Molecular dynamics simulations of the mononuclear zinc-beta-lactamase from Bacillus cereus complexed with benzylpenicillin and a quantum chemical study of the reaction mechanism

Herein, we present results from MD simulations of the Michaelis complex formed between the B. cereus zinc-beta-lactamase enzyme and benzylpenicillin. The structural and dynamical effects induced by substrate-binding, the specific role of the conserved residues, and the near attack conformers of the Michaelis complex are discussed. Quantum chemical methods (HF/6-31G* and B3LYP/6-31G*) are also applied to study the hydrolysis reaction of N-methylazetidinone catalyzed by a monozinc system consisting of the side chains of the histidine residues (His86, His88, and His149) complexed with Zn-OH and the side chains of Asp90 and His210. From this model system, we built molecular-mechanics representations of the prereactive complex and transition state configurations docked into the active site. Linear-scaling semiempirical calculations coupled with a continuum solvent model were then performed on these static models. We propose that the experimental rate data for the B. cereus enzyme is compatible with a one-step mechanism for the hydrolysis of beta-lactam substrates in which His210 acts as a proton donor.     

Potential acting on the trapped electron

If the absorption of a trapped electron can be shown to correspond to bound—free transitions, it should be possible to calculate the potential acting on the trapped electron inversely from its absorption spectrum. In this paper we present the method of calculating the potential acting on a trapped electron from the observed absorption spectrum.     

Untersuchungen über die Oxydation von Butylbenzol in flüssiger Phase in Gegenwart von Kobalt- und Mangansalzen der Pyridincarbonsäuren

Zusammenfassung Es wurde der Einfluß der Kobalt- und Mangansalze der -, - und -Pyridincarbonsäuren auf die Luftoxydation von Rutylbenzol in flüssiger Phase untersucht. Dabei wurde festgestellt, daß das Kobaltpicolinat, Manganisonicotinat und Kobaltisonicotinat den Oxydationsverlauf zur Bildung von Carbonylverbindungen und Säuren lenken. Das Manganpicolinat weist ein selektives Oxydationsvermögen auf, vorwiegend zur Bildung von Estern.

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Liquid phase oxidation of butyl-benzene in presence of Co and Mn pyridine carboxylates

The influence of Co- and Mn-salts of -, - and -pyridinecarboxylic acids, resp., on the oxidation of butylbenzene by air has been studied. It has been found that the Co salt of picolinic acid, Mn and Co isonicotinate direct the oxidation process in favour of carbonyl compounds and acids. With the Mn salt of picolinic acid, the oxidation mainly gives esters.

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Mit 5 Abbildungen     

Polysaccharides of subspecies of Cousinia

Institute of the Chemistry of Plant Substances, Uzbek SSR Academy of Sciences, Tashkent. Institute of Organic Chemistry, Kirghiz SSR Academy of Sciences, Frunze. Translated from Khimiya Prirodnykh Soedinenii, No. 5, pp. 750–751, September–October, 1988.     

Application of high-performance liquid chromatography of some antibiotics in clinical microbiology

During recent years high-performance liquid chromatography has become an excellent tool for the determination of antibiotics in biological fluids. Compared with biological assays, the major benefits of this method are specificity and rapidity. In particular, the determination of biologically inactive metabolites emphasizes that this technique plays an outstanding role for the analysis of antibiotics. This paper describes how the method can be used in the analysis of several antibiotics and demonstrates the efficacy of this method for clinical microbiology. Methods for the determination in biological fluids of acylaminopenicillins (azlocillin, mezlocillin, piperacillin and aspoxicillin), quinolones (ciprofloxacine, norfloxacine and ofloxacine), a penem (imipenem) and a cephalosporin (cefixime) are summarized. Furthermore, their application to in vitro studies and their trial in clinical studies are described.     

Simple thiazocine-2-acetic acid derivatives via ring-closing metathesis

A new protocol for synthesis of 2-heterocylylacetic acid derivatives involving conjugate addition of allyl mercaptan to an acrylate containing a tethered olefinic site followed by RCM (ring-closing metathesis) is described. In this series, sulfanyl derivatives were unreactive, while sulfoxide and sulfone analogues provided the corresponding thiazocines in fair to excellent yields. Use of the sulfoxide oxidation state as a protecting group for sulfides inert to RCM is demonstrated also. Thus, oxidation of sulfide 9 [N-allyl-N-[2-(allylthio)-4-(1H-indol-1-yl)-4-oxobutyl]-4-methylbenzenesulfonamide] followed by cyclization yielded the corresponding thiazocine sulfoxide 12. Deprotection (deoxygenation) of 12 was accomplished using Lawesson's reagent, producing 1-[[4-[4-(methylphenyl)sulfonyl]-3,4,5,8-tetrahydro-2H-1,4-thiazocin-2-yl]acetyl]-1H-indole (21) in 67% unoptimized yield.     

Novel annulene dications from methylated [2.2]metacyclophane monoenes and [e]-ring benzannelated dimethyldihydropyrene

Tetramethyl- and hexamethyl-substituted [2.2]metacyclophane monoenes (10 and 11) are transformed into their corresponding trans-dimethyldihydroethanophenanthrenium dications (14(2+) and 15(2+)) in FSO(3)H x SbF(5) (4:1) and FSO(3)H x SbF(5) (1:1) with SO(2)ClF or SO(2) as the solvent; these 10 pi-dications are equivalent to the C-4/C-5 diprotonated dications of the 2,7-dimethyl derivative of trans-DMDHP, 3a. The trans-12c,12d-dimethyl-12c,12d-dihydrobenzo[e]pyrene (6) reacts with FSO(3)H/SO(2)ClF under surprisingly mild conditions to give initially a persistent diprotonated dication (6H(2)(2+)) and, subsequently, the oxidation dication (6(2+)); the 6(2+):6H(2)(2+) ratio reaches 4:1 after 1 week at low temperature. Protonation of the anti-metacyclophane (13) was also examined. Charge delocalization mode and tropicity in the resulting dications are gauged via detailed NMR studies at 500 MHz.     

A transannular reaction during the base catalysed rearrangement of bicyclo(4.3.0)-2β-hydroxy-2α-vinyl-1β-Methyl-8-oxo-Δ6,7-nonene

Synthesis and rearrangement of bicyclo(4.3.0) - 2β - hydroxy - 2α - vinyl - 1β - methyl - 8 - oxo - Δ⁶ - nonene was observed to yield a transannular reaction product tricycio - (6.3.0.0^1,8) - 2 - methyl - 8α - hydroxy - 4 - oxo - Δ² - undecene 16. Spectral evidence supports the assigned structure.