N-heterocyclic carbene gold(i) and silver(i) complexes bearing functional groups for bio-conjugation

Abstract

This work describes several synthetic approaches to append organic functional groups to gold and silver N-heterocyclic carbene (NHC) complexes suitable for applications in biomolecule conjugation. Carboxylate appended NHC ligands (3) lead to unstable AuI complexes that convert into bis-NHC species (4). A benzyl protected carboxylate NHC-AuI complex 2 was synthesized but deprotection to produce the carboxylic acid functionality could not be achieved. A small library of new alkyne functionalized NHC proligands were synthesized and used for subsequent silver and gold metalation reactions. The alkyne appended NHC gold complex 13 readily react with benzyl azide in a copper catalyzed azide-alkyne cycloaddition reaction to form the triazole appended NHC gold complex 14. Cell cytotoxicity studies were performed on DLD-1 (colorectal adenocarcinoma), Hep-G2 (hepatocellular carcinoma), MCF-7 (breast adenocarcinoma), CCRF-CEM (human T-Cell leukemia), and HEK (human embryonic kidney). Complete spectroscopic characterization of the ligands and complexes was achieved using 1H and 13C NMR, gHMBC, ESI-MS, and combustion analysis.

Recent Developments in the Medicinal Applications of Silver-NHC Complexes and Imidazolium Salts

“…Three alkyne functionalized Ag(I)-NHC compounds were synthesized and evaluated for their applications in biomolecule conjugation [ 84 ]. The cytotoxicity of 62 ( Figure 12 ) was found to be in the micromolar range against a variety of human cancer cell lines including DLD-1 (colon; IC 50 = 6.8 ± 0.8 μM), Hep-G2 (liver; IC 50 = 6.9 ± 0.7 μM), MCF-7 (IC 50 =17.1 ± 0.4 μM), and HEK (liver, IC 50 = 22.6 ± 0.9 μM).…”

“… Structures of Ag(I)-NHC complexes from Garner et al ( 62 ) [ 84 ], Bjørsvik et al ( 63 and 64 ) [ 85 ], and Sanchez et al ( 65 ) [ 86 ]. …”

Silver(I)‐N‐heterocyclic carbene complexes challenge cancer; evaluation of their anticancer properties and in silico studies

“…Since 1990, there has been growing tendency upon production of metal‐NHC complexes in different chemistry areas such as catalysis chemistry and inorganic chemistry (Mora et al, 2019). Although Metal‐NHC complexes have been essentially used in catalytic chemistry (Nolan, 2011), it has been noticed that these complexes show effective antifungal, antibacterial, and anticancer properties that can be used in medical applications and anticancer activity of these complexes is being extensively explored (Citta et al, 2013; Eloy et al, 2012; Garner et al, 2014; Li et al, 2014; Sanchez et al, 2015; Sandtorv et al, 2015).…”

PC-3 İnsan Prostat Kanser Hücre Hattı Üzerine [1-(2-Metil-2-Propenil)-3-(2-Metilbenzil)Benzimidazolyum Klorür Ligandı ve Bu Ligandın Gümüş(I) Kompleksinin Sitotoksik Aktivitesi

“…Son yıllarda organometalik bileşikler, tıbbi tedavi edicilerin önemli bir kısmını oluşturmakta olup, metal içeren N-heterosiklik karben bileşikleri (M-NHC) koordinasyon kimyasında önemli bir bileşik grubudur [3][4][5] . NHC bileşiklerinin sağlıklı hücreler üzerinde kanserli hücrelere göre daha az toksik etki göstermeleri, tümör hücreleri tarafından daha kolay absorbe edilmeleri ve vücuttan atılımlarının daha kolay olmaları gibi özelliklerinden dolayı tıbbi kimyada önemli bir yeri bulunmaktadır [6][7][8][9] . Gümüş, memeli hücreleri için düşük toksik etkiye sahip metallerden birisi olup yıllardan beri tıbbi amaçla kullanılmaktadır 10,11 .…”