Tubiferal A, a backbone-rearranged triterpenoid lactone isolated from the myxomycete Tubifera dimorphotheca, possessing reversal of drug resistance activity

Tubiferal A, a novel rearranged triterpenoid lactone, has been isolated from field-collected fruit bodies of the myxomycete, Tubifera dimorphotheca, and its structure elucidated by spectral data. Tubiferal A (1) possesses a 9,10-secocycloartan-16,21-olide skeleton, and this new compound exhibited a reversal effect of vincristine (VCR) resistance (more than 4-fold) against VCR-resistant KB cell lines. Tubiferal B (2), corresponding to the seco acid of 1 was also isolated, but showed no comparable activity.     

Adsorption of immunogamma globulin onto various synthetic calcium hydroxyapatite particles

This paper presents data on adsorption of immunogamma globulin (IgG) onto synthetic rodlike calcium hydroxyapatite particles (CaHaps) with various particle lengths and calcium/phosphate (Ca/P) atomic ratios ranging from 1.54 to 1.65 and compares the obtained results to those of acidic (bovine serum albumin, BSA), neutral (myoglobin, MGB), and basic (lysozyme, LSZ) proteins reported before. The effect of electrolyte concentration on IgG adsorption was also examined. The initial rate of IgG adsorption was similar to that of BSA and was slower than that of MGB and LSZ. This fact was interpreted by the difference in the structural stability and molecular weight of these proteins. The isotherms of IgG adsorption onto the CaHap particles were of pseudo-Langmuir type. The saturated amount of adsorbed IgG values (nsIgG) for the particles with mean particle length less than 70 nm decreased with increasing Ca/P ratio. The adsorption behavior of IgG molecules was very similar to that of basic LSZ, though IgG has zero net charge. The nsIgG value was increased with increased mean particle length of CaHaps; the relationship was less significant than that for BSA but similar to those for MGB and LSZ. The similar adsorption behavior of IgG and LSZ suggested that the Fab parts of IgG molecules preferentially adsorb onto CaHap to provide the reversed Y-shaped conformation of IgG. The change of the adsorption mode of IgG molecules from the reversed Y-shaped conformation to side-on by "spreading" the Fc part of IgG molecules onto the particle surface over a longer adsorption time was suggested. The nsIgG value was increased with increasing electrolyte concentration by screening the intra- and intermolecular electrostatic interactions of proteins.     

Direct injection analysis of bisphenol A in serum by combination of isotope imprinting with liquid chromatography-mass spectrometry

A restricted access media-molecularly imprinted polymer was prepared using bisphenol A (BPA)-d16 as a template molecule, and was successfully applied to direct injection analysis of BPA in serum combined with column-switching LC-MS.     

Preparation of 5,5-dicyano- and 5-cyano-5-ethoxycarbonyl-5,6-dihydro-3,7-diphenyl-4H-1,2-diazepines and their halogenations

5,5-Dicyano- and 5-cyano-5-ethoxycarbonyl-5,6-dihydro-3,7-diphenyl-4H-1,2-diazepines were prepared by the condensation of α-bromoacetophenone azine with malononitrile and ethyl cyanoacetate in the presence of sodium ethoxide, respectively. Halogenations of the dihydrodiazepines gave pyridazines, diazanorcaradienes, 4,4,6,6-tetrachlorodihydrodiazepines, and/or a 4-chloropyrazole whose relative yields strongly depended upon the nature of 5-substituents of the dihydrodiazepines as well as the reaction conditions.     

Peroxidase activity of cationic metalloporphyrin-antibody complexes

Peroxidase activity of a complex of water-soluble cationic metalloporphyrin with anti-cationic porphyrin antibody is reported. Antibody 12E11G, which was prepared by immunization with a conjugate of 5-(4-carboxyphenyl)-10,15,20-tris(4-methylpyridyl)porphine iodide (3MPy1C), bound to tetramethylpyridylporphyrin iron complex (FeIII-TMPyP) with the dissociation constant of 2.6 x 10(-7) M. The complex of antibody 12E11G with FeIII-TMPyP catalyzed oxidation of pyrogallol, catechol, and guaiacol. A Lineweaver-Burk plot for the oxidation of pyrogallol catalyzed by the FeIII-TMPyP-antibody complex showed Km=8.6 mM and kcat=680 min(-1). Under the same conditions, Km and kcat for horseradish peroxidase (HRP) were 0.8 mM and 1750 min(-1), respectively. Although the binding interaction of the antibody to the substrates was one order lower than that of native HRP, the peroxidase activity of this system was in the same order of magnitude as that of HRP.     

