Proton hydrates as soft ion/ion proton transfer reagents for multiply deprotonated biomolecules

Ion/ion proton transfer from protonated strong gaseous bases such as pyridine and 1,8-bis(dimethylamino)naphthalene (i.e., the proton sponge), to multiply charged anions derived from a sulfated pentasaccharide drug, Arixtra™, gives rise to extensive fragmentation of the oligosaccharide. This drug serves as a model for sulfated glycosaminoglycans, an important class of polymers in glycobiology. The extent of fragmentation appears to correlate with the proton affinity of the molecule used to transfer the proton, which in turn correlates with the reaction exothermicity. Consistent with tandem mass spectrometry results, anions with sodium counter-ions are more stable with respect to fragmentation under ion/ion proton transfer conditions than ions of the same charge state with protons counter-ions. Proton hydrates were found to give rise to much less anion fragmentation and constitute the softest protonation agents thus far identified for manipulating the charge states of multiply charged biopolymer anions. The reaction exothermicities associated with proton hydrates comprised of five or more water molecules are lower than that for protonated proton sponge, which is among the softest reagents thus far examined for ion/ion proton transfer reactions. The partitioning of ion/ion reaction exothermicity among all of the degrees of freedom of the products may also differ for proton hydrates relative to protonated molecules. However, a difference in energy partitioning need not be invoked to rationalize the results reported here.