Continuous Flow Synthesis and Antimicrobial Evaluation of NHC* Silver Carboxylate Derivatives of SBC3 in vitro and in vivo

N-Heterocyclic silver carbene compounds have been extensively studied and shown to be active agents against a host of pathogenic bacteria and fungi. By incorporating hypothesised virulence targeting substituents into NHC-silver systems via salt metathesis, an atom efficient complexation process can used to develop new complexes to target the passive and active systems of a microbial cell. The incorporation of fatty acids and an FtsZ inhibitor have been achieved, and creation of both the intermediate salt and subsequent silver complex has been streamlined into a continuous flow process. Biological evaluation was conducted with in vitro toxicology assays showing these novel complexes had excellent inhibition against Gram-negative strains E. coli, P. aeruginosa and K. pneumonia; further studies also confirmed the ability to inhibit biofilm formation in Methicillin-resistant S. aureus and C. Parapsilosis. In vivo testing using a murine thigh infection model showed promising inhibition of MRSA for the lead compound SBC3, which is derived from 1,3-dibenzyl-4,5-diphenylimidazol-2-ylidene(NHC*).

Syntheses and crystal structures of two new silver–organic frameworks based on N-pyrazinesulfonyl-glycine: weak Ag···O/N interaction affecting the coordination geometry

Two new metal–organic frameworks, namely, [Ag2(L)]n (1) and {[Ag2.5(L)(bpy)2]·(NO3)0.5·(H2O)4.5}n (2), where H2L=N-pyrazinesulfonyl-glycine and bpy=4,4′-bipyridine, have been synthesized and characterized by single-crystal X-ray diffraction, IR spectroscopy, and elemental analysis. X-ray diffraction crystallographic analyses indicate that 1 displays a silver carboxylate-sulfonamide layer structure containing an uncommon heptanuclear [Ag7] cluster wherein four silver(I) atoms form an Ag4 plane with in a three-connected (6, 3) net. The molecular structure of 2 has three crystallographically independent two-coordinate Ag centers with an intersecting Ag-bpy chain structure in a six-connected (3, 6) or a four-connected (4, 4) topology. The L2− ligand serves as a μ7-(η2-O,N), (η2-O′,N′), O,O″,O″′,N,N″ ligand in 1 and as a μ3-(η2-O,N), N,O′ ligand in 2. In the crystal, a 3D supramolecular architecture is formed by coordinative bonding in 1, but through O–H···O bonding as well as π···π stacking in 2. The two compounds show a combination of coordinative bonds, ligand-supported Ag···Ag interactions and weak Ag···O/N coordinative interactions in the solid state.