Tethered N-Heterocyclic Carbene-Carboranyl Silver Complexes for Cancer Therapy

Abstract

Silver complexes of tethered N-heterocyclic carbene-carboranyl ligands have been prepared and fully characterized. The first example of silver bonded directly to the cage of o-carborane has been identified in the solid state. The presence of a carboranyl N substituent on the N-heterocyclic carbene significantly enhances the in vitro cytotoxicity of the silver complex against HCT116 p53+/+ and HCT116 p53–/– colon cancer cells in comparison to a phenyl derivative. Conversely, the presence of a carboranyl on the backbone of a xanthine-derived N-heterocyclic carbene decreases the in vitro cytotoxicity of the silver complex in comparison to its phenyl derivative. Stability studies on the xanthine-derived ligands and complexes show that decomposition via deboronation occurs in hydrous dimethyl sulfoxide, which may attribute to the contrasting in vitro behaviors of the carborane-containing complexes.

The key role of R–NHC coupling (R = C, H, heteroatom) and M–NHC bond cleavage in the evolution of M/NHC complexes and formation of catalytically active species

“…Protonolysis reactions proceed very easily for Li/NHC 105 , 108 and Mg/NHC 112 complexes. Other complexes, including Ag I /NHC, 191 , 193 , 197 – 199 , 201 Al III /NHC, 119 In III /NHC, 119 Y III /NHC 125 and Ce III /NHC, 125 Mn I /NHC, Zn II /NHC, 213 Mo VI /NHC 130 and Ni II /NHC, 214 are also susceptible to protonolysis; the efficiency depends on the structure of NHC ligands, co-ligands and reaction conditions ( Table 1 column 3). For example, (NHC) 2 NiX 2 complexes (X = Cl, Br, I) suffer facile hydrolysis in aqueous MeCN or THF at 70 °C to give azolium salts and Ni(OH) 2 .…”

N‐Heterocyclic Carbenes Carrying Weakly Coordinating Anions

“…Silver complexes of tethered N‐heterocyclic carbene‐carboranyl ligands have been prepared, starting from the protonated carbene and Ag 2 O in dichloromethane. The in vitro cytotoxicity of these complexes were examined against the colon cancer cells [34] …”

“…The in vitro cytotoxicity of these complexes were examined against the colon cancer cells. [34] Rhodium(I) and iridium(I) complexes with WCA-NHC ligands were prepared by our group in 2013. [20] The reaction of 6 b with dimeric [M(COD)Cl] 2 (M = Rh, Ir; COD = cyclooctadiene), afforded, after separation of LiCl, the zwitterionic complexes [(F 5 C 6 ) 3 B-IDipp]M(COD) (12 a: M = Rh; 12 b: M = Ir; Figure 6).…”

Silver Binding to Bacterial Glutaredoxins Observed by NMR

“…Silver salts have traditionally been utilized as antimicrobials, with a resurgence in modern medicine for preventing infection during the treatment of severe burn [22]. Recent research has worked towards adapting silver(I) for the treatment of drug resistant bacterial infection [23][24][25][26][27], and the treatment of cancers [28][29][30][31]. While the exact mechanism for silver(I) ion's effectiveness as an antimicrobial is not fully understood, multiple studies point to its ability to increase reactive oxygen species (ROS) [32][33][34][35].…”