Exploring Isomerism in Isolated Cyclodextrin Oligomers through Trapped Ion Mobility Mass Spectrometry

Abstract

Cyclodextrin (CD) macrocycles are used to create a wide range of supramolecular architectures which are also of interest in applications such as selective gas adsorption, drug delivery, and catalysis. However, predicting their assemblies and identifying the possible isomers in CD oligomers have always remained challenging due to their dynamic nature. Herein, we interacted CDs (α, β, and γ) with a divalent metal ion, Cu 2+ , to create a series of Cu 2+ -linked CD oligomers, from dimers to pentamers. We characterized these oligomers using electrospray ionization mass spectrometry and probed isomerism in each of these isolated oligomers using high resolution trapped ion mobility spectrometry. Using this technique, we separated multiple isomers for each of the Cu 2+ -interlinked CD oligomers and estimated their relative population, which was not accessible previously using other characterization techniques. We further carried out structural analysis of the observed isomers by comparing the experimental collision cross sections (CCSs) to that of modeled structures. We infer that the isomeric heterogeneity reflects size-specific packing patterns of individual CDs (e.g., close-packed/linear). In some cases, we also reveal the existence of kinetically trapped structures in the gas phase and study their transformation to thermodynamically controlled forms by examining the influence of activation of the ions on isomer interconversion.

Isomerism of Cyclodextrin Tetramer Induced by Alkali Halide Cluster Ions Observed by Ion Mobility Spectrometry–Mass Spectrometry

“…This observation is in line with the previous report from Chakraborty et al, suggesting that metal-linked β-CD tetramers are mainly present as closely packed assemblies rather than linear forms in the gas phase. 9 Additionally, various tetramer isomers were Similarly, K Tet 2+ with n = 0−2 showed ATD peaks at 57−58 ms, showing nearly the same CCS values (∼650 Å 2 ) compared to Na Tet 2+ . The CCS of Na Tet 2+ with n = 0 was smaller than the others with a value of 631 Å 2 .…”

“…The observation of oligomers up to a dodecamer in the mass spectra suggests the facile generation of CD aggregation in the gas phase, aligning with earlier findings. 9,21 All of the detected oligomers presented a series of peaks involving clusters of alkali metal chloride (MCl) n (n = 1, 2, 3,...).…”

“…Particularly, a "bucket-wheel"-shaped β-CD trimer has been previously reported to have a stable assembly with metal centers such as Sn 4+ and Cu 2+ . 5,9 Based on the bucket-wheel-shaped trimer, a highly closed-packed tetramer structure was constructed, featuring a central cavity where metal ions could be accommodated, as illustrated in Figure 4a. The results from semi-empirical calculations suggested that two sodium cations are positioned at the center of the tetramer's BW motif for [(β-CD) 4 + 2Na] 2+ with each sodium cation having a coordination number of 6.…”

“…For example, several IMS-MS studies on CD oligomers with metal cations have successfully identified the channel-like linear assemblies for CD dimers and trimers, while a compact cluster can be formed for larger assemblies starting from trimers. 9,21 Herein, we report the presence of two distinguishable assembly structures of the β-CD tetramer with alkali halide cluster ions [(β-CD) 4 + (MCl) n M z ] z+ ( M Tet z+ ; M = Li, Na, K, or Rb and n = 0, 1, 2,...), which were observed by IMS-MS. Since the expected collision cross-section (CCS) values are strongly dependent on the assembly structures, as illustrated in Figure 1, the structural isomerism of tetramers can be investigated by IMS-MS.…”

A concise guide to chemical reactions of atomically precise noble metal nanoclusters

“…26,91,144–146,147 High-resolution mass spectrometry (HR MS) coupled with soft ionization can precisely determine the composition of the core and ligands as well as the charge states of the nanocluster. 55,148 Other advanced mass spectrometric (MS) techniques, like ion mobility MS (IM-MS) 97,149–153 and tandem MS (MS/MS), 19,154,155 are becoming increasingly powerful to understand the size, shape, and structural evolution. Single-crystal X-ray crystallography has made it possible to resolve the structures of several thiol (–SR)-capped nanoclusters, like Au 25 (SR) 18 , 134 Au 28 (SR) 20 , 156 Au 38 (SR) 24 , 157 Au 40 (SR) 24 , 158 Au 52 (SR) 32 , 159 Au 40 (SR) 24 , 160 Au 92 (SR) 44 , 159 Au 102 (SR) 44 , 131 Au 133 (SR) 52 , 161 Ag 44 (SR) 30 , 162 Ag 25 (SR) 18 , 163 Ag 29 (SR) 12 , 164 and more.…”