Effect of basic amino acids on photoreaction of ketoprofen in phosphate buffer solution

Photoreaction of ketoprofen (KP), one of the widely used nonsteroidal anti-inflammatory drugs (NSAIDs), was studied with transient absorption spectroscopy in phosphate buffer solution (pH 7.4) in the presence of basic amino acids of histidine (His), lysine (Lys) and arginine (Arg). Deprotonated form of KP (KP(-)) excited with UV-light irradiation gave rise to carbanion through a decarboxylation reaction. It was found that carbanion abstracted a proton from the side chain of the protonated amino acids to yield 3-ethylbenzophenone ketyl biradical (EBPH); however, no reaction was observed with alanine. The relative yield of EBPH by the proton transfer reaction with His was ca. 40 times larger than that of the other two basic amino acids, suggesting that the proton-donating ability of His (protonated His) should be quite high. The information on the photoreaction mechanism of NSAIDs with basic amino acids was essential to understand primary reaction of excited NSAIDs in vivo causing photosensitization on human skin.     

Physicochemical analyses of phase transition and dehydration processes of a new oral 1beta-methylcarbapenem antibiotic agent,CS-834

The characterizations of the anhydrate (A-form), monohydrate (B1-form), and dihydrate (B2-form) of CS-834 were investigated by powder X-ray diffraction, differential scanning calorimetry (DSC), thermogravimetry-differential thermal analysis (TG-DTA), infrared spectroscopy, and Karl Fischer moisture titration. The typical DSC curve of the B2-form showed five endothermic peaks at 35.0, 46.4, 56.2, 99.2, and 190.4 degrees C and an exothermic peak at 123.4 degrees C. In TG-DTA analysis, the three peaks at 35.0, 46.4, and 56.2 degrees C had a total weight loss of 7.3%, corresponding to the release of two water molecules. From morphological observation under thermomicroscopy, the endothermic peak at 99.2 degrees C was attributed to the melting of the dehydrous crystals (B0-form) and the exothermic peak at 123.4 degrees C to the recrystallization to the A-form crystals. The endothermic peak at 190.4 degrees C was due to the melting of the A-form crystals. After incubation for 6.0 h at 35, 50, 60, and 80 degrees C, the powder X-ray diffraction patterns of the B2-form indicated that it was converted into the A-form via the B1-form and B0-form. Thus CS-834 exists in homologous hydrous crystal forms in multiple-phase transformations with the dehydration of two water molecules.     

Novel method for evaluation of chemicals based on ligand-dependent recruitment of GFP labeled coactivator to estrogen receptor displayed on bacterial magnetic particles

We established a novel method to evaluate endocrine disrupting chemicals (EDCs) by assembling the estrogen receptor-ligand binding domain (ERLBD) and GFP labeled coactivator on magnetic nanoparticles. EDC can promote or inhibit coactivator recruitment to the ligand-ERLBD complex. ERLBD was displayed on the surface of nano-sized bacterial magnetic particles (BacMPs) produced by the magnetic bacterium, Magnetospirillum magneticum AMB-1. Our method resulted in 38 molecules of ERLBD molecules on a BacMPs with diameter of 75 nm. Furthermore, ligand-dependent recruitment assays of GFP labeled coactivator to ERLBD-BacMPs was performed by measuring the fluorescence intensity. 17β-estradiol (E2), estriol, diethylstilbestrol, zeralenone (full agonist), octylphenol (partial agonist) and ICI 182,780 (antagonist) were evaluated by this method. Full agonists tested showed increased fluorescence with increasing agonist concentration. Octylphenol had lower fluorescence intensity than E2. ICI 182,780 did not produce any fluorescence. The method developed in this study can evaluate the estrogenic potential of chemicals by discriminating whether they are an ER full agonist, partial agonist, or antagonist. Finally, this method is amenable adaptation into a high throughput format by using automated magnetic separation.     

Decarboxylation of crystalline 2-carboxy-3-hydroxy-dibenzo [a,c] tropone followed by solid-state crystallization

Thermal decarboxylation of 2-carboxy-3-hydroxydibenzo[a,c]tropone (1) in a crystalline environment produces 3-hydroxydibenzo [a,c]tropone (2) accompanied by disordering of the crystalline lattice. Spectroscopic data on the decarboxylated solid suggest that 2 does not form intermolecular hydrogen bonds under the influence of the structure of the mother crystal of 1. Upon annealing, crystallization of 2 takes place and the crystal structure eventually becomes identical to that of the crystal obtained by recrystallization from ethanol. The process of crystallization of 2 is discussed in terms of the crystal structures of both the starting compound 1 and the decarboxylated product 2.     

