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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 (Tchar). 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. [ABSTRACT FROM AUTHOR]

A low-energy collision induced dissociation (CID) (low-energy CID) approach that can determine both activation energy and activation entropy has been used to evaluate gas-phase binding energies of host-guest (H-G) complexes of a heteroditopic hemicryptophane cage host (Zn (II)@1) with a series of biologically relevant guests. In order to use this approach, preliminary calibration of the effective temperature of ions undergoing resonance excitation is required. This was accomplished by employing blackbody infrared radiative dissociation (BIRD) which allows direct measurement of activation parameters. Activation energies and pre-exponential factors were evaluated for more than 10 H-G complexes via the use of low-energy CID. The relatively long residence time of the ions inside the linear ion trap (maximum of 60 s) allowed the study of dissociations with rates below 1 s-1. This possibility, along with the large size of the investigated ions, ensures the fulfilment of rapid energy exchange (REX) conditions and, as a consequence, accurate application of the Arrhenius equation. Compared with the BIRD technique, low-energy CID allows access to higher effective temperatures, thereby permitting one to probe more endothermic decomposition pathways. Based on the measured activation parameters, guests bearing a phosphate (-OPO32-) functional group were found to bind more strongly with the encapsulating cage than those having a sulfonate (-SO³-) group; however, the latter ones make stronger bonds than those with a carboxylate (-CO2-) group. In addition, it was observed that the presence of trimethylammonium (-N(CH3)3+) or phenyl groups in the guest's structure improves the strength of H-G interactions. The use of this technique is very straightforward, and it does not require any instrumental modifications. Thus, it can be applied to other H-G chemistry studies where comparison of bond dissociation energies is of paramount importance. [ABSTRACT FROM AUTHOR]

In advancing host-guest (H-G) chemistry, considerable effort has been spent to synthesize host molecules with specific and well-defined molecular recognition characteristics including selectivity and adjustable affinity. An important step in the process is the characterization of binding strengths of the H-G complexes that is typically performed in solution using NMR or fluorescence. Here, we present a mass spectrometry-based multimodal approach to obtain critical energies of dissociation for two hemicryptophane cages with three biologically relevant guest molecules. A combination of blackbody infrared radiative dissociation (BIRD) and high-pressure collision-induced dissociation (high-pressure CID), along with RRKM modeling, was employed for this purpose. For the two tested hemicryptophane hosts, the cage containing naphthyl linkages exhibited stronger interactions than the cage bearing phenyl linkages. For both cages, the order of guest stability is choline > acetylcholine > betaine. The information obtained by these types of mass spectrometric studies can provide new insight into the structural features that most influence the stability of H-G pairs, thereby providing guidance for future syntheses.Graphical Abstract [ABSTRACT FROM AUTHOR]