Density functional study of the structures of lead sulfide clusters (PbS)n (n = 1-9)

The structures of (PbS)n (n = 1-9) clusters are investigated with density functional theory at the B3LYP level. Various pseudopotential basis sets on lead and the 6-31+G basis set on sulfur were employed. Full geometry optimization and extensive searches of the potential energy surface were carried out for clusters with n = 1-6. We find that even small PbS clusters (n > 2) start to take on the characteristic features of the rock salt structure of solid-state PbS (galena). The origin of some of the structural aspects of these crystals is shown to be associated with the partial covalent nature of the Pb-S bond. The magnitude of the HOMO-LUMO gap oscillates with increasing size of the clusters, in agreement with the observed behavior of the corresponding UV absorption bands of ultrasmall PbS quantum dots. Direct conformation of this oscillation was found by CIS(D) calculations, for which the absorption with the largest oscillator strength oscillates as the clusters grow from PbS to (PbS)9.     

Synthesis and evaluation of novel pyrimido-acridone, -phenoxadine, and -carbazole as topoisomerase II inhibitors

As part of a series of studies to discover new topoisomerase II inhibitors, novel pyrimidoacridones, pyrimidophenoxadines, and pyrimidocarbazoles were synthesized, and in vitro and in vivo antitumor activities and DNA-protein and/or DNA-topoisomerase II cross-linking activity as an indicator of topoisomerase II-DNA cleavable complex formation were evaluated. The pyrimidocarbazoles possessed high in vitro and in vivo potencies. Compound 26 (ER-37326), 8-acetyl-2-[2-(dimethylamino)ethyl]-1H-pyrimido[5,6,1-jk]carbazole-1,3(2H)-dione, showed in vitro growth inhibitory activity with respective IC(50) values of 0.049 microM and 0.35 microM against mouse leukemia P388 and human oral cancer KB. In vivo, this compound inhibited the tumor growth of mouse sarcoma M5076 implanted into mice with T/C values of 42% and 13% at 3.13 and 6.25 mg/kg/d respectively without significantly affecting the body weight. In addition, compound 26 (ER-37326) increased the formation of DNA-topoisomerase II cross-linking in P388 cells.     

Chlorotrimethylsilane promoted asymmetric Michael reaction of chiral enamines of α-alkyl β-keto esters

By the promotion of chlorotrimethylsilane, asymmetric Michael reaction of the chiral enamines (2) of α-alkyl β-keto esters (1) with methyl vinyl ketone and ethyl acrylate proceeded to afford, after hydrolysis, either enantiomer of the corresponding adducts (4) in a good enantioselectivity.     

Heterogeneously catalyzed aerobic oxidative biaryl coupling of 2-naphthols and substituted phenols in water

The oxidative coupling reaction can efficiently be promoted by supported ruthenium catalyst Ru(OH)x/Al2O3. A variety of 2-naphthols and substituted phenols can be converted to the corresponding biaryl compounds in moderate to excellent yields using molecular oxygen as a sole oxidant in water without any additives. The catalysis is truly heterogeneous in nature, and Ru(OH)x/Al2O3 can easily be recovered after the reaction. The catalyst can be recycled seven times with the maintenance of the catalytic performance, and the total turnover number reaches up to 160. The results of competitive coupling reactions suggest that the present oxidative biaryl coupling reaction proceeds via the homolytic coupling of two radical species and the Ru(OH)x/Al2O3 catalyst acts as an one-electron oxidant. Two radical species are coupled to give the corresponding biaryl product, and the one-electron reduced catalyst is reoxidized by molecular oxygen. The amounts of O(2) uptake and H(2)O formation were almost one-quarter and one-half the amount of substrate consumed, respectively, supporting the reaction mechanism. The kinetic data and kinetic isotope effect show that the reoxidation of the reduced catalyst is the rate-limiting step for the coupling reaction.     

Intramolecular Substitution Reaction of Alkylidene‐Lithium Carbenoids: Regioselective Synthesis of Indenes

Intramolecular substitution reaction of geminal dibromo alkenes proceeds to afford indenes, dihydronaphthalenes, dihydrofurans, and dihydropyran via in situ generated lithium alkylidene carbenoids, which have a carbon or oxygen nucleophilic moiety. This reaction provides a regioselective method for the preparation of polysubstituted indenes.