La2@Cs(17 490)‐C76: A New Non‐IPR Dimetallic Metallofullerene Featuring Unexpectedly Weak Metal–Pentalene Interactions

Although all the pure‐carbon fullerene isomers above C₆₀ reported to date comply with the isolated pentagon rule (IPR), non‐IPR structures, which are expected to have different properties from those of IPR species, are obtainable either by exohedral modification or by endohedral atom doping. This report describes the isolation and characterization of a new endohedral metallofullerene (EMF), La₂@C₇₆, which has a non‐IPR fullerene cage. The X‐ray crystallographic result for the La₂@C₇₆/[Ni^II(OEP)] (OEP=octaethylporphyrin) cocrystal unambiguously elucidated the C_s(17 490)‐C₇₆ cage structure, which contains two adjacent pentagon pairs. Surprisingly, multiple metal sites were distinguished from the X‐ray data, which implies dynamic behavior for the two La³⁺ cations inside the cage. This dynamic behavior was also corroborated by variable‐temperature ¹³⁹ La NMR spectroscopy. This phenomenon conflicts with the widely accepted idea that the metal cations in non‐IPR EMFs invariably coordinate strongly with the negatively charged fused‐pentagon carbons, thereby providing new insights into modern coordination chemistry. Furthermore, our electrochemical and computational studies reveal that La₂@C_s(17 490)‐C₇₆ has a larger HOMO–LUMO gap than other dilanthanum‐EMFs with IPR cage structures, such as La₂@D_3h(5)‐C₇₈ and La₂@I_h(7)‐C₈₀, which implies that IPR is no longer a strict rule for EMFs.     

In Situ Observation of Thiol Michael Addition to a Reversible Covalent Drug in a Crystalline Sponge

A reversible Michael addition reaction between thiol nucleophiles and cyanoenones has been previously postulated to be the mechanism‐of‐action of a new family of reversible covalent drugs. However, the hypothetical Michael adducts in this mechanism have only been detected by spectroscopic methods in solution. Herein, the crystallographic observation of reversible Michael addition with a potent cyanoenone drug candidate by means of the crystalline‐sponge method is reported. After inclusion of the cyanoenone substrate, the sponge crystal was treated with a thiol solution. Subsequent crystallographic analysis confirmed the single‐crystal‐to‐single‐crystal transformation of the substrate into the impermanent Michael adduct.     

Color‐Tunable Solid‐State Fluorescence Emission from Carbazole‐Based BODIPYs

Several carbazole‐based boron dipyrromethene (BODIPY) dyes were synthesized by organometallic approaches. Thiazole, benzothiazole, imidazole, benzimidazole, triazole, and indolone substituents were introduced at the 1‐position of the carbazole moiety, and boron complexation of each dipyrrin generated the corresponding compounds 1 , 2 a , and 3 – 6 . The properties of these products were investigated by UV/Vis and fluorescence spectroscopy, cyclic voltammetry, X‐ray crystallography, and DFT calculations. These compounds exhibited large Stokes shifts, and compounds 1 , 2 a , and 3 – 5 fluoresced both in solution and in the solid state. Complex 2 a showed the highest fluorescence quantum yield (Φ_F) in the solid state, therefore boron complexes of the carbazole–benzothiazole hybrids 2 b – f , which had several different substituents, were prepared and the effects of the substituents on the photophysical properties of the compounds were examined. The fluorescence properties showed good correlation with the results of crystal‐packing analyses, and the dyes exhibited color‐tunable solid‐state fluorescence.     

Molecular weight segregation on surfaces of polyethylene blended films as estimated from nanoscratch tests using scanning probe microscopy

Nanoscratch tests using scanning probe microscopy (SPM) were performed on films prepared from two polyethylene (PE) materials polymerized by using a metallocene catalyst system with different molecular weights (MWs). Blended samples were prepared by dissolving both PE materials at various ratios in hot p-xylene. The pure and blended samples were compression molded into films at 180 degrees C for different holding times in the molten state. The results of SPM nanoscratch tests with an applied load of 30 nN indicated that the lower-MW surface could be easily plowed with wear debris but the higher-MW surface was less deformed. However, the deformation pattern of the blended film surface was similar to that of the lower-MW surface. These results suggest that MW segregation occurs during holding in the molten state as lower-MW components rise to the film surface.     

Stereoselective Self‐Aggregation of 31‐Epimerically Pure Amino Analogs of Zinc Bacteriochlorophyll‐d in an Aqueous Micelle Solution

Zinc bacteriochlorophyll‐d analogs possessing an amino group instead of the original hydroxy group at the C3¹ position were prepared by chemical modification of naturally occurring chlorophyll‐a. The synthetic 3¹‐epimers were successfully separated by reverse phase HPLC to give diastereomerically pure samples. The stereochemistry of the chiral C3¹‐center in the separated amines was determined by NMR analysis of their diastereomeric amides as well as by their asymmetric synthesis from authentic stereoisomers. Both the epimers were monomeric in tetrahydrofuran to give sharp electronic absorption bands, while they self‐aggregated to form chlorosomal oligomers with the redshifted bands in an aqueous Triton X‐100 micelle solution (pH = 6.9). The resulting oligomers deaggregated by addition of p‐toluenesulfonic acid to give monomeric N‐protonated ammonium species. The aggregation and deaggregation were dependent on the 3¹‐stereochemistry, indicating that each epimer produced supramolecularly different self‐aggregates.