TIC ligand, which is similar to the highly conserved three-histidine ((His)3) ligand environment in the catalytic site of Cu-NiR, had the highest Cu-NiR activity. This result suggests that the (His)3 ligand environment is essential for acceleration of the Cu-NiR reaction. The highest Cu-NiR activity for the Et-TIC complex can be explained by the structural and spectroscopic characterizations and the molecular orbital calculations presented in this paper. Based on these results, the functional role of the (His)3 ligand environment in Cu-NiR is discussed.     

LOV-like flavin-Cys adduct formation by introducing a Cys residue in the BLUF domain of TePixD

BLUF and LOV are blue-light sensor domains that possess flavin as a common chromophore but exhibit distinct photoreactions. Ile66 located in the BLUF domain of a cyanobacterial photosensor protein, TePixD, was replaced with Cys to mimic the LOV domain. Light-induced Fourier transform infrared spectra of the I66C TePixD showed that a flavin-Cys adduct, typical of the photoinduced intermediates of LOV domains, was formed in the I66C BLUF domain. This result demonstrates that different types of flavin photoreactions can be realized in the same domain if key amino acids are properly arranged near the flavin and the domain structure itself is not a crucial factor to determine the photoreaction type.     

Site-specific synthesis of oxo-bridged mixed-valence binuclear complexes on mesoporous silica

We report the site-specific synthesis of mixed valence TiIV-O-FeII complexes within the pores of ordered mesoporous silica (SBA-15). By using 6-di- tert-butylpyridine as the selective activator of tripodally linked TiIV-OH groups of Ti-grafted SBA-15, the FeCl2.4H2O complexes reacted selectively with the nucleophilic TiIV-O(-) groups. The formation of Si-O-FeII byproducts, due to the reaction with the abundant Si-OH groups, was successfully restricted and the selectivity for forming the TiIV-O-FeII complexes exceeded 80%. The metal-metal interaction of TiIV-O-FeII complexes was confirmed by the appearance of TiIV/FeII --> TiIII/Fe III metal-to-metal charge transfer band, and their coordination, valency, and spin state were characterized by diffuse transmission UV-vis, Fourier transform IR, and Fe K-edge X-ray absorption fine structure measurements. It was also confirmed that the present methods can be extended to other metal combinations of TiIV-O-NiII and TiIV-O-MnII. The electron transfer processes occurring under photoinduced metal-to-metal charge transfer of oxo-bridged mixed valence complexes on silica supports have recently been proven as a new class of visible-light-sensitive redox centers. Thus, the present synthetic procedure allows the fabrication of a variety of photochemical reaction centers according to the molecular-level design.     

Influence of graft interface polarity on hydration/dehydration of grafted thermoresponsive polymer brushes and steroid separation using all-aqueous chromatography

We have prepared poly( N-isopropylacrylamide) (PIPAAm) brush-grafted surfaces with varied temperature-responsive hydrophobic properties through surface-initiated atom transfer radical polymerization (ATRP). These temperature-responsive surfaces were characterized by chromatographic analysis using modified silica beads as a chromatographic stationary phase in aqueous mobile phase. Mixed silane self-assembled monolayers (SAMs) comprising ATRP initiator and silanes with various terminal functional groups were formed on the silica bead surfaces. IPAAm was then polymerized by ATRP using the CuCl/CuCl2/Me6TREN catalyst system in 2-propanol at 25 degrees C for 16 h. The chromatographic retention behavior of steroids on the resulting PIPAAm brushes made on more polar silane components was distinct from that on more apolar silane interfaces. Retention times for steroids on PIPAAm mixed apolar silane graft interfaces were significantly longer than those on analogous polar silane interfaces due to enhanced dehydration of PIPAAm brushes on apolar silane-grafted surfaces. Changes in retention factor, k', on polar silane PIPAAm-grafted interfaces were relatively large compared to that on apolar PIPAAm grafted interfaces due to larger hydration/dehydration alterations of grafted PIPAAm brushes on the former surfaces. Applied step-temperature gradients from 50 to 10 degrees C show that PIPAAm brushes on polar silane interfaces tend to hydrate more, leading to shorter retention times. In conclusion, the polarity of the grafted interface significantly influences the grafted PIPAAm brush hydration/dehydration characteristics and subsequently also the temperature-modulated separation of bioactive compounds in all-aqueous chromatography.     

Superperiodic assembly of 2,6-diethynylpyridine through weak hydrogen bonds at the 1-phenyloctane/HOPG interface

Regardless of the absence of alkyl chains and conventional hydrogen bonding sites as well as its small size, 2,6-diethynylpyridine forms an ordered array at the interface between 1-phenyloctane and highly oriented pyrolytic graphite (HOPG) under room temperature conditions, as revealed by scanning tunneling microscopy. We propose a model for the superperiodic molecular arrangement with reference to the bulk crystal structure, in which the surface pattern is governed by weak C-H...N and C-H...pi hydrogen bonds as well as the periodic potential of the underlying graphite surface.     

Dimensions of a free linear polymer and polymer immobilized on silica nanoparticles of a zwitterionic polymer in aqueous solutions with various ionic strengths

The dimensions and intermolecular interactions of a surface-grafted and unbound free polyampholyte, poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC), were estimated in aqueous solutions with various ionic strengths. Free linear PMPC was synthesized by atom-transfer radical polymerization (ATRP), and static light scattering (SLS) and dynamic light scattering (DLS) were carried out for the PMPC solutions with various concentrations of NaCl, c s. The hydrodynamic radius R H and the second virial coefficient A 2 of PMPC were independent of c s (0-0.5 M), though both R H and A 2 of polyampholytes usually strongly depend on the ionic strength. PMPC-immobilized silica nanoparticles (PMPC-SiNP) were also synthesized by surface-initiated ATRP, and DLS was carried out as for the solutions of linear PMPC to investigate the dependence of the dimensions of PMPC immobilized on a solid surface on the ionic strength. The molecular weight and surface density of PMPC immobilized on SiNP were estimated from the results obtained by GPC, NMR, and thermogravimetric analysis. The independence of R H of PMPC-SiNP was also observed, but its magnitude was larger than that of linear PMPC, although the molecular weight of PMPC immobilized on SiNP was smaller than that of linear PMPC. The larger dimension of PMPC immobilized on SiNP was explained by the excluded volume effect between the immobilized polymer chains.     

Efficient total synthesis of (+)-negamycin, a potential chemotherapeutic agent for genetic diseases

Herein, we describe an efficient strategy for the total synthesis of (+)-negamycin using commercially available achiral N-Boc-2-aminoacetaldehyde as starting material with 42% overall yield for a limited number of steps.