Jump to ContentJump to Main Navigation
Show Summary Details
More options …

Zeitschrift für Naturforschung B

A Journal of Chemical Sciences

IMPACT FACTOR 2018: 0.961

CiteScore 2018: 0.91

SCImago Journal Rank (SJR) 2018: 0.263
Source Normalized Impact per Paper (SNIP) 2018: 0.505

See all formats and pricing
More options …
Volume 73, Issue 11


Biolabeling with cobaltocinium tags

Susanne Müller-Bomke
  • Westfälische Wilhelms-Universität Münster, Institute of Inorganic and Analytical Chemistry, Corrensstraße 30, 48149 Münster, Germany
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Michael Sperling
  • Westfälische Wilhelms-Universität Münster, Institute of Inorganic and Analytical Chemistry, Corrensstraße 30, 48149 Münster, Germany
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Heiko Hayen
  • Westfälische Wilhelms-Universität Münster, Institute of Inorganic and Analytical Chemistry, Corrensstraße 30, 48149 Münster, Germany
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Uwe Karst
  • Corresponding author
  • Westfälische Wilhelms-Universität Münster, Institute of Inorganic and Analytical Chemistry, Corrensstraße 30, 48149 Münster, Germany
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2018-08-15 | DOI: https://doi.org/10.1515/znb-2018-0093


A label for amino and thiol functionalities of peptides and proteins based on the activated cobaltocinium hexafluorophosphate succinimide ester (CoS) is presented. Despite the known selectivity of a succinimide ester towards amines, CoS also modifies cysteine residues under the same reaction conditions. The derivatized biomolecules were investigated using liquid chromatography with subsequent electrospray-mass spectrometric detection (LC/ESI-MS). In combination with their remarkable stability under physiological conditions, easy handling and good spectroscopic properties, cobaltocinium ions provide all requirements for a powerful labeling reagent. Furthermore, in direct comparison to the isoelectronic well-established ferrocene reagents, the higher redox potential and the chemical stability of the cobaltocinium moiety add to the benefits as a derivatizing agent for bioanalysis.

Keywords: amines; biolabeling; cobaltocinium; electrospray ionization-mass spectrometry (ESI-MS); thiols

Dedicated to: Professor Bernt Krebs on the occasion of his 80th birthday.


  • [1]

    A. Leitner, W. Lindner, Current chemical tagging strategies for proteome analysis by mass spectrometry, J. Chromatogr. B 2004, 813, 1.CrossrefGoogle Scholar

  • [2]

    A. Tholey, D. Schaumlöffel, Metal labelling for quantitative protein and proteome analysis using inductively coupled plasma mass spectrometry, Trends Anal. Chem. 2010, 29, 399.CrossrefGoogle Scholar

  • [3]

    D. Kretschy, G. Koellensperger, S. Hann, Elemental labelling combined with liquid chromatography inductively coupled plasma mass spectrometry for quantification of biomolecules: a review, Anal. Chim. Acta 2012, 750, 98.CrossrefWeb of ScienceGoogle Scholar

  • [4]

    B. Campanella, E. Bramanti, Detection of proteins by hyphenated techniques with endogenous metal tags and metal chemical labeling, Analyst 2014, 139, 4124.CrossrefGoogle Scholar

  • [5]

    Z. R. Liu, X. T. Li, G. Y. Xiao, B. B. Chen, M. He, B. Hu, Application of inductively coupled plasma mass spectrometry in the quantitative analysis of biomolecules with exogenous tags, a review, Trends Anal. Chem. 2017, 93, 78.Web of ScienceCrossrefGoogle Scholar

  • [6]

    M. Salmain, G. Jaouen, Side-chain selective and covalent labelling of proteins with transition organometallic complexes. Perspectives in biology, C. R. Chimie 2003, 6, 249.CrossrefGoogle Scholar

  • [7]

    H. E. Amouri, Y. Besace, J. Vaissermann, G. Jaouen, Synthesis, reactivity and X-ray molecule structure of the activated ester complex [(η5-C5H4COONS)Co(CO)2] (NS=N-succinimidyl), J. Organomet. Chem. 1996, 515, 103.CrossrefGoogle Scholar

  • [8]

    D. Pröfrock, A. Prange, Chemical labels and natural element tags for the quantitative analysis of bio-molecules, J. Anal. At. Spectrom. 2008, 23, 432.Web of ScienceCrossrefGoogle Scholar

  • [9]

    S. Bomke, M. Sperling, U. Karst, Organometallic derivatizing agents in bioanalysis, Anal. Bioanal. Chem. 2010, 397, 3483.CrossrefWeb of ScienceGoogle Scholar

  • [10]

    G. Schwarz, L. Mueller, S. Beck, M. W. Linscheid, DOTA based metal labels for protein quantification: a review, J. Anal. At. Spectrom. 2014, 29, 221.Web of ScienceCrossrefGoogle Scholar

  • [11]

    T. C. de Bang, S. Husted, Lanthanide elements as labels for multiplexed and targeted analysis of proteins, DNA and RNA using inductively-coupled plasma mass spectrometry, Trends Anal. Chem. 2015, 72, 45.Web of ScienceCrossrefGoogle Scholar

  • [12]

    Y. Liang, L. M. Yang, Q. Wang, An ongoing path of element-labelling/tagging strategies towards quantitative bioanalysis using ICP-MS, Appl. Spectrosc. Rev. 2015, 51, 117.Google Scholar

