Impact of various lipophilic substituents on ruthenium(II), rhodium(III) and iridium(III) salicylaldimine-based complexes: synthesis, in vitro cytotoxicity studies and DNA interactions

  • Irwin Cassells
  • Tameryn Stringer
  • Alan T. Hutton
  • Sharon Prince
  • Gregory S. Smith
Original Paper


A series of bidentate salicylaldimine ligands was prepared and reacted with either [RuCl(µ-Cl)(p-cymene)]2, [RhCl(µ-Cl)(Cp*)]2 or [IrCl(µ-Cl)(Cp*)]2. All of the compounds were characterised using an array of spectroscopic and analytical techniques, namely, nuclear magnetic resonance (NMR) spectroscopy, infrared (IR) spectroscopy and mass spectrometry. Single crystal X-ray diffraction (XRD) was used to confirm the bidentate coordination mode of the salicylaldimine ligand to the metal centre. The platinum group metal (PGM) complexes were screened against the MCF7 breast cancer cell line. The ruthenium and iridium salicylaldimine complexes showed comparable or greater cytotoxicity than cisplatin against the MCF7 cancer cells, as well as greater cytotoxicity than their rhodium counterparts. Three of the salicylaldimine complexes showed potent activity in the range 18–21 µM. Two of these complexes had a greater affinity for cancerous cells than for CHO non-cancerous cells (SI > 4). Preliminary mechanistic studies suggest that the ruthenium complexes undergo solvation prior to 5′-GMP binding, whereas the iridium complexes were inert to the solvation process.

Graphical abstract


Salicylaldimine Ruthenium–arene Rhodium Iridium Anticancer activity 



Financial support from the University of Cape Town (UCT) and the National Research Foundation (NRF) of South Africa and the Medical Research Council (MRC) of South Africa is gratefully acknowledged. Dr Serah Kimani and Ms Sandra Jordaan are thanked for their contributions.


