Synthesis and characterization of two cyanoxime ligands, their precursors, and light insensitive antimicrobial silver(I) cyanoximates

• Two new cyanoxime ligands and their precursors were synthesized.
• Compounds were characterized using NMR, UV–Vis spectra, X-ray analysis.
• Two new light-stable silver(I) cyanoximates were obtained and characterized.
• Acrylate-based polymeric composites containing Ag(I) cyanoximates were prepared.
• Antimicrobial activity and biofilm inhibition of two silver(I) complexes was established.

High-yield syntheses of N-piperidine-cyanacetamide (1), N-morpholyl-cyanacetamide (4) and their oxime derivatives N-piperidine-2-cyano-2-oximino-acetamide (HPiPCO, 2) and N-morpholyc-2-cyano-2-oximino-acetamide (HMCO, 5) were developed using two-step preparations. At first, the reactions of neat cyanoacetic acid esters and the respective cyclic secondary amines such as piperideine and morpholine afforded pure cyan-acetamides, which were converted into cyanoximes at room temperature using the nitrosation reaction with gaseous CH3ONO. The synthesized compounds were investigated by means of IR, 1H, 13C and UV–Vis spectroscopy. Crystal structures of two starting substituted cyan-acetamides and two target cyanoximes were determined. Silver(I) complexes of AgL composition (L = PipCO, 3; MCO, 6) were prepared in high yield. Both metal complexes are thermally stable above 100 °C, and remarkably stable to high intensity visible light. The stability of dried AgL compounds towards short wavelength UV-radiation (a frequently used germicidal light) was examined using diffusion reflectance spectroscopy. Both complexes demonstrate slow photoreduction within ∼3 h, observable as a gradual color change and darkening due to the formation of fine (nano-scale) particles of metallic silver. The complex Ag(MCO), 6, is about 2.6 times less stable towards UV-radiation than its more lypophyllic analog Ag(PipCO), 3. Antimicrobial and biofilm growth inhibition properties of the prepared solid acrylate-based polymeric composites containing embedded silver(I) cyanoximates were investigated using three human pathogens: Pseudomonas aeruginosa PAO1 (wound isolate), Staphylococcus aureus NRS70 (methicillin resistant respiratory isolate), and Streptococcus mutans UA159 (cariogenic dental isolate). Studies showed that both 3 and 6 compounds completely abolished the growth of PAO1 at 0.5 weight% concentration, and the growth of UA159 and NRS70 at 1% concentration. Thus, the data demonstrate that complexes 3 and 6 inhibit both planktonic and biofilm growth of Gram-positive and Gram-negative bacterial pathogens. The demonstrated thermal stability and pronounced antimicrobial activity of both silver(I) cyanoximates indicates the strong potential for the studied complexes to be used as light insensitive antimicrobial additives to light-curable adhesives that set indwelling devices in place.

Two silver(I) complexes of AgL composition (L = new cyanoxime ligands PipCO, 3; MCO, 6) were prepared in high yield and characterized by elemental analysis and IR spectroscopy. Both complexes are thermally stable, and totally stable to high intensity visible light. Silver(I) cyanoximates showed a very good tolerance and miscibility with the flowable acrylate-based light-curable composites commonly used in dental practice. Several solid, light-cured polymeric composites containing different mass percent (0.5%, 1%, 2,5% and 5%) of dispersed in the polymer complexes 3 and 6 were fabricated. Antimicrobial and biofilm growth inhibition properties of prepared solid polymeric composites containing silver(I) cyanoximates were investigated on three human pathogens such as: Pseudomonas aeruginosa PAO1 (wound isolate), Staphylococcus aureus NRS70 (methicillin resistant respiratory isolate), and Streptococcus mutans UA159 (cariogenic dental isolate). Studies showed that both 3 and 6 compounds completely abolished the growth of PAO1 at a 0.5 wt% concentration, and the growth of UA159 and NRS70 at a 1% concentration. Moreover, the data demonstrates that complexes 3 and 6 also inhibit both planktonic and biofilm growth of Gram-positive and Gram-negative bacterial pathogens with the former complex performing slightly better.Figure optionsDownload as PowerPoint slide