DFT and Mass Spectrometry Study of (−)ESI-Induced Fragmentation of the Highly Toxic Rodenticide Tetramethylenedisulfotetramine

The toxic heteroadamantane rodenticide, tetramethylenedisulfotetramine (TETS, C4H8N4O4S2; 240 g/mol), undergoes an unusual in-source condensation reaction and ionization process when ionized by (−)electrospray ionization (ESI) under acidic conditions. TETS either condenses to hexamethylenetrisulfohexamine (HEXS, C6H12N6O6S3; 360 g/mol), which is protonated in the acidic mobile phase prior to losing a methylene group, or [M + H – CH2]− where M = HEXS, to form the precursor ion at m/z 347, or directly forms the precursor ion m/z 227, [M + H – CH2]− where M = TETS. Experimental and computational data suggest that the precursor ions are formed in the microdroplet rather than through gas-phase collision-induced dissociation. Here, potential mechanisms of the ionization pathways of TETS, HEXS, and hexamethylenetetramine (HMT), a related heteroadamantane with no sulfonyl moieties, within the ESI source were investigated with density functional theory. The quantum theory of atoms in molecules, interacting quantum atoms, and fragment energy methods were applied to rationalize activation barriers. Results suggest that the proposed pathways could be achieved on the ESI microdroplet time scale (∼10 μs) for TETS and HEXS, which had similar activation energies, but not for HMT. LC/MS/MS experiments were also performed to consider the effect of instrument parameters on fragmentation. The capillary voltage was the only parameter tested that statistically significantly affected the formation of m/z 347 relative to m/z 227, suggesting that capillary voltage is an important contributor to the condensation reaction rather than ionization rates.