Study of gas‐phase molecular recognition using Fourier transform ion cyclotron resonance mass spectrometry (FTICR/MS)

Abstract

The application of Fourier transform ion cyclotron resonance (FTICR) mass spectrometry to the quantitative study of molecular recognition in the gas phase is reviewed. Because most quantitative measurements are dependent on accurate determination of the pressure of a neutral reagent, methods for accurate pressure measurement in FTICR, including gauge calibration using a reaction with known rate constants (the traditional method), exothermic proton transfer rate measurement (often the best method when accurate neutral pressures in the trapping cell are desired), and linewidth measurement (a little-used, but generally applicable method) are discussed. The use of rate constant measurements in molecular recognition is illustrated with examples employing natural abundance isotopic labeling to study self-exchange and 2 : 1 ligand:metal complex formation kinetics in crown ether-alkali cation systems. Self-exchange rates do not correlate with alkali cation/crown cavity size relationships, whereas 2 : 1 complex formation kinetics correlate strongly with size relationships. The use of exchange equilibrium constant measurements to characterize molecular recognition is illustrated by alkali cation exchanges between 18-crown-6 and the isomers of dicyclohexano-18-crown-6. These experiments show that the alkyl-substituted ligand binds alkali cations better than unsubstituted 18-crown-6 in the gas phase, in accordance with expectations based on the higher polarizability of the alkyl-substituted ligand. Further, the metal binding thermochemistry differs for the two dicyclohexano-18-crown-6 isomers, with the bowl-shaped cis-syn-cis isomer binding all the alkali cations more strongly than the cis-anti-cis isomer. The measurement of entropies and enthalpies associated with one of the most subtle forms of molecular recognition, enantiomeric discrimination, is illustrated by studies of the discrimination between enantiomers of chiral amines by dimethyldiketopyridino-18-crown-6. This chiral ligand binds chiral primary ammonium cations that have the opposite absolute configuration at their stereocenter more strongly than the enantiomer with the same absolute configuration. Gas-phase studies show that this enantiomeric discrimination is enthalpic in origin, likely related to more favorable pi-pi stacking for the preferred enantiomer. Entropy disfavors binding of the preferred enantiomer.

Structural relationships in small molecule interactions governing gas-phase enantioselectivity and zwitterionic formation

“…It also allows better understanding of the intrinsic properties of noncovalent complexes [12]. Cyclodextrin complexes are particularly attractive as they provide highly defined if not rudimentary systems for studying host-guest complexes.…”

“…Subsequently, other gas-phase methods have been used for determining enantiospecificity [22]. Radiolysis, Fourier-transform ion cyclotron resonance mass spectrometry (FTICR-MS), and resonance-enhanced multiphoton ionization time-of flight (REMPI-TOF) spectroscopy are techniques previously used for gas-phase chiral recognition [12,[23][24][25][26][27][28]. Cooks et al performed gas-phase chiral analysis of enantiomeric amino acid mixtures by using competitive fragmentation of trimeric transition-metalbound complexes with mass spectrometry [29 -37].…”

ESI-FTICR mass spectrometric study of alcohol complexation properties of mono- and diphosphonate-bridged cavitands

“…Mass spectrometry (MS) with a soft ionization technique such as electrospray ionization (ESI) [19 -22] is nowadays challenging these more traditional methods in the study of host-guest interactions [23,24]. As a technique, ESI-MS is positioned somewhere between the solution state and the gas phase.…”

Linewidth Pressure Measurement: A New Technique for High Vacuum Characterization

“…Most commonly, ionization gauge transducers on FTICR instruments are placed outside the high-field region of the magnet, sometimes as much as a meter or more away from the ion trapping cell. Gas conductance between the transducer and the trapping cell can result in pressure differences between the transducer and trapping cell of as much as an order of magnitude [14]. When pressure measurements are critical, corrections for this difference must be made, typically by measuring the rate of a well-characterized ion-molecule reaction in the trapping cell and using the known rate constant to determine the actual pressure in the trapping cell [14].…”