Biomimetic hydrolysis of penicillin G catalyzed by dinuclear zinc(II) complexes: structure-activity correlations in beta-lactamase model systems

A series of highly preorganized pyrazolate-based dinuclear zinc complexes has been studied as functional synthetic analogues of metallo-beta-lactamases, a class of bacterial enzymes that cause serious clinical problems because of their degradation of common beta-lactam antibiotics. We have investigated the hydrolytic cleavage of penicillin G mediated by the different dinuclear zinc complexes, and have deduced structure-activity correlations. While cooperative effects of the adjacent metal ions might be operative, these are found to either enhance or diminish beta-lactamase activity with respect to a single free zinc. Drastic differences in activity are ascribed to a lack of accessible binding sites after incorporation of the substrate within the bimetallic pocket of 2 and 4, whereas partial detachment of hemilabile ligand side arms in 1 and 3 opens up available coordination sites for nucleophile activation and/or for binding and polarisation of the beta-lactam amide oxygen atom. This interpretation has been corroborated by NMR spectroscopic and mass spectrometric evidence as well as by X-ray crystallography of several adducts formed between the pyrazolate-based dinuclear zinc scaffolds and the small substrate analogue oxazetidinylacetate (oaa), 5-7. In all adducts, the carboxylate group of oaa is the primary anchoring site and is nested in a bridging position within the bimetallic pocket. However, zinc binding of the beta-lactam amide oxygen atom has been confirmed crystallographically for the first time in 7, in which additional open-site coordination sites are available.     

Über die Struktur des Hydrazinium-Monofluorids

Zusammenfassung Hydrazinium-Monofluorid N₂H₅F, das einzige noch unbekannte Hydrazinium-Monohalogenid, wurde im Nuklearinstitut Joef Stefan synthetisiert. Farblose durchsichtige nadelförmige Kristalle (Dichte 1,47 g/cm³) wurden uns für eine Strukturanalyse zur Verfügung gestellt.Weissenberg- und Präzessionsdiagramme wurden für eine dreidimensionale Synthese aufgenommen und die Intensität von 81% der gesamten Reflexe gemessen. Die Substanz kristallisiert orthorhombisch. Auf Grund der Reflexauslöschung ist die Raumgruppe P2₁2₁2₁ möglich. Die berechneten Zellkonstanten sowie die berechnete und gemessene Dichte sind in Tab. 1 wiedergegeben.Wegen der kurzen -Achse ist die Aufklärung der Struktur in der Projektion möglich. Da uns die Auflösung derPatterson-Synthese der gleich schweren Atome wegen nicht gelang, wurde eine Permutations-Synthese nachWoolfson mit den sieben stärksten Reflexen durchgeführt. Weiter wurden siebenFourier-Synthesen gemacht und zuletzt einR-Wert 15% erhalten, ohne die Wasserstoffatome zu berücksichtigen. Eine Differenz-Synthese verbesserte denR-Wert nur unwesentlich. Eine weitere Verfeinerung in der Projektion ist wegen der Atomüberlappungen nicht anwendbar. Die relativen Atomkoordinaten sind in der Tab. 2 wiedergegeben.Weitere Strukturuntersuchungen sind noch im Gange.

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Structure of hydrazinium monofluorideShort communication

     

An analysis for heat equations arises in diffusion process using new Yang-Abdel-Aty-Cattani fractional operator

The heat equation is parabolic partial differential equation and occurs in the characterization of diffusion progress. In the present work, a new fractional operator based on the Rabotnov fractional-exponential kernel is considered. Next, we conferred some fascinating and original properties of nominated new fractional derivative with some integral transform operators where all results are significant. The fundamental target of the proposed work is to solve the multidimensional heat equations of arbitrary order by using analytical approach homotopy perturbation transform method and residual power series method, where new fractional operator has been taken in new Yang-Abdel-Aty-Cattani (YAC) sense. The obtained results indicate that solution converges to the original solution in language of generalized Mittag-Leffler function. Three numerical examples are discussed to draw an effective attention to reveal the proficiency and adaptability of the recommended methods on new YAC operator.     

Conservatory of Kaup-Kupershmidt Equation to the Concept of Fractional Derivative with and without Singular Kernel

Making use of the traditional Caputo derivative and the newly introduced Caputo-Fabrizio derivative with fractional order and no singular kernel, we extent the nonlinear Kaup-Kupershmidt to the span of fractional calculus. In the analysis, different methods of fixed-point theorem together with the concept of piccard L-stability are used, allowing us to present the existence and uniqueness of the exact solution to models with both versions of derivatives. Finally, we present techniques to perform some numerical simulations for both non-linear models and graphical simulations are provided for values of the order α = 1.00; 0.90. Solutions are shown to behave similarly to the standard well-known traveling wave solution of Kaup-Kupershmidt equation.     

The Prins Reaction in the Fragrance Industry: 100th Anniversary (1919–2019)

The Prins reaction, an acid‐catalyzed condensation of alkenes with aldehydes, is used extensively in the fragrance industry. This year we celebrate the 100th anniversary of the discovery of this reaction. In honor of this occasion we present an overview of the diverse applications of the Prins reaction in the synthesis of flavor and fragrance ingredients. To pay tribute to the inventor of the Prins reaction, Hendrik Jacobus Prins, we also provide some insight into his life, scientific, and entrepreneurial accomplishments.     

Iron‐Catalyzed C−H Activation with Propargyl Acetates: Mechanistic Insights into Iron(II) by Experiment,Kinetics, Mössbauer Spectroscopy,and Computation

An iron‐catalyzed C?H/N?H alkyne annulation was realized by using a customizable clickable triazole amide under exceedingly mild reaction conditions. A unifying mechanistic approach combining experiment, spectroscopy, kinetics, and computation provided strong support for facile C?H activation by a ligand‐to‐ligand hydrogen transfer (LLHT) mechanism. Combined Mössbauer spectroscopic analysis and DFT calculations were indicative of high‐spin iron(II) species as the key intermediates in the C?H activation manifold.     

Dendrimer design using Cu(I)-catalyzed alkyne-azide "click-chemistry"

The chemoselective [3+2] cycloaddition of an azide on to an alkyne, catalyzed by Cu(1), has become known as "click-chemistry". The ease with which this reaction can be carried out and the formation of pure product without the need for further purification, offer a tremendous potential in developing monodisperse 1,4-disubstituted 1,2,3-triazole heterocycle based macromolecules of a diverse nature. The versatility of this approach in designing dendrimers or functionalizing them at the periphery with desired molecules has rekindled hopes in developing nanomaterials, at scales that can accelerate their entry into industrial usage.