THE UNIVERSITY OF AKRON

Dr. Chrys Wesdemiotis

Research Interests

Mass Spectrometry and Tandem Mass Spectrometry:  Fundamental Studies and Analytical Applications to Macromolecules

Mass spectrometry (MS) offers the potential to pursue research in gas phase ion chemistry, instrumentation development, and chemical analysis.  Our group combines work in these areas to develop multidimensional MS methodologies for the characterization of synthetic polymers, biopolymers, and polymer-biomolecule interfaces and conjugates.  Research is performed with online and offline LC/MS, tandem mass spectrometry (MS/MS), and ion mobility mass spectrometry (IM/MS) instrumentation equipped with vacuum and ambient ionization methods as well as a variety of MS/MS activation methods.

1. Synthetic Polymers

Synthetic polymers are found in a large array of products that have resulted in improved living conditions and better health.  The physical and mechanical properties that make a synthetic polymer suitable for a particular application depend on the size, chemical composition, end groups, and architecture of the polymer.  Our group uses established and new MS methods to determine the latter, chemical features, whose knowledge is essential for correlating polymer structure to specific properties and functions.

1a. Single-Stage MS

Single-stage (one-dimensional) mass spectrometry provides the accurate masses of the constituents of a polymer or copolymer, from which the corresponding compositions can be deduced with unsurpassed sensitivity, specificity, and speed.   As a dispersive method, MS is ideally suited for the identification of the minor synthetic products and degradation products of polymer synthesis, which are difficult to detect by integrative methods, such as IR or NMR spectroscopy.  Our group uses MALDI, ESI, and APCI mass spectrometry for the complete analysis of new synthetic polymers and materials; the minor and/or degradation products detected by MS are crucial for establishing polymerization mechanisms, confirming the origin of unknown samples, and comparing products prepared in different batches or by different methods.

1b. LC/MS

Blends of differently sized polymers can be separated into their components or into narrower molecular weight mixtures by gel permeation chromatography (GPC).  This liquid chromatography (LC) method separates based on hydrodynamic volume.  On the other hand, interactive LC disperses on the basis of chemical composition, functionality, and mass.  Our group investigates interactive LC for the analysis of copolymers and derivatized polymers that contain components of different polarities.  For example, we recently found that reverse-phase LC of poly(ethylene glycol) / poly(propylene glycol) (PEG / PPG) copolymers can be optimized to yield fractions with constant (or very narrow) PPG content, as illustrated in Figure 1.

 Wes Figure 1

Fig. 1.  (a) LC chromatogram of a random PEG/PPG copolymer (Mn = 970); (b) ESI mass spectrum of the fraction eluting at 20.7-21.1 min.

 1c. Multistage MS

In tandem (MS/MS) or multistage (MSn) mass spectrometry, a specific precursor ion is mass-selected and induced to decompose into structurally indicative fragments, which are identified in a subsequent mass-analysis step.  A series of studies in our group focuses on the acquisition, interpretation, and classification of the MS/MS and MSn mass spectra of synthetic polymers.  Knowledge of the fragmentation mechanisms of polymer ions is the first step in the development of MS/MS and MSn strategies for the characterization of polymer sequences and architectures. We recently elucidated the fragmentation pathways of polystyrenes and polyacrylates and developed a protocol for the determination of branched architectures (Figure 2). 

 Wes Figure 2

 

Fig. 2.  MALDI-MS/MS spectrum of the [4-mer + Li]+ from a hyperbranched polyacrylate (synthesis by Pugh et al.).  The fragments marked by green stars diagnose the branched architecture shown, and the ones marked by violet stars diagnose a differently branched isomer.  R = (CH2)11-O-C6H4-p-C6H4-p-CN.

Precursor ions are induced to decompose by collisionally activated dissociation, CAD, or electron transfer dissociation, ETD.  The former can be applied to singly as well as multiply charged precursor ions, whereas the latter is only applicable to ions with more than one charge.  ETD is widely used in peptide sequencing.  Current research in our group tests the advantages of ETD vs. CAD for synthetic polymers containing unsaturated functionalities.

1d. Degradation / MS

Considerable research efforts are devoted to the development of selective degradation / mass spectrometry techniques for the characterization of polymers that are not analyzable directly by MS or other spectroscopic means.  Mild thermal degradation is employed to cleave large or complex polymer systems to smaller oligomers, which can subsequently be identified by MS and MSn, to thereby gain structural data about the original polymer.  With (co)polymers containing biodegradable constituents, enzymatic digestion provides a means to cleave selectively the biodegradable components.  The mass spectra obtained from the degradation products provide valuable structural insight about the composition of large polymer networks or complex formulations, which are very challenging to characterize otherwise.

