Analytical and Bioanalytical Chemistry

, Volume 411, Issue 4, pp 953–964 | Cite as

An integrated approach to study novel properties of a MALDI matrix (4-maleicanhydridoproton sponge) for MS imaging analyses

  • Davide Corinti
  • Maria Elisa Crestoni
  • Simonetta FornariniEmail author
  • Maren Pieper
  • Karsten Niehaus
  • Marco GiampàEmail author
Research Paper


The chemical properties accounting for the operation of a valuable matrix used in matrix-assisted laser desorption ionization (MALDI) to perform mass spectrometry imaging (MSI), namely 3-(4,5-bis(dimethylamino)napthalen-1-yl)furan-2,5-dione (4-maleicanhydridoproton sponge, MAPS), have been elucidated also by comparison with the parent molecule 1,8-bis(dimethylamino) naphthalene (so-called proton sponge, PS). Both compounds present the bis(dimethylamino) groups, apt to efficiently trap a proton imparting positive charge. Only MAPS, though, owns the maleicanhydrido function acting as electrophile and yielding covalently bound adducts with a variety of analytes. In this way, MAPS performs as “carrier” for the analyte (A) of interest, at the same time minimizing the presence of useless, background ions. The covalent character of the adducts, [MAPS+H + A]+, is testified by their collision-induced dissociation pattern, quite distinct from the one displayed by [PS + H]+, while PS does not form any [PS + H + A]+, thus confirming the key role of the maleicanhydrido functionality of MAPS. Vibrational spectroscopy of [MAPS+H + A]+ adducts (A = H2O, NH3) provided further structural evidence. The presence of a mobile proton on A was found to be a requisite for adduct formation by electrospray ionization of acetonitrile solutions, pointing to a possible role of MAPS in discriminating competing analytes based on molecular features. The performance of MAPS has been verified in MALDI-MSI of Atropa belladonna berries, exploiting MAPS binding to atropine.

Graphical abstract


MALDI Mass spectrometry imaging Structure elucidation IR ion spectroscopy FT-ICR mass spectrometry 



The authors acknowledge funding for this study provided by Università di Roma “La Sapienza,” by the Graduate Cluster Industrial Biotechnology (CLIB2021) and by the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 731077.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

216_2018_1531_MOESM1_ESM.pdf (470 kb)
ESM 1 (PDF 469 kb)


