Synthesis, physicochemical properties and antimicrobial activity of mono-/dinitroxyl amides

Abstract

Two comparative sets of mono-/dinitroxyl amides were designed and prepared. The novel TEMPO and/or PROXYL derivatives were fully characterised and their spin, redox and antimicrobial properties were determined. Cyclic voltammetry revealed (quasi)reversible redox behavior for most of the studied radicals. Moreover, the electron-withdrawing substituents increased the oxidation potential of nitroxides in comparison to electron-donating groups. While EPR spectra of monoradicals featured the typical three-line signal, the spectra of biradicals showed more complex splitting patterns. The in vitro biological assay revealed that unlike pyrrolidinyl derivatives, the piperidinyl nitroxides significantly inhibited the growth of Staphylococcus sp.

Polyradical PROXYL/TEMPO‐Derived Amides: Synthesis, Physicochemical Studies, DFT Calculations, and Antimicrobial Activity

“…Similarly, as we have shown previously, the best inhibition was observed in the case of S. epidermidis . Notably, the most active TEMPO tetraradicals 10T and 12T and hexaradical 13T also inhibited the growth of S. aureus .…”

“…Although rare, there are known examples of various TEMPO derivatives with interesting bioactivity, including antifungal and anti‐inflammatory properties. Recently, we have shown that, unlike PROXYL radicals, mono‐/dinitroxyl amides containing the TEMPO moiety exhibit potentially useful antimicrobial activities . Notably, piperidinyl radicals significantly inhibited the growth of Staphylococcus sp.…”

“…Notably, piperidinyl radicals significantly inhibited the growth of Staphylococcus sp. Moreover, the more electron withdrawing a substituent present on the piperidine ring was, the stronger the antibacterial effect of the respective nitroxide against Staphylococcus epidermidis …”

Polyradical PROXYL/TEMPO Conjugates Connected by Ester/Amide Bridges: Synthesis, Physicochemical Studies, and DFT Calculations

“…Nitroxides are generally known for their significant redox activity with corresponding Noxoammonium cations to be formed during one-electron electrochemical oxidation. [30,32,33] In our case, the voltammetric profile for all studied compounds 1-9 ( Figure S2 in Supporting Information) confirmed undergoing one-electron transfer during particular electrode reaction with half-wave potentials (E 1/2 ) ranging from À 51 mV to À 17 mV vs Ag/AgCl (3 mol L À 1 KCl) reference electrode. Table 3 summarizes the experimentally determined values of the redox parameters for the studied nitroxides.…”

“…The redox properties of studied dinitroxides 1 – 5 and trinitroxides 6 – 9 were evaluated using cyclic voltammetry (CV) with the polarization rate value of 100 mV s −1 in Britton‐Robinson (BR) buffer solution (BR, pH 7), on a glassy carbon electrode (GCE). Nitroxides are generally known for their significant redox activity with corresponding N ‐oxoammonium cations to be formed during one‐electron electrochemical oxidation [30,32,33] . In our case, the voltammetric profile for all studied compounds 1 – 9 (Figure S2 in Supporting Information) confirmed undergoing one‐electron transfer during particular electrode reaction with half‐wave potentials ( E 1/2 ) ranging from −51 mV to −17 mV vs Ag/AgCl (3 mol L −1 KCl) reference electrode.…”