COVE R STORY
Coupling ion mobility spectrometry with mass spec provides SENSITIVITY to analyte mass, charge, and shape MITCH JACOBY, C&EN CHICAGO
ARMED WITH high-end spectrometers,
Although a few variants of the ion mobility technique are practiced currently, the methods are related in that they generally send a packet of analyte ions through a gas-filled drift tube, or cell, by applying an electrostatic push. As the ions collide with the gas molecules, the interactions lead to complex ion trajectories and a distribution of travel times through the cell that depends on the mass, charge, and shape of the ions. The dependence of ion mobility on those properties is complex, but in general, compact ions tend to move more quickly through the drift tube than elongated ones. A few instrument makers, among them Waters and Thermo Fisher Scientific, recently began offering complete MS systems that incorporate IMS capabilities (C&EN, Sept. 15, 2008, page 11). Wesdemiotis,
distributions, which crowds spectra and scientists can often ferret out molecules’ complicates mass determination. most subtle details. Sometimes, however, Another challenge in analyzing synthetic overlapping signals make it difficult or impolymers is that they can be complex mixpossible for a single type of analytical tool tures. “Polymers are often sold by batch to reveal even the most basic molecular properties, not molecular structure,” properties, such as chemical identity. In lamented James H. Scrivens, a chemistry those cases, researchers tend to double up. Mass/charge “Doubling up” was 2,000 L9 exactly the focus of a polymer-analysis symL8 posium at Pittcon 2010. Researchers there discussed the limitations L7 1,500 of analyzing synthetic macromolecules by L6 mass spectrometry C6 alone and the benefits L5 of combining mass C5 1,000 spectrometry with ion L4 mobility spectrometry C4 (IMS). L3 Mass spectrometry C3 methods are routinely L2 500 used to determine C2 polymer molecular L1 weights and molecular1.29 3.86 6.43 9.00 11.57 weight distributions, Drift time, milliseconds the identities of end groups, and a wide variMULTIDIMENSIONAL Plots of IMS/MS data readily highlight distinct ion families not recognizable ety of other structural from MS measurements. The data points highlighted here correspond to linear (L) and cyclic (C) and compositional polybutylene adipate oligomers containing the indicated number of repeat units (subscripts). characteristics, according to Chrys Wesdemiotis, a professor of chemistry and polymer professor at the University of Warwick, in Scrivens, and other speakers at the session science at the University of Akron, in Ohio. England. For that reason, manufacturers presented data measured with Waters’ “On the basis of mass measurements may choose to vary starting materials and Synapt and new Synapt G2 instruments, alone, however, it is often difficult or imalter formulations and reaction conditions which feature an IMS device sandwiched possible to distinguish between isobaric as needed, without specifying the details of between quadrupole and time-of-flight and isomeric components,” Wesdemiotis the product composition. As a result, mass mass spectrometers. That configuration stressed. Those designations refer to ions spectra collected from such samples are offers researchers the flexibility to use IMS that have the same mass but differ chemicomplex and convoluted because the mateto examine all analyte ions simultaneously cally (isobaric) or structurally (isomeric). rials consist of products that exhibit a range or to choose ions of a given mass-to-charge In addition, electrospray ionization, a comof molecular weights along with a mixture ratio and analyze them selectively. It also mon method to ionize complex and fragile of impurities and by-products. Coupling provides a platform for mass analyzing the molecules such as polymers, often leads to IMS to MS can help simplify the mass analyions as they separate according to their overlap in the ionized molecules’ charge sis and solve other analytical problems. drift times in the IMS cell. WWW.CEN-ONLINE.ORG
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CHRYS WESDEMIOTIS/U AKRON
DOUBLING UP ON MASS ANALYSIS
A quick glance at an IMS/MS spectrum reveals the combination’s power. Lines, streaks, and other data-point groupings correspond to visibly recognizable ion families that stand out from other families because of differences in chemical composition and structure. DEMONSTRATING the benefits of the
