Professor Christian Hartinger

Habilitation in Inorganic Chemistry (2009), Mag. rer. nat. (1999), Dr. rer. nat. (2001) fromt the University of Vienna, Austria

Biography

2016–, Professor at the University of Auckland (New Zealand)

2011–2015, Associate Professor at the University of Auckland (New Zealand)

2009–2011, Assistant/Associate Professor at the University of Vienna (Austria)

2006–2008, Erwin-Schrödinger-Fellow, EPFL (Switzerland)

1998–2006, Research/University Assistant, University of Vienna (Austria)

Research | Current

Recent research has focused on bioorganometallics with a particular interest in the synthesis of anticancer active mono-, di- and trinuclear compounds with (thio)pyr(id)onato ligands. We design our complexes to exhibit their antitumor activity in the tumor tissue (focusing on selective transport into the tumor) or to possess new modes of action (e.g., dinuclear Ru complexes with lower toxicity than Pt compounds and non-common DNA binding modes). We were the first who could demonstrate that the linkage of two Ru centers can result in improved anticancer activity, possibly by crosslinking biological macromolecules. The most active complex was up to 10-fold more active in resistant cancer cell lines than in the respective wild-type cells. These results indicate that the compounds might be an option to tackle the common problem of developed resistance of tumors, frequently occurring during chemotherapy. Furthermore, we have modified Ru(arene) complexes with maleimide to react selectively with thiol-containing biomolecules, introduced a multitude of bioactive ligand systems and created orally available metallodrugs.

In our group the development of new drug molecules is complemented by extensive bioanalytical studies to elucidate the mode of action of tumor-inhibiting metal complexes. Biophysical methods (separation methods, online and offline MS) have been developed and applied for studies e.g. on the Ru(III) bisindazole compound KP1019. Those experiments contributed to the selection of KP1019 for clinical development, being currently in clinical phase I/IIa trials in a modified formulation. Capillary electrophoresis hyphenated to inductively-coupled plasma mass spectrometry (CE-ICP-MS) was used to show that a Ga-based drug candidate binds in human blood serum preferentially to transferrin, whereas Ru complexes are most often found mainly attached to human serum albumin (HSA). Application of modern mass spectrometry methods resulted for the first time in the binding site elucidation of a metal-based drug on proteins by employing top-down mass spectrometric approaches. The bioanalytical studies are rounded off by the introduction of new methods, such as the first coupling of microemulsion electrokinetic chromatography (MEEKC) to ICP-MS and the development of a new interface to couple CE with ICP-MS. More recently, we have reported studies on the identification of proteins as binding partners for metal-based anticancer agents in cancer cells and we have developed interest in the structural characterisation of the adducts formed between proteins and metal species, all of which help us to better understand how the compounds behave in a biological environment and how to improve their pharmacological activity.

Teaching | Current

CHEM220 - structure and bonding

CHEM320 - bioinorganic chemistry

CHEM691 - coordination

CHEM720 - medicinal inorganic chemistry

CHEM740 - mass spectrometry and applications

CHEM793 - coordination

CHEM795 - ethics, publishing, citing, literature search

CHEM796 - coordination

Distinctions/Honours

2017, Hill Tinsley Medal of the New Zealand Association of Scientists

2017, Hood Fellowship (outgoing to Cambridge, UK)

2016, New Zealand Institute of Chemistry Maurice Wilkins Centre Prize

2016, Society of Biological Inorganic Chemistry Early Career Award

2015, Fellow of the New Zealand Centre at Beijing University                   

2015 – present, Elected member to the Council of the Society of Biological Inorganic Chemistry (SBIC)

2013, Visiting Professor at the University of Vienna, Austria

2011, Carl-Duisberg-Memorial Prize (German Chemical Society)

2010, Visiting Professor, Chimie ParisTech, France

2010, Innovative Teaching Award Bank Austria

2009, Best paper award in Applied Organometallic Chemistry

2006, Schrödinger Fellowship of the Austrian Science Fund

2005, Award of the “Theodor-Körner-Fonds zur Förderung der Wissenschaft und Kunst”

Areas of expertise

Medicinal Chemistry, Biological Inorganic Chemistry, Coordination and Organometallic Chemistry, Development of Anticancer Compounds, Bioanalytical Chemistry (Mass Spectrometry, Capillary Electrophoresis, Hyphenated Systems)

Committees/Professional groups/Services

2017, co-chair of SPACC24, Auckland, New Zealand

2016, chair of AsBIC8, Auckland, New Zealand

2016 – present, Member of the ISBOMC Advisory Committee

2015 – present, Elected member to the Council of the Society of Biological Inorganic Chemistry (SBIC)

