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.     

The composition of the evolved gases from the thermal decomposition of certain metal sulfates

By the use of TG—MS, the thermal dissociation of anhydrous CuSO₄ and Al₂(S0₄)₃ was found to proceed according to the reactions:

followed by the reactions:

No SO₃ was indicated in the dissociation of alunite. The sulfate ion appears to dissociate by at least two different mechanisms although the parameter which controls the mechanisms has not been elucidated.     

Concentrated electrolyte solutions at high temperatures and pressures

A survey is given of recent experimental results obtained from high-temperature, high-pressure investigations with water, aqueous solutions, and ionic fluids. Data on the static dielectric constant of water to 550°C and 5 kbar are given and discussed with respect to their relation to water structure. Infrared and Raman spectra of HDO in pure water have been obtained to 400°C and 4 kbar, which give information on hydrogen bonding. Xe–H₂O and CO₂–H₂O mixtures were investigated in the infrared. Ni(II) and Cu(II) complexes were investigated by absorption spectroscopy in aqueous solutions of high chloride content to 350°C and 2–6 kbar. The gas-liquid critical point of ammonium chloride was found at 880°C and 1635 bars. This fluid appears to be predominantly ionic even in the critical region. The possibility of converting pure polar fluids such as ammonia and water into concentrated ionic solutions by self-ionization at very high pressures is mentioned.This paper was presented at the symposium, The Physical Chemistry of Aqueous Systems, held at the University of Pittsburgh, Pittsburgh, Pennsylvania, June 12–14, 1972, in honor of the 70th birthday of Professor H. S. Frank.     

Extraction of Nitric,Perchloric, and Hydrochloric Acid by N,N-dibutyl Diethyl Carbamyl Phosphonate

Extraction of nitric, perchloric, and hydrochloric acid by N,N-dibutyl diethyl carbamyl phosphonate in carbon tetrachloride was investigated. The data obtained are treated in terms of stepwise neutralization of the acid with the formation of species y · HA and y · 2HA in the organic phase, where y stands for the extractant and HA for the acid. The equilibrium constants, K?₁ and K?₂ for nitric acid were found to equal 0.24 ± 0.02 and 0.017 ± 0.005, respectively. In case of HClO₄ and HCl K?₁ were found to equal 0.031 ± 0.003 and 0.0039 ± 0.0005, respectively. A third phase was observed when extraction of HClO₄ was performed using acid concentration higher than 3.5 molar. The preference for partition of different acids was discussed on the light of the competition of the proton between the acid anion, water and the basic extractant as well as the degree of the ionization of different acids.     

Zur Stereochemie konjugierter Systeme, 1. Mitt.: Eindeutige Benennung von Konstellationen konjugierter Systeme

Zusammenfassung Die bekannten Begriffecis undtrans werden durch den Begriffinter ergänzt und für den dreidimensionalen Raum definiert. Fußend auf der Internationalen Nomenklatur (IUPAC) wird ein in acht Regeln gefaßtes System vorgeschlagen, das die eindeutige Charakterisierung aller möglichen räumlichen Konstellationen beliebiger konjugierter Systeme durch die Benennung gestattet.Mit 2 Abbildungen     

Translational energy disposal in molecular collisions: The transfer of momentum constraint

A Franck—Condon type argument, which requires the least transfer of momenta to the nuclei during a collision is outlined and applied to the analysis of translational energy disposal and its dependence on the initial translational energy. Using the maximal entropy procedure of information theory we are able to proceed directly from the assumed (model) constraint to the product state distribution.     

Reaction of tellurium(iv) with dithizone

With an excess of dithizone over tellurium, the extraction of Te(IV) from 1 M perchloric acid solutions into a carbon tetrachloride solution (o) of dithixone follows the relation

When the acidity is varied, again with a sufficiently large excess of dithissone, the following relation seems to be approached;

(μ=1.0).     

Some Specific Features of Conjugate Addition Reactions with Lithium and Magnesium o-Carborane Derivatives

Reactions of lithium and magnesium o-carborane derivatives with ethyl -nitrocinnamate, ethyl -(3-indolyl)--nitroacrylate, and diethyl m-nitrobenzylidenemalonate were studied. Some specific features of these reactions were established, and preparative methods for the synthesis of previously unknown o-carborane derivatives were developed.     

Synthesis and Structure of the [Co(NioxH)2(Thio)2]2[SiF6] Complex

Anhydrous compound [Co(NioxH)₂(Thio)₂]₂[SiF₆] (I) was synthesized. Its structure was determined by X-ray diffraction analysis. The structures and character of intramolecular and intermolecular hydrogen bonds of complex Iand the previously studied [Co(NioxH)₂(Thio)₂]₂[SiF₆] · 3H₂O complex were compared.