Interleukin-1beta stimulates matrix metalloproteinase-2 expression via a prostaglandin E2-dependent mechanism in human chondrocytes

IL-1beta is known promote cyclooxygenase-2 (COX- 2) and matrix metalloproteinase-2 (MMP-2) expression. This study focuses on the characterization of the signaling cascade associated with IL-1beta-induced matrix metalloproteinase-2 (MMP-2) regulation in human chondrocytes. The decrease in collagen levels in the conditioned media was prevented by a broad spectrum MMP inhibitor, suggesting that IL-1beta promotes the proteolytic process leading to MMP-2 activation. IL-1beta-related MMP-2 expression was found to be dependent on prostaglandin E2 (PGE2) production. In addition, the induction of COX-2 and MMP-2 was inhibited by the pretreatment of chondrocytes with a SB203580 or Ro 31-8220, indicating the involvement of protein kinase C (PKC) or p38 mitogen-activated protein kinase (MAPK). However, there is no cross-talk between PKC and p38 MAPK in the IL-1beta-induced MMP-2 activation. Taken together, these results demonstrated that IL-1beta induces MMP-2 expression through the PGE2-dependent mechanism in human chondrocytes.     

Styrene polymerization in ternary microemulsions: effects of water-soluble and oil-soluble initiators

The polymerization of styrene in ternary microemulsions stabilized by the cationic surfactant tetradecyltrimethylammonium bromide was studied as a function of concentrations of water-soluble (potassium persulfate, KPS) and oil-soluble (AIBN) initiators. At a particular molar ratio of the initiators, similar maximum rates of polymerization can be achieved from using both types of the initiators. In addition, both initiated systems produced microlatexes with similar hydrodynamic radius, number of polymer particles, molecular weight of polystyrene and number of polymer chain per latex particle. But the dependencies of these latex parameters on concentrations of KPS and AIBN may not be the same. The polymerization mechanism appears to be similar, irrespective of using KPS or AIBN. It is discussed in terms of effective radicals produced for the polymerization. While the different dependencies of some latex parameters on concentrations of the initiators are attributed to the different efficiencies of the initiators in producing effective radicals.     

Expedient synthesis of indoles from N-Boc arylhydrazines

The readily available N-Boc arylhydrazines undergo efficient Fischer cyclizations to provide the indoles in good yields, when reacted with enolizable ketones.     

High-performance liquid chromatographic assays for protoporphyrinogen oxidase and ferrochelatase in human leucocytes

Rapid, sensitive and specific high-performance liquid chromatographic assays are described for protoporphyrinogen oxidase and ferrochelatase in human leucocytes. The enzyme reaction products were separated and quantitated by reversed-phase high-performance liquid chromatography with fluorescence detection. The optimal pH for the protoporphyrinogen oxidase assay was 8.6 and the Michaelis constant for protoporphyrinogen IX was 9.78 +/- 0.96 microM (mean +/- S.D.). The mean (+/- S.D.) activity of protoporphyrinogen oxidase in fourteen apparently healthy subjects was 0.146 +/- 0.023 nmol protoporphyrin IX per min per mg protein. In one patient with variegate porphyria, the activity was 0.028 nmol protoporphyrin IX per min per mg protein. The optimal pH for ferrochelatase was 7.4 and with protoporphyrin and Zn2+ as substrates, the Michaelis constants were 1.49 and 8.33 microM, respectively. The mean activity of ferrochelatase in ten control subjects was 0.24 nM Zn-protoporphyrin or 2.05 nM Zn-mesoporphyrin formed per h per mg protein.     

Isothermal vapor–liquid equilibrium at 303.15 K and excess molar volumes at 298.15 K for the ternary system of propyl vinyl ether + 1-propanol + 2,2,4-trimethyl-pentane and its binary sub-systems

Isothermal vapor–liquid equilibrium data determined by the static method at 303.15 K are reported for the binary systems propyl vinyl ether + 1-propanol, 1-propanol + 2,2,4-trimethylpentane and propyl vinyl ether + 2,2,4-trimethylpentane and also for the ternary system propyl vinyl ether + 1-propanol + 2,2,4-trimethyl-pentane. Additionally, new excess volume data are reported for the same systems at 298.15 K. The experimental binary and ternary vapor–liquid equilibrium data were correlated with different G^E models and excess molar volume data were correlated with the Redlich–Kister equation for the binary systems and the Cibulka equation for the ternary system, respectively.     

