Luminescent di- and polynuclear organometallic gold(I)-metal (Au2, {Au2Ag}n and {Au2Cu}n) compounds containing bidentate phosphanes as active antimicrobial agents

Abstract

The reaction of new dinuclear gold(I) organometallic complexes containing mesityl ligands and bridging bidentate phosphanes [Au(2)(mes)(2)(μ-LL)] (LL=dppe: 1,2-bis(diphenylphosphano)ethane 1a, and water-soluble dppy: 1,2-bis(di-3-pyridylphosphano)ethane 1b) with Ag(+) and Cu(+) lead to the formation of a family of heterometallic clusters with mesityl bridging ligands of the general formula [Au(2)M(μ-mes)(2) (μ-LL)][A] (M=Ag, A=ClO(4)(-), LL=dppe 2a, dppy 2b; M=Ag, A=SO(3)CF(3)(-), LL=dppe 3a, dppy 3b; M=Cu, A=PF(6)(-), LL=dppe 4a, dppy 4b). The new compounds were characterized by different spectroscopic techniques and mass spectrometry The crystal structures of [Au(2)(mes)(2)(μ-dppy)] (1b) and [Au(2)Ag(μ-mes)(2)(μ-dppe)][SO(3)CF(3)] (3a) were determined by a single-crystal X-ray diffraction study. 3a in solid state is not a cyclic trinuclear Au(2)Ag derivative but it gives an open polymeric structure instead, with the {Au(2)(μ-dppe)} fragments "linked" by {Ag(μ-mes)(2)} units. The very short distances of 2.7559(6) Å (Au-Ag) and 2.9229(8) Å (Au-Au) are indicative of gold-silver (metallophilic) and aurophilic interactions. A systematic study of their luminescence properties revealed that all compounds are brightly luminescent in solid state, at room temperature (RT) and at 77 K, or in frozen DMSO solutions with lifetimes in the microsecond range and probably due to the self-aggregation of [Au(2)M(μ-mes)(2)(μ-LL)](+) units (M=Ag or Cu; LL=dppe or dppy) into an extended chain structure, through Au-Au and/or Au-M metallophilic interactions, as that observed for 3a. In solid state the heterometallic Au(2)M complexes with dppe (2a-4a) show a shift of emission maxima (from ca. 430 to the range of 520-540 nm) as compared to the parent dinuclear organometallic product 1a while the complexes with dppy (2b-4b) display a more moderate shift (505 for 1b to a max of 563 nm for 4b). More importantly, compound [Au(2)Ag(μ-mes)(2)(μ-dppy)]ClO(4) (2b) resulted luminescent in diluted DMSO solution at room temperature. Previously reported compound [Au(2)Cl(2)(μ-LL)] (LL dppy 5b) was also studied for comparative purposes. The antimicrobial activity of 1-5 and Ag[A] (A=ClO(4)(-), SO(3)CF(3)(-)) against gram-positive and gram-negative bacteria and yeast was evaluated. Most tested compounds displayed moderate to high antibacterial activity while heteronuclear Au(2)M derivatives with dppe (2a-4a) were the more active (minimum inhibitory concentration 10 to 1 μg mL(-1)). Compounds containing silver were ten times more active to gram-negative bacteria than the parent dinuclear compound 1a or silver salts. Au(2)Ag compounds with dppy (2b, 3b) were also potent against fungi.

Figure 1

Structure of the polymeric cation [(μ-Ag){Au₂(μ-mes)₂(μ-dppe)}]⁺_n in compound 3a.

Figure 2

View of the structure of compound 1b (2 molecules) showing: a) the interactions of Au atoms and the H of a CH₃ group from one mesityl ligand and an H from a pyridyl ring of the dppy ligand and b) One of the four C---H…π contacts in this molecule (two molecules of 1b, with complementary C15---H15…Cg3 contacts drawn as dashed lines. Symmetry codes (i): (-x, 1-y, 2-z); (ii): (x, −1+y, z); (iii): (−x, −y, 2-z)). Selected distances: Au(1)-C(1) 2.067(4); Au(1)-P(1) 2.295(1) Å. Selected angles: C(1)-Au(1)-P(1) 178.0(1); C(1)-Au(1)-C(2) 122.1 (3); C(1)-Au(1)-C(6) 119.5(3)°.

Figure 3

One link of the polymeric cation {[Au₂Ag(μ-mes)₂(μ-dppy)]_n}⁽ⁿ⁺⁾, from compound 2c. The chain is propagated at Ag1A---N3B and at N3A---Ag1Cⁱ. Symmetry code i: (1-x,-y,-0.5+z).

Figure 4

Excitation (dash line) and emission (solid line) spectra in the solid state of: (a) compound 2a at room temperature (RT); (b) compound 4a at RT; (c) gold precursor 1a at RT; (d) gold precursor 1a at 77 K.

Figure 5

Excitation and emission spectra in the solid state of: (a) compound 2b at RT; (b) compound 2b at LT.

Figure 6

The minimal bactericidal concentration was determined by growing E. coli or S. aureus in the presence of 2a (Fig 5a) or 3a (Fig 5b) at 10 ug/ml over 24 hours. At each time point dilutions of the cell cultures were plated onto Mueller Hinton plates and the number of colony forming units were used to calculate the cell concentration. The results show that nearly all bacteria were killed by the 2a or 3a compounds by 18 hours. Control cells incubated in the absence of compounds 2a or 3a continued to grow as expected.

Scheme 1

Preparation of the Di and Polynuclear Organometallic Gold(I)-M (Au₂, {Au₂Ag}_n and {Au₂Cu}_n) Compounds.