1e. Ion Mobility Mass Spectrometry (IM/MS)

 Wes Figure 3

Fig. 3.  (a) Ion mobility vs. m/z of the ions formed by ESI of a pegylated sorbitan trioleate; (b,c) mass spectra of the separated charge states. 

In IM/MS, ions travel through a drift cell pressurized with a carrier gas.  The drift time through this cell depends on the mass, charge, and shape of the ions.  Hence, it allows one to differentiate isomeric or isobaric compositions with different geometries.  IM/MS is a powerful method for the analysis of protein conformations.  Our group explores its power to simplify the complexity of polymer mass spectra, to identify minor impurities and byproducts which are often buried under the signals produced from the major polymer components, and to distinguish (co)polymer isomers and isobars.  Figure 3 shows the distributions of drift times vs. mass-to-charge ratios of the ions formed upon ESI of a pegylated sorbitan trioleate.  The spectra within the slice at m/z ~1,000 indicate the presence of singly and doubly charged oligomers with significantly different drift times (and, hence, geometries).  Such separation allows for definitive identification of the surfactant's components, even the minor ones, which is impossible from the simple mass spectrum alone.

1f. Polymer-Biomolecule Interactions and Interfaces

Wes Figure 4 

Fig. 4.  ESI mass spectrum of a poly(ethylene imine) - adenosine monophosphate mixture, showing the formation of noncovalent complexes between the polymer and the nucleotide.  PEI is used for nucleic acid transport in vivo.

Synthetic polymers are widely used for biomedical purposes, for example, in the manufacture of stents and implants, drug delivery systems, biosensors, and corrective devices.  Biomolecules can adhere on the surface of such polymers by adsorption and adsorbed biomolecules can affect the biocompatibility and in vivo performance of the polymer hosts.  Our group exposes polymers engineered for biomedical use to biological solutions and characterizes the adsorbed biopolymers either by extracting them from the surfaces and analyzing them by MSn and LC/MSn methods, or by direct surface MALDI imaging techniques.  In control studies, the adsorption of single biomolecules, biopolymers, or analogs is investigated.  These studies aim at assessing the biocompatibility of the new materials and also reveal fundamental information about the guest-host interactions that can develop in these assemblies (Figure 4).

2. Biopolymers

Our group is an active participant in the Integrated Biosciences Program, an interdisciplinary combination of integrative biology, biochemistry, bioinformatics, and bioengineering.  In synergistic research with groups in the Departments of Biology and Polymer Science, we employ mass spectrometry methods for the characterization of proteins, lipids, and their glycoconjugates.  Ongoing investigations aim at the identification of the proteins present in gecko foot pads using comparative proteomics approaches.  Concurrent work explores new mass spectrometry methods for the analysis of peptide sequences and glycolipid structures and examines fundamental aspects of the tandem mass spectrometry characteristics of such biopolymers.

Selected Publications

  1. Li, X.; Chan, Y.-T.; Newkome, G.R.; Wesdemiotis, C.  Gradient tandem mass spectrometry interfaced with ion mobility separation for the characterization of supramolecular architectures.  Anal. Chem. 2011, 83, 1284-1290 (DOI: 10.1021/ac1022875). 

  2. Wesdemiotis, C.; Solak, N.; Polce, M.J.; Dabney, D.E.; Chaicharoen, K.; Katzenmeyer, B.C.  Fragmentation pathways of polymer ions.  Mass Spectrom. Rev. 2011, 30, 523-539 (DOI: 10.1002/mas.20282).

  3. Li, X.; Li, G.; Casiano-Maldonado, M.; Zhang, D.; Wesdemiotis, C.  Top-down multidimensional mass spectrometry methods for synthetic polymer analysis.  Macromolecules 2011, 44, 4555-4564 (DOI: 10.1021/ma200542p).

  4. Smiljanic, D.; Wesdemiotis, C.  Non-covalent complexes between single-stranded oligodeoxynucleotides and poly(ethylene imine).  Int. J. Mass Spectrom. 2011, 304, 148-153 (DOI: 10.1016/j.ijms.2010.06.035).

