The cysteine radical cation: structures and fragmentation pathways

Abstract

A theoretical study on the structures, relative energies, isomerization reactions and fragmentation pathways of the cysteine radical cation, [NH₂CH(CH₂SH)COOH]˙⁺, is reported. Hybrid density functional theory (B3LYP) has been used in conjunction with the 6-311++G(d,p) basis set. The isomer at the global minimum, Captodative-1, has the structure NH₂C˙(CH₂SH)C(OH)₂⁺; the stability of this ion is attributed to the captodative effect in which the NH₂ functions as a powerful π-electron donor and C(OH)₂⁺ as a powerful π-electron acceptor. Ion Distonic-S-1, H₃N⁺CH(CH₂S˙)COOH, in which the radical is formally situated on the S atom, is higher in enthalpy (ΔH°₀) than Captodative-1 by 6.1 kcal mol^–1, but is lower in enthalpy than another isomer Distonic-C-1, H₃N⁺C˙(CH₂SH)COOH, by 8.2 kcal mol^–1. Isomerization of the canonical radical cation of cysteine, [H₂NCH(CH₂SH)COOH]˙⁺, (Canonical-1), to Captodative-1 has an enthalpy of activation of 25.8 kcal mol^–1, while the barrier against isomerization of Canonical-1 to Distonic-S-1 is only 9.6 kcal mol^–1. Two additional transient tautomers, one with the radical located at C_α and the charge on SH₂, and the other a carboxy radical with the charge on NH₃, are reported. Plausible fragmentation pathways (losses of small molecules, CO₂, CH₂S, H₂S and NH₃, and neutral radicals COOH˙, HSCH₂˙ and NH₂˙) from Canonical-1 are examined.