Study of the Interaction of Some Potential Anticancer Gold(III) Complexes with Biologically Important Thiols Using NMR, UV–Vis, and Electrochemistry

Abstract

The interaction of gold(III) complexes [Au(en)Cl2]Cl, [Au(en)2]Cl3, [Au(cis‐DACH)Cl2]Cl, and [Au(cis‐DACH)2]Cl3 (en = ethylenediamine, DACH = cis‐1,2‐diaminocyclohexane) with biologically important thiols, such as glutathione (GSH), dl‐penicillamine (PSH), mercaptoacetic acid (MAA), and N‐(2‐mercaptopropionyl)glycine (MPG), has been studied using 1H, 13C NMR, UV–vis spectroscopy and electrochemistry in aqueous solution. Kinetic data revealed that the reactivity of their substitution reaction followed the order: [Au(en)Cl2]+ > [Au(en)2]3+ > [Au(cis‐DACH)Cl2]+ > [Au(cis‐DACH)2]3+. The thiol reactivity increased with decreasing its size, viz. MAA ≫ MPG > PSH > GSH. Square wave stripping voltammetry displayed peaks for Au(III) and Au(I) at +0.875 V and +1.4 V respectively. The interaction of the complexes with thiols resulted in reduction of gold(III) to gold(I) and thiol ligands (RSH) were oxidized to disulfide (RSSR).

Cyclometalated Gold(III) Complexes Bearing DACH Ligands

“…The (1 R ,2 R )-(+)-1,2-diaminocyclohexane (DACH) ligand is featured in the FDA-approved platinum­(II) complex, oxaliplatin, which displays a different spectrum of activity from cisplatin with no cross resistance. , In catalysis, DACH and its derivatives have been employed in the prominent Pd-catalyzed asymmetric allylic alkylation reaction for the construction of stereogenic centers and C–C, C–O, C–S, C–N bond formation. , Whereas the DACH ligand has gained traction, motivated by the outlined successes in the fields of catalysis and medicine, very few gold DACH compounds exist. − Synthesis of diverse gold DACH compounds can reveal structural insights that could lead to a new class of organogold reagents for useful applications. By combining the N-donor DACH ligand and the strong σ-donating character of C, N cyclometalated ligands, distinct gold­(III) structure scaffolds can be obtained.…”

Spectroscopic and Electrochemical Studies of the Interaction of Some Gold(III) Complexes with Biologically Relevant Thiones

“…Table shows that the rate constant for the reaction of [Au( cis ‐DACH)Cl 2 ]Cl and [Au( cis ‐DACH) 2 ]Cl 3 with DIAZ is slower than that with Tu. The reactivity of these thione ligands with these complexes are shown to be less than that for cyanide and higher than that for glutathione, dl ‐penicillamine, mercaptoacetic acid, and N ‐(2‐mercaptopropionyl)glycine . It is also much greater than that for other nucleophiles such as inosine, guanosine‐5′‐monophosphate, l ‐histidine, and inosine‐5′‐monophosphate toward the [Au (cis ‐DACH)Cl 2 ]Cl complex .…”

“…Moreover, the well‐established antiarthritic properties of gold(I) thiolates stimulated a considerable interest in the study of gold compounds . However, the interaction of gold(III) complexes with thiols and thiones is still unclear and is an underdeveloped field in modern inorganic chemistry .…”

“…We recently reported the synthesis and characterization of gold(III) complexes with DACH and examined the effect of stereochemistry of DACH on tumor activity . Additionally, the interaction of gold(III) complexes with cyanide and some thiolates has been studied. In continuation of our previous work on the interaction of gold(III)–DACH complexes, herein the interaction of [Au( cis ‐DACH)Cl 2 ]Cl and [Au( cis ‐DACH) 2 ]Cl 3 with 13 C, 15 N‐enriched thiourea (Tu) and 1,3‐diazinane‐2‐thione (DIAZ) by 1 H, 13 C, and 15 N NMR spectroscopy, UV–vis spectroscopy, and electrochemistry is reported.…”