Synthesis and structure activity relationship studies of benzothieno[3,2-b]furan derivatives as a novel class of IKKbeta inhibitors

As a novel class of IKKbeta inhibitors, a series of tricyclic furan derivatives was designed and synthesized based on the structure of known thiophene IKKbeta inhibitors. Among the various fused furan derivatives synthesized, a benzothieno[3,2-b]furan derivative 13a displayed potent inhibitory activity towards IKKbeta in enzymatic and cellular assays. The potent inhibitory activity originates from an intramolecular non-bonded S...O interaction which was confirmed by the X-ray structure of JNK3 with 16k. The introduction of further substituents on the core structure led to the discovery of the 6-alkoxy derivatives, which possessed a comparable IKKbeta inhibitory activity to 13a and an improved metabolic stability. Among these, appropriately lipophilic compounds 16a, h, i, and 13g (log D>2) were found to possess good oral bioavailability.     

Synthesis of pendant-type anthraquinone-bridged cofacial dinuclear platinum(II) complexes and their emission properties

Anthraquinone-bridged mononuclear and dinuclear complexes, [PtCl(AQ-amide-tpy)](PF6) (1), [Pt2Cl2(AQ-amide-tpy2)](PF6)2 (2), and [Pt2Cl2(AQ-eth-tpy2)](PF6)2 (3), were synthesized and their photochemical properties were investigated. Amide-bound mononuclear complex 1 exhibited only metal-to-ligand charge transfer (MLCT) absorption and emission, whereas dinuclear complex 2 exhibited a low-energy emission around 700 nm at room temperature. Emission lifetime analysis indicated that this emission was originated from the metal-metal-to-ligand charge transfer (MMLCT) excited state, implying the existence of an intramolecular Pt-Pt interaction at the photoexcited state. 3 with rigid ethynylene linkers showed a low-energy absorption around 520 nm (epsilon = approximately 1100 M(-1) cm(-1)) in addition to an 1MLCT absorption, which was ascribed to a 3MLCT absorption from the consideration of the Pt-Pt distance on a geometry-optimized structure. The emission of 3 appeared at 600 nm, which is higher in energy compared with the emission of 2. It is postulated that the restriction of the Pt-Pt distance flexibility in the rigid structure of 3 prevents the significant increase of the Pt-Pt interaction at the excited state.     

Synthesis and spectroscopic characterization of copper(II)-nitrito complexes with hydrotris(pyrazolyl)borate and related coligands

This study focuses on the geometric (molecular) structures, spectroscopic properties, and electronic structures of copper(II)-nitrito complexes as a function of second coordination sphere effects using a set of closely related coligands. With anionic hydrotris(pyrazolyl)borate ligands, one nitrite is bound to copper(II). Depending on the steric demand of the coligand, the coordination mode is either symmetric or asymmetric bidentate, which leads to different ground states of the resulting complexes as evident from EPR spectroscopy. The vibrational spectra of these compounds are assigned using isotope substitution and DFT calculations. The results demonstrate that nu sym(N-O) occurs at higher energy than nu asym(N-O), which is different from the literature assignments for related compounds. UV-vis absorption and MCD spectra are presented and analyzed with the help of TD-DFT calculations. The principal binding modes of nitrite to Cu(II) and Cu(I) are also investigated applying DFT. Using a neutral tris(pyrazolyl)methane ligand, two nitrite ligands are bound to copper. In this case, a very unusual binding mode is observed where one nitrite is eta1-O and the other one is eta1-N bound. This allows to study the properties of coordinated nitrite as a function of binding mode in one complex. The N-coordination mode is easily identified from vibrational spectroscopy, where N-bound nitrite shows a large shift of nu asym(N-O) to >1400 cm-1, which is a unique spectroscopic feature. The optical spectra of this compound exhibit an intense band around 300 nm, which might be attributable to a nitrite to Cu(II) CT transition. Finally, using a bidentate neutral bis(pyrazolyl)methane ligand, two eta1-O coordinated nitrite ligands are observed. The vibrational and optical (UV-vis and MCD) spectra of this compound are presented and analyzed.     

