Antiplasmodial Drugs in the Gas Phase: A CID and DFT Study of Quinolon-4(1H)-Imine Derivatives

Abstract

The gas-phase behavior of 12 quinolon-4(1H)-imine derivatives with antiplasmodial activity was investigated using electrospray ionization tandem mass spectrometry together with collision induced dissociation and density functional theory (DFT) calculations. The most probable protonation site was predicted by calculating the proton affinity (PA) values for each possible protonation site and it was found to be the imine nitrogen for all compounds under study. Fragmentation pathways of the protonated molecules were proposed and the assignment of product ion structures was performed taking into account theoretical calculations. The nature of the quinoline substituent was found to influence the gas-phase behavior of the compounds under study. The data acquired allowed to bracket the proton affinity of the quinolin-4-imine scaffold, which can be a useful starting point to choose appropriate references for determining PA values of this scaffold.

Protonation Sites, Tandem Mass Spectrometry and Computational Calculations of o-Carbonyl Carbazolequinone Derivatives

“…However, given that the above calculations were carried out without considering the activation of the ion, it is possible that additional proton migration, induced by collisions, can occur following the initial protonation step [ 63 ].…”