Kinetically controlled Ag+-coordinated chiral supramolecular polymerization accompanying a helical inversion

We report kinetically controlled chiral supramolecular polymerization based on ligand–metal complex with a 3 : 2 (L : Ag⁺) stoichiometry accompanying a helical inversion in water. A new family of bipyridine-based ligands (d-L1, l-L1, d-L2, and d-L3) possessing hydrazine and d- or l-alanine moieties at the alkyl chain groups has been designed and synthesized. Interestingly, upon addition of AgNO₃ (0.5–1.3 equiv.) to the d-L1 solution, it generated the aggregate I composed of the d-L1AgNO₃ complex (d-L1 : Ag⁺ = 1 : 1) as the kinetic product with a spherical structure. Then, aggregate I (nanoparticle) was transformed into the aggregate II (supramolecular polymer) based on the (d-L1)₃Ag₂(NO₃)₂ complex as the thermodynamic product with a fiber structure, which led to the helical inversion from the left-handed (M-type) to the right-handed (P-type) helicity accompanying CD amplification. In contrast, the spherical aggregate I (nanoparticle) composed of the d-L1AgNO₃ complex with the left-handed (M-type) helicity formed in the presence of 2.0 equiv. of AgNO₃ and was not additionally changed, which indicated that it was the thermodynamic product. The chiral supramolecular polymer based on (d-L1)₃Ag₂(NO₃)₂ was produced via a nucleation–elongation mechanism with a cooperative pathway. In thermodynamic study, the standard ΔG° and ΔH_e values for the aggregates I and II were calculated using the van''t Hoff plot. The enhanced ΔG° value of the aggregate II compared to that of the formation of aggregate I confirms that aggregate II was thermodynamically more stable. In the kinetic study, the influence of concentration of AgNO₃ confirmed the initial formation of the aggregate I (nanoparticle), which then evolved to the aggregate II (supramolecular polymer). Thus, the concentration of the (d-L1)₃Ag₂(NO₃)₂ complex in the initial state plays a critical role in generating aggregate II (supramolecular polymer). In particular, NO₃⁻ acts as a critical linker and accelerator in the transformation from the aggregate I to the aggregate II. This is the first example of a system for a kinetically controlled chiral supramolecular polymer that is formed via multiple steps with coordination structural change.

The nanoparticles were transformed into the supramolecular polymer as the thermodynamic product, involving a helical inversion from left-handed to right-handed helicity.     

The effect of the counteranion on the formation of mesoporous materials under the acidic synthesis process

The presence of various counteranions at the interfacial region of the silicate-surfactant mesophase introduces opportunities for manipulation of the phase structure. Well-ordered 3D-hexagonal P63/mmc, cubic Pmn, 2D-hexagonal p6mm, and cubic Iad mesoporous materials have been synthesized with the same surfactant, cetyltriethylammonium bromide, in the presence of various acids. The counteranions of acidic media have resulted in increasing the surfactant packing parameter g in the order SO42- < Cl- < Br- < NO3-, which leads to the different time course of formation of mesostructures. The effect of counteranions on the formation of mesostructures is explained in terms of not only the adsorption strength on the headgroups of the surfactant micelle but also the rate of silica condensation affecting the charge density matching between the surfactant and silica. It has been found that the mesophase is always transformed from the larger g parameter into the smaller one. The distinct morphologies of the 3D-hexagonal P63/mmc mesophases have been rationally explained by supposing this particular mesostructure. The cubic Iad phase has been first synthesized under acidic conditions.     

Dynamics of superionic Rb3H(SeO4)2 single crystals studied by H and Rb spin-lattice relaxation

The ¹H and ⁸⁷Rb spin-lattice relaxation and spin-spin relaxation times in superionic Rb₃H(SeO₄)₂ single crystals grown by the slow evaporation method were measured over the temperature range 160-450 K. The temperature dependencies of the ¹H T₁, T_1ρ, and T₂ are measured. In the ferroelastic phase, T₁ differs from T_1ρ, which is in turn different from T₂, although these three relaxation times converge to similar values near 410 K. This transition seems to occur at temperature which is about 40 K lower than the superionic transition temperature. The observation of liquid-like values of the ¹H T₁, T_1ρ, and T₂ in the high temperature is compatible with the phase being superionic, indicating that the destruction and reconstruction of hydrogen bonds does indeed occur at high temperature. In addition, the ⁸⁷Rb T₁ and T₂ values at high temperature were similar (on the order of milliseconds), a trend that was also observed for ¹H T₁ and T₂. This behavior is expected for most hopping-type ionic conductors, and could be attributed to interactions between the mobile ions and the neighboring group ions within the crystal. The motion giving rise to this liquid-like behavior is related to the superionic motion.     

Scaffold-based molecular design with a graph generative model

Searching for new molecules in areas like drug discovery often starts from the core structures of known molecules. Such a method has called for a strategy of designing derivative compounds retaining a particular scaffold as a substructure. On this account, our present work proposes a graph generative model that targets its use in scaffold-based molecular design. Our model accepts a molecular scaffold as input and extends it by sequentially adding atoms and bonds. The generated molecules are then guaranteed to contain the scaffold with certainty, and their properties can be controlled by conditioning the generation process on desired properties. The learned rule of extending molecules can well generalize to arbitrary kinds of scaffolds, including those unseen during learning. In the conditional generation of molecules, our model can simultaneously control multiple chemical properties despite the search space constrained by fixing the substructure. As a demonstration, we applied our model to designing inhibitors of the epidermal growth factor receptor and show that our model can employ a simple semi-supervised extension to broaden its applicability to situations where only a small amount of data is available.

We propose a scaffold-based graph generative model for designing novel drug candidates that include the desired scaffold as a substructure.