Fragmentation reactions of protonated α,ω‐diamino carboxylic acids: The importance of functional group interactions

Abstract

Protonated members of a homologous series of biologically significant α,ω‐diamino carboxylic acids were subjected to collision induced dissociation (CID). The resulting fragmentation patterns were studied using isotopic labeling, quantum mechanical computations, and pseudo MS3 experiments conducted primarily on an ion trap mass spectrometer. Each protonated α,ω‐diamino acid showed a primary neutral loss of either ammonia or water; a clear explanation was developed for the observed variation of the two losses within the series. Protonated 2,3‐diaminopropanoic acid, 2,4‐diaminobutanoic acid, and 2,7‐diaminoheptanoic acid gave secondary losses of water, carbon monoxide, and a loss of water plus carbon monoxide, respectively. In the parallel pathways characterized for the fragmentations of protonated ornithine and lysine, the α‐nitrogen of the diamino acid was maintained in the cyclic iminium product formed by successive losses of NH3 and (H2O + CO), whereas the side‐chain nitrogen was retained by consecutive losses of H2O and (CO, NH3). The 1‐piperideine ion from protonated lysine was fragmented further, losing ethylene from carbons 4 and 5. Protonated 2,6‐diaminopimelic acid fragmented by analogous reactions. Detailed mechanistic schemes for the fragmentation of both protonated 2,3‐diaminopropanoic and ornithine were generated from MP2/DFT computations. This work highlights the participation of the side‐chain amino group, which distinguishes the gas‐phase chemistry of protonated α,ω‐diamino acids from the well‐documented fragmentation reactions of protonated α‐amino acids bearing a hydrogen atom or an alkyl side chain. In general, the results further illustrate the importance of intramolecular separations affecting the specific interactions between functional groups leading to the fragmentation of multifunctional ions.

Intramolecular interactions and the neutral loss of ammonia from collisionally activated, protonated ω-aminoalkyl-3-hydroxyfurazans

“…Upon MS/MS, the prominent loss of the side chain nitrogen from OrnH + and LysH + was confirmed by isotopic labeling, and computations showed that the nucleophilic displacement of the protonated, side chain amino group by the α-amino group of OrnH + to form a favorable five-membered ring was feasible. 38 …”

“…Upon MS/MS, the prominent loss of the side chain nitrogen from OrnH + and LysH + was confirmed by isotopic labeling, and computations showed that the nucleophilic displacement of the protonated, side chain amino group by the α-amino group of OrnH + to form a favorable five-membered ring was feasible. 38 In the current investigation, a reasonable energy (174 kJ mol -1 ) was computed for the cyclic five-membered transition structure TS3a(ol)-3b(ol) formed upon loss of ammonia from the most stable conformation of 3a(ol) (Figure 4(a)). This displacement of ammonia from the aminopropyl side chain by N5 in the ring of 3a is analogous to the process characterized for OrnH + (computed barrier = 153 kJ mol -1 ).…”

“…Accurate masses were measured on a Bruker Daltonic Compact QToF spectrometer. 38 The energetics of fragmentation processes were computed using DFT and Møller-Plesset perturbation theory (MP2) within the Gaussian 09 suite of programs (Revision C.01). 40 Geometry optimizations and frequency calculations were performed using the ωB97X-D/6-311 + G(d) functional.…”

“…Gas phase ions were generated by positive-ion electrospray (ESI(+)) and mass spectra were acquired on Thermo-Finnigan LCQ-DUO ion trap and Micromass Quattro triple quadrupole mass spectrometers. Instrument settings 38 , 39 are provided in the supplemental material (Tables S1 and S2). Pseudo MS 3 spectra and precursor-ion scans were acquired after an ion (e.g.…”

“…37 Note that protonation of the primary amino group created structural connections matching the structure of ammonia. 37 The loss of ammonia from the terminal position of an aliphatic chain has been documented for several protonated, structural analogs, such as diaminoalkanes, 42 diamino, dicarboxylic acids, 38,42 aminoalcohols, 43 muscimol, an aminomethyl substituted hydroxyisoxazole, [44][45][46] and amlodipine, an aminoethoxymethyl substituted dihydropyridine calcium channel blocker. 47,48 In particular, the structures of both tautomers of the 3-hydroxyfurazans 3a and 4a closely resemble the structures of the monoprotonated forms of the common, naturally occurring diamino acids ornithine (OrnH + ) and lysine (LysH + ) (Figure 3).…”