Micromolecular inhibitors of superoxide radicals

Background: Currently, there is a growing interest in new copper (Cu2+) heterocyclic coordination compounds (CC), isothiosemicarbazide derivates, which demonstrated multiple beneficial properties, but their effect on reactions with free radicals such as the superoxide radical has not been investigated. Material and methods: The action of new micromolecular complexes of copper (Cu2+) chloride and bromide with methyl n- (prop-2-en-1-yl) -2- (pyridin2-ylmethylidene) hydrazine carbimidothioate on capturing activity of the superoxide radical was determined by the spectrophotometric method in vitro experiments. Results: It was established that the micromolecular complexes of copper (II) chloride and bromide with methyl n-(prop-2-en-1-yl)-2-(pyridin-2- ylmethylidene) hydrazine carbimidothioate have been found to possess strong superoxide radical inhibitor properties when interacting with a superoxide radical. In addition to this, the IC50 of the studied compounds depends on the nature of the acid-ligand in the internal sphere of the complex and increases in the following sequence: Cl- –Br- . Conclusions: The established property of mentioned compounds is new, because their use as micromolecular inhibitors of superoxide radicals has not been described so far. The synthesized CC expand the arsenal of superoxide radical inhibitors with high biological activity. Their possible significance for the development of new treatment strategies for diseases associated with the overproduction of superoxide radicals is discussed.

Pd(II)-catalyzed enantioselective C(sp3)–H arylation of cy-clopropanes and cyclobutanes guided by tertiary alkyla-mines.

ABSTRACT: Strained aminomethyl-cycloalkanes are a recurrent scaffold in medicinal chemistry due to their unique structural features that give rise to a range of biological properties. Here, we report a palladium-catalyzed enantioselective C(sp3)–H arylation of aminome-thyl-cyclopropanes and -cyclobutanes with aryl boronic acids. A range of native tertiary alkylamine groups are able to direct C–H cleavage and forge carbon-aryl bonds on the strained cycloalkanes framework as single diastereomers and with excellent enantiomeric ratios. Cen-tral to the success of this strategy is the use of a simple N-acetyl amino acid ligand, which not only controls the enantioselectivity but also promotes -C–H activation of over other pathways. Computational analysis of the cyclopalladation step provides an understanding of how enantioselective C–H cleavage occurs and revealed distinct transition structures to our previous work on enantioselective desymme-trization of N-iso-butyl tertiary alkylamines. This straightforward and operationally simple method simplifies the construction of func-tionalized aminomethyl-strained cycloalkanes, which we believe will find widespread use in academic and industrial settings relating to the synthesis of biologically active small molecules.