Benchmarking higher energy collision dissociation (HCD) by investigation of binding energies of gas‐phase host–guest complexes of hemicryptophane cages

Abstract

Synthesis of host molecules that feature well-defined characteristics for molecular recognition of guest molecules is often a major aim of synthetic host-guest (H-G) chemistry. A key consideration in evaluating the selectivity of hosts and the affinities of guests is the measurement of binding energies of obtained H-G complexes. In contrast to nuclear magnetic resonance (NMR) or fluorescence measurements that are capable of measuring binding strengths in solution, mass spectrometry offers the opportunity to measure gas-phase binding energies. Presented in this article is a higher energy collision dissociation (HCD) approach for determining critical energies of dissociation of H-G complexes. Experiments were performed on electrospray ionization (ESI)-generated H-G pairs in an LTQ-XL/Orbitrap hybrid instrument. The presented HCD approach requires preliminary calibration of the internal energy distribution of generated ions that was achieved by the use of activation parameters that were known from previous low-energy collision-induced dissociation (low-energy CID) experiments. Internal energy deposition was modeled based on a truncated Maxwell-Boltzmann distribution and characteristic temperature (T char ).Using this method, critical energies of dissociation were determined for 10 H-G biologically relevant complexes of the heteroditopic hemicryptophane cage host (Host). Obtained results are compared with those found previously by low-energy CID. The use of this HCD technique is relatively straightforward, although its implementation does require knowledge (or a presumption) about the Arrhenius pre-exponential factor of the complexes to obtain their critical energies of dissociation.

Bond-Dissociation Energies to Probe Pyridine Electronic Effects on Organogold(III) Complexes: From Methodological Developments to Application in π-Backdonation Investigation and Catalysis

“…This number varies for each complex and depends on E lab , on the effective collision cross section of each complex, which are determined by ion mobility experiments, and on the inelasticity coefficient (Eta) specific to each complex. This approach has the great advantage to be independent for any calculated BDE values used as references on the contrary to the model developed by Bayat et al 38 Therefore, it does not suffer from the lack of precision that may be encountered with the choice of the theoretical method to calculate thermochemistry data for the reference ion.…”

“…In a previous work, Bayat et al proposed a kinetic model, based on RRKM theory − and using MassKinetics software, to extract critical energy ( E 0 ) from HCD fragmentation curves. In this approach, a calibration of the internal energy distribution deposited during the HCD experiment is performed and a linear relationship between the average internal energy of the ions < E int > and the collision energy in the laboratory frame ( E lab ) is established for a model complex used as a reference (see the SI for more details) and for which an initial guess of its critical energy has to be made.…”