Dissociative Protonation Sites:  Reactive Centers in Protonated Molecules Leading to Fragmentation in Mass Spectrometry

Abstract

It is often found in mass spectrometry that when a molecule is protonated at the thermodynamically most favorable site, no fragmentation occurs, but a major reaction is observed when the proton migrates to a different position. For benzophenones, acetophenones, and dibenzyl ether, which are all preferentially protonated at the oxygen, deacylation or dealkylation was observed in the collision-induced dissociation of the protonated molecules. For para-monosubstituted benzophenones, electron-withdrawing substituents favor the formation of RC6H4CO+ (R = substituent), whereas electron-releasing groups favor the competing reaction leading to C6H5CO+. The ln[(RC6H4CO+)/(C6H5CO+)] values are well-correlated with the sigmap+ substituent constants. In the fragmentation of protonated acetophenones, deacetylation proceeds to give an intermediate proton-bound dimeric complex of ketene and benzene. The distribution of the product ions was found to depend on the proton affinities of ketene and substituted benzenes, and the kinetic method was applied in identifying the reaction intermediate. Protonated dibenzyl ether loses formaldehyde upon dealkylation, via an ion-neutral complex of the benzyloxymethyl cation and neutral benzene. These gas-phase retro-Friedel-Crafts reactions occurred as a result of the attack of the proton at the carbon atom to which the carbonyl or the methylene group is attached on the aromatic ring, which is described as the dissociative protonation site.

Ion-neutral complexes resulting from dissociative protonation: Fragmentation of α-furanylmethyl benzyl ethers and 4-N,N-dimethylbenzyl benzyl ethers

“…Early studies showed that in dibenzyl ether, as well as in its derivatives, the oxygen atom was the thermodynamically favored site of protonation [19]. This result is in agreement with the fact that the proton affinity (PA) values of ethers (ϳ810 kJ/mol) are usually higher than those of benzenes (ϳ750 kJ/ mol) [25].…”

“…The compounds selected in this study were expected to have the particular fragmentation loss of CH 2 O, which occurs when a proton migrates from the thermodynamically favored site to the key dissociative protonation site [19,23,24]. The compounds tested were selected to be representative of different kinds of molecules, including (1) ␣-aromatic heterocycle methyl benzyl ethers, and (2) substituted-benzyl benzyl ethers.…”

“…However, the loss of 30 Da in molecular mass, which has been confirmed by FTICR-MS/MS to result from the loss of CH 2 O, cannot be rationalized without invoking skeletal rearrangements before the fragmentation. In this study, we propose a similar ion-neutral complex intermediate involved mechanism that is based on the mechanism of CH 2 O loss from dibenzyl ether [19]. In the mechanism, the proton is transferred from O to C on the skeleton via a 1,3-H shift, and then an ion-neutral complex intermediate is formed as the result of C-C bond elongation.…”

“…Recently, a pathway involving an ion-neutral complex intermediate has been proposed by one of us to explain the loss of a CH 2 O molecule from protonated dibenzyl ether under collision-induced dissociation (CID) conditions [19]. This dissociation is completely different from the rearrangement process involving the difficult formation of a C ␤ -C ␤ bond between two phenyl rings that was reported earlier by Kingston et al [22].…”

Ammonia elimination from protonated nucleobases and related synthetic substrates

“…The amino group is not the best protonation site for the nucleobases and the model systems, and we have to discuss how the amino group can serve as the dissociative protonation site [46] or consider alternative mechanisms for ammonia elimination. Some guidance is provided by the emerging understanding of NH 3 elimination from peptides [47].…”