technique, Scrivens reported his group’s analysis of several polysorbate products used as surfactants and emulsifiers. One of the materials, known as Polysorbate 20 or Tween 20, is prepared commercially by dehydrating sorbitol and reacting the product with a carboxylic acid and ethylene oxide. Because the dehydration step can lead to a mixture of sorbitan and isosorbide and because ethoxylation is not easily controlled, Tween 20 is an ill-defined complex mixture of polymers that is “extremely unlikely” to yield even to the most advanced and timeconsuming methods of chromatographic separation, Scrivens stressed. Much of its complexity can be sorted out quickly, however, by using IMS/MS. Unlike Tween 20’s convoluted mass spectrum, its IMS/MS data reveal families of ions arising from related yet distinct compounds. Analysis of those families shows HO
CH2CH2O
O
n
O
OCH2CH2
m
OH
Isosorbide polyethoxylate
HO
CH2CH2O
OCH2CH2 w
O
x
OH
OCH2CH2 OCH2CH2
Polysorbate monoester
y
OH
OCR z
O
that the product consists of three major components: a polysorbate monolaurate ester containing 23 OC2H4 groups; sorbitan polyethoxylate, a closely related compound that contains one less OC2H4 group and lacks the laurate (C11H23) ester unit; and isosorbide polyethoxylate, a derivative of the isosorbide that’s present in the starting material as a result of overdehydration of sorbitol. Scrivens pointed out that the same type of analysis readily reveals the composition of other “tweens,” such as Tween 40, which WWW.CEN-ONLINE.ORG
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WAT E RS
COVER STORY
COMBINATION PLATTER
Ions traversing Waters’ Synapt G2 instrument are separated by shape, charge, and mass in a Tri Wave ion mobility spectrometer, in addition to being analyzed in quadrupole and time-of-flight mass spectrometers.
consists mainly of a polysorbate monoester with a palmitate (C15H31) group. Wesdemiotis highlighted other benefits of coupling IMS to MS. For example, a singly charged ion and a doubly charged ion with twice the mass have the same mass-to-charge ratio and therefore overlap when the compounds are analyzed by MS alone. In the combined method, however, ions group according to their charge state, which separates coincident ions and simplifies analysis. Drawing on the example of polybutylene adipate, Wesdemiotis showed that data fell into four distinct drift-time regions corresponding to +1 through +4 charge states. In addition, the +1 group was subdivided according to the number of repeat units in the oligomer and further divided according to oligomer geometry: Compact cyclic oligomers drifted more quickly than linear oligomers containing the same number of repeat units. TAKING FURTHER advantage of the sensi-
tivity of IMS/MS to ion shape, Wesdemiotis teamed up with Akron colleague George R. Newkome, postdoc Xiaopeng Li, and graduate student Yi-Tsu Chan to examine supramolecular architectures. The researchers prepared bis-terpyridine ligands containing seven six-membered rings and treated them with a cadmium solution. The group’s aim was to form macrocyclic hexamers composed of six ligands coordinated to a total of six cadmium ions. Conventional MS analysis of the product suggests that the hexamer is indeed formed. But the possibility of overlapping signals reduces the
certainty of that conclusion. For example, the MS peak at 1,187 amu could correspond to a quadruply charged hexamer, a doubly charged trimer, or both ions. On the basis of IMS/MS analysis, the team determined that the signal at 1,187 amu arises predominantly from the 4+ hexamer—but the 2+ trimer also contributes to that signal. Furthermore, the hexamer signal consists of a large peak and a small satellite separated by a relatively small difference in drift time. Wesdemiotis noted that the team carried out control studies with other kinds of ligands and confirmed that the larger signal corresponds to the macrocyclic hexamer. The satellite peak confirms the presence of a small concentration of the linear hexamer, which drifts more slowly than the cyclic compound. The researchers conducted similar IMS/MS deconvolutions on other overlapping signals, thereby demonstrating the suitability of the combination method to analyzing architectures of supramolecular assemblies (J. Am. Chem. Soc. 2009, 131, 16395). IMS/MS is starting to attract devotees among analytical scientists who recognize the decisive benefits that come from coupling mass analysis with shape-dependent ion separation. As Scrivens put it, “The ability to track families of ions is one extraordinarily powerful aspect of this technique.” More generally, he added, IMS/ MS offers a platform “for separating and visualizing all of these different types of compounds in one high-information-content experiment that is superior to other approaches.” ■ WWW.CEN-ONLINE.ORG
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