Rationalizing the formation of quasi-molecular anions due to tautomerization of chloroquine-cinnamide hybrid molecule during analysis by electrospray ionization (ESI) – mass spectrometry (MS) and through density functional theory (DFT) calculations

Abstract

Molecules that contain amide groups often have interesting biological and pharmacological properties. However, analysing these molecules using electrospray ionization (ESI) - mass spectrometry (MS) can be a challenging scientific endeavour due to their chargeability, particularly in negative ESI mode. In this study, a newly synthesized anti-malarial compound, N-(2-((6-chloronaphthalen-1-yl) amino) ethyl) cinnamamide, and its structural analogues were observed to generate strong quasi-molecular anions during ESI-MS, despite not being predisposed to anion formation based on their structural configuration. To uncover the mechanism underlying this anion formation, density functional theory calculations were performed, revealing that the formation of the anions is attributed to the imidic tautomer generated at the ESI chamber/probe's ion source. This leads to ionization occurring on the newly formed OH resulting from the enolization of the imidic form of the molecule.