Abstract This thesis is concerned with the synthesis of -sultams and the development of new routes for the synthesis of bicyclic versions of these molecules as potential anti-bacterials. The synthesis of 1-azetines, 1,2-thiazetin-1,1-dioxides and isothiazol-1,1-dioxides as precursors of bicyclic heterocycles is described. 1-Azetines were synthesised from azetidin-2-ones prepared via the [2+2] c...

Nitrile hydratase (NHase, EC 4.2.1.84) is a metalloenzyme which catalyses the conversion of nitriles to amides. The high efficiency and broad substrate range of NHase have led to the successful application of this enzyme as a biocatalyst in the industrial syntheses of acrylamide and nicotinamide and in the bioremediation of nitrile waste. Crystal structures of both cobalt(III)- and iron(III)-de...

Self-assembled monolayers (SAMs) of nitrile-substituted oligo(phenylene ethynylene) thiols (NC-OPEn) with a variable chain length n (n ranging from one to three structural units) on Au(111) were studied by synchrotron-based high-resolution X-ray photoelectron spectroscopy and near-edge absorption fine-structure spectroscopy. The experimental data suggest that the NC-OPEn molecules form well-def...

The anti-AIDS drug rilpivirine undergoes conformational changes to bind HIV-1 reverse transcriptase (RT), which is an essential enzyme for the replication of HIV. These changes allow it to retain potency against mutations that otherwise would render the enzyme resistant. Here we report that water molecules play an essential role in this binding process. Femtosecond experiments and theory expose...

Fluorinated highly functionalized cispentacin derivatives were synthetised starting from an unsaturated bicyclic β-lactam through C=C bond functionalization via the dipolar cycloaddition of a nitrile oxide, isoxazoline opening, and fluorination by OH/F exchange.

Galactosides and lactosides bearing triazoles or isoxazoles, regiospecifically prepared by [1,3]-dipolar cycloadditions between alkynes, azides or nitrile oxides, provided specific galectin-1 and -3 inhibitors with potencies as low as 20 microM.

A three-component reaction of 2-alkynylbenzaldehyde, sulfonohydrazide, and nitrile catalyzed by silver triflate under mild conditions is reported, which generates pyrazolo[5,1-a]isoquinolin-2-amines in good to excellent yields.

a classical theory is developed which calculates the momentum transfer rate constant between an ion and a non-polar molecule. the model takes into consideration the effect of diffraction outside the capture limit on the rate constants. the theory is used to calculate momentum transfer rate constant for cl- with trans-dichloroethylene and para-difluorobenzene. theoretical results are compared to...

Nitrile hydratases (NHases) possess a mononuclear iron or cobalt cofactor whose coordination environment includes rare post-translationally oxidized cysteine sulfenic and sulfinic acid ligands. This cofactor is located in the α-subunit at the interfacial active site of the heterodimeric enzyme. Unlike canonical NHases, toyocamycin nitrile hydratase (TNHase) from Streptomyces rimosus is a unique...