Pd-P(t-Bu)(3)-catalyzed consecutive cross-coupling of p-phenylenedizinc compound with two different electrophiles leading to unsymmetrically 1,4-disubstituted benzenes

Pd-P(t-Bu)3 was found to be a chemoselective catalyst for the reaction of p-phenylenedizinc compound with equimolar amounts of carbon electrophiles to afford the single cross-coupling products in good yields, effectively suppressing the formation of double cross-coupling products. The subsequent additions of other electrophiles to the resulting solutions caused the second cross-coupling of the incipient products to take place, achieving a novel and efficient one-pot synthesis of unsymmetrically 1,4-disubstituted benzenes. The origin of the observed high chemoselectivity was speculated.     

Unimodality of the Freely Selfdecomposable Probability Laws

We show that any freely selfdecomposable probability law is unimodal. This is the free probabilistic analog of Yamazato’s result in (Ann. Probab. 6:523–531, 1978).     

A High‐Valent Iron(IV) Peroxo Core Derived from O2

Dioxygen‐tolerant [NiFe] hydrogenases catalyze not only the conversion of H₂ into 2 H⁺ and 2 e^? but also the reduction of O₂ to H₂O. Chemists have sought to mimic such bifunctional catalysts with structurally simpler compounds to facilitate analysis and improvement. Herein, we report a new [NiFe]‐based catalyst for O₂ reduction via an O₂ adduct. Structural investigations reveal the first example of a side‐on iron(IV) peroxo complex.     

Systemically Injectable Enzyme‐Loaded Polyion Complex Vesicles as In Vivo Nanoreactors Functioning in Tumors

The design and construction of nanoreactors are important for biomedical applications of enzymes, but lipid‐ and polymeric‐vesicle‐based nanoreactors have some practical limitations. We have succeeded in preparing enzyme‐loaded polyion complex vesicles (PICsomes) through a facile protein‐loading method. The preservation of enzyme activity was confirmed even after cross‐linking of the PICsomes. The cross‐linked β‐galactosidase‐loaded PICsomes (β‐gal@PICsomes) selectively accumulated in the tumor tissue of mice. Moreover, a model prodrug, HMDER‐βGal, was successfully converted into a highly fluorescent product, HMDER, at the tumor site, even 4 days after administration of the β‐gal@PICsomes. Intravital confocal microscopy showed continuous production of HMDER and its distribution throughout the tumor tissues. Thus, enzyme‐loaded PICsomes are useful for prodrug activation at the tumor site and could be a versatile platform for enzyme delivery in enzyme prodrug therapy.     

The first total synthesis and structural determination of YCM1008A

The first total synthesis and structural determination of YCM1008A, a Ca²⁺ signaling inhibitor, have been achieved. The N-methoxy pyrano-pyridone moiety was synthesized by successive O- and N-conjugate additions with diketoamide 15. The absolute structure was determined to be (2R,3R,4S,8′R)-configuration.     

Precolumn fluorescence labeling method for simultaneous determination of hydroxyzine and cetirizine in human serum

A highly selective and sensitive method was developed for simultaneous determination of the antihistaminic drug hydroxyzine (HZ) and its pharmacologically active metabolite cetirizine (CZ) in human serum using haloperidol as internal standard. The method was based on fluorescence labeling of both drugs with a fluorescent arylboronic acid 4-(4,5-diphenyl-1H-imidazol-2-yl)phenyl boronic acid followed by separation on silica column using a mobile phase consisting of acetonitrile and water (90:10, v/v%) containing triethylamine and acetic acid. The labeling reaction conditions were optimized and the liquid-liquid extraction method was successfully applied to extract the both drugs from serum. The linearity range was 0.025-2.00 microg/mL for HZ and CZ. The limit of detection (S/N = 3) was 10 and 5 ng/mL for HZ and CZ, respectively.     

Formation of supramolecular nanobelt arrays consisting of cobalt(II) "picket-fence" porphyrin on Au surfaces

Adlayers of cobalt(II) 5,10,15,20-tetrakis(alpha,alpha,alpha,alpha-2-pivalamidophenyl)porphyrin (CoTpivPP) were prepared by immersing either Au(111) or Au(100) substrate in a benzene solution containing CoTpivPP molecules, and they were investigated in 0.1 M HClO4 and 0.1 M H2SO4 by cyclic voltammetry and in situ scanning tunneling microscopy (STM). The adlayer structure and electrochemical properties of CoTpivPP are compared to those of 5,10,15,20-tetraphenyl-21H,23H-porphine cobalt(II) (CoTPP). Characteristic nanobelt arrays consisting of CoTpivPP molecules were produced on both Au(111) and Au(100) surfaces. The stability of the nanobelt arrays was controlled by manipulating the electrode potential. On the other hand, the formation of nanobelt arrays consisting of O2-adducted CoTpivPP molecules depended upon the crystallographic orientation of Au. The state of O2 trapped in the cavity of CoTpivPP was distinctly observed in STM images as a bright spot in the nanobelt array formed on reconstructed Au(100)-(hex) surface, but not on Au(111) surface. This result suggests that the arrangement of underlying Au atoms plays an important role in the formation of nanobelt arrays with the sixth ligand coordination.     

Solid-state 17O NMR study of the electric-field-gradient and chemical shielding tensors in polycrystalline amino acids

We have presented a systematic experimental investigation of carboxyl oxygen electric-field-gradient (EFG) and chemical shielding (CS) tensors in crystalline amino acids. Three 17O-enriched amino acids were prepared: L-aspartic acid, L-threonine, and L-tyrosine. Analysis of two-dimensional 17O multiple-quantum magic-angle spinning (MQMAS), MAS, and stationary NMR spectra yields the 17O CS, EFG tensors and the relative orientations between the two tensors for the amino acids. The values of quadrupolar coupling constants (CQ) are found to be in the range of 6.70-7.60 MHz. The values of deltaiso lie in the range of 268-292 ppm, while those of the delta11 and delta22 components vary from 428 to 502 ppm, and from 303 to 338 ppm, respectively. There is a significant correlation between the magnitudes of delta22 components and C--O bond lengths. Since C--O bond length may be related to hydrogen-bonding environments, solid-state 17O NMR has significant potential to provide insights into important aspects of hydrogen bonds in biological systems.     

Heterogeneous Pd/C-catalyzed ligand-free, room-temperature Suzuki-Miyaura coupling reactions in aqueous media

A mild and efficient ligand-free Suzuki-Miyaura coupling reaction catalyzed by heterogeneous Pd/C was developed. Aryl bromides and triflates undergo the cross-coupling with aryl boronic acids in excellent yields without the presence of any additives in aqueous media at room temperature. Aryl vinyl boronic acids are also applicable to this coupling reaction and provide the trans-stilbene derivatives in high yields. The application of wet-type Pd/C to the coupling reaction was achieved without any loss of activity under aerobic conditions, and the reuse of Pd/C is feasible for a fifth run without significant loss of activity. Inductively coupled plasma (ICP) mass-spectrometric analysis of the filtrate from the reaction mixture of 4-bromonitrobenzene with phenylboronic acid demonstrated that the palladium metal hardly leached into the solution within the limits of the detector (<1 ppm), thus suggesting that the present Suzuki-Miyaura reaction proceeded by heterogeneous catalysis.