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.     

Mononuclear nonheme ferric-peroxo complex in aldehyde deformylation

A mononuclear nonheme ferric-peroxo complex bearing a macrocyclic tetradentate N4 ligand, [(TMC)Fe(III)-O2]+, was prepared and used in mechanistic studies of aldehyde deformylation; a catalytic aldehyde deformylation by a nonheme iron(II) complex, [Fe(II)(TMC)]2+, and molecular oxygen is reported as well.     

Antibacterial activities of polystyrene-block-poly(4-vinyl pyridine) and poly(styrene-random-4-vinyl pyridine)

Styrene was polymerized in the presence of benzoyl peroxide (BPO) and 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) to yield polystyrene-TEMPO (PS-TEMPO) macroinitiator. The PS-TEMPO macroinitiator with different molecular weight was reacted with 4-vinyl pyridine (4-VP) to synthesize polystyrene-block-poly(4-vinyl pyridine) (PS-b-PVP), which was then quaternized with n-octyl iodide. Antibacterial activity of the quaternized copolymers was assessed against a gram negative bacterium (Pseudomonas aeruginosa) and a gram positive one (Staphylococcus aureus) by using the shake flask test method, and the results were compared with those of poly(styrene-random-4-vinyl pyridine) (P(ST-r--VP)). The quaternized copolymers inhibited greatly the growth of the bacteria, and PS-b-PVP was more active than P(ST-r-VP), which was ascribed to the fact that the content of quaternized 4-VP units on the surface of the particles of the former copolymer was higher than that corresponding to the latter one.     

Formation of nanostructured polymer filaments in nanochannels

We describe the use of hard etching methods to create nanodimensional channels and their use as templates for the formation of polymer filament arrays with precise dimensional and orientational control in a single integrated step. The procedure is general as illustrated by the radical, coordination, and photochemical polymerizations that were performed in these nanochannels. The nanochannel templates (20 nm high, 20-200 nm wide, and 100 mum long) were fabricated by the combined use of electron-beam lithography and a sacrificial metal line etching technique. Radical polymerization of acrylates, metal-catalyzed polymerization of norbornene, and photochemical polymerization of 1,4-diiodothiophene were carried out in these nanochannels. The polymers grown follow the dimensions and orientation of the channels, and the polymer filaments can be released without breaking. The approach opens up the possibility of just-in-place manufacturing and processing of patterns and devices from nanostructured polymers using well-established polymer chemistry.     

Infrared-visible and visible-visible double resonance spectroscopy of 1-hydroxy-9,10-anthraquinone-(H2O)n (n=1,2) complexes

The structures of hydrated 1-hydroxyanthraquinone complexes (1-HAQ), 1-HAQ(H2O)n=1,2, with intramolecular and intermolecular hydrogen bonding interactions were studied using laser spectroscopic methods such as laser induced fluorescence, fluorescence-detected infrared, infrared-visible hole burning, and visible-visible hole burning spectroscopy. In the 1:1 complex 1-HAQ(H2O)1, the water binds to the free carbonyl group of 1-HAQ not associated with intramolecular hydrogen bond. The second water in the 1:2 complex, 1-HAQ(H2O)2, binds to the first water of the 1:1 complex rather than other hydrogen bonding sites of 1-HAQ. A pair of two geometric isomers was produced in a supersonic jet for each of the 1:1 and 1:2 complexes. Both isomers of each complex have the same vibrational spectra in the region of the OH stretching vibration of water, but have different energies for the 0-0 band of vibronic transition due to the asymmetry of the two phenyl rings in 1-HAQ. The 0-0 bands for all four species of 1-HAQ(H2O)n=1,2 were unambiguously assigned by comparing with the results of ab initio calculations, which yielded the structures, vibrational frequencies, and relative energies of the frontier molecular orbitals.     

Condensation reaction of 3-(methacryloxypropyl)-trimethoxysilane and diisobutylsilanediol in non-hydrolytic sol-gel process

The condensation reaction of 3-methacryloxypropyl-trimethoxysilane (MPTS) and diisobutylsilanediol (DIBSD) in a non-hydrolytic sol-gel process was investigated in terms of the reaction time and the catalyst amount for fabrication of inorganic-organic hybrid materials. The degree of condensation, which was characterized by ²⁹Si NMR, ¹H NMR and Abbe refractometry, increases with increased the reaction time and greater catalyst amount. However, a the large catalyst amount breaks the methacryl group during the condensation reaction. Thus, the reaction time and the catalyst amount were optimized to synthesize the condensed methacryl oligosiloxanes.     

Factors affecting the catalytic epoxidation of olefins by iron porphyrin complexes and H2O2 in protic solvents

The catalytic epoxidation of cyclohexene by iron(III) porphyrin complexes and H2O2 has been investigated in alcohol solvents to understand factors affecting the catalyst activity in protic solvents. The yields of cyclohexene oxide and the Fe(III/II) reduction potentials of iron porphyrin complexes were significantly affected by the protic solvents, and there was a close correlation between the product yields and the reduction potentials of the iron porphyrin catalysts. The role of alcohol solvents was proposed to control the electronic nature of iron porphyrin complexes that determines the catalyst activity in the epoxidation of olefins by H2O2. We have also demonstrated that an electron-deficient iron porphyrin complex can catalyze the epoxidation of olefins by H2O2 under conditions of limiting substrate with high conversion efficiency in a solvent mixture of CH3OH and CH2Cl2.     

Dual-purpose sample trap for on-line strong cation-exchange chromatography/reversed-phase liquid chromatography/tandem mass spectrometry for shotgun proteomics. Application to the human Jurkat T-cell proteome

A dual-purpose sample-trapping column is introduced for the capacity enhancement of proteome analysis in on-line two-dimensional nanoflow liquid chromatography (strong cation-exchange chromatography followed by reversed-phase liquid chromatography) and tandem mass spectrometry. A home-made dual trap is prepared by sequentially packing C18 reversed-phase (RP) particles and SCX resin in a silica capillary tubing (1.5 cm x 200 microm I.D. for SCX, 0.7 cm x 200 microm for RP) ended with a home-made frit and is connected to a nanoflow column having a pulled tip treated with an end frit. Without having a separate fraction collection and concentration process, digested peptide mixtures were loaded directly in the SCX part of the dual trap, and the SCX separation of peptides was performed with a salt step elution initiated by injecting only 8 microL of NH4HCO3 solution from the autosampler to the dual trap. The fractionated peptides at each salt step were directly transferred to the RP trap packed right next to the SCX part for desalting, and a nanoflow LC-MS-MS run was followed. During the sample loading-SCX fractionation-desalting, flow direction was set to bypass the analytical column to prevent contamination. The entire 2D-LC separation and MS-MS analysis were automated. Evaluation of the technique was made with an injection of 15 microg peptide mixtures from human Jurkat T-cell proteome, and the total seven salt step cycles followed by each RPLC run resulted in an identification of 681 proteins.     

Synthesis of pyrido[3,4-<Emphasis Type="Italic">d</Emphasis>]pyrimidines by condensation of ethyl 1-benzyl-3-oxopiperidine-4-carboxylate with morpholine-4-carboxamidine

A method has been developed for the synthesis of 4-amino-substituted 7-benzyl-2-morpholin-4-yl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidines by condensation of ethyl 1-benzyl-3-oxopiperidine-4-carboxylate with morpholine-4-carboxamidine and subsequent reaction of the 7-benzyl-2-morpholin-4-yl-5,6,7,8-tetrahydro-3H-pyrido[3,4-d]pyrimidin-4-one with trifluoromethanesulfonic anhydride and secondary amines. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 762–768, May, 2007.