Gas phase reactions of cysteine with charged electrophiles: Regioselectivities of the dimethylchlorinium ion and the methoxymethyl cation

The gas phase reactions of cysteine with the dimethylchlorinium ion, (CH3)(2)Cl+, and the methoxymethyl cation, CH3OCH2+, have been studied by using chemical ionization tandem mass spectrometry (CI/MS/MS). The structures of the [M + CH](+) and [M + CH3](+) ions in the CH3Cl CI plasma and the [M + CH](+), [M + CH3](+), and [M + CH3OCH2](+) ions formed in the (CH3)(2)O CI plasmas have been probed by using MS/MS techniques. Where possible, these MS/MS spectra were compared to those generated for ions of known structure (i.e., the [M + H](+) ions of N-methylcysteine, S-methylcysteine, cysteine methyl ester, and (R)-thiozolidine-4-carboxylic acid, which were produced under isobutane CI conditions). Structure assignment of the [M + CH3](+) ions was also facilitated via the use of labeled cysteine, H2NCH(CD2SH)CO2H, and via qualitative comparison of MS3 spectra of the immonium and episulfonium ions, [M + CH3 - ROH - CO](+) and [M + CH3 - NH2R](+), respectively, where R = H or CH3, with those of the standard compounds. Taken together, the experimental data suggest that the regioselectivity for the formation of the [M + CH3](+) ions is very different for the two methyl cation donors (CH3OCH2+ and (CH3)(2)Cl+). For the case of the dimethylchlorinium ion, the data reveal that methylation occurs at all sites, with the degree of methylation at each site following the order N > S > O. In constrast, the degree of methylation at each site follows the order S > N > O for the methoxymethyl cation, Furthermore, the structures of various [M + CH3](+) and [M + CH](+) ions derived from cysteine has been modeled by using ab-initio calculations at the MP2(FC)/6-31G*//HF/6-31G* level of theory, It was found that the ab-initio stability order for the [M + CH3](+) ions is N > S > O of C=O group > O of OH group, while the most stable [M + CH](+) ion was found to be N-protonated (R)-thiozolidine-4-carboxylic acid.