Silver(I) complexes with hydantoins and allantoin : Synthesis, crystal and molecular structure, cytotoxicity and pharmacokinetics

Coordination polymers [Ag(L1,3)]n (L1 = hydantoin, L3 = 5,5-dimethylhydantoin), {[Ag(L2)].0.5H2O}n (L2 = 1-methylhydantoin) and [Ag(NH3)(L4)]n (L4 = allantoin) were prepared and characterized by elemental analysis, spectroscopic (IR, FTIR and NMR), thermal and mass spectrometry methods. The crystal structure of {[Ag(1-methylhydantoin)]·0,5H2O}n was determined and analyzed. Three 1-methylhydantoinate ligands create a T-shape (CN = 3) coordination sphere around the Ag+ ion. Additionally, a short Ag⋯Ag distance of 2.997 Å was found in the structure resulting in the expanded [3 + 2] environment of a distorted square shape. The [Ag(L2)] entities are bound to each other by the bridging organic ligands. Thus a two-dimensional coordination polymer is created with water molecules located between the layers. In contrast to hydantoins, the allantoin complex contains an additional ammonia molecule in the coordination sphere. Moreover, in the Ag–alla complex the M-organic ligand binding site is shifted to the N-atom of the ureid chain. Free ligands are cytotoxically inactive against human MCF-7 and A549 cancer cell lines and mouse fibroblasts Balb/3T3. The silver hydantoin complexes exhibit a very strong activity against these lines. (The introduction of the methyl groups to the ring slightly increases resistance only against the A549 cell line.) In contrast, the silver complex of allantoin shows only a weak activity which may be related to the presence of the cytotoxic ammonia group in the composition of the compound and/or the different binding site of the ligand. Calculated in silico physiochemical parameters are promising for the future application of the complexes as drugs.

Graphical AbstractThe reactions between silver(I) nitrate and hydantoin, its 1-methyl- and 5,5-dimethyl-derivatives and 5-ureidohydantoin (allantion) afforded the silver complexes (1–4). The X-ray analysis for the 1-methylhydantoin exhibited a complicated structure of the species with atypical silver CN = 3 and strong argentophilic interaction.Figure optionsDownload as PowerPoint slide