O,O′‑Diester Methylenediphosphonotetrathioate: Synthesis, Characterization, and Potential Applications

A new transformation of methylene-bis­(phosphonic dichloride) into tetrathiobisphosphonate derivatives is reported. The reaction of methylene-bis­(phosphonic dichloride) with 1,2-ethanedithiol in bromoform in the presence of AlCl3 formed methylene-bis­(1,3,2-dithiaphospholane-2-sulfide), which gave rise to O,O′-diester-methylenediphosphonotetrathioate analogues 1a–k upon reaction with phenols and alkyl alcohols in the presence of DBU. Reaction mechanisms are proposed, and all products were characterized by 31P, 13C, and 1H NMR. An X-ray crystal structure was obtained for intermediate 2. The potential of the novel scaffold for selective coordination of metal-ions was examined by coordination of Hg­(II) and Pb­(II) by 1f, as determined by FT-IR, and chelation of Zn­(II), but not Ca­(II), by 1b, as determined by 31P/1H NMR. UV–vis measurements of 1g–Ni­(II) mixture revealed a 2:1 ligand:metal complex. These derivatives are potential antioxidants, and their ability to inhibit ·OH formation in Fenton reactions was quantified by ESR measurements. Analogue 1g proved to be a most potent antioxidant (IC50 53 μM), inhibiting the Cu­(I)-catalyzed Fenton reaction at lower concentrations than GSH, ascorbic acid, and EDTA. Analogue 1c inhibited the Fe­(II)-catalyzed Fenton reaction at about the same concentrations as ascorbic acid (IC50 83 vs 93 μM). In summary, the novel compounds, 1a–k, proved to chelate various borderline/soft Lewis acid metal-ions, and may be useful as antioxidants and metal extractors.