A general mechanism for the oxidative cleavage of amine disulfides and cystine in aqueous iodine. Isolation of cyclic sulfinamides

Abstract

When disulfides are cleaved by aqueous iodine, neighboring group participation facilitates the rate of reaction and the formation of cyclized products. The series of bis-disulfides [X(CH2)3S]2 was prepared, X = N(CH3)2, 1, NH2, 2, N(CH3)3+, 3, as well as [NH2(CH2)4S]2, 4. The tertiary amine, 1, is oxidized by aqueous I2 at a rate which is accelerated by as much as 106 over the rate of reaction of the quaternary ammonium iodide salt 3. The oxidation products of 1 are the sulfinic and sulfonic acids while 3 yields the sulfonic acid. Aqueous iodine reacts with the primary amines 2 and 4 at moderately accelerated rates to give the cyclic sulfinamides, isothiazolidine 1-oxide from 2 and tetrahydro-1,2-thiazine 1-oxide from 4. This oxidative cyclization reaction is the most direct route to these cyclic sulfinamides. At a given pH, the rate law for the oxidation of 1 and 2 is -d[RSSR]/dt = -fe[RSSR][y. At high pH, compound 4 has the same rate law. The kinetic data for 4 at low pH and for 3 resemble those reported in a classical study of the aqueous iodine oxidative cleavage of cystine.2 The kinetics and mechanisms of these reactions will be discussed.

Synthesis of Guanosine and Deoxyguanosine Phosphoramidites with Cross-Linkable Thioalkyl Tethers for Direct Incorporation into RNA and DNA

“…Synthesis of the tert -butyl disulfide protected thiopropylamine hydrochloride ( 10 ) is shown in Scheme 2 and starts with treatment of 3-chloropropylammonium chloride ( 11 ) with sodium thiosulfate to give 12 , followed by treatment with I 2 to give 13 , as described by Doi and Musker 36. We find that purification of the crude disulfide ( 13 ) using a falling film distillation apparatus with toluene as the refluxing solvent gives a much better yield (80%) than standard vacuum distillation.…”

Preparation of DNA and RNA Fragments Containing Guanine N2‐Thioalkyl Tethers

“…Carry out all operations involving organic solvents and reagents in a wellventilated fume hood, with appropriate personal protective equipment (at minimum, safety glasses, and gloves). 3-chloropropylammonium chloride (S.1) is reacted with sodium thiosulfate, followed by treatment with iodine, to give S.2 (Doi and Musker, 1985). The free thioalkylamine (S.3) is obtained by treating S.2 with dithiothreitol (DTT).…”

“…The preparation of S.4 is shown in Figure 1. The first step is reaction of 3chloropropylammonium chloride (S.1) with sodium thiosulfate followed by treatment with iodine to give S.2 (Doi and Musker 1985). A falling film distillation apparatus with toluene as the refluxing solvent gives S.2 in a yield of about 80%, which is much better than the yield from standard distillation.…”

Dissociation of copper(ii) ternary complexes containing cystine

“…8 In solution, disulfide bonds in organic compounds are fragile and easily broken when attacked by nucleophiles CN À and SCN À , or by electrophiles such as metal ions Cu 2+ , Co 2+ and Ni 2+ . 9 The situation is more complicated in cystine-containing peptides where competition from other functional groups, including COO À , NH 2 and amide oxygens, decreases the interaction between a metal ion and the disulfide bond. [9][10][11][12][13][14] Introduction of metal ion/cystine-containing peptide complexes into the gas phase can readily be achieved using electrospray ionization mass spectrometry.…”

“…9 The situation is more complicated in cystine-containing peptides where competition from other functional groups, including COO À , NH 2 and amide oxygens, decreases the interaction between a metal ion and the disulfide bond. [9][10][11][12][13][14] Introduction of metal ion/cystine-containing peptide complexes into the gas phase can readily be achieved using electrospray ionization mass spectrometry. Disulfide-containing peptides complexed with a divalent transition metal ion such as Zn 2+ , Ni 2+ and Cu 2+ 15,16 have been shown to give significant amounts of cleavage of the disulfide bridge (either by breaking the S-S or C-S bond) using sustained off-resonance irradiation collision-induced dissociation (SORI-CID).…”