  1. 1.
    Fack F, Tardito S, Hochart G, Oudin A, Zheng L, Fritah S, et al. Altered metabolic landscape in IDH-mutant gliomas affects phospholipid, energy, and oxidative stress pathways. EMBO Mol Med. 2017;9:1681–95.CrossRefGoogle Scholar
  2. 2.
    Dekker TJA, Jones EA, Corver WE, van Zeijl RJM, Deelder AM, Tollenaar RAEM, et al. Towards imaging metabolic pathways in tissues. Anal Bioanal Chem. 2015;407:2167–76.CrossRefGoogle Scholar
  3. 3.
    Trim PJ, Snel MF. Small molecule MALDI MS imaging: current technologies and future challenges. Methods. 2016;104:127–41.CrossRefGoogle Scholar
  4. 4.
    Karas M, Krüger R. Ion formation in MALDI: the cluster ionization mechanism. Chem Rev. 2003;103:427–39.CrossRefGoogle Scholar
  5. 5.
    Knochenmuss R. Ion formation mechanisms in UV-MALDI. Analyst. 2006;131:966–86.CrossRefGoogle Scholar
  6. 6.
    Baker TC, Han J, Borchers CH. Recent advancements in matrix-assisted laser desorption/ionization mass spectrometry imaging. Curr Opin Biotechnol. 2017;43:62–9.CrossRefGoogle Scholar
  7. 7.
    Calvano CD, Monopoli A, Cataldi TRI, Palmisano F. Maldi matrices for low molecular weight compounds: an endless story? Anal Bioanal Chem. 2018;410:4015–38.CrossRefGoogle Scholar
  8. 8.
    Shroff R, Svatoš A. Proton sponge: a novel and versatile MALDI matrix for the analysis of metabolites using mass spectrometry. Anal Chem. 2009;81:7954–9.CrossRefGoogle Scholar
  9. 9.
    Thomas A, Charbonneau JL, Fournaise E, Chaurand P. Sublimation of new matrix candidates for high spatial resolution imaging mass spectrometry of lipids: enhanced information in both positive and negative polarities after 1,5-diaminonapthalene deposition. Anal Chem. 2012;84:2048–54.CrossRefGoogle Scholar
  10. 10.
    Swor CD, Zakharov LN, Tyler DR. A colorimetric proton sponge. J Org Chem. 2010;75:6977–9.CrossRefGoogle Scholar
  11. 11.
    Ozeryanskii VA, Pozharskii AF. Simple and hydrolytically stable proton sponge based organic cation displaying hydrogen bonding and a number of related phenomena. Tetrahedron. 2013;69:2107–12.CrossRefGoogle Scholar
  12. 12.
    Giampà M, Lissel MB, Patschkowski T, Fuchser J, Hans VH, Gembruch O, et al. Maleic anhydride proton sponge as a novel MALDI matrix for the visualization of small molecules (<250: M / z) in brain tumors by routine MALDI ToF imaging mass spectrometry. Chem Commun. 2016;52:9801–4.CrossRefGoogle Scholar
  13. 13.
    Shroff R, Rulisek L, Doubsky J, Svatos A. Acid-base-driven matrix-assisted mass spectrometry for targeted metabolomics. Proc Natl Acad Sci. 2009;106:10092–6.CrossRefGoogle Scholar
  14. 14.
    Napagoda M, Rulíšek L, Jančařík A, Klívar J, Šámal M, Stará IG, et al. Azahelicene superbases as MAILD matrices for acidic analytes. ChemPlusChem. 2013;78:937–42.CrossRefGoogle Scholar
  15. 15.
    Marshall AG, Hendrickson CL, Jackson GS. Fourier transform ion cyclotron resonance mass spectrometry: a primer. Mass Spectrom Rev. 1998;17:1–35.CrossRefGoogle Scholar
  16. 16.
    Oomens J, Sartakov BG, Meijer G, von Helden G. Gas-phase infrared multiple photon dissociation spectroscopy of mass-selected molecular ions. Int J Mass Spectrom. 2006;254:1–19.CrossRefGoogle Scholar
  17. 17.
    Polfer NC. Infrared multiple photon dissociation spectroscopy of trapped ions. Chem Soc Rev. 2011;40:2211–21.CrossRefGoogle Scholar
  18. 18.
    Roithová J. Characterization of reaction intermediates by ion spectroscopy. Chem Soc Rev. 2012;41:547–59.CrossRefGoogle Scholar
  19. 19.
    Fridgen TD. Infrared consequence spectroscopy of gaseous protonated and metal ion cationized complexes. Mass Spectrom Rev. 2009;28:586–607.CrossRefGoogle Scholar
  20. 20.
    Eyler JR. Infrared multiple photon dissociation spectroscopy of ions in Penning traps. Mass Spectrom Rev. 2009;28:448–67.CrossRefGoogle Scholar
  21. 21.
    MacAleese L, Maître P. Infrared spectroscopy of organometallic ions in the gas phase: from model to real world complexes. Mass Spectrom Rev. 2007;26:583–605.CrossRefGoogle Scholar
  22. 22.
    Sinha RK, Maître P, Piccirillo S, Chiavarino B, Crestoni ME, Fornarini S. Cysteine radical cation: a distonic structure probed by gas phase IR spectroscopy. Phys Chem Chem Phys. 2010;12:9794–800.CrossRefGoogle Scholar
  23. 23.
    Filippi A, Fraschetti C, Piccirillo S, Rondino F, Botta B, D’Acquarica I, et al. Chirality effects on the IRMPD spectra of basket resorcinarene/nucleoside complexes. Chem Eur J. 2012;18:8320–8.CrossRefGoogle Scholar
  24. 24.
    Prell JS, O’Brien JT, Williams ER. IRPD spectroscopy and ensemble measurements: effects of different data acquisition and analysis methods. J Am Soc Mass Spectrom. 2010;21:800–9.CrossRefGoogle Scholar
  25. 25.
    Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, et al. Gaussian 09, revision D.01. Wallingford: Gaussian Inc; 2009. Scholar
  26. 26.
    Lee C, Yang W, Parr RG. Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density. Phys Rev B. 1988;37:785–9.CrossRefGoogle Scholar
  27. 27.