  5. Wang, J.-L.; Li, X.; Lu, X.; Hsieh, I.-F.; Cao, Y.; Moorefield, C.N.; Wesdemiotis, C.; Cheng, S.Z.D.; Newkome, G.R.  Stoichiometric self-assembly of shape-persistent 2D complexes:  a facile route to a symmetric supramolecular spoked wheel.  J. Am. Chem. Soc. 2011, 133, 11450-11453 (DOI: 10.1021/ja203645m).

  6. Chan, Y.-T.; Li, X.; Carri, G.A.; Moorefield, C.N.; Newkome, G.R.; Wesdemiotis, C.  Design, synthesis, and traveling wave ion mobility mass spectrometry characterization if iron(II)- and ruthenium(II)-terpyridine metallomacrocycles.  J. Am. Chem. Soc. 2011, 133, 11967-11976 (DOI: 10.1021/ja107307u).

  7. Li, X.; Chan, Y.-T.; Casiano-Maldonado, M.; Yu, J.; Carri, G.A.; Newkome, G.R.; Wesdemiotis, C.  Separation and characterization of metallosupramolecular libraries by ion mobility mass spectrometry.  Anal. Chem. 2011, 83, 6667-6674 (DOI: 10.1021/ac201161u).

  8. Hsu, P.Y.; Ge, L.; Li, X.; Stark, A.Y.; Wesdemiotis, C.; Niewiarowski, P.H.; Dhinojwala, A.  Direct evidence of phospholipids in gecko footprints and spatula-substrate contact interface detected using surface-sensitive spectroscopy.  J. R. Soc. Interface 2012, 9, 657-664 (DOI: 10.1098/rsif.2011.0370).

  9. Yu, X.; Zhang, W.-B.; Yue, K.; Li, X.; Liu, H.; Xin, Y.; Wang, C.-L.; Wesdemiotis, C.; Cheng, S.Z.D.  Giant molecular shape amphiphiles based on polystyrene-hydrophilic [60]fullerene conjugates:  click synthesis, solution self-assembly, and phase behavior.  J. Am. Chem. Soc. 2012, 134, 7780-7787 (DOI: 10.1021/ja3000529).

  10. Smiljanic, D.; Wesdemiotis, C.  Ternary complexes of poly(ethylene imine), single-stranded oligodeoxynucleotides and glutamic acid moieties.  Int. J. Mass Spectrom. 2012, 316-318, 235-243 (DOI: 10.1016/j.ijms.2012.02.016).

  11. Scionti, V.; Katzenmeyer, B.C.; Solak, N.; Li, X.; Wesdemiotis, C.  Interfacing multistage mass spectrometry with liquid chromatography or ion mobility separation for synthetic polymer analysis.  Eur. J. Mass Spectrom. 2012, 18, 113-137 (DOI: 10.1255/ejms.1175).

  12. Wang, S.-F.; Li, X.; Agapov, R.L.; Wesdemiotis, C.; Foster, M.D.  Probing surface concentration of cyclic/linear blend films using surface layer MALDI-TOF mass spectrometry.  ACS Macro Lett. 2012, 1, 1024-1027 (DOI: 10.1021/mz300271w).

  13. Zheng, J.; Smith Callahan, L.A.; Hao, J.; Guo, K.; Wesdemiotis, C.; Weiss, R.A.; Becker, M.L.  Strain-promoted crosslinking of PEG-based hydrogels via copper-free cycloaddition.  ACS Macro Lett. 2012, 1, 1071-1073 (DOI: 10.1021/mz3003775).

  14. Scionti, V.; Wesdemiotis, C.  Electron transfer dissociation versus collisionally activated dissociation of cationized biodegradable polyesters.  J. Mass Spectrom. 2012, 47, 1442-1449. (DOI: 10.1002/jms.3097).

  15. Yol, A.M.; Dabney, D.E.; Wang, S.-F.; Laurent, B.A.; Foster, M.D.; Quirk, R.P.; Grayson, S.M.; Wesdemiotis, C.  Differentiation of linear and cyclic polymer architectures by MALDI tandem mass spectrometry (MALDI-MS2).  J. Am. Soc. Mass Spectrom. 2013, 24, 74-82 (DOI: 10.1007/s13361-012-0497-5).

