Water-Soluble Silver(I) Complexes Featuring the Hemilabile 3,7-Dimethyl-1,3,5-triaza-7-phosphabicyclo[3.3.1]nonane Ligand: Synthesis, Characterization, and Antimicrobial Activity

Abstract

This paper describes the preparation and comprehensive characterization of a series of water-soluble cationic silver(I)-centered complexes featuring the hemilabile P, N-ligand known as 3,7-dimethyl-1,3,5-triaza-7-phosphabicyclo[3.3.1]nonane (herein abbreviated as PTN(Me)) and differing types of monoanionic counterions including known biologically active sulfadiazine and triclosan. The complexes primarily differed though the number of coordinating PTN(Me) ligands. The bis-substituted Ag(I) complexes revealed P, N bidentate coordination, while the only P-monocoordination of the metal center was observed for the tris-substituted systems. The bis-ligated silver compounds were observed to quickly degrade upon photoexposure or in contact with air. In contrast, the tris-ligated complexes demonstrated greater stability, in particular, a high resistance to photo-decomposition. Calculated geometry optimized models using the density functional theory method (BP86) revealed for the bis-substituted PTN(Me) Ag(I) species that the total enthalpy of the tetrahedral C-symmetric structure is marginally lower by -0.6 kcal mol compared to the planar C structure, which is analogous for the corresponding [Au(PTN(Me))] complex with Δ H = -0.5 kcal mol. Hence both types of complexes feature free rotation of the PTN ligand about the M-P bond axis. This series of Ag(I) and bis-PTN(Me) Au(I) complexes were evaluated using the agar well diffusion test for potential antimicrobial and antifungal activity. The nature of the counterion was found to have a strong correlation with the area of microbiological growth inhibition. Silver(I) complexes bearing the deprotonated triclosan as the counterion demonstrated the greatest activity, with large zones of growth inhibition, with the tris-ligated triclosan complex obtaining of a high clearance of 42 mm against the Gram-negative Escherichia coli. In contrast, the previously reported [Au(PTN(Me))]Cl complex demonstrated activity only against E. coli, which is lower than that observed for the silver(I) PTN(Me) species.

New Findings in Metal Complexes with Antiproliferative Activity Containing 1,3,5‐Triaza‐7‐phosphaadamantane (PTA) and Derivative Ligands

“…[39] The ligand PTN was found to be P,Nbidentate when only two ligands are coordinated to the metal, while only P-mono-coordination to the metal center was observed for complexes with three ligands. [39] The ligand PTN was found to be P,Nbidentate when only two ligands are coordinated to the metal, while only P-mono-coordination to the metal center was observed for complexes with three ligands.…”

“…Very attractive antiproliferative water soluble silver complexes were obtained with the PTA derivative 3,7‐dimethyl‐1,3,5‐triaza‐7‐phosphabicyclo[3.3.1]nonane (PTN) [ 53(a–f)‐54(a–f) ] (Scheme ) . The ligand PTN was found to be P,N ‐bidentate when only two ligands are coordinated to the metal, while only P‐mono‐coordination to the metal center was observed for complexes with three ligands.…”

In vitro anti-bacterial and time kill evaluation of binuclear tricyclohexylphosphanesilver(I) dithiocarbamates, {Cy3PAg(S2CNRR′)}2

“…myocrisin and auranofin, are used for the treatment of rheumatoid arthritis [5]. Notably, silver and its compounds [6,7] and silver-based nanoparticles [8] have long been known to possess strong inhibitory and bactericidal effects as well as a broad spectrum of anti-microbial activities for bacteria, fungi and viruses, and continue to attract significant attention [9][10][11][12]. Silver generally exhibits higher toxicity to microorganisms with lower toxicity to mammalian cells compared with other metals [13].…”

New Silver(I) Coordination Compound Loaded into Polymeric Nanoparticles as a Strategy to Improve In Vitro Anti-Helicobacter pylori Activity

“…Silver­(I) complexes are potential novel therapeutic drugs due to their antiproliferative activity in vitro and the low toxicity of Ag in humans. − The rate of release of Ag­(I) ions and other physicochemical properties, such as water solubility and stability, can be modulated using suitable ligands. Thiosemicarbazones constitute a particularly interesting class of ligands due to their rich coordination capabilities and their well-established antiviral, antitumor, antifungal, antimalarial, and antibacterial activities, among others. , …”