Utilizing ion mobility and tandem mass spectrometry to evaluate the structure and behaviour of multimeric cyclodextrin complexes

Abstract

Characterizing noncovalent complexes of molecular dimers and higher complexes using tandem mass spectrometry (MS/MS) can be hindered due to spectral overlap in both the MS and the MS/MS. We investigated the structures and dissociation energetics of multimeric β-cyclodextrin (β-CD) complexes alone or with substrates using combinations of ion mobility spectrometry (IMS), MS/MS, and Rice–Ramsperger–Kassel–Marcus (RRKM) unimolecular rate modelling. The doubly charged β-CD dimers ([(β-CD)2 – 2H+]2−) dissociate to two [β-CD – H+]− ions with the same m/z. IMS was used to separate source generated [(β-CD)2 – 2H+]2− from [β-CD – H+]− and the extent of [(β-CD)2 – 2H+]2− dissociation versus collision energy was determined by modelling changes in the ion’s isotopic profile. The RRKM derived critical energy (E0) for dissociation of [(β-CD)2 – H+]− and [(β-CD)2 – 2H+]2− were 1.85 ± 0.11 eV and 1.79 ± 0.09 eV, respectively, corresponding to a slight decrease in complex stability due to increased charge–charge repulsion in the dianion. This approach was extended to include dimeric complexes complexed to 4,4′-(propane-1,3-diyl) dibenzoic acid (PDDA) and ibuprofen (Ibu).

Noncovalent Complexes of Cyclodextrin with Small Organic Molecules: Applications and Insights into Host–Guest Interactions in the Gas Phase and Condensed Phase

“…Relative to [2CD] + , a smaller CCS value was observed for the [2CD + CA] + complexes, implying that CA was “sandwiched” between two CDs and, thus, had adopted a more compact conformation. Sandwich-like CD complexes were also reported between β-CD and 4,4-(propane-1,3-diyl) dibenzoic acid (PDDA) or Ibuprofen (Ibu) [ 178 ]. When the CCS values were compared, an obvious change was noted during the formation of the noncovalent complexes with [2CD − 2H + ] 2− or [CD – H + ] − .…”

Probing topology of supramolecular complexes between cyclodextrins and alkali metals by ion mobility-mass spectrometry

“…(Liu & Clemmer, 1997;Klein et al, 2018;Fenn & McLean, 2011;S. Lee et al, 1997) ESI with Traveling-Wave Ion Mobility Spectrometry (ESI-TWIMS) was used to study negatively charged mono-to trimeric -CD (Berland et al, 2014), or positively charged complexes like amino--CD/sesamins, (Sugahara et al, 2015) α-and β-CD with o-, m-and p-coumaric acids, (Kralj et al, 2009) with piperine/curcumin, (Nag et al, 2018) or with amino acids. (S.-S. Lee et al, 2018;Chen et al, 2018).…”

Gas-Phase Fragmentation of Cyclic Oligosaccharides in Tandem Mass Spectrometry

“…[15,16]. The separation of these ions (for example, [M + H] + and [2M + 2H] 2+ ) by mass spectrometry alone is impossible (because of m / z = n m /n z ), but they are separable by ion mobility spectrometry (IMS) due to their difference in size and shape [17,18].…”