Molecular characteristics of the inhibition of human neutrophil elastase by nonsteroidal antiinflammatory drugs

Nonsteroidal antiinflammatory drugs(NSAIDs) are known as clinically effective agents for treatment of inflammatory diseases. Inhibition of cyclooxygenase has been thought to be a major facet of the pharmacological mechanism of NSAIDs. However, it is difficult to ascribe the antiinflammatory effects of NSAIDs solely to the inhibition of prostaglandin synthesis. Human neutrophil elastase (HNElastase; HNE, EC 3.4.21.37) has been known as a causative factor in inflammatory diseases. To investigate the specific relationship between HNElastase inhibition and specificity of molecular structure of several NSAIDs, HNElastase was purified by Ultrogel AcA54 gel filtration, CM-Sephadex ion exchange, and HPLC (with TSK 250 column) chromatography. HNElastase was inhibited by aspirin and salicylate in a competitive manner and by naproxen, ketoprofen, phenylbutazone, and oxyphenbutazone in a partial competative manner, but not by ibuprofen and tolmetin. HNElastase-phenylbutazone-complex showed strong Raman shifts at 200, 440, 1124, 1194, 1384, 1506, and 1768 cm(-1). The Raman bands 1194, 1384, and 1768 cm(-1) may represent evidences of the conformational change at -N=N-phi radical, pyrazol ring, and -C=O radical of the elastase-drug complex, respectively. Phenylbutazone might be bound to HNElastase by ionic and hydrophobic interaction, and masked the active site. Inhibition of HNElastase could be another mechanism of action of NSAIDs besides cyclooxygenase inhibition in the treatment of inflammatory diseases. Different inhibition characteristics of HNE-lastase by NSAIDs such as aspirin, phenylbutazone-like drugs and ineffective drugs could be important points for drawing the criteria for appropriate drugs in clinical application.     

Oxidation of n-Butanol and 2-Pentanol with Molecular Oxygen in Supercritical CO2

Oxidation of n-butanol and 2-pentanol using molecular oxygen in supercritical (SC) CO2 with and without co-solvent is investigated. The results showed that the reaction selectivity is high when the reaction is carried out in SC CO2. It has been observed that co-solvent affects conversion and selectivity of the reaction considerably.     

A new two‐dimensional CdII coordination polymer constructed by pyrazine‐2,3‐dicarboxyl­ate

In the title compound, poly[μ₅‐pyrazine‐2,3‐dicarboxyl­ato‐cadmium(II)], [Cd(C₆H₂N₂O₄)]_n or [Cd(pdc)]_n, where pdc is the pyrazine‐2,3‐dicarboxyl­ate anion, the Cd^II atom is six‐coordinated by five carboxyl­ate O atoms and one N atom from five different pdc ligands in a distorted octa­hedral CdO₅N coordination geometry. Two Cd^II atoms are bridged by carboxyl­ate groups of the pdc ligands to create a dimeric unit. The dimeric units are further connected by the pdc ligands to generate an inter­esting two‐dimensional structure.     

Hydrogen‐bonded supramolecule of N,N′‐bis(4‐pyridylmethyl)oxalamide and a zigzag chain structure of catena‐poly[[[dichloridocobalt(II)]‐μ‐N,N′‐bis(4‐pyridylmethyl)oxalamide‐κ2N4:N4′] hemihydrate]

N,N′‐Bis(4‐pyridylmethyl)oxalamide, C₁₄H₁₄N₄O₂, exists as a dimer which is extended into a two‐dimensional network with other dimers through pyridine–amide hydrogen bonds. The crystal structure of the title coordination polymer, {[CoCl₂(C₁₄H₁₄N₄O₂)]·0.5H₂O}_n, features a one‐dimensional zigzag chain, in which the cobalt ion sits at a twofold symmetry position and adopts a tetrahedral geometry, and the bridging ligand lies on an inversion center and connects to Co^II ions in a bis‐monodentate mode. Furthermore, two interwoven chains create a cavity of ca 8.6 × 8.6 Å, which produces a three‐dimensional channel. Water molecules are held in the channel by hydrogen bonds.     

