Amazing stability of phosphate-quaternary amine interactions

Abstract

We have previously used MALDI mass spectrometry to highlight ammonium- or guanidinium-aromatic interactions via cation-pi bonding and ammonium- or guanidinium-phosphate interactions through salt bridge formation. In the present work, the gas-phase stability and dissociation pathways of the interaction between phosphorylated peptides and compounds containing quaternary amines are demonstrated using electrospray ionization mass spectrometry. The presence of one quaternary amine in a compound is enough to form a noncovalent complex with a phosphorylated residue. However, if two quaternary amines are present in one molecule, the electrostatic interactions of the quaternary amines with the phosphate results in a "covalent-like" stability, and these bonds can withstand fragmentation by collision-induced dissociation at energies similar to those that fragment covalent bonds. Such interactions are important in accounting for physiological, pathophysiological, and pharmacological effects of many therapeutic compounds and small molecules containing quaternary amines or phosphates.

Figure 1

Chem 3D molecular models of hexamethonium, decamethonium, and succinylcholine.

Figure 2

(a) ESI spectrum of the NCX formed between ACH and each A3pXA3 peptide. (b) MSMS of the NCX of ACH-A3pSA3 at m/z 756, CE = 15 V.

Figure 3

(a) ESI spectrum of the NCX formed between DCM and each A3pXA3 peptide. (b) MSMS of the NCX of DCM-A3pSA3 at m/z 868, CE = 30 V. (c) MSMS of the NCX of DCM-A3pTA3 at m/z 882, CE = 30 V. (d) MSMS of the NCX of DCM-A3pYA3 at m/z 944, CE = 30 V.