Fluorinated Phenyl Sulfate Derivatives as Advanced Thermometer Anions for Electrospray Ionization Tandem Mass...

To achieve a more accurate evaluation of the internal energy distributions of ions activated by collision-induced dissociation (CID) in the collision cell, fluorine-containing phenyl sulfates were systematically screened by calculating their dissociation energies using quantum chemical calculations at the DLPNO-CCSD(T)/CBS//ωB97X-D/def2-TZVPPD level of theory. Fluorine substitution at the ortho- and meta-positions of phenyl sulfate lowers the dissociation energy, thereby promoting dissociation. In contrast, fluorine substitution at the para position has little effect on the dissociation energy. Although para-trifluoromethyl substitution reduces the dissociation energy, it significantly decreases the dissociation rate. Notably, despite the reduced dissociation energy upon para-trifluoromethyl substitution, 4-trifluoromethyl phenyl sulfate exhibits the strongest resistance to dissociation owing to its markedly slower dissociation rate. The experimentally observed dissociation behavior showed good agreement with the dissociation energies predicted by quantum chemical calculations. These fluorine-containing phenyl sulfates, which predominantly generate a single fragment ion due to sulfur trioxide loss, were experimentally demonstrated to be suitable thermometer ions for characterizing the internal energy distributions of ions produced by CID-activated ions. By enabling systematic control of the dissociation energy through fluorine substitution patterns, this approach allows more accurate determination of internal energy distributions of CID-activated ions. The reported method provides a useful strategy for determining optimal voltages in negative electrospray ionization and subsequent tandem mass spectrometric analysis of acidic analyte molecules.