Poly[bis[aquaneodymium(III)]‐μ2‐oxalato‐di‐μ4‐succinato]

In the title compound, [Nd₂(C₄H₄O₄)₂(C₂O₄)(H₂O)₂]_n, the flexible succinate anion assumes the gauche conformation and bridges the nine‐coordinate Nd atoms to generate two‐dimensional layers parallel to (010). The coordination polymer layers are linked into a three‐dimensional framework by the rigid oxalate ligands. The oxalate ions are located on a center of inversion.     

Cadinene Derivatives from Eupatorium adenophorum

A new norsesquiterpene named eupatorone (= (4S,4aR,6R)‐1‐acetyl‐6‐(acetyloxy)‐4,4a,5,6‐tetrahydro‐4,7‐dimethylnaphthalen‐2(3H)‐one; 1 ) and a new sesquiterpene derivative named 2‐deoxo‐2‐(acetyloxy)‐9‐oxoageraphorone (= (1R,4S,4aR,6R,8aS)‐6‐(acetyloxy)‐3,4,4a,5,6,8a‐hexahydro‐4,7‐dimethyl‐1‐(1‐methylethyl)naphthalen‐2(1H)‐one; 2 ), together with the five known cadinene derivatives 3 – 7 were isolated from the flower of Eupatorium adenophorum (Spreng. ). Their structures were established by extensive NMR experiments, including 1D and 2D NMR.     

Structural Consequences of S → Se Substitution in some Symmetrical [M(S2CNR2)3] Complexes

The consequences of replacement of the symmetrically chelate ligands in [M(E₂CNR₂)₃] (E = S, Se) complexes of potential 32 symmetry by analogous mixed S,Se unsymmetrical chelates are explored for both small (M = Co) and large (M = In) metal atoms, and R = primary (Et) and secondary (ⁱPr) alkyl substituents by way of low‐temperature single crystal X‐ray studies of [(Co(SSeCNEt₂)₃] ([Co(Se₂CNEt₂)₃] also determined as datum), and [In(SSeCNR₂)₃], R = Et, ⁱPr. The structure of [(ⁱPr₂N·CS·Se)₂] is also recorded.     

Diaqua­bis[2′‐(4,5‐diaza­fluoren‐9‐yl­idene)picolinohydrazidato‐κ2N,O]zinc(II) tetra­hydrate: a metal–water chain complex containing cyclic water hexa­mers

In the title compound, [Zn(C₁₇H₁₀N₅O)₂(H₂O)₂]·4H₂O, cyclic water hexa­mers forming one‐dimensional metal–water chains are observed. The water clusters are trapped by the co‐operative association of coordination inter­actions and hydrogen bonds. The Zn^II ion resides on a centre of symmetry and is in an octa­hedral coordination environment comprising two O atoms and two N atoms from two 2′‐(4,5‐diaza­fluoren‐9‐yl­idene)picolinohydrazidate ligands and two water mol­ecules.     

Spectroscopic Interrogation of Layer-by-layer Assembled Films of Conjugated Polyelectrolytes

Layer-by-layer fluorescent conjugated polyelectrolyte films have been studied. The photoluminescence of conjugate polyelectrolytes was observed to be highly tunable during this film assembly process. Efficient photoinduced electron transfer from thus prepared highly luminescent film to a natural electron-transfer protein cytochrome c has also been observed.     

Chimeric (alpha/beta + alpha)-peptide ligands for the BH3-recognition cleft of Bcl-XL: critical role of the molecular scaffold in protein surface recognition

Molecules that bind to specific surface sites on proteins are of great interest from both fundamental and practical perspectives. We are exploring a ligand development strategy that is based on oligomers with discrete folding propensities ("foldamers"); we target a specific cleft on the cancer-associated protein Bcl-xL because this system is well characterized structurally. In vivo, this cleft binds to alpha-helical segments (BH3 domains) of other proteins. We evaluated several types of helical foldamer, built entirely from beta-amino acid residues or from mixtures of alpha- and beta-amino acid residues, and ultimately identified foldamers in the latter class that bind very tightly to Bcl-xL. Our results suggest that combining different types of foldamer backbones will be an effective and general strategy for creating high-affinity and specific ligands for protein surface sites.