  16. Zhang, L.; Katzenmeyer, B.C.; Cavicchi, K.A.; Weiss, R.A.; Wesdemiotis, C.  Sulfonation distribution in sulfonated polystyrene ionomers measured by MALDI-ToF MS.  ACS Macro Lett. 2013, 2, 217-221 (DOI: 10.1021/mz3006632).

  17. Lu, X.; Li, X.; Cao, Y.; Schultz, A.; Wang, J.-L.; Moorefield, C.N.; Wesdemiotis, C.; Cheng, S.Z.D.; Newkome, G.R.  Self-assembly of a supramolecular, three-dimensional, spoked, bicycle-like wheel.  Angew. Chem. Int. Ed. 2013, 52, 7728-7731 (DOI: 10.1002/anie.201302362).

  18. Tang, W.; Ma, Y.; Xie, S.; Guo, K.; Katzenmeyer, B.; Wesdemiotis, C.; Becker, M.L.  Valency-dependent affinity of bioactive hydroxyapatite-binding dendrons.  Biomacromolecules 2013, 14, 3304-3313 (DOI:10.1021/bm400908c).

  19. Solak Erdem, N.; Alawani, N.; Wesdemiotis, C.  Characterization of polysorbate 85, a nonionic surfactant, by liquid chromatography vs. ion mobility separation coupled with tandem mass spectrometry.  Anal. Chim. Acta 2014, 808, 83-93 (DOI: 10.1016/j.aca.2013.07.026).

  20. Casiano-Maldonado, M.; Lim, G.T.; Li, X.; Reneker, D.H.; Puskas, J.E.; Wesdemiotis, C.  Protein adsorption on thermoplastic elastomeric surfaces:  a quantitative mass spectrometry study.  Int. J. Mass Spectrom. 2013, 354-355, 391-397 (DOI: 10.1016/j.ijms.2013.08.007).

  21. Li, Y.; Guo, K.; Su, H.; Li, X.; Feng, X.; Wang, Z.; Zhang, W.; Zhu, S.; Wesdemiotis, C.; Cheng, S.Z.D.; Zhang, W.-B.  Tuning "thiol-​ene" reactions toward controlled symmetry breaking in polyhedral oligomeric silsesquioxanes.  Chem. Sci. 2014, 5, 1046-1053 (DOI: 10.1039/c3sc52718b).

  22. Yol, A.M.; Wesdemiotis, C.  Multidimensional mass spectrometry methods for the structural characterization of cyclic polymers.  React. Funct. Polym. 2014, 80, 95-108 (DOI: 10.1016/j.reactfunctpolym.2014.03.010).

  23. Xie, T.-Z.; Liao, S.-Y.; Guo, K.; Lu, X.; Dong, X.; Huang, M.; Moorefield, C.N.; Cheng, S.Z.D.; Liu, X.; Wesdemiotis, C.; Newkome, G.R.  Construction of a highly symmetric nanosphere via a one-pot reaction of a tristerpyridine ligand with Ru(II).  J. Am. Chem. Soc. 2014, 136, 8165-8168 (DOI: 10.1021/ja502962j).

  24. Çelikbıçak, Ö.; Salih, B.; Wesdemiotis, C.  Strong ionic interactions in noncovalent complexes between poly(ethylene imine), a cationic electrolyte, and Cibacron Blue, a nucleotide mimic – implications for oligonucleotide vectors.  J. Mass Spectrom. 2014, 49, 597-607 (DOI: 10.1002/jms.3379).

  25. Wang, J.; Liu, B.; Wesdemiotis, C. Pang, Y.  Binuclear Zn(II)−Zn(II) complex from a 2-hydroxybenzohydrazide-derived Schiff base for selective detection of pyrophosphate.  Dalton Trans. 2014, 43, 14142-14146 (DOI: 10.1039/C4DT01799D).

  26. Lu, X.; Li, X.; Guo, K.; Wang, J.; Huang, M.; Wang, J.-L.; Xie, T.-Z.; Moorefield, C.N.; Cheng, S.Z.D.; Wesdemiotis, C.; Newkome, G.R.  One ligand in dual Roles: self-assembly of a bis-rhomboidal-shaped, three-dimensional molecular wheel.  Chem. Eur. J. 2014, 20, 13094-13098 (DOI:10.1002/chem.201404358).

  27. Yol, A.M.; Janoski, J.; Quirk, R.P.; Wesdemiotis, C.  Sequence analysis of styrenic copolymers by tandem mass spectrometry.  Anal. Chem. 2014, 86, 9576-9582 (DOI:10.1021/ac5019815).

