, Volume 32, Issue 1, pp 33–47 | Cite as

New platinum(II) and palladium(II) complexes with substituted terpyridine ligands: synthesis and characterization, cytotoxicity and reactivity towards biomolecules

  • Aleksandar SavićEmail author
  • Tiziano Marzo
  • Federica Scaletti
  • Lara Massai
  • Gianluca Bartoli
  • Richard Hoogenboom
  • Luigi Messori
  • Rik Van DeunEmail author
  • Kristof Van Hecke


A series of palladium(II) (13) and platinum(II) chloride complexes (4 and 5) with 2,2′:6′,2″-terpyridine (terpy) derivatives substituted at the 4′ position, was synthesized and fully characterized. Single crystal X-ray diffraction analysis of complexes 2, 3 and 5 showed tridentate coordination of the 4′-substituted terpyridine (terpy) ligands to the metal center. Moreover, in vitro cytotoxic activity of these complexes toward a panel of human cancer cell lines (lung cancer A549, colorectal cancer HCT116, ovarian cancer IGROV-1) and toward normal cell line HDF (dermal fibroblast) was determined by Trypan Blue exclusion assay. Overall, the tested compounds manifested a relevant cytotoxicity for the selected cancer cell lines with complex 4 also showing a modest cytotoxicity on the normal cell lines. To better understand the mode of action of these metal complexes, their reactivity with three model proteins, i.e. hen egg white lysozyme (HEWL), cytochrome c (cyt c) and ribonuclease A (RNase A) were comparatively investigated through ESI–MS analysis. The results highlighted a different behavior between the two series of complexes being platinum compounds more reactive toward RNase and cyt c than palladium compounds. Based on the obtained results, it is proposed that in presence of RNase A and cyt c, the platinum complexes undergo activation through release of labile ligands followed by binding to the protein. In contrast, palladium complexes revealed a far lower reactivity implying the likely occurrence of a different mechanism of action.


Platinum and palladium complexes Single crystal X-ray diffraction analysis Anticancer drugs Interactions with biomolecules 



A.S., R.V.D. and K.V.H. thank the Erasmus Mundus Basileus V project. T.M. thanks AIRC-FIRC (Fondazione Italiana per la Ricerca sul Cancro, 3-years Fellowship for Italy Project Code: 18044) and University of Pisa (PRA_2017_25) for financial support. CIRCMSB, Dr. Serena Pillozzi and Prof. Annarosa Arcangeli are also acknowledged. CISM (University of Florence) is acknowledge for recording ESI–MS spectra. K.V.H. and R.V.D. thank the Hercules Foundation (Project AUGE/11/029 “3D-SPACE: 3D Structural Platform Aiming for Chemical Excellence”) for funding. K.V.H. thanks the Research Foundation—Flanders (FWO) (Project for financial support.

Supplementary material

10534_2018_155_MOESM1_ESM.pdf (1010 kb)
Supplementary material 1 (PDF 1009 kb)


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Copyright information

© Springer Nature B.V. 2018

Authors and Affiliations

  • Aleksandar Savić
    • 1
    Email author
  • Tiziano Marzo
    • 2
    • 3
  • Federica Scaletti
    • 2
  • Lara Massai
    • 2
  • Gianluca Bartoli
    • 4
  • Richard Hoogenboom
    • 5
  • Luigi Messori
    • 2
  • Rik Van Deun
    • 6
    Email author
  • Kristof Van Hecke
    • 7
  1. 1.Faculty of ChemistryUniversity of BelgradeBelgradeSerbia
  2. 2.Department of ChemsitryUniversity of FlorenceSesto FiorentinoItaly
  3. 3.Department of Chemistry and Industrial ChemistryUniversity of PisaPisaItaly
  4. 4.Department of Experimental and Clinical MedicineUniversity of FlorenceFlorenceItaly
  5. 5.Department of Organic and Macromolecular Chemistry, Supramolecular Chemistry Group, Centre of Macromolecular Chemistry (CMaC)Ghent UniversityGhentBelgium
  6. 6.Department of Chemistry, L³–Luminescent Lanthanide LabGhent UniversityGhentBelgium
  7. 7.Department of Chemistry, XStructGhent UniversityGhentBelgium

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