On the Different Mode of Action of Au(I)/Ag(I)-NHC Bis-Anthracenyl Complexes Towards Selected Target Biomolecules

Abstract

Gold and silver N-heterocyclic carbenes (NHCs) are emerging for therapeutic applications. Multiple techniques are here used to unveil the mechanistic details of the binding to different biosubstrates of bis(1-(anthracen-9-ylmethyl)-3-ethylimidazol-2-ylidene) silver chloride [Ag(EIA)2]Cl and bis(1-(anthracen-9-ylmethyl)-3-ethylimidazol-2-ylidene) gold chloride [Au(EIA)2]Cl. As the biosubstrates, we tested natural double-stranded DNA, synthetic RNA polynucleotides (single-poly(A), double-poly(A)poly(U) and triple-stranded poly(A)2poly(U)), DNA G-quadruplex structures (G4s), and bovine serum albumin (BSA) protein. Absorbance and fluorescence titrations, mass spectrometry together with melting and viscometry tests show significant differences in the binding features between silver and gold compounds. [Au(EIA)2]Cl covalently binds BSA. It is here evidenced that the selectivity is high: low affinity and external binding for all polynucleotides and G4s are found. Conversely, in the case of [Ag(EIA)2]Cl, the binding to BSA is weak and relies on electrostatic interactions. [Ag(EIA)2]Cl strongly/selectively interacts only with double strands by a mechanism where intercalation plays the major role, but groove binding is also operative. The absence of an interaction with triplexes indicates the major role played by the geometrical constraints to drive the binding mode.

Two novel Pd thiosemicarbazone complexes as efficient and selective antitumoral drugs

“…In fact, in poly(rU)•poly (rA)•poly(rU), one of the grooves is occupied by the third strand, hampering the interaction between the complex and the nucleic acid. 39 To confirm the groove binding mode, ethidium bromide (EtBr) displacement tests were undertaken. EtBr is a wellknown DNA intercalator reported in many procedures.…”

Synthesis, characterization and biological activity of bis[3-ethyl-4-aryl-5-(2-methoxypyridin-5-yl)-1-propyl-1,3-dihydro-2H-imidazol-2-ylidene]gold(i) complexes

“…[19][20][21][22][23][24][25][26][27][28][29][30][31][32] Many bis-NHC gold(I) complexes displayed a remarkable cytotoxicity in low micromolar or even nanomolar ranges (see e.g., ref. [33][34][35][36].…”

Anthracenyl Functionalization of Half-Sandwich Carbene Complexes: In Vitro Anticancer Activity and Reactions with Biomolecules

“…N-Heterocyclic carbene (NHC) ligands provide a flexible backbone for functionalization with bioactive groups, fluorophores, and other functional groups . Gold­(I) and silver­(I) complexes with NHC ligands bearing an anthracene moiety showed anticancer potency through the inhibition of thioredoxin reductase by targeting mitochondria − and the interaction with biomolecules, while a platinum­(II) derivative has been shown to interact with DNA …”