Homobimetallic Au(I)–Au(I) and Heterotrimetallic Au(I)–Fe(II)–Au(I) Complexes with Dialkyldithiophosphates and Phosphine Ligands: Structural Characterization, DFT Analysis, and Tyrosinase Inhibitory and Biological Effects

Abstract

The role of bridging and terminal ligand electronic and steric properties on the structure and antiproliferative activity of two-coordinated gold(I) complexes was investigated on seven novel binuclear and trinuclear gold(I) complexes synthesized by the reaction of either Au2(dppm)Cl2, Au2(dppe)Cl2, or Au2(dppf)Cl2 with potassium diisopropyldithiophosphate, K[(S-O i Pr)2], potassium dicyclohexyldithiophosphate, K[(S-OCy)2], or sodium bis(methimazolyl)borate, Na(S-Mt)2, which afforded air-stable gold(I) complexes. In 1–7, the gold(I) centers adopt a two-coordinated linear geometry and are structurally similar. However, their structural features and antiproliferative properties highly depend upon subtle ligand substituent changes. All complexes were validated by 1H, 13C{1H}, 31P NMR, and IR spectroscopy. The solid-state structures of 1, 2, 3, 6, and 7 were confirmed using single-crystal X-ray diffraction. A density functional theory geometry optimization calculation was used to extract further structural and electronic information. To investigate the possible cytotoxicities of 2, 3, and 7, in vitro cellular tests were carried out on the human cancerous breast cell line MCF-7. 2 and 7 show promising cytotoxicity.

Heteroleptic Silver(I) and Gold(I) N-Heterocyclic Carbene Complexes: Structural Characterization, Computational Analysis, Tyrosinase Inhibitory, and Biological Effects

“…Therefore, in our research work, we set out to explore the derivative reactions of the simplest NHC-M-Cl system to find out more about the structural features of the resulting heteroleptic metal complexes. Also, as part of an ongoing chemistry in our group exploring the bioinorganic chemistry of sulfur donor ligands, we functionalized NHC-M­(I)-Cl (M = Ag and Au) complexes with dialkylditihiophosphate and bis­(2-mercapto-1-methylimidazolyl)­borate ligands. − Sodium or potassium salts of these two ligand classes are benchtop-stable and form thermally stable metal complexes for different applications. To our best knowledge, this is the first report about the coordination of these sulfur donor ligands to the silver­(I) gold­(I) metal ions having NHC ligands. − As mentioned above, the stability of NHC complexes of silver­(I) and gold­(I) in physiological conditions is vital in their application as metallodrugs.…”

“…According to the results, while the highest and lowest inhibitory potencies were observed for the complex 3 (inhibition rate 80%) and complexes 1 and 7 (with an inhibition rate ∼27% for both complexes), respectively, other complexes showed moderate inhibitory effect against diphenolase activity of the enzyme (Table ). Complex 3 exhibited outstanding potential, which is evident from its lower IC 50 (10 μM) value compared to the standard inhibitor, kojic acid (IC 50 16 μM). ,,,− Considering that all the tested complexes have the five-membered imidazol-2-ylidene, it seems that this moiety does not play an effective role in the enzyme inhibition, and since complex 3 has close structural similarities with other complexes (particularly with complexes 1 and 2 ). It can be suggested that the metal center and the substituent type are the most determinant factors for the inhibitory potency of these series compounds.…”

“…Twenty microliters of 5 mg/mL MTT reagent was then added to each well and incubation continued for 4 h. At the end of the incubation time, the solution was removed and 100 μL of DMSO was added to each well to solve formed violet formazan crystals. Then, the plate was read at 575 nm by using an ELISA reader and cell viability percentages were finally calculated as described previously . Graphpad Prism 6.01 software (GraphPad Software Inc., San Diego, CA, USA) was used for statistical analyses by one-way ANOVA followed by Tukey’s test.…”

“…The MTT in vitro cell proliferation assay was used to evaluate the preliminary anticancer activity of the synthetic complexes 2 and 8 in accordance with our previous study. , Briefly, MCF-7 cells were harvested, counted, and seeded at 12 × 10 3 cells per well in a 96-well plate for 48 h. After that, cells were treated with different concentrations of complexes 2 and 8 and incubated for 48 h at 37 °C (with 5% CO 2 ). The compounds were first dissolved in DMSO and diluted with the medium for preparation of the stock solutions.…”