Weak ferromagnetism in a semiconducting (ethylenedithiodiselena- dithiafulvalenoquinone-1,3-diselenolemethide)2.FeBr4 salt

The 2:1 salts of a new bent donor molecule, ethylenedithiodiselenadithiafulvalenoquinone-1,3-diselenolemethide (EDT-DSDTFVODS) and either an FeBr(4)- or a GaBr(4)- ion exhibit semiconducting properties and had small activation energies. The Fe(III) d spins of the FeBr(4)- salt are initially subject to a strong antiferromagnetic interaction and afterward exhibited a weak ferromagnetism at 3.8 K with a very small remanent magnetization of ca. 4 x 10(-2) mu(B) and a spin-flop near 25 kOe along the intercolumnar direction.     

Highly sequence specific RNA terminal labeling by DNA photoligation

We report the nonenzymatic terminal labeling of oligoribonucleotide (ORN) by using template-directed photoligation through 5-carboxyvinyl-2'-deoxyuridine ((CV)U) with high selectivity.     

Vibrational assignment of the 4-hydroxycinnamyl chromophore in photoactive yellow protein

Photoactive yellow protein (PYP) is a bacterial photoreceptor containing a 4-hydroxycinnamyl chromophore. We report the Raman spectra for the dark state of PYP whose chromophore is isotopically labeled with 13C at the carbonyl carbon atom or at the ring carbon atoms. Spectra have been also measured with PYP in D2O where the exchangeable protons are deuterated. Most of the observed Raman bands are assigned on the basis of the observed isotope shifts and normal mode calculations using a density functional theory. We discuss the implication for the analysis of the infrared spectra of PYP. The comprehensive assignment provides a satisfactory framework for future investigations of the photocycle mechanism in PYP by vibrational spectroscopy.     

A new class of chiroptical molecular switches based on the redox-induced conformational changes

A series of optically active bis(catecholketal)s 1-3 were prepared, and their chiroptical properties were investigated experimentally and theoretically, demonstrating that they undergo conformational changes upon 1-e(-) oxidation and can be used as redox-responsive chiroptical molecular switches.     

Implementation of divide-and-conquer method including Hartree-Fock exchange interaction

The divide-and-conquer (DC) method, which is one of the linear-scaling methods avoiding explicit diagonalization of the Fock matrix, has been applied mainly to pure density functional theory (DFT) or semiempirical molecular orbital calculations so far. The present study applies the DC method to such calculations including the Hartree-Fock (HF) exchange terms as the HF and hybrid HF/DFT. Reliability of the DC-HF and DC-hybrid HF/DFT is found to be strongly dependent on the cut-off radius, which defines the localization region in the DC formalism. This dependence on the cut-off radius is assessed from various points of view: that is, total energy, energy components, local energies, and density of states. Additionally, to accelerate the self-consistent field convergence in DC calculations, a new convergence technique is proposed.     

Investigation of combustion modes and pressure of reflective shuttling detonation combustor

Detonation combustors are considered promising alternatives to conventional combustors because they offer high thermal efficiency and fast combustion. However, especially for the rotating detonation combustor, the theoretical propulsive performance has not been confirmed in experimental studies because the highly unsteady flow field hinders the measurements process. To understand the involved phenomena in more detail, a reflective shuttling detonation combustor (RSDC) with a rectangular combustion chamber was developed. The interior of the chamber can easily be visualized owing to its two-dimensional quality. Utilizing the RSDC, several combustion tests with gaseous ethylene and oxygen were conducted for different values of mass flow rates and equivalence ratios. Combustion modes from the tests were classified into four types based on the fast Fourier transform (FFT) analysis of the luminous intensity of the CH* self-luminescence images captured by a high-speed camera and a band pass filter. Simultaneously, the theoretical total pressure of a conventional isobaric combustor was compared to the static pressure measured at the bottom of the RSDC chamber. For the detonation modes, the ratio between experimentally measured static pressure and the theoretical pressure varied depending on the location in the chamber owing to the distribution of the time-averaged static pressure. Furthermore, the pressure ratio of the detonation modes was up to 18% lower than that of the deflagration mode potentially owing to the flow velocity induced by the detonation waves.