Mononuclear silver(I) complexes with 1,7-phenanthroline as potent inhibitors of Candida growth

Abstract

Mononuclear silver(I) complexes with 1,7-phenanthroline (1,7-phen), [Ag(NO-O,O') (1,7-phen-N7)] (1) and [Ag(1,7-phen-N7)]X, X = ClO (2), CFSO (3), BF (4) and SbF (5) were synthesized and structurally characterized by NMR (H and C), IR and UV-Vis spectroscopy and ESI mass spectrometry. The crystal structures of 1, 3 and 4 were determined by single-crystal X-ray diffraction analysis. In all these complexes, 1,7-phen coordinates to the Ag(I) ion in a monodentate fashion via the less sterically hindered N7 nitrogen atom. The investigation of the solution stability of 1-5 in DMSO revealed that they are sufficiently stable in this solvent at room temperature. Complexes 1-5 showed selectivity towards Candida spp. in comparison to bacteria, effectively inhibiting the growth of four different Candida species with minimal inhibitory concentrations (MIC) between 1.2 and 11.3 μM. Based on the lowest MIC values and the lowest cytotoxicity against healthy human fibroblasts with selectivity index of more than 30, the antifungal potential was examined in detail for the complex 1. It had the ability to attenuate C. albicans virulence and to reduce epithelial cell damage in the cell infection model. Induction of reactive oxygen species (ROS) response has been detected in C. albicans, with fungal DNA being one of the possible target biomolecules. The toxicity profile of 1 in the zebrafish model (Danio rerio) revealed improved safety and activity in comparison to that of clinically utilized silver(I) sulfadiazine.

Antimicrobial Activity and DNA/BSA Binding Affinity of Polynuclear Silver(I) Complexes with 1,2-Bis(4-pyridyl)ethane/ethene as Bridging Ligands

“…where K A stands for the binding constant of the silver(I) complex with ctDNA and n stands for the apparent number of binding sites. DNA interaction assay using gel electrophoresis has also been conducted according to the previously published procedure [17] e quenching of the emission intensity of tryptophan residues of BSA at 352 nm was monitored using the increasing concentration of the complexes 1-3 (up to 464.9 μM). Fluorescence spectra were recorded in the range 280-500 nm with an excitation wavelength of 275 nm.…”

“…e crucial factors in determining the antimicrobial effectiveness of silver(I) complexes are the type of the ligand donor atom bound to the Ag(I) ion and the strength of the resulting Ag-donor bonds [12]. us, silver(I) complexes with various aromatic nitrogen-donor ligands have shown remarkable and broad-spectrum antimicrobial activity against a panel of bacterial and fungal strains as a consequence of a relatively weak Ag-N bond which can be easily cleaved in the reactions with biological target molecules [13][14][15][16][17][18][19][20][21]. As a continuation of our efforts in the synthesis of silver(I) complexes as potential antimicrobial agents, in the present study, we used two aromatic nitrogen-containing heterocycles (N-heterocycles) in which two pyridine rings are linked by-CH 2 -CH 2 -and-CH═CH-groups, 1,2-bis(4pyridyl)ethane (bpa) and 1,2-bis(4-pyridyl)ethene (bpe), respectively.…”

Synthesis and structural analysis of polynuclear silver(I) complexes with 4,7-phenanthroline

“…The Ag1-N1/N2(4,7-phen) bond distances in 1 ( Table I) adopt values of 2.305(5) and 2.251(5) Å, respectively, and are comparable with those observed in the other pseudo tetrahedral silver(I) complexes with aromatic N-heterocycles. [8][9][10][11][12][13][14] The Ag1-N3 (acetonitrile) bond distance of 2.284 (7) Å falls in the normal range of 2.18-2.33 Å. 26 On the other hand, the Ag1-O1 bond distance of 2.505(6) Å is much longer than usual covalent silver(I)-oxygen bonds of approximately 2.3 Å.…”

“…1,2 Generally, silver(I) complexes with these ligands are known to possess significant antibacterial activity against a wide range of Gram-positive and Gram-negative bacteria and have shown remarkable activity against different Candida species. [3][4][5][6][7][8][9][10][11][12][13][14] Moreover, they have manifested cytotoxic activity against different human tumor cell line, being more active and less toxic to humans than the clinically used platinum(II) complexes. 15 Their effectiveness is thought to be the consequence of the presence of a weak Ag−N bond, which can be easily cleaved in the interaction with thiol-containing proteins and DNA, the process that is a prerequisite for their action.…”

“…Almost all of the synthesized silver(I) complexes with 4,7-phen are polynuclear species, with the exception of [Ag 2 (H 2 O) 0.58 (4,7--phen) 3 ](SbF 6 ) 2 complex, which is obtained in the reaction of AgSbF 6 with an equimolar amount of 4,7-phen in the ethanolic solution. 14 Contrary to 4,7-phen, its structural isomer 1,7-phenanthroline affords mononuclear silver(I) complexes, namely [Ag(NO 3 )(1,7-phen) 2 ] and [Ag(1,7-phen) 2 ]X (X = ClO 4 in which it is monodentately coordinated via the less sterically hindered N7 nitrogen atom 12. …”