Modeling of the gas‐phase ion chemistry of protonated arginine

Abstract

Arginine is often involved at the C-terminus of peptides obtained from tryptic digests of proteins. The very basic guanidine group of the side-chain of arginine has a large effect on the backbone fragmentation of protonated peptides. Furthermore, arginine exhibits specific fragmentation reactions involving its side-chain. Various tautomerization states, conformers and side-chain dissociation channels of protonated arginine were studied using theoretical methods. The guanidine loss of protonated arginine is proved to be an S(N)2 substitution on the delta-carbon of the side-chain, starting from species containing the N(epsilon)H-C(+)(N(eta)H(2))(N(eta')H(2)) or -N(epsilon) (+)H(2)-C(N(eta)H)(N(eta')H(2)) moieties and leads to formation to either protonated guanidine or protonated proline. In the corresponding transition structures the proline moiety is protonated. Under low-energy collision conditions the extra proton transfers to the guanidine moiety, leading to the formation of C(+)(NH(2))(3). On the other hand, the lifetime of the fragmenting species under high-energy collision conditions is shorter, resulting in enhanced formation of protonated proline and its dissociation products. The first step of ammonia loss is the leaving of a preformed NH(3) from tautomers containing the -N(epsilon)H-C(N(eta)H(3) (+))(N(eta')H) or -N(epsilon)-C(N(eta)H(3) (+))(N(eta')H(2)) moieties. The resulting protonated carbodiimide group can be stabilized by intramolecular nucleophilic attack, leading to ring formation. Overall, reactions involved in the ammonia loss from protonated arginine can be considered as an S(N)1 substitution on the central zeta-carbon of the guanidine group.

Fragmentation of protonated dipeptides containing arginine. Effect of activation method

“…One notes, for example, the elimination of HNCO to form m/z 172; this fragmentation route implies a cyclization on loss of NH 3 involving a carbonyl oxygen. (We assume that NH 3 loss occurs from the guanidino group, as observed for protonated arginine [27,28]. The m/z 172 ion is a major product in the fragmentation of the [MH Ϫ NH 3 ] ϩ ions in the quadrupole ion trap ( Figure 5), although we cannot confirm that this also represents loss of HNCO.…”

“…A particularly noteworthy fragmentation product is that observed at m/z 100 ([C 3 H 6 N 3 O] ϩ ) for the [MH Ϫ NH 3 ] ϩ ion derived from Gly-Arg. A plausible pathway to this product is presented in Scheme 4, where we assume that the loss of NH 3 from MH ϩ is accompanied in part by cyclization involving the amide nitrogen, similar to the cyclization described by Paizs and coworkers [27] in their modeling of the fragmentation of protonated arginine. We also have assumed that the neutral product of 115 Da is proline.…”

A study of b1+H2O and b1-ions in the product ion spectra of dipeptides containing N-terminal basic amino acid residues

“…If the imine has a higher proton affinity than the departing acid, the ated lysine in KV. This was unexpected since the highly resonance-stabilized protonated guanidinyl group, with additional stabilization by hydrogen bonds to the ␣-amino and carbonyl groups that effectively sequesters the proton, should fragment at higher°energy° [33]. …”

Ammonia elimination from protonated nucleobases and related synthetic substrates

“…The "mobile proton model" holds that intramolecular proton migration to various protonation sites can occur before fragmentation. In cases with impediments to proton mobility [48], the ammonia elimination might occur as the result of complex mechanisms [49,50]. Hence, the potential energy surfaces of the protonated systems were explored to search for and to determine the energy profiles of paths for proton migration leading to the formation of ammonium ions.…”