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Due to the so-called “antibiotic resistance crisis” new antibacterial agents are urgently sought to treat multidrug-resistant pathogens. A group of gold- or silver-based complexes, of general formula [M(PEt3)X] (with M=Au or Ag, and X=Cl, Br or I), alongside with three complexes bearing a positive or negative charge—[Au(PEt3)2]Cl, K[Au(CN)2] and [Ag(PEt3)2]NO3—were prepared and comparatively tested with auranofin on a representative panel of pathogens including Gram-positive, Gram-negative and Candida strains. Interestingly, all the gold and silver complexes tested were active on Gram-positive strains, with the gold complexes having greater efficacy. The effects of the gold compounds were potentiated to a larger extent than silver compounds when tested in combination with a permeabilizing agent. A number of relevant structure–activity relationships emerged from the comparative analysis of the observed antibacterial profiles, shedding new light on the underlying molecular mechanisms of the action of these compounds.

Trichomonas vaginalis causes the most common, nonviral sexually transmitted infection. Only metronidazole (Mz) and tinidazole are approved for treating trichomoniasis, yet resistance is a clinical problem. The gold(I) complex, auranofin, is active against T. vaginalis and other protozoa but has significant human toxicity. In a systematic structure-activity exploration, we show here that diversification of gold(I) complexes, particularly as halides with simple C1-C3 trialkyl phosphines or as bistrialkyl phosphine complexes, can markedly improve potency against T. vaginalis and selectivity over human cells compared to that of the existing antirheumatic gold(I) drugs. All gold(I) complexes inhibited the two most abundant isoforms of the presumed target enzyme, thioredoxin reductase, but a subset of compounds were markedly more active against live T. vaginalis than the enzyme, suggesting that alternative targets exist. Furthermore, all tested gold(I) complexes acted independently of Mz and were able to overcome Mz resistance, making them candidates for the treatment of Mz-refractory trichomoniasis.

Neutral complexes of the type AuX(PEt3) (X = Br, CN, SCN) were prepared and characterized by infrared and Raman spectroscopy, with the major emphasis on the assignment of the gold-ligand vibrations and discerning the mode of bonding for the ambidentate ligands. The photosensitive cationic complexes [(Au(SMe2)(PEt3)]PF6 and {Au[SC(NH2)2](PEt3)}(Cl in addition to [Au(OH2)(PEt3)]NO3 and (μ-S)[(PEt3)Au]2 were also prepared and characterized by infrared and NMR spectroscopy. In both cases in which the ambidentate ligands SCN- and SC(NH2)2 were complexed with Au(I), the sulfur atom coordinates to the metal, providing evidence for a symbiotic relationship in these complexes.

Electronic absorption and magnetic circular dichroism (MCD) spectra are reported at room temperature for acetonitrile solutions of tetra-n-butylammonium salts of AuX2-, X = Cl-, Br-, and I-, the hexafluorophosphate salt of Au(PEt3)2+, and the mixed complexes AuCl(PR3), R = Me and Et, and AuX(PEt3), X = Br- and I-. The Au(PEt3)2+ ion exhibits several strong bands in the UV region, which are assigned as metal to ligand charge-transfer (MLCT) transitions. The AuX2- ions show weak low-energy vibronic d → s transitions and higher energy intense d → p transitions. In addition AuBr2- and AuI2- spectra display ligand to metal charge-transfer (LMCT) transitions. The spectra of the AuX(PR3) complexes are interpreted as a combination of MLCT, LMCT, and d → p type transitions; the weak d → s transitions are not visible in the spectra of the mixed complexes. Spectral assignments are discussed together with the ligand dependence of relative orbital energies among the highest energy occupied and lowest energy empty MO's.

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