2015, Organiser of the 1st Auckland Symposium On Medicinal Inorganic Chemistry

2014, Co-chair ISBOMC 7, Vienna, Austria

2013–2016, Deputy Head of School (Research), School of Chemical Sciences, University of Auckland

2013–2016, Editor of Metallodrugs

2013–present, Associate Editor of Frontiers in Inorganic Chemistry

2010–2012, Management Committee Member COST CM0902 “Molecular Machineries for Ion Translocation Across Biomembranes”

2007, Co-organizer COST WG meeting in Villars-sur-Ollons

2007, local organizing and scientific committee member of ICBIC13

2005, (Co-)Organizer of CESAR meeting on anticancer research

Selected publications and creative works (Research Outputs)

  • Sullivan, M. P., Nieuwoudt, M. K., Bowmaker, G. A., Lam, N. Y. S., Truong, D., Goldstone, D. C., & Hartinger, C. G. (2018). Unexpected arene ligand exchange results in the oxidation of an organoruthenium anticancer agent: the first X-ray structure of a protein-Ru(carbene) adduct. Chemical communications (Cambridge, England), 54 (48), 6120-6123. 10.1039/c8cc02433b
    Other University of Auckland co-authors: David Goldstone, Cather Simpson, Matthew Sullivan, Dianna Truong, Michel Nieuwoudt, Graham Bowmaker
  • Meier, S. M., Kreutz, D., Winter, L., Klose, M. H. M., Cseh, K., Weiss, T., ... Jana, S. (2017). An Organoruthenium Anticancer Agent Shows Unexpected Target Selectivity For Plectin. Angewandte Chemie (International ed. in English), 56 (28), 8267-8271. 10.1002/anie.201702242
  • Sullivan, M. P., Groessl, M., Meier, S. M., Kingston, R. L., Goldstone, D. C., & Hartinger, C. G. (2017). The metalation of hen egg white lysozyme impacts protein stability as shown by ion mobility mass spectrometry, differential scanning calorimetry, and X-ray crystallography. Chemical Communications, 53 (30), 4246-4249. 10.1039/c6cc10150j
    Other University of Auckland co-authors: Richard Kingston, David Goldstone, Matthew Sullivan
  • Holtkamp, H., Grabmann, G., & Hartinger, C. G. (2016). Electrophoretic separation techniques and their hyphenation to mass spectrometry in biological inorganic chemistry. Electrophoresis, 37 (7-8), 959-972. 10.1002/elps.201500502
  • Kubanik, M., Holtkamp, H., Söhnel T, Jamieson, S. M. F., & Hartinger, C. G. (2015). Impact of the halogen substitution pattern on the biological activity of organoruthenium 8-hydroxyquinoline anticancer agents. Organometallics, 34 (23), 5658-5668. 10.1021/acs.organomet.5b00868
    URL: http://hdl.handle.net/2292/34196
    Other University of Auckland co-authors: Stephen Jamieson, Tilo Söhnel
  • Babak, M. V., Meier, S. M., Huber, K. V. M., Reynisson, J., Legin, A. A., Jakupec, M. A., ... Bennett, K. L. (2015). Target profiling of an antimetastatic RAPTA agent by chemical proteomics: Relevance to the mode of action. Chemical Science, 6 (4), 2449-2456. 10.1039/c4sc03905j
    Other University of Auckland co-authors: Johannes Reynisson
  • Babak, M. V., Plażuk D, Meier, S. M., Arabshahi, H. J. O., Reynisson, J., Rychlik, B., ... Strobl, S. (2015). Half-sandwich ruthenium(II) biotin conjugates as biological vectors to cancer cells. Chemistry, 21 (13), 5110-5117. 10.1002/chem.201403974
    Other University of Auckland co-authors: Johannes Reynisson, Muhammad Hanif
  • Meier, S. M., Novak, M. S., Kandioller, W., Jakupec, M. A., Roller, A., Keppler, B. K., & Hartinger, C. G. (2014). Aqueous chemistry and antiproliferative activity of a pyrone-based phosphoramidate Ru(arene) anticancer agent. Dalton Trans, 43 (26), 9851-9855. 10.1039/c4dt00569d

Identifiers

Contact details

Primary office location

SCIENCE CENTRE 302 - Bldg 302
Level 10, Room 1031
23 SYMONDS ST
AUCKLAND 1010
New Zealand

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