title: O,O'-Diester methylenediphosphonotetrathioate: synthesis, characterization, and potential applications.
abstract: 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 AlCl(3) 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 (31)P, (13)C, and (1)H 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 (31)P/(1)H 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 (IC(50) 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 (IC(50) 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.
authors.affiliation: Department of Chemistry, Bar-Ilan University, Ramat-Gan 52900, Israel.
authors.forename: Aviran
authors.initials: A
authors.lastname: Amir
authors.forename: Alon H
authors.initials: AH
authors.lastname: Sayer
authors.forename: Rostislav
authors.initials: R
authors.lastname: Zagalsky
authors.forename: Linda J W
authors.initials: LJ
authors.lastname: Shimon
authors.forename: Bilha
authors.initials: B
authors.lastname: Fischer
mesh_terms: D000475:Alkenes / Q000138:chemical synthesis* / Q000737:chemistry*; D000975:Antioxidants / Q000737:chemistry*; D002384:Catalysis; D002614:Chelating Agents / Q000737:chemistry*; D003300:Copper / Q000737:chemistry*; D018360:Crystallography, X-Ray; D007477:Ions / Q000737:chemistry*; D058116:Lewis Acids / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008670:Metals / Q000737:chemistry*; D015394:Molecular Structure; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis* / Q000737:chemistry*
chemical_list: D000475:Alkenes; D000975:Antioxidants; D002614:Chelating Agents; D007477:Ions; D058116:Lewis Acids; D008670:Metals; C583343:O,O'-diester methylenediphosphonotetrathioate; D013438:Sulfhydryl Compounds; D003300:Copper