Intercluster Reactions Show That (CH 3 ) 2 S + CH 2 CO 2 H is a Better Methyl Cation Donor Than (CH 3 ) 3 N + CH 2 CO 2 H

Abstract

The intrinsic methylating abilities of the known biological methylating zwitterionic agents, dimethylsulfonioacetate (DMSA), (CH₃)₂S⁺CH₂CO₂⁻ (1) and glycine betaine (GB), (CH₃)₃N⁺CH₂CO₂⁻ (2), have been examined via a range of gas phase experiments involving collision-induced dissociation (CID) of their proton-bound homo- and heterodimers, including those containing the amino acid arginine. The relative yields of the products of methyl cation transfer are consistent in all cases and show that protonated DMSA is a more potent methylating agent than protonated GB. Since methylation can occur at more than one site in arginine, the [M + CH₃]⁺ ion of arginine, formed from the heterocluster [DMSA + Arg + H]⁺, was subject to an additional stage of CID. The resultant CID spectrum is virtually identical to that of an authentic sample of protonated arginine-O-methyl ester but is significantly different to that of an authentic sample of protonated N^G-methyl arginine. This suggests that methylation has occurred within a salt bridge complex of [DMSA + Arg + H]⁺, in which the arginine exists in the zwitterionic form. Finally, density functional theory calculations on the model salts, (CH₃CO₂⁻)[(CH₃)₃S⁺] and (CH₃CO₂⁻)[(CH₃)₄N⁺], show that methylation of CH₃CO₂⁻ by (CH₃)₃S⁺ is both kinetically and thermodynamically preferred over methylation by (CH₃)₄N⁺.