  28. Tang, W.; Policastro, G.M.; Hua, G.; Guo, K.; Zhou, J.; Wesdemiotis, C.; Doll, G.L.; Becker, M.L.  Bioactive surface modification of metal oxides via catechol-bearing modular peptides: multivalent-binding, surface retention, and peptide bioactivity.  J. Am. Chem. Soc. 2014, 136, 16357-16367 (DOI: 10.1021/ja508946h).

  29. Lu, X.; Li, X.; Guo, K.; Xie, T.-Z.; Moorefield, C.N.; Wesdemiotis, C.; Newkome, G.R.  Probing a hidden world of molecular self-assembly: concentration-dependent, three-dimensional supramolecular interconversions.  J. Am. Chem. Soc. 2014, 136, 18149-18155 (DOI: 10.1021/ja511341z).

  30. Katzenmeyer, B.C.; Cool, L.R.; Williams, J.P.; Craven, K.; Brown, J.M.; Wesdemiotis, C.  Electron transfer dissociation of sodium cationized polyesters: reaction time effects and combination with collisional activation and ion mobility separation.  Int. J. Mass Spectrom. 2015, 378, 303-311 (DOI: 10.1016/j.ijms.2014.09.021).

  31. Liu, X.; Lin, K.; Kasko, A.M.; Wesdemiotis, C.  Tandem mass spectrometry and ion mobility mass spectrometry for the analysis of molecular sequence and architecture of hyperbranched glycopolymers.  Analyst 2015, 140, 1182-1191 (DOI: 10.1039/C4AN01599A).

  32. Xie, T.-Z.; Guo, K.; Guo, Z.; Gao, W.-Y.; Wojtas, L.; Ning, G.-H.; Huang, M.; Lu, X.; Li, J.-Y.; Liao, S.-Y.; Chen, Y.-S.; Moorefield, C.N.; Saunders, M.J.; Cheng, S.Z.D.; Wesdemiotis, C.; Newkome, G.R.  Precise molecular fission and fusion: quantitative self-assembly and chemistry of a metallo-cuboctahedron.  Angew. Chem. Int. Ed. 2015, 54, 9224-9229 (DOI: 10.1002/anie.201503609).

  33. Guo, K.; Guo, Z.; Ludlow, J.M. III; Xie, T.; Liao, S.; Newkome, G.R.; Wesdemiotis, C.  Characterization of metallosupramolecular polymers by top-down multidimensional mass spectrometry methods.  Macromol. Rapid Comm. 2015, 36, 1539-1552 (DOI: 10.1002/marc.201500084).

  34. Alalwiat, A.; Grieshaber, S.E.; Paik, B.A.; Kiick, K.L.; Jia, X.; Wesdemiotis, C.  Top-down mass spectrometry of hybrid materials with hydrophobic peptide and hydrophilic or hydrophobic polymer blocks.  Analyst 2015, 140, 7550-7564 (DOI: 10.1039/c5an01600b).

  35. Liu, X.; Wesdemiotis, C.  Electron transfer dissociation of doubly charged ions with different cationizing agents.  Eur. J. Mass Spectrom. 2015, 21, 713-723 (DOI: 10.1255/ejms.1393).

  36. Katzenmeyer, B.C.; Hague, S.F.; Wesdemiotis, C.  Multidimensional mass spectrometry with separation by polarity or shape for the characterization of sugar-based nonionic surfactants.  Anal. Chem. 2016, 88, 851-857 (DOI: 10.1021/acs.analchem.5b03400).

  37. Zhang, W.; Huang, M.; Su, H.; Zhang, S.; Yue, K.; Dong, X.-H.; Li, X.; Liu, H.; Zhang, S.; Wesdemiotis, C.; Lotz, B.; Zhang, W.-B.; Li, Y.; Cheng, S.Z.D.  Toward controlled hierarchical heterogeneities in giant molecules with precisely arranged nano building blocks.  ACS Cent. Sci. 2016, 2, 48-54 (DOI:10.1021/acscentsci.5b00385).

  38. Crotty, S.; Schubert, S.; Gerișlioǧlu, S.; Endres, K.; Wesdemiotis, C.; Schubert, U.S.  Polymer architectures via mass spectrometry and hyphenated techniques.  Anal. Chim. Acta 2016, 932, 1-21 (DOI: 10.1016/j.aca.2016.05.024).