Igor Huskić

Mechanosynthesis of nitrosobenzenes: a proof-of-principle study in combining solvent-free synthesis with solvent-free separations

Mechanochemical Oxone oxidation of selected para-substituted anilines was used as a rapid and solvent-free route to nitrosobenzenes; besides avoiding bulk solvents and short reaction times, this method exploits high vapour pressures of nitrosobenzenes for the solvent-free separation of the product by sublimation, demonstrating an entirely solvent-free route to chemical synthesis and product isolation.

3-Oxo-hexahydro-1H-isoindole-4-carboxylic Acid as a Drug Chiral Bicyclic Scaffold: Structure-Based Design and Preparation of Conformationally Constrained Covalent and Noncovalent Prolyl Oligopeptidase Inhibitors

Bicyclic chiral scaffolds are privileged motifs in medicinal chemistry. Over the years, we have reported covalent bicyclic prolyl oligopeptidase inhibitors that were highly selective for POP over a number of homologous proteins. Herein, we wish to report the structure-based design and synthesis of a novel class of POP inhibitors based on hexahydroisoindoles. A docking study guided the selection of structures for synthesis. The stereochemistry, decoration, and position within the molecule of the bicyclic scaffolds were assessed virtually. Following the synthesis of the best candidates, in vitro assays revealed that one member of this chemical series was more active than any of our previous inhibitors with a Ki of 1.0 nM. Additional assays also showed that the scaffold of this potent inhibitor, in contrast to one of our previously reported chemical series, is highly metabolically stable, despite the foreseen potential sites of metabolism. Interestingly, computer docking calculations accurately predicted the optimal features of the inhibitors.

Minerals with metal-organic framework structures

The rare minerals stepanovite and zhemchuzhnikovite are unique examples of naturally occurring open metal-organic frameworks. Metal-organic frameworks (MOFs) are an increasingly important family of advanced materials based on open, nanometer-scale metal-organic architectures, whose design and synthesis are based on the directed assembly of carefully designed subunits. We now demonstrate an unexpected link between mineralogy and MOF chemistry by discovering that the rare organic minerals stepanovite and zhemchuzhnikovite exhibit structures found in well-established magnetic and proton-conducting metal oxalate MOFs. Structures of stepanovite and zhemchuzhnikovite, exhibiting almost nanometer-wide and guest-filled apertures and channels, respectively, change the perspective of MOFs as exclusively artificial materials and represent, so far, unique examples of open framework architectures in organic minerals.

Green and rapid mechanosynthesis of high-porosity NU- and UiO-type metal–organic frameworks

The use of a dodecanuclear zirconium acetate cluster as a precursor enables the rapid, clean mechanochemical synthesis of high-microporosity metal-organic frameworks NU-901 and UiO-67, with surface areas up to 2250 m2 g-1. Real-time X-ray diffraction monitoring reveals that mechanochemical reactions involving the conventional hexanuclear zirconium methacrylate precursor are hindered by the formation of an inert intermediate, which does not appear when using the dodecanuclear acetate cluster as a reactant.