Reductive metalation of cyclic and acyclic pseudopeptidic bis-disulfides and back conversion of the resulting diamidato/dithiolato complexes to bis-disulfides.
Cyclic and acyclic pseudopeptidic bis-disulfides built on an o-phenylene diamine scaffold were prepared: (N(2)H(2)S(2))(2), 1a, N(2)H(2)(S-SCH(3))(2), 1b, and N(2)H(2)(S-StBu)(2), 1c. Reductive metalation of these disulfides with (PF(6))[Cu(CH(3)CN)(4)] in the presence of Et(4)NOH as a base, or with (Et(4)N)[Fe(SEt)(4)] and Et(4)NCl, yields the corresponding diamidato/dithiolato copper(III) or iron(III) complex, (Et(4)N)[Cu(N(2)S(2))], 2, or (Et(4)N)(2)[Fe(N(2)S(2))Cl], 5. These complexes display characteristics similar to those previously described in the literature. The mechanism of the metalation with copper has been investigated by X-band electron paramagnetic resonance (EPR) spectroscopy at 10 K. After metalation of the bis-disulfide 1c and deprotonation of the amide nitrogens, the reductive cleavage of the S-S bonds occurs by two one-electron transfers leading to the intermediate formation of a copper(II) complex and a thyil radical. Complexes 2 and 5 can be converted back to the cyclic bis-disulfide 1a with iodine in an 80% yield. Reaction of 5 with iodine in the presence of CH(3)S-SCH(3) affords a 1/1 mixture of the acyclic N(2)H(2)(S-SCH(3))(2) disulfide 1b and cyclic bis-disulfide 1a. From 2, the reaction was monitored by (1)H NMR and gives 1b as major product. While there is no reaction of 2 or 5 with tBuS-StBu and iodine, reaction with an excess of tBuSI affords quantitatively the di-tert-butyl disulfide 1c. To assess the role of the Cu(III) oxidation state, control experiments were carried out under strictly anaerobic conditions with the copper(II) complex, (Et(4)N)(2)[Cu(N(2)S(2))], 6. Complex 6 is oxidized to 2 by iodine, and it reacts with an excess of tBuSI, yielding 1c as final product, through the intermediate formation of complex 2.
Desbenoît
Nicolas
N
Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, Université Paris Descartes, UMR 8601, CNRS, 45 rue des Saints Pères, 75270 Paris Cedex 06, France.
Galardon
Erwan
E
Frapart
Yves
Y
Tomas
Alain
A
Artaud
Isabelle
I
D000577:Amides / Q000737:chemistry*; D003300:Copper / Q000737:chemistry*; D004220:Disulfides / Q000737:chemistry*; D004578:Electron Spin Resonance Spectroscopy; D007501:Iron / Q000737:chemistry*; D009942:Organometallic Compounds / Q000737:chemistry*; D010084:Oxidation-Reduction; D057786:Peptidomimetics / Q000737:chemistry*; D013455:Sulfur / Q000737:chemistry*
D000577:Amides; D004220:Disulfides; D009942:Organometallic Compounds; D057786:Peptidomimetics; D013455:Sulfur; D003300:Copper; D007501:Iron