Photo‐Cross‐Linked Small‐Molecule Microarrays as Chemical Genomic Tools for Dissecting Protein–Ligand Interactions

We have developed a unique photo‐cross‐linking approach for immobilizing a variety of small molecules in a functional‐group‐independent manner. Our approach depends on the reactivity of the carbene species generated from trifluoromethylaryldiazirine upon UV irradiation. It was demonstrated in model experiments that the photogenerated carbenes were able to react with every small molecule tested, and they produced multiple conjugates in most cases. It was also found in on‐array immobilization experiments that various small molecules were immobilized, and the immobilized small molecules retained their ability to interact with their binding proteins. With this approach, photo‐cross‐linked microarrays of about 2000 natural products and drugs were constructed. This photo‐cross‐linked microarray format was found to be useful not merely for ligand screening but also to study the structure–activity relationship, that is, the relationship between the structural motif (or pharmacophore) found in small molecules and its binding affinity toward a protein, by taking advantage of the nonselective nature of the photo‐cross‐linking process.     

Development of a novel compression tester and rheo-mechanical properties of wet-mass powder. I--Effect of kneading time on the rheo-mechanical properties

In our previous paper [Watano S., et al., Chem. Phram. Bull., 49(1), 64-68, (2001)], a compaction tester was developed to quantitatively evaluate the water dispersion condition of wet kneaded masses prepared by a paddle type kneader. It was also demonstrated that the physical properties of pellets prepared by extrusion granulation after the kneading could be well predicted by the vertical pressure transmission obtained through the compaction tester. However, in this compression tester, the vertical pressure transmission was just obtained and rheological and mechanical properties (so called rheo-mechanical properties) of wet mass-powder that should be the most important to determine the deformation process were not well studied. In this study, a novel compression tester, which can measure both vertical and radial pressure transmissions, has been developed. Based on the compression test, mechanical property (Young's modulus) and rheological property (effective internal friction) of wet mass powder prepared by different kneading times were quantitatively investigated. Granules (pellets) were then obtained through the extrusion granulation and fluidized bed drying, and the physical properties (strength and disintegration time) of the obtained pellet were evaluated. The relationship between the granule (pellet) physical properties and the mechanical and rheological (rheo-mechanical) properties was analyzed.     

Double Asymmetric Synthesis and a New Strategy for Stereochemical Control in Organic Synthesis

This account examines double asymmetric induction from theoretical and practical viewpoints. In the context of four major organic reactions-the aldol, Diels-Alder, catalytic hydrogenation, and epoxidation-it is shown that a double asymmetric induction can be analyzed in terms of the single asymmetric reactions of each of the two chiral reactants. A rule which qualitatively relates the results of these single asymmetric reactions with the outcome of the double asymmetric reaction is proposed. A powerful new strategy based on this rule for the predictable creation of new chiral centers is discussed and the use of this strategy for the synthesis of sugars and macrolides is presented.     

Photochemical reaction of 8-azaxanthine with nucleophiles

Photolysis of 1,3,7-trimethyl-8-azaxanthine $\text{(1)}$ in the presence of primary and secondary alkylamines gave 6-alkylamino-5-methylamino-1,3-dimethyluracils $\text{(2)}$, whereas irradiation of $\text{1}$ in methanol yielded 5-hydroxy-6-methoxy-1,3-dimethyluracil $\text{(3)}$.     

Structures of polyhedra determined by submodular functions on crossing families

The present paper shows that for any submodular functionf on a crossing family with , if the polyhedron is nonempty, then there exist a unique distributive lattice with and a unique submodular function with such thatB(f) coincides with the base polyhedron associated with the submodular system . Here, iff is integer-valued, thenf ₁ is also integer-valued. Based on this fact, we also show the relationship between the independent-flow problem considered by the author and the minimum cost flow problem considered by J. Edmonds and R. Giles.     

Horner-wadsworth-emmons reaction: Use of lithium chloride and an amine for base-sensitive compounds

A mild olefination procedure, utilizing LiCl and an amine, has been developed for use with base-sensitive aldehydes and phosphonates.     

How can temperature affect reverse micellar extraction using sucrose fatty acid ester?

The reverse micellar extraction of lysozyme using sucrose fatty acid ester was found to be greatly affected by the temperature in the extraction process. For example, lysozyme was perfectly extracted from the feed aqueous phase to the reverse micellar organic phase at 25°C, while it was not extracted at 5°C at all. After entrapping lysozyme into the reverse micelles, lysozyme was recovered from the reverse micellar organic phase to the recovery aqueous phase only by decreasing the temperature in the backward extraction. Moreover, lysozyme solubilized in the reverse micellar organic solution could be recovered without the recovery aqueous solution at 3°C, and its activity was retained at 95%.     

Macrolides. Recent Progress in Chemistry and Biochemistry

The progress of macrolide chemistry and biochemistry over the past several years has indeed been remarkable. This review attempts to cover the important contributions which have been made in the fields of structural and synthetic chemistry as well as in the biosynthesis and mode of antimicrobial activity of the “polyoxo” macrolide antibiotics. Emphasis has been placed on the recent synthetic achievements in this field.     

Electrodeposition of flattened Cu nanoclusters on a p-GaAs(001) electrode monitored by in situ optical second harmonic generation

In situ optical second harmonic generation (SHG) technique was employed to investigate the shape and density of Cu nanoclusters, which were electrochemically formed on p-GaAs(001) electrode surfaces. Since GaAs is not a centrosymmetric medium, a significant portion of SHG signal arises from the bulk dipole susceptibility, but it was possible to separate a surface-induced signal from a bulk-induced signal by choosing an appropriate experimental geometry and appropriate data processing. The rotational anisotropy (RA) pattern of the SHG signal from a p-GaAs(001) electrode changed in both shape and magnitude during potential cycling in an electrolyte solution containing Cu2+. The surface plasmon-induced SHG signal from Cu nanoclusters deposited on GaAs was attributed to the modulation source for the RA-SHG pattern. More detailed study was carried out with both in situ SHG and ex situ AFM measurements for Cu nanoclusters deposited by potential step. The results showed that the SHG signal at the present optical geometry was sensitive to the number of oblate or flattened Cu nanoclusters with lateral diameter larger than 30 nm and that the SHG enhancement occurred because of resonant coupling between the surface plasmon induced in the flattened Cu nanoclusters and the near-infrared fundamental light.     

Cyano-bridged gadolinium(III)-tungstate(V) bimetallic assembly with a one-dimensional chain structure

In this paper, we report the crystal structure and magnetic properties of the cyano-bridged gadolinium-tungstate bimetallic assembly, GdIII(DMF)6[WV(CN)8](DMF =N,N-dimethylformamide). X-Ray single crystal analysis shows that this compound crystallizes in the monoclinic system of space group P2(1)/c with cell constants a= 16.40(2)A, b= 11.08(1)A, c= 21.18(2)A, beta= 91.09(8) degrees, and Z= 4. The crystal consists of one-dimensional linear chains, in which [GdIII(DMF)6]3+ and [WV(CN)8]3- ions are linked in an alternating fashion. The magnetic data show that this compound is a paramagnet with an antiferromagnetic coupling of -0.58 cm-1 between GdIII(S= 7/2) and WV(S= 1/2).