Competing Noncovalent Host-guest Interactions and H/D Exchange: Reactions of Benzyloxycarbonyl-Proline Glycine Dipeptide Variants with ND₃

Abstract

A combination of density functional theory calculations, hydrogen/deuterium exchange (HDX) reactions, ion mobility-mass spectrometry, and isotope labeling tandem mass spectrometry was used to study gas-phase "host-guest" type interactions of a benzyloxycarbonyl (Z)-capped proline (P) glycine (G) model dipeptide (i.e., Z-PG) and its various structural analogues with ND3. It is shown that in a solvent-free environment, structural differences between protonated and alkali metal ion (Na(+), K(+), or Cs(+))-complexed species of Z-PG affect ND3 adduct formation. Specifically, [Z-PG + H](+) and [Z-PG-OCH3 + H](+) formed gas-phase ND3 adducts ([Z-PG (or Z-PG-OCH3) + H + ND3](+)) but no ND3 adducts were observed for [Z-PG + alkali metal](+) or [Z-PG + H - CO2](+). Experimentally measured and theoretically calculated collision cross sections (CCSs) of protonated and alkali metal ion-complexed Z-PG species showed similar trends that agreed with the observed structural differences from molecular modeling results. Moreover, results from theoretical ND3 affinity calculations were consistent with experimental HDX observations, indicating a more stable ND3 adduct for [Z-PG + H](+) compared to [Z-PG + alkali metal](+) species. Molecular modeling and experimental MS results for [Z-PG + H](+) and [Z-PG + alkali metal](+) suggest that optimized cation-π and hydrogen bonding interactions of carbonyl groups in final products are important for ND3 adduct formation. Graphical Abstract ᅟ.

Automated peak width measurements for targeted analysis of ion mobility unresolved species

“…Helium (He) gas pressure readout for the helium cell (used for collisional cooling prior to entrance to the IM cell [22]) was ~1.4 bar. All reported gas pressures were from direct instrument readouts and have not been corrected for chemical sensitivity or geometry factors [46][47][48]. potential difference between the exit of the IM cell and entrance of the transfer cell.…”

“…Ions were generated externally using ESI (flow rate of ~ 5 µL min -1 ) operated in positive-ion mode (capillary voltage of 3.5 kV). Ions generated during ESI were transferred via a quadrupole ion guide to a hexapole accumulation cell [47]. After 4 seconds of accumulation, trapped ions were transferred from the accumulation hexapole to the ICR cell via a transfer hexapole.…”