  • [13]

    J. E. Sheats, M. Rausch, Synthesis and properties of cobalticinium salts. I. Synthesis of monosubstituted cobalticinium salt, J. Org. Chem. 1970, 35, 3245.CrossrefGoogle Scholar

  • [14]

    E. O. Fischer, G. E. Herberich, Über die Reaktivität des Di-cyclopentadienyl-kobalt(III)-Kations, Chem. Ber. 1961, 94, 1517.CrossrefGoogle Scholar

  • [15]

    T. J. Gill, L. T. Mann, Studies of synthetic polypeptide antigens, J. Immun. 1966, 5, 906.Google Scholar

  • [16]

    F. Noor, A. Wüstholz, R. Kinscherf, N. Metzler-Nolte, A cobaltocenium-peptide bioconjugate shows enhanced cellular uptake and directed nuclear delivery, Angew. Chem. Int. Ed. 2005, 44, 2429.CrossrefGoogle Scholar

  • [17]

    J. T. Chantson, M. V. V. Falzacappa, S. Crovella, N. Metzler-Nolte, Solid-phase synthesis, characterization, and antibacterial activities of metallocene-peptide bioconjugates, Chem. Med. Chem. 2006, 1, 1268.CrossrefGoogle Scholar

  • [18]

    J. T. Chantson, M. V. V. Falzacappa, S. Crovella, N. Metzler-Nolte, Antibacterial activities of ferrocenoyl- and cobaltocenium-peptide bioconjugates, J. Org. Chem. 2005, 690, 4564.CrossrefGoogle Scholar

  • [19]

    I. Lavastre, J. Bescancon, P. Brossiert, C. Moise, The use of metallocenic esters of N-hydroxysuccinimide for metallohapten synthesis, Appl. Organom. Chem. 1991, 5, 143.CrossrefGoogle Scholar

  • [20]

    A. L. Bordes, B. Limoges, P. Brossier, C. Degrand, Simultaneous homogenous immunoassay of phenytoin and phenobarbital using a Nafion-loaded carbon paste electrode and two redox cationic labels, Anal. Chim. Acta 1997, 356, 195.CrossrefGoogle Scholar

  • [21]

    D. R. van Staveren, T. Weyhermüller, N. Metzler-Nolte, Organometallic β-turn mimetics. A structural and spectroscopic study of inter-stand hydrogen bonding in ferrocene and cobaltocenium conjugates of amino acids and dipeptides, Dalton Trans. 2003, 210.Google Scholar

  • [22]

    A. Maurer, H.-B. Kraatz, N. Metzler-Nolte, Synthesis and electrochemical characterization of metallocene-PNA oligomers, Eur. J. Inorg. Chem. 2005, 16, 3207.Google Scholar

  • [23]

    P. D. Beer, C. Hazlewood, D. Hesek, J. Hodacova, S. E. Stokes, Anion recognition by acyclic redox-responsive amide-linked cobaltocenium receptors, J. Chem. Soc. Dalton Trans. 1993, 8, 1327.Google Scholar

  • [24]

    P. D. Beer, S. E. Stokes, Anion recognition by amide-linked pyridyl and pyridinium substituted cobaltocinium receptors, Polyhedron 1995, 7, 873.Google Scholar

  • [25]

    S. Wiese, T. Gronemeyer, R. Ofman, M. Kunze, C. P. Grou, J. A. Almeida, M. Eisenacher, C. Stephan, H. Hayen, M. Pawlas, C. Bunse, L. Schollenberger, T. Korosec, H. R. Waterham, W. Schliebs, R. Erdmann, J. Berger, H. E. Meyer, W. Just, J. E. Azevedo, R. J. A. Wanders, B. Warscheid, Proteomic characterization of mouse kidney peroxisomes by tandem mass spectrometry and protein correlation profiling, Mol. Cell. Proteomics 2007, 6, 2045.CrossrefGoogle Scholar

  • [26]

    M. Brinkley, A brief survey of methods for preparing protein conjugates with dyes, haptens and crosslinking reagents, Bioconjugate Chem. 1992, 3, 2.CrossrefGoogle Scholar

  • [27]

    T. Pfeifer, R. Janzen, T. Steingrobe, M. Sperling, C. Engelhard, W. Buscher, Development of a novel low-flow ion source/sampling cone geometry for inductively coupled plasma mass spectrometry and application in hyphenated techniques, Spectrochim. Acta, Part B 2012, 76, 48.Web of ScienceCrossrefGoogle Scholar

About the article

aThis author’s part of the work was carried out at Leibniz-Institut für Analytische Wissenschaften – ISAS – e.V., Otto-Hahn-Straße 6b, 44227 Dortmund, Germany

Received: 2018-05-20

Accepted: 2018-07-19

Published Online: 2018-08-15

Published in Print: 2018-11-27

Citation Information: Zeitschrift für Naturforschung B, Volume 73, Issue 11, Pages 781–791, ISSN (Online) 1865-7117, ISSN (Print) 0932-0776, DOI: https://doi.org/10.1515/znb-2018-0093.

Export Citation

©2018 Walter de Gruyter GmbH, Berlin/Boston.Get Permission

Comments (0)

Please log in or register to comment.
Log in