Fragmentation of aromatic sulfonamides in electrospray ionization mass spectrometry: elimination of SO₂ via rearrangement

Abstract

Arylsulfonamides are attractive pharmacophores for drug candidates. Fragmentation behaviors of selected aromatic sulfonamides were investigated using electrospray ionization mass spectrometry in the positive ion mode. Some of the sulfonamides afforded unique loss of 64 (loss of SO(2)) ions upon collision-induced dissociation followed by intramolecular rearrangements in the gas phase. This SO(2) elimination-rearrangement pathway leading to the generation of [M + H - SO(2)](+) ions appeared to be susceptible to substitutions on the aromatic (Ar) ring that would affect the Ar--sulfur bond strength and the stability of the partially positive charge developed at the ipso position upon bond dissociation. Electron withdrawing groups such as chlorine attached to the aromatic ring at ortho position seem to promote the SO(2) extrusion. Although this fragmentation pathway in atmospheric pressure ionization MS is less predictable than in electron impact MS, it is a frequently encountered reaction. The absence of this fragmentation pathway in some of the arylsulfonamides indicates that other factors such as nucleophilicity of the nitrogen may also play a role in the process. With respect to the site of attachment of the migrating NR'R'', ipso-substitution on the aromatic ring is evident since this fragmentation mechanism is operative in the fully ortho-substituted arylsulfonamides.

Derivatization of bisphenol A and its analogues with pyridine‐3‐sulfonyl chloride: multivariate optimization and fragmentation patterns by liquid chromatography/Orbitrap mass spectrometry

“…The former was proposed as the product ion produced by the loss of SO 2 (63.9619 u) from the ion at m/z 354.0792 via rearrangement of the sulfonyl group (Scheme 1(a)). Elimination of SO 2 via rearrangement has been previously observed in the product ion spectra of PS derivatives of estrogens,27 dansyl derivatives of some phenolic compounds,30 and some aromatic sulfonamides 31, 32…”

Fragmentation of toxicologically relevant drugs in positive‐ion liquid chromatography–tandem mass spectrometry

“…1998; Klagkou et al, 2003;Sun, Dai, & Liu, 2008). Fragments with charge-retention at the other side of the molecule, for example, ions with m/z 74 and 57 (H 3 N þ C 4 H 9 and þ C 4 H 9 ) are observed as well.…”

“…The fragment ion with m/z 377 shows secondary fragmentation involving a rearrangement in the SO 2 group, resulting in the loss of SO to a fragment ion with m/z 329 and subsequent loss of C 2 H 6 to a fragment ion with m/z 299 (see Scheme 8). The rearrangement in the SO 2 group resulting in the loss of SO is also observed and extensively studied for sulphonamide antibiotics (Niessen, 1998;Klagkou et al, 2003;Sun, Dai, & Liu, 2008). Secondary fragmentation of the 1-methylpiperazine ring (m/z 99 or 100) leads to a fragment ion with m/z 58 (C 3 H 8 N þ ).…”

Quantitation of tetramethylene disulfotetramine in human urine using isotope dilution gas chromatography mass spectrometry (GC/MS and GC/MS/MS)

“…The most abundant fragments of the native and the labeled compounds differed by 3 instead of 4 mass units, indicating that the molecular ion of the labeled compound had lost 13 C 1 . This further indicates that significant rearrangement had occurred during fragmentation, which had also been reported for compounds containing sulfones [19]. For the GC/MS/MS instrument, Fig.…”