Competing noncovalent host-guest interactions and H/D exchange: reactions of benzyloxycarbonyl-proline glycine dipeptide variants with ND3.
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.
Department of Chemistry and Biochemistry, Baylor University, Waco, TX, 76706, USA.
Mahsan
M
Miladi
Department of Chemistry and Biochemistry, Baylor University, Waco, TX, 76706, USA.
Abayomi D
AD
Olaitan
Department of Chemistry and Biochemistry, Baylor University, Waco, TX, 76706, USA.
Behrooz
B
Zekavat
Department of Chemistry and Biochemistry, Baylor University, Waco, TX, 76706, USA. Touradj_Solouki@baylor.edu.
Touradj
T
Solouki
D000641:Ammonia / Q000737:chemistry*; D041961:Deuterium Exchange Measurement / Q000379:methods*; D004151:Dipeptides / Q000737:chemistry*; D005998:Glycine / Q000737:chemistry*; D008958:Models, Molecular; D011392:Proline / Q000031:analogs & derivatives* / Q000737:chemistry; D021241:Spectrometry, Mass, Electrospray Ionization
D004151:Dipeptides; C506055:benzyloxycarbonylproline; D000641:Ammonia; D011392:Proline; D005998:Glycine
Adduct formation; H/D exchange; Host-guest; Ion mobility; Ion-molecule reactions