    Becke AD. Density-functional thermochemistry. III. The role of exact exchange. J Chem Phys. 1993;98:5648–52.CrossRefGoogle Scholar
  28. 28.
    Chiavarino B, Crestoni ME, Fornarini S, Scuderi D, Salpin JY. Interaction of cisplatin with 5′-dgmp: a combined irmpd and theoretical study. Inorg Chem. 2015;54:3513–22.CrossRefGoogle Scholar
  29. 29.
    Corinti D, Coletti C, Re N, Piccirillo S, Giampà M, Crestoni ME, et al. Hydrolysis of cis- and transplatin: structure and reactivity of the aqua complexes in a solvent free environment. RSC Adv. 2017;7:15877–84.CrossRefGoogle Scholar
  30. 30.
    Lias SG, Bartmess JE, Liebman JF, Holmes JL, Levin RD. In: Linstrom PJ, Mallard WG, editors. Ion energetics data in NIST chemistry WebBook, NIST standard reference database number 69. Gaithersburg: National Institute of Standards and Technology; 2016.Google Scholar
  31. 31.
    Turecek F, Moss CL, Pikalov I, Pepin R, Gulyuz K, Polfer NC, et al. Gas-phase structures of phosphopeptide ions: a difficult case. Int J Mass Spectrom. 2013;354:249–56.CrossRefGoogle Scholar
  32. 32.
    Wang D, Gulyuz K, Stedwell CN, Yu L, Polfer NC. Effect of phenol and acidic side chains on the protonation sites of b2ions confirmed by IRMPD spectroscopy. Int J Mass Spectrom. 2012;330:144–51.CrossRefGoogle Scholar
  33. 33.
    Yacovitch TI, Heine N, Brieger C, Wende T, Hock C, Neumark DM, et al. Vibrational spectroscopy of bisulfate/sulfuric acid/water clusters: structure, stability, and infrared multiple-photon dissociation intensities. J Phys Chem A. 2013;117:7081–90.CrossRefGoogle Scholar
  34. 34.
    Chiavarino B, Crestoni ME, Schütz M, Bouchet A, Piccirillo S, Steinmetz V, et al. Cation-pi interactions in protonated phenylalkylamines. J Phys Chem A. 2014;118:7130–8.CrossRefGoogle Scholar
  35. 35.
    Corinti D, Coletti C, Re N, Chiavarino B, Crestoni ME, Fornarini S. Cisplatin binding to biological ligands revealed at the encounter complex level by IR action spectroscopy. Chem Eur J. 2016;22:3794–803.CrossRefGoogle Scholar
  36. 36.
    Corinti D, De Petris A, Coletti C, Re N, Chiavarino B, Crestoni ME, et al. Cisplatin primary complex with l-histidine target revealed by IR multiple photon dissociation (IRMPD) spectroscopy. ChemPhysChem. 2017;18:318–25.CrossRefGoogle Scholar
  37. 37.
    Zehnacker A. Chirality effects in gas-phase spectroscopy and photophysics of molecular and ionic complexes: contribution of low and room temperature studies. Int Rev Phys Chem. 2014;33:151–207.CrossRefGoogle Scholar
  38. 38.
    Voronina L, Rizzo TR. Spectroscopic studies of kinetically trapped conformations in the gas phase: the case of triply protonated bradykinin. Phys Chem Chem Phys. 2015;17:25828–36.CrossRefGoogle Scholar
  39. 39.
    Scott Hopkins W, Marta RA, Steinmetz V, McMahon TB. Mode-specific fragmentation of amino acid-containing clusters. Phys Chem Chem Phys. 2015;17:28548–55.CrossRefGoogle Scholar
  40. 40.
    Graham Cooks R, Patrick JS, Kotiaho T, McLuckey SA. Thermochemical determinations by the kinetic method. Mass Spectrom Rev. 1994;13:287–339.CrossRefGoogle Scholar
  41. 41.
    McLuckey SA, Cameron D, Cooks RG. Proton affinities from dissociations of proton-bound dimers. J Am Chem Soc. 1981;103:1313–7.CrossRefGoogle Scholar
  42. 42.
    Kohnen KL, Sezgin S, Spiteller M, Hagels H, Kayser O. Localization and organization of scopolamine biosynthesis in Duboisia myoporoides R. Br Plant Cell Physiol. 2018;59:107–18.CrossRefGoogle Scholar
  43. 43.
    Dong Y, Li B, Malitsky S, Rogachev I, Aharoni A, Kaftan F, et al. Sample preparation for mass spectrometry imaging of plant tissues: a review. Front Plant Sci. 2016;7:60.Google Scholar
  44. 44.
    Ashtiania F, Sefidkonb F. Tropane alkaloids of Atropa belladonna L. and Atropa acuminata Royle ex Miers plants. J Med Plants Res. 2011;29:6515–22.Google Scholar
  45. 45.
    Robinson KN, Steven RT, Bunch J. Matrix optical absorption in UV-MALDI MS. J Am Soc Mass Spectrom. 2018;29:501–11.CrossRefGoogle Scholar
  46. 46.
    Ehring H, Karas M, Hillenkamp F. Role of photoionization and photochemistry in ionization processes of organic molecules and relevance for matrix-assisted laser desorption ionization mass spectrometry. Org Mass Spectrom. 1992;27:472–80.CrossRefGoogle Scholar
  47. 47.
    Calvano CD, Monopoli A, Ditaranto N, Palmisano F. 1,8-Bis (dimethylamino)naphthalene/9-aminoacridine: a new binary matrix for lipid fingerprinting of intact bacteria by matrix assisted laser desorption ionization mass spectrometry. Anal Chim Acta. 2013;798:56–63.CrossRefGoogle Scholar
  48. 48.
    Shimanouchi T. Tables of molecular vibrational frequencies. Consolidate Volume I: National Bureau of Standards; 1972.Google Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Dipartimento di Chimica e Tecnologie del FarmacoUniversità di Roma “La Sapienza”RomeItaly
  2. 2.Center for Biotechnology and Department for Proteome and Metabolome Research, Faculty of BiologyBielefeld UniversityBielefeldGermany

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