Synthesis, Structure and Bactericide Activity of (Aminophosphane)gold(I) Thiolate Complexes

Abstract

Reaction of the aminophosphane ligands 2‐(diphenylphosphanylamino)pyridine (Ph2PNHpy, 1) and 3‐(diphenylphosphanylamino)‐1,2,4‐triazole [Ph2PNH(Htrz), 2] with the gold(I) compound [AuCl(tht)] (tht = tetrahydrothiophene) gave the complexes [AuCl(Ph2PNHpy)] (3) and [AuCl{Ph2PNH(Htrz)}] (4), respectively. A series of new gold(I) thiolate derivatives were synthesized from the reactions of complex 3 or 4 with 1 equiv. of a deprotonated thiol ligand. Complexes [Au(SR)(PPh2NHpy)] (5–8) were prepared by reaction of complex 3 with the corresponding thiol HSR [HSR = 2‐mercaptopyridine (2‐HSpy), 2‐mercaptonicotinic acid (2‐H2‐mna), 2‐thiouracil (2‐HTU) or 2‐thiocytosine (2‐HTC)] in the presence of sodium carbonate or triethylamine. Complexes [Au(SR){PPh2NH(Htrz)}] (9–11) were prepared by the treatment of complex 4 with triethylamine and the respective thiol HSR [HSR = 2‐mercaptopyridine (2‐HSpy), 2‐thiocytosine (2‐HTC) or 6‐thioguanine (6‐HTG)]. The susceptibility of Enterococcus faecalis ATCC25923, Staphylococcus aureus ATCC29213 and Escherichia coli TG1 towards the synthesized gold(I) complexes was evaluated. Some of them exhibit powerful anti‐bacterial activity, being more efficient against Gram‐positive microorganisms. Complexes 7–9 and 11 present excellent activity against E. faecalis, whereas the highest sensitivity of S. aureus was against complexes 7 and 8. The structures of complexes 4, 5, 8 and 9 were determined by X‐ray structural analysis. None of the four compounds shows aurophilic interactions between the gold(I) centres in the crystals. The four complexes possess intermolecular hydrogen bonds that lead to supramolecular arrangements.

(Aminophosphane)gold(I) and silver(I) complexes as antibacterial agents

“…We confirmed the molecular structures of complexes 6, 9 and 10 by an X-ray crystallographic study, although the last one was previously published [36]. Complex 6 ( Figure 2) crystallizes in a monoclinic system with two independent units in the asymmetric unit.…”

“…These ligands were chosen because other phosphane-gold derivatives are known to have antibacterial activity and because the presence of the amine group allows and easy functionalisaton, making possible the introduction of relevant biological moieties. These compounds were tested in vitro to study their activity against Gram-negative S. typhimurium SV5015 and E. coli ATCC 10536 strains and the Gram-positive L. monocytogenes EGD-e and S. aureus ATCC 11632 strains using the paper disc diffusion method (for the qualitative determination) and for those complexes that were found to show inhibitory activity, serial dilutions in liquid broth method were performed (for determination of MIC (minimum inhibitory concentration) and MBC (minimum bactericidal concentration)).This paper is a continuation of a previous study using the same ligand [36], in which the susceptibility of (aminophosphane)gold(I) thiolate complexes against Enterococcus faecalis ATCC 25923, S. aureus ATCC 29213 and E. coli TG1 was demonstrated. Some of them were found to exhibit powerful antibacterial activity, being more efficient against Grampositive microorganisms.…”

“…those with an N-Au-P core [7,36] (Table 1 and 2). Gold(I) phosphine derivatives present no activity against E. coli and S. typhimurium (Table 1 and 2), although in some water soluble gold(I) phosphine complexes have been reported to have activity in these bacteria [58].…”

Synthesis and antimicrobial activities of gold(I) sulfanylcarboxylates

“…In this last field, the compounds under investigation include a major collection of the type R 3 PAuL, in which the gold atom is coordinated to a phosphine ligand and L is an O- [26,27], N- [28,29], Cl- [30] or S- [29,[31][32][33][34][35] 2 ], Na 3 [Au(mna) 2 ] (H 2 mna 02-mercaptonicotinic acid) [13] and the cationic complexes [Au(L) 2 ](NO 3 ) 3 (L01-[2-(acridin-9-ylamino)ethyl]-1,3-dimethylthiourea) [34]. For the latter ligand, compounds of the type [Au(L)]Br, [Au(L)] SCN and [Au(L)]Cl were also prepared [34] and the coexistence of an S-donor ligand and a Cl ligand was also described for [LAuCl] (where L 02,3-diphenyl-1,3,4-thiadiazolium-5-thiolato-S exo ) [36].…”

The effects of phosphanegold(I) thiolates on the biological properties of Acanthamoeba castellanii belonging to the T4 genotype

“…Moreover, closely related compounds have shown potential as anti-microbial agents against Gram-positive bacteria [15]. Gold(I) compounds have potential medical applications and shown to possess anti-tumour activities [16, 17], anti-parasitic [18] and anti-microbial activities [19–21] via a variety of mechanisms including respiration. In this study, for the first time, we determined the effects of phosphanegold(I) thiolates, AAu1–AAu3, Fig.…”