Light Insensitive Silver(I) Cyanoximates As Antimicrobial Agents for Indwelling Medical Devices

Abstract

Ten silver(I) cyanoximates of AgL composition (L = NC-C(NO)-R, where R is electron withdrawing groups: -CN, -C(O)NR(2), -C(O)R' (alkyl), -C(O)OEt, 2-heteroaryl fragments such as 2-pyridyl, 2-benzimidazolyl, 2-benzoxazolyl, 2-benzthiazolyl) were synthesized and characterized using spectroscopic methods and X-ray analysis. Crystal structures of four complexes were determined and revealed the formation of two-dimensional (2D) coordination polymers of different complexity in which anions exhibit bridging or combined chelate and bridging binding modes. In these compounds, anions are in the nitroso form. All studied AgL complexes are sparingly soluble in water and are thermally stable to 150 °C. Synthesized compounds demonstrated remarkable insensitivity toward visible light and UV-radiation, which was explained based on their polymeric structures with multiple covalent bonds between bridging cyanoxime ligands and Ag(I) centers. All 10 silver(I) cyanoximates were tested in vitro on the subject of their antimicrobial activity against both Gram-positive and Gram-negative microorganisms such as Escherichia coli, Klebsiella pneumoniae, Proteus sp., Pseudomonas aeruginosa, Enterococcus hirae, Streptococcus mutans, Staphylococcus aureus, and Mycobacterium fortuitum as well as against Candida albicans in solutions, and in the solid state as pressed pellets and dried filter paper disks presoaked with solutions of AgL in DMF. Results showed pronounced antimicrobial activity for all investigated complexes. A combination of five factors: (1) light insensitivity, (2) poor water solubility, (3) high thermal stability, (4) lack of toxicity of organic ligands, and (5) in vitro antimicrobial activity allows development of silver(I) cyanoximates for medical applications. These include antimicrobial additives to acrylate glue, cured by UV-radiation, used in introduction of prosthetic joints and dental implants, and prevention of biofilm formation on several types of indwelling medical devices.

An Excursion into the Intriguing World of Polymeric Tl(I) and Ag(I) Cyanoximates

“…However, there is a large group of 13 visible light insensitive AgL complexes, namely with L = CCO (Figure 3), which are stable to day light for years of continuous exposure (ESI 14). This property has several important practical implications [19][20][21] which will be briefly discussed further in this work.…”

“…Therefore, in recent years seven crystal structures of complexes with AgL composition were determined [19][20][21], as well as three crystal structures of solvates of AgL·S composition [51] (L = BOCO, S = DMF; L = BOCO, S = DMSO; L = BTCO, S = H 2 O). It should be noted, however, that the growth of crystals of silver(I) cyanoximates that are suitable for the X-ray analysis is a challenge due to their polymeric nature and, therefore, low solubility in common organic solvents and water.…”

“…These primarily covalent bonds are shorter than the sum of ionic radii and are arranged in practically linear fashion in structures of Ag(DCO), Ag(BCO) and Ag(ECO) with N1-Ag-N2 angles between 160 and 166° (ESI 15-17). There are also two, or three (like in Ag(PiCO) (ESI 18) and Ag(BCO) (ESI 17)) significantly longer than the sum of their ionic radii Ag---O contacts which have electrostatic origin and help in stabilization of a crystal lattice [21]. With those two (or three) longer distances the coordination polyhedra of silver(I) can be viewed as seesaw for Ag(DCO) and Ag(ECO) (ESI 15,16), or as distorted trigonal bipyramid for Ag(BCO), or distorted trigonal prism in the structure of Ag(PiCO) respectively (ESI 17,18).…”

“…These compounds turned out to be coordination polymers of different complexity in which anionic cyanoximes act as bridging ligands sometimes showing unusual binding modes. Silver(I) polymeric cyanoximates showed quite remarkable stability towards visible light, which can be utilized in several practical applications [19][20][21], while polymeric thallium(I) cyanoximates are attractive building blocks and templates [22] for the preparation of mixed valence Tl(I)/Tl(III) systems that may exhibit electrical conductivity. This is an important property in design of molecular wires and in other molecular electronics applications [23].…”

Silver-Based Hybrid Materials from meta- or para-Phosphonobenzoic Acid: Influence of the Topology on Silver Release in Water

“…This scenario was indeed observed with Ag6(3-PO3-C6H4-COO)2 (4) 41,3230 which released less than 2% of the silver present in the starting materials and that showed excellent bactericidal properties against clinically relevant Gram negative and Gram positive bacterial strains (including MRSA strains). 3129 Other recent studies have also reported the bactericidal properties of cobalt 42 , silver 43,44 and copper-based 45 metal-organic-6 frameworks. In the recent study from Jones et al 4441 , it was shown that the quantities of silver released in solution were almost identical irrespective of the structure of the polymeric material tested.…”