Detailed mechanistic investigation into the S-nitrosation of cysteamine

Moshood K Morakinyo; Itai Chipinda; Justin Hettick; Paul D Siegel; Jonathan Abramson; Robert Strongin; Bice S Martincigh; Reuben H Simoyi

doi:10.1139/v2012-051

Detailed mechanistic investigation into the S-nitrosation of cysteamine

Can J Chem. 2012;9(9):724-738. doi: 10.1139/v2012-051. Epub 2012 Aug 22.

Authors

Moshood K Morakinyo¹, Itai Chipinda², Justin Hettick², Paul D Siegel², Jonathan Abramson³, Robert Strongin¹, Bice S Martincigh⁴, Reuben H Simoyi⁵

Affiliations

¹ Department of Chemistry, Portland State University, Portland, OR 97207-0751, USA.
² Allergy and Clinical Immunology Branch, Health Effects Laboratory Division, National Institute of Occupational Safety and Health, Centers for Disease Control and Prevention, 1095 Willowdale Road, Morgantown, WV 26505, USA.
³ Department of Physics, Portland State University, Portland, OR 97207-0751, USA.
⁴ School of Chemistry, University of KwaZulu-Natal Westville Campus, Private Bag X54001, Durban 4000, Republic of South Africa.
⁵ Department of Chemistry, Portland State University, Portland, OR 97207-0751, USA; School of Chemistry, University of KwaZulu-Natal Westville Campus, Private Bag X54001, Durban 4000, Republic of South Africa.

Abstract

The nitrosation of cysteamine (H₂NCH₂CH₂SH) to produce cysteamine-S-nitrosothiol (CANO) was studied in slightly acidic medium by using nitrous acid prepared in situ. The stoichiometry of the reaction was H₂NCH₂CH₂SH + HNO₂ → H₂NCH₂CH₂SNO + H₂O. On prolonged standing, the nitrosothiol decomposed quantitatively to yield the disulfide, cystamine: 2H₂NCH₂CH₂SNO → H₂NCH₂CH₂S-SCH₂CH₂NH₂ + 2NO. NO₂ and N₂O₃ are not the primary nitrosating agents, since their precursor (NO) was not detected during the nitrosation process. The reaction is first order in nitrous acid, thus implicating it as the major nitrosating agent in mildly acidic pH conditions. Acid catalyzes nitrosation after nitrous acid has saturated, implicating the protonated nitrous acid species, the nitrosonium cation (NO⁺) as a contributing nitrosating species in highly acidic environments. The acid catalysis at constant nitrous acid concentrations suggests that the nitrosonium cation nitrosates at a much higher rate than nitrous acid. Bimolecular rate constants for the nitrosation of cysteamine by nitrous acid and by the nitrosonium cation were deduced to be 17.9 ± 1.5 (mol/L)^-1 s^-1 and 6.7 × 10⁴ (mol/L)^-1 s^-1, respectively. Both Cu(I) and Cu(II) ions were effective catalysts for the formation and decomposition of the cysteamine nitrosothiol. Cu(II) ions could catalyze the nitrosation of cysteamine in neutral conditions, whereas Cu(I) could only catalyze in acidic conditions. Transnitrosation kinetics of CANO with glutathione showed the formation of cystamine and the mixed disulfide with no formation of oxidized glutathione (GSSG). The nitrosation reaction was satisfactorily simulated by a simple reaction scheme involving eight reactions.

Keywords: cysteamine; kinetics; nitric oxide; nitrosation; thiols.

Abstract

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