Silver(I) compounds of the anti-inflammatory agents salicylic acid and p-hydroxyl-benzoic acid which modulate cell function

•Synthesis and characterization of three silver(I) complexes•Silver complexes' interaction with CT-DNA•Intermolecular hydrogen bonds lead to stronger interaction with CT-DNA.•The cone angle of the arylphosphines affects the cytotoxicity of the complexes.

Silver nitrate reacts with salicylic acid (salH2) or p-hydroxy-benzoic acid (p-HbzaH2) and equimolar amount of NaOH to yield a white precipitations which are then treated with tri(p-tolyl)phosphine (tptp) or tri(m-tolyl)phosphine (tmtp) to yield the complexes [Ag(tptp)2(salH)] (1), [Ag(tptp)2(p-Hbza)] (2) and [Ag(tmtp)2(salH)] (3). Complexes 1 and 3 are also obtained when aspirin (aspH) is used. The acetic ester of salicylic acid is hydrolyzed to form the complexes 1 and 3. However, when aspirin and tptp are used, a mixture of products was obtained which contains both 1 and an ionic complex of formula {[Ag(tptp)4]+[(salH)−]∙[(CH3)2NCHO)]∙(H2O)} (1a). The complexes were characterized by m.p., e.a., mid-FT-IR, 1H-,31P-NMR, HRMS, UV–vis spectroscopic techniques and X-ray crystallography. Two phosphorus and one carboxylic oxygen atoms form a trigonal planar geometry around Ag(I) ions in complexes 1–3. Complex 1a consists of a [Ag(tptp)4]+ cation and a deprotonated salH− counter anion. The influence of 1–3 on the viability of MCF-7 (breast) and HeLa (cervix) adenocarcinoma cells, is evaluated. DNA binding tests indicate the ability of 1–3 to modify the activity of cells. The binding constants of 1–3 towards calf-thymus DNA, reveal stronger interaction of 2. Changes in fluorescent emission light of ethidium bromide (EB) in the presence of DNA suggest intercalation or electrostatic interactions into DNA for 1 and 3. Docking studies on DNA-complex interactions confirm the binding of 1–3 in the minor groove of B-DNA. Moreover, the influence of 1–3 on the peroxidation of linoleic acid to hydroperoxylinoleic acid by the enzyme lipoxygenase (LOX) was kinetically and theoretically studied.

Graphical abstractMixed ligand silver(I) complexes of carboxylic acid: Salicylic (drug against pain and fever) and 4-hydroxybenzoic acid (antioxidant agent) with formulae [Ag(tptp)2(salH)] (1), [Ag(tptp)2(p-Hbza)] (2) and [Ag(tmtp)2(salH)] (3) (tptp = tri(p-tolyl)phosphine, tmtp = tri(m-tolyl)phosphine) were evaluated for their binding properties towards CT-DNA and the results are compared with their in vitro cytotoxicity.Figure optionsDownload full-size imageDownload as PowerPoint slide