Intercluster Reactions Show That (CH3)2S+CH2CO2H is a Better Methyl Cation Donor Than (CH3)3N+CH2CO2H

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 NG-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+.