Base oxidation at 5' site of GG sequence in double-stranded DNA induced by UVA in the presence of xanthone analogues: relationship between the DNA-damaging abilities of photosensitizers and their HOMO energies

UVA contributes to skin cancer by solar UV light. Photosensitizers are believed to play an important role in UVA carcinogenesis. We investigated the mechanism of DNA damage induced by photoexcited xanthone (XAN) analogues (XAN, thioxanthone [TXAN] and acridone [ACR]), exogenous photosensitizers, and the relationship between the DNA-damaging abilities and their highest occupied molecular orbital (HOMO) energies. DNA damage by these photosensitizers was examined using 32P-labeled DNA fragments obtained from the p53 tumor suppressor gene. Photoexcited XAN caused DNA cleavage specifically at 5'-G of the GG sequence in the double-stranded DNA only when the DNA fragments were treated with piperidine, suggesting that DNA cleavage is due to base modification with little or no strand breakage. With denatured single-stranded DNA, the extent of XAN-sensitized photodamage was decreased. An oxidative product of G, 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dGuo), was formed by photoexcited XAN, and the 8-oxo-dGuo formation was decreased in single-stranded DNA. TXAN and ACR induced DNA photodamage as did XAN, although the order of DNA-damaging ability was XAN > TXAN > ACR. These findings suggest that photoexcited XAN analogues induce nucleobase oxidation at 5'-G of GG sequence in double-stranded DNA through electron transfer. The HOMO energies of these photosensitizers, estimated from ab initio molecular orbital (MO) calculation, decreased in the following order: XAN > TXAN > ACR. Extents of DNA damage increased exponentially with the HOMO energies of XAN analogues. This study suggests that DNA-damaging abilities of photosensitizers can be estimated from their HOMO energies.     

Nanotribology of ethers: effects of molecular asymmetry and fluoroalkyl chains

The tribological properties of the molecularly thin films of asymmetric ether (1,3-dimethylbutyl octyl ether, AE) and fluorinated asymmetric ether (1H,1H,2H,2H-perfluorooctyl-1,3-dimethylbutyl ether, FAE) were investigated. Friction forces and dynamic thicknesses (thicknesses during sliding) were simultaneously measured using the surface forces apparatus, and the effects of molecular asymmetry and fluoroalkyl chains on the friction properties are analyzed. The friction forces (both kinetic and static) and dynamic thicknesses are larger for the AE film than for the FAE film. The two ethers exhibit stick-slip friction at low sliding velocity, but the stick-slip patterns are different. For the AE film, one stick-slip cycle consists of two or more spikes; a large spike is followed by one or more small spike(s) in the cycle. On the other hand, regular stick-slip spikes are observed for the FAE film. The results suggest that the responsible friction mechanisms are completely different between the two ether films. The asymmetric shape of the AE molecule results in a variety of shear-ordered liquid structures in confinement, and the friction (stick-slip) behavior follows the "phase-transition model". In contrast, the FAE molecule is rigid, and the shape of the molecule is rather close to a symmetric cylinder, which leads to a well-ordered two-layer film in confinement. The each molecular layer is strongly adsorbed on adjacent mica substrate and behaves as a fluorinated coating. The friction is governed by the molecular scale "bumpiness" of the fluoroalkyl chains lying on mica surfaces and basically follows the "cobblestone model". The advantage of the thin FAE film as a practical lubricant is also discussed.     

An efficient construction of bridged chiral tetracyclic indolidines, a core structure of asperparaline, via stereocontrolled catalytic Pauson-Khand reaction

A reaction of chiral enyne 22 derived from l-proline with a catalytic amount of cobalt (0) octacarbonyl in the presence of N-methylmorphorine N-oxide gave tricyclic enone 24 in 54% yield (73% based on consumed starting material). Treatment of enone 11 with aqueous methylamine followed by silica gel afforded bridged tetracyclic indolidine 1, a common structural motif of natural metabolites, an asperparaline series of compounds and also a potential intermediate for the synthesis of a paralytic alkaloid, asperparaline C (4), in 70% yield.     

Fragment interaction analysis based on local MP2

We have developed a fragment interaction analysis based on local MP2 (FILM) in the context of the fragment molecular orbital (FMO) scheme. The primary purpose of this work is to provide a tool for analyzing inter-fragment interaction associated with dispersion interactions in a large molecule such as protein and DNA. Our implementation of local MP2 (LMP2) is based on the algorithm developed by Pulay and Werner. A potential of FILM was demonstrated using the human immunodeficiency virus type 1 protease (HIV-1 PR) complexed with lopinavir (LPV). The total energy, binding affinity, and inter-fragment interaction energy (IFIE) by the FMO method using LMP2 were compared with those obtained by canonical MP2 and the site-specific information in dispersion interaction was obtained. It turned out that the FILM is a useful tool for analyzing the dispersion interaction between an amino acid residue and a specific site of a ligand.     

A concise formal total synthesis of mappicine and nothapodytine B via an intramolecular hetero Diels-Alder reaction

A six-step formal total synthesis of a natural alkaloid, mappicine (3), has been achieved. The highlight of our synthetic strategy is an intramolecular hetero Diels-Alder reaction that was used for the construction of the CD ring system of mappicine (3). In addition, it was demonstrated that the Sonogashira coupling reaction of 2-chloro-3-hydroxymethylquinoline (8c) with trimethylsilylacetylene proceeded at room temperature in excellent yield.     

