Extending the competitive threshold collision-induced dissociation of Zn(II) ternary complexes using traveling-wave ion mobility-mass spectrometry

The competitive threshold collision-induced dissociation (TCID) of the ternary complex [amb5+Zn(II)+NTA]− → [amb5+Zn(II)]− + NTA or → [NTA+Zn(II)]− + amb5, where amb5 = His-Cys-Gly-Pro-Gly-Gly-Cys or Asp-His-Gly-Pro-Gly-Gly-Cys and NTA = nitrilotriacetic acid, were studied using traveling-wave ion mobility-mass spectrometry (TWIMMS). The analyses included calculating the reaction cross sections as a function of center-of-mass collision energy at three pressures of the argon collision gas, which covers the pressure range available in the TWIMMS instrument. The ternary complex contained one of the amb5 peptides, whose His, Cys and/or Asp substituent groups could compete with the NTA carboxylate sites for binding Zn(II). A new molecular modeling procedure was developed, initially using PM6 geometry-optimizations and thermochemical analyses to locate low-energy conformers of the ternary complex and its products that also had collision cross sections (ΩHe), measured using the ion size scaled Lennard-Jones (L-J) method, that were close to the TWIMMS measured ΩHe. A selection of these conformers were further geometry-optimized at the DFTB/3OB_D4 level of theory and using these as starting structures, molecular dynamics (MD) simulations were conducted to sample the ensemble of structures L-J ΩHe at 300 K. From these analyses, a selection of reactant and product conformers whose L-J ΩHe best matched the TWIMMS ΩHe were used in the TCID fitting of the center-of-mass energy-dependent, reaction cross sections extrapolated to zero pressure. The TCID fitting determined the threshold energies of the two product channels which in the absence of an activation barrier in excess of the energy of the products equates to the 0 K dissociation enthalpies (ΔH0). The difference in ΔH0 for the two competing reactions allowed for a relative gas-phase Zn(II) affinity scale to be constructed for the amb5 peptides studied here and from our previous published amb5 research.