Studies on organic fluorine compounds II

Résumé Les esters éthyliques et tertiobutyliques ont été synthétisés à partir des esters correspondants de l'acide oxalique et fluoroacétique par une condensation de Claisen Wislicenus.En injection intrapéritonéale effectuée sur des souris et des rats, ces esters se sont montrés pratiquement non toxiques. En revanche, ils exercent (sous forme d'énolates sodiques hydro-solubles) une action inhibitrice prononcée sur la croissance de l'Escherichia coli etAerobacter aerogenes dans des milieux de cultures synthétiques.

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Part I:E. Bergmann andI. Blank, J. chem. Soc., in press (1953).     

Antibiotic activity of organic compounds and their average quasi-valence number

Summary It is shown that the average quasi-valence numbers of antibiotics inhibiting protein synthesis are well defined and lie in the region of average quasi-valence numbers of amino acids, while the average quasi-valence numbers of antibiotics inhibiting DNA or RNA synthesis have higher values. Possible explanations of these findings and their implications on the design and selection of antibiotics are discussed.     

Cytostatic activity of organic compounds and their average quasi-valence number

Summary It is found that the average quasi-valence numbers of alkylating cytostatics lie in the region of potential carcinogens, while the average quasi-valence numbers of antimetabolites predominantly cover the region of noncarcinogens. Implications of this finding on the design of new drugs are discussed.     

Microbial degradation of aliphatic branched compounds: Isobutyric, 2,2-dimethylmalonic and 2,2-dimethylsuccinic acids

Riassunto Da colture di arricchimento si è isolato un ceppo diPseudomonas putida capace di crescere in presenza di acido isobutirrico, unAchromobacter sp. capace di crescere in presenza degli acidi 2,2-dimetilmalonico e isobutirrico e un altroAchromobacter sp. capace di crescere in presenza degli acidi 2,2-dimetilsuccinico, 2,2-dimetilmalonico ed isobutirrico. Esperienze di induzione sequenziale hanno dimostrato che l'acido 2,2-dimetilmalonico viene degradato ad acido isobutirrico per decarbossilazione enzimatica.

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This work was supported by a grant of C.N.R. for the International Biological Program.     

Inhibition of respiratory oxidation of reduced sulfur compounds by intact cells ofThiobacillus denitrificans (strain RT) grown on thiosulfate

Thiobacillus denitrificans strain RT, an obligate sulfur-oxidizing chemolithoautotroph, was grown under microaerophilic conditions with thiosulfate as the only energy source. The rates of tetrathionate, thiosulfate, elemental sulfur (S^o) and sulfite oxidation were measured respirometrically with an oxygen electrode, using actively growing cells. Cells oxidized thiosulfate, elemental sulfur (S^o) and sulfite, but not tetrathionate. The thiosulfateoxidizing activity and elemental sulfur-oxidizing activity (SOA) were almost totally inhibited by 50 M myxothiazol (>80%), an inhibitor of the quinone-cytochrome b region, and by 10 M of the uncoupler carbonyl cyanide m-chlorophenylhydrazone (CCCP) (>82%). Sulfite-oxidizing activity was also significantly inhibited (>60%) by 50 M myxothiazol and 10 M CCCP. 1 mM KCN totally inhibited (>90%) all respiratory activities. This study confirms that a sulfur-oxidizing activity appears during microaerophilic growth ofThiobacillus denitrificans strain RT on thiosulfate. The SOA is linked to the respiratory chain, probably releasing electrons in the quinone-cytochrome b region.To whom correspondence should be addressed. Submitted by R. Bachofen.     

Correlation of the biological activity of organic compounds by means of the linear free energy relationships

Zusammenfassung Die linearen Beziehungen der Änderungen der freien Energie kann man für die Korrelation der biologischen Wirkung verschiedener Typen organischer Verbindungen mit Konstanten angehen, deren Wert durch die Struktur der Substituenten bestimmt wird. Neben den aus der theoretischen organischen Chemie gut bekannten Beziehung (Taftsche und Hammettsche Gleichungen, Korrelation der Reaktivität konjugierter und aromatischer Systeme mit den quantenchemischen Reaktivitätsindizes), die verwendbar sind, wenn der aktivitätsbestimmende Schritt eine chemische Reaktion ist, wurden Gleichungen vorgeschlagen die gültig sind, wenn es sich beim kritischen Schritt um einen physikalischen Prozess handelt.     

Microbial corrosion of concrete

Summary Sulphuric-acid-producing thiobacilli cause severe corrosion of concrete walls in sewage pipelines. The bacteria excrete sulphuric acid, which degrades carbonaceous binding material. Nitrifying organisms have been found in high cell numbers on historical sandstone buildings as well as on concrete buildings. The nitric acid, which is excreted by these organisms as metabolic end-product, also causes severe corrosion. The microorganisms are able to metabolize inorganic substances like ammonia and NO originating from air pollution.The natural process was remodelled by means of simulation experiments. It became evident that mineral-acid-producing bacteria play an important role in biodeterioration of building materials.     

Microbial legradation of bitumen

Summary Bitumen is commonly employed as a matrix for the long-term storage of low and intermediate level radioactive waste. As bitumen can be degraded by microbial activity, it is of great significance to determine the rates at which it may occur in nuclear waste repositories.Experiments have been carried out under optimal culture conditions using bitumen with a highly increased surface area. The potential of different microbial consortia to degrade bitumen has been examined. The investigations showed clearly that bitumen-degrading organisms are ubiquitous. In general the organisms formed biofilms on the accessible substrate surface area. Under oxic culture conditions a bitumen degradation rate of 20–50 g bitumen · m^–2· y^–1 leading to a CO₂ liberation of 15–40 l was observed. Anoxic conditions yielded a 100 times smaller degradation rate of 0.2–0.6 g bitumen · m^–2 · y^–1 and a CO₂ production of 0.15–0.45 l.Based on linear extrapolation the experimentally determined degradation rates would lead to a 25–70% deterioration of the bitumen matrix under oxic and 0.3–0.8% under anoxic conditions within 1000 years.     

Microbial degradation of bitumen

Summary A blown bitumen Mexphalte R 90/40 with a high content of saturated hydrocarbons was degraded by several microorganisms to the same extent. In batch cultures ofSaccharomycopsis lipolytica, maximal biodegradation was estimated to be about 9% w/w, 3.2·10^–3 g/cm² and 3.1·10^–3 cm of degraded bitumen. The Mexphalte R 90/40 degradation rate was closely coupled to biofilm formation. The microbial activity concerned predominantly the oxidation of saturated hydrocarbons. A direct distillation bitumen 80/100 with a low content of saturated hydrocarbons and a high content of aromatic hydrocarbons and resins was more resistant to biodegradation.     

A redox cycling model for the action of beta-adrenoceptor agonists

A cyclic redox mechanism for the action of beta-adrenoceptor agonists is proposed. It has the following features: a) beta-adrenoceptor agonists act by 'reductive activation' of the beta-adrenoceptor (R); b) the redox state of R is reciprocally coupled to the redox state of the guanine nucleotide binding protein (G); c) binding of GTP to G reverses the agonist-induced alteration of the redox states of R and G; d) according to a specific version of the model the activation process involves a disulfide-thiol interchange reaction which leads to a GTP-revertible cross-linking of R and G by a disulfide bond. The way in which desensitization events may interfere with the proposed redox cycle is discussed.