Direct catalytic asymmetric aldol reaction of hydroxyketones: asymmetric Zn catalysis with a Et(2)Zn/linked-BINOL complex

Full details of our newly developed catalyses with asymmetric zinc complexes as mimics of class II zinc-containing aldolase are described. A Et(2)Zn/(S,S)-linked-BINOL complex was developed and successfully applied to direct catalytic asymmetric aldol reactions of hydroxyketones. A Et(2)Zn/(S,S)-linked-BINOL 1 = 2/1 system was initially developed, which efficiently promoted the direct aldol reaction of 2-hydroxy-2'-methoxyacetophenone (7d). Using 1 mol % of (S,S)-linked-BINOL 1 and 2 mol % of Et(2)Zn, we obtained 1,2-dihydroxyketones syn-selectively in high yield (up to 95%), good diastereomeric ratio (up to 97/3), and excellent enantiomeric excess (up to 99%). Mechanistic investigation of Et(2)Zn/(S,S)-linked-BINOL 1, including X-ray analysis, NMR analysis, cold spray ionization mass spectrometry (CSI-MS) analysis, and kinetic studies, provided new insight into the active oligomeric Zn/(S,S)-linked-BINOL 1/ketone 7d active species. On the basis of mechanistic investigations, a modified second generation Et(2)Zn/(S,S)-linked-BINOL 1 = 4/1 with molecular sieves 3A (MS 3A) system was developed as a much more effective catalyst system for the direct aldol reaction. As little as 0.1 mol % of (S,S)-linked-BINOL 1 and 0.4 mol % of Et(2)Zn promoted the direct aldol reaction smoothly, using only 1.1 equiv of 7d as a donor (substrate/ligand = 1000). This is the most efficient, in terms of catalyst loading, asymmetric catalyst for the direct catalytic asymmetric aldol reaction. Moreover, the Et(2)Zn/(S,S)-linked-BINOL 1 = 4/1 system was effective in the direct catalytic asymmetric aldol reaction of 2-hydroxy-2'-methoxypropiophenone (12), which afforded a chiral tetrasubstituted carbon center (tert-alcohol) in good yield (up to 97%) and ee (up to 97%), albeit in modest syn-selectivity. Newly developed (S,S)-sulfur-linked-BINOL 2 was also effective in the direct aldol reaction of 12. The Et(2)Zn/(S,S)-sulfur-linked-BINOL 2 = 4/1 system gave aldol adducts anti-selectively in good ee (up to 93%). Transformations of the aldol adducts into synthetically versatile intermediates were also described.     

Theoretical study on the electronic spectrum of TcO 4 −

Summary The theoretical electronic spectrum of TcO ₄ ^– calculated by the SAC(symmetry adapted cluster)/SAC-CI method is presented. The spectrum is in good agreement with the experimental one. The observed peaks are assigned and the existence of several absorptions in the energy region higher than that observed is predicted. The difference and the similarity between the electronic spectra of TcO ₄ ^– and MnO ₄ ^– are clarified. The spectral difference between TcO ₄ ^– and MnO ₄ ^– is due to a remarkably high energy shift of the 3¹T₂ state of TcO ₄ ^– .     

Synchrotron radiation based Mössbauer absorption spectroscopy of various nuclides

Synchrotron-radiation (SR) based Mössbauer absorption spectroscopy of various nuclides is reviewed. The details of the measuring system and analysis method are described. Especially, the following two advantages of the current system are described: the detection of internal conversion electrons and the close distance between the energy standard scatterer and the detector. Both of these advantages yield the enhancement of the counting rate and reduction of the measuring time. Furthermore, SR-based Mössbauer absorption spectroscopy of ⁴⁰K, ¹⁵¹Eu, and ¹⁷⁴Yb is introduced to show the wide applicability of this method. In addition to these three nuclides, SR-based Mössbauer absorption spectroscopy of ⁶¹Ni, ⁷³Ge, ¹¹⁹Sn, ¹²⁵Te, ¹²⁷I, ¹⁴⁹Sm, and ¹⁸⁹Os has been performed. We continue to develop the method to increase available nuclides and to increase its ease of use. The complementary relation between the time-domain method using SR, such as nuclear forward scattering and the energy-domain methods such as SR-based Mössbauer absorption spectroscopy is also noted.     

Slow dynamics in glycerol: collective de gennes narrowing and independent angstrom motion

The slow dynamics of microscopic density correlations in supercooled glycerol was studied by time-domain interferometry using ⁵⁷Fe-nuclear resonant scattering gamma rays of synchrotron radiation. The dependence of the relaxation time at 250 K on the momentum transfer q is maximum near the first peak of the static structure factor S(q) at q ～ 15 nm ^?1. The q-dependent behavior of the relaxation time known as de Gennes narrowing was confirmed in glycerol. Conversely, de Gennes narrowing around the second and third peaks of S(q) at q ～ 26 nm ^?1 and 54 nm ^?1 was not detected. The q dependence of the relaxation time was found to follow a power-law equation with power-law index of 1.9(2) in the q region well above the first peak of S(q) up to ～ 60 nm ^?1, which corresponds to angstrom scale, within experimental error. This suggests that in the angstrom-scale dynamics of supercooled glycerol, independent motions dominate over collective motion.