A comprehensive study on rearrangement reactions in collision-induced dissociation mass spectrometric fragmentation of protonated diphenyl and phenyl pyridyl ethers.

Abstract

Recently, we have reported a forced degradation study of a pharmaceutical drug regorafenib which contains a phenyl pyridyl ether derivative as building block. We observed interesting rearrangements in two of its degradation products in tandem mass spectrometry (MS/MS) experiments. As diphenyl ether derivatives are also molecular building blocks of biological importance and used as herbicides and flame retardants, we decided to investigate specifically the fragmentation behavior of these compounds along with phenyl pyridyl derivatives in detail using high-resolution electrospray ionization (ESI) MS/MS. To understand the fragmentation reactions of protonated substituted diphenyl ethers and phenyl pyridyl ethers, ESI-MS/MS experiments were performed using a quadrupole time-of-flight (QTOF) mass spectrometer. In contrast to radical cations of diphenyl ether derivatives which do not eliminate CO, the [M + H]+ ions of substituted diphenyl ethers undergo rearrangement reactions after loss of neutral molecules (H2 O, HCl, etc.) to form a bicyclic structure containing a keto group and do eliminate CO. Similar rearrangement followed by fragmentation was observed for protonated phenyl pyridyl ethers and the degradation products formed from regorafenib and sorafenib. The protonated ions of substituted diphenyl ethers and phenyl pyridyl ethers on collision-induced dissociation have exhibited interesting rearrangement reactions, despite the nature of the substituent on both the aryl moieties. The proposed fragmentation patterns of these compounds give an insight into the understanding of gas-phase reactions in mass spectrometric studies of diphenyl ether and phenyl pyridyl ether derivatives.