  1. 1.
    Perone M (1884) Ann Chem Pharm 51:1–29CrossRefGoogle Scholar
  2. 2.
    Rosenberg B, VanCamp L, Trosko JE, Mansour VH (1969) Nature 222:385–386CrossRefPubMedGoogle Scholar
  3. 3.
    Bhandari PR (2012) J Adv Pharm Technol Res 3:202–209CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Hartinger CG, Metzler-Nolte N, Dyson PJ (2012) Organometallics 31:5677–5685CrossRefGoogle Scholar
  5. 5.
    Zhang P, Sadler PJ (2017) J Organomet Chem 839:5–14CrossRefGoogle Scholar
  6. 6.
    Bergamo A, Masi A, Peacock A, Habtemariam A, Sadler PJ, Sava G (2010) J Inorg Biochem 104:79–86CrossRefPubMedGoogle Scholar
  7. 7.
    Berndsen RH, Weiss A, Abdul UK, Wong TJ, Meraldi P, Griffioen AW, Dyson PJ, Nowak-Sliwinska P (2017) Sci Rep 7:43005CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Lucas SJ, Lord RM, Wilson RL, Phillips RM, Sridharan V, McGowan PC (2012) Dalton Trans 41:13800–13802CrossRefPubMedGoogle Scholar
  9. 9.
    Lucas SJ, Lord RM, Basri AM, Allison SJ, Phillips RM, Blacker AJ, McGowan PC (2016) Dalton Trans 45:6812–6815CrossRefPubMedGoogle Scholar
  10. 10.
    Yang J, Shi R, Zhou P, Qiu Q, Li H (2016) J Mol Structure 1106:242–258CrossRefGoogle Scholar
  11. 11.
    Stringer T, Hendricks DT, Guzgay H, Smith GS (2012) Polyhedron 31:486–493CrossRefGoogle Scholar
  12. 12.
    Correia I, Roy S, Matos CP, Borovic S, Butenko N, Cavaco I, Marques F, Lorenzo J, Rodríguez A, Moreno V, Pessoa JC (2015) J Inorg Biochem 147:134–146CrossRefPubMedGoogle Scholar
  13. 13.
    Govender P, Sudding LC, Clavel CM, Dyson PJ, Therrien B, Smith GS (2013) Dalton Trans 42:1267–1277CrossRefPubMedGoogle Scholar
  14. 14.
    Rahman FU, Ali A, Khan I, Guo R, Chen L, Wang H, Li ZT, Lin Y, Zhang DW (2015) Polyhedron 100:264–270CrossRefGoogle Scholar
  15. 15.
    Rahman FU, Ali A, Guo R, Wang WK, Wang H, Li ZT, Lin Y, Zhang DW (2015) Dalton Trans 44:9872–9880CrossRefPubMedGoogle Scholar
  16. 16.
    Sharma V, Beatty A, Wey SP, Dahlheimer J, Pica CM, Crankshaw CL, Bass L, Green MA, Welch MJ, Piwnica-Worms D (2000) Chem Biol 7:335–343CrossRefPubMedGoogle Scholar
  17. 17.
    Stringer T, Taylor D, Guzgay H, Shokar A, Au A, Smith PJ, Hendricks DT, Land KM, Egan TJ, Smith GS (2015) Dalton Trans 44:14906–14917CrossRefPubMedGoogle Scholar
  18. 18.
    Nkoana W, Nyoni D, Chellan P, Stringer T, Taylor D, Smith PJ, Hutton AT, Smith GS (2014) J Organomet Chem 752:67–75CrossRefGoogle Scholar
  19. 19.
    Govender P, Renfrew AK, Clavel CM, Dyson PJ, Therrien B, Smith GS (2011) Dalton Trans 40:1158–1167CrossRefPubMedGoogle Scholar
  20. 20.
    Rahman FU, Ali A, Guo R, Zhang YC, Wang H, Li ZT, Zhang DW (2015) Dalton Trans 44:2166–2175CrossRefPubMedGoogle Scholar
  21. 21.
    Isanbor C, O’Hagan D (2006) J Fluor Chem 127:303–319CrossRefGoogle Scholar
  22. 22.
    Adams M, Barnard L, de Kock C, Smith PJ, Wiesner L, Chibale K, Smith GS (2016) Dalton Trans 45:5514–5520CrossRefPubMedGoogle Scholar
  23. 23.
    Adams M, de Kock C, Smith PJ, Land KM, Liu N, Hopper M, Hsiao A, Burgoyne AR, Stringer T, Meyer M, Wiesner L, Chibale K, Smith GS (2015) Dalton Trans 44:2456–2468CrossRefPubMedGoogle Scholar
  24. 24.
    Kühnert J, Ecorchard P, Lang H (2008) Eur J Inorg Chem 2008:5125–5137CrossRefGoogle Scholar
  25. 25.
    Ornelas C (2011) New J Chem 35:1973–1985CrossRefGoogle Scholar
  26. 26.
    Kirk KL (2006) J Fluor Chem 127:1013–1029CrossRefGoogle Scholar
  27. 27.
    Temmink OH, Emura T, De Bruin M, Fukushima M, Peters GJ (2007) Cancer Sci 98:779–789CrossRefPubMedGoogle Scholar
  28. 28.
    Bennett MA, Huang TN, Matheson TW, Smith AK, Ittel S, Nickerson W (2007) 16. (η6-Hexamethylbenzene)ruthenium complexes. In: Inorganic Syntheses, Wiley, Hoboken, pp 74–78Google Scholar
  29. 29.
    White C, Yates A, Maitlis PM, Heinekey DM (2007) (η5-Pentamethylcyclopentadienyl)rhodium and -iridium compounds. In: Inorganic Syntheses, Wiley, Hoboken, pp 228–234Google Scholar
  30. 30.
    Maqeda L, Makhubela BCE, Smith GS (2015) Polyhedron 91:128–135CrossRefGoogle Scholar
  31. 31.
    SAINT Version 7.60a (2006) Bruker AXS Inc., MadisonGoogle Scholar
  32. 32.
    Sheldrick GM (2004) SHELXS-97, SHELXL-2014 and SADABS version 2.05, University of Göttingen, GermanyGoogle Scholar
  33. 33.
    Barbour LJ (2001) J Supramol Chem 1:189–191CrossRefGoogle Scholar
  34. 34.
    Atwood JL, Barbour LJ (2003) Cryst Growth Des 3:3CrossRefGoogle Scholar
  35. 35.
    Carmichael J, DeGraff WG, Gazdar AF, Minna JD, Mitchell JB (1987) Cancer Res 47:943–946PubMedGoogle Scholar
  36. 36.
    Srisawat T, Chumkaew P, Heed-Chim W, Sukpondma Y, Kanokwiroon K (2013) Trop J Pharm Res 12:71–76Google Scholar
  37. 37.
    Mosmann T (1983) J Immunol Methods 65:55–63CrossRefPubMedGoogle Scholar
  38. 38.
    Abate G, Aseffa A, Selassie A, Goshu S, Fekade B, WoldeMeskal D, Miörner H (2004) J Clin Microbiol 42:871–873CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Stringer T, Taylor D, de Kock C, Guzgay H, Au A, An SH, Sanchez B, O’Connor R, Patel N, Land KM, Smith PJ, Hendricks DT, Egan TJ, Smith GS (2013) Eur J Med Chem 69:90–98CrossRefPubMedGoogle Scholar
  40. 40.
    Shin YG, Bolton JL, van Breemen RB (2002) Comb Chem High Throughput Screen 5:59–64CrossRefGoogle Scholar
  41. 41.
    Prough DS, Bidani A (1999) Anesthesiology 90:1247–1249CrossRefPubMedGoogle Scholar
  42. 42.
    Burgoyne AR, Kaschula CH, Parker MI, Smith GS (2016) Eur J Inorg Chem 2016:1267–1273CrossRefGoogle Scholar
  43. 43.
    Scolaro C, Chaplin AB, Hartinger CG, Bergamo A, Cocchietto M, Keppler BK, Sava G, Dyson PJ (2007) Dalton Trans 43:5065–5072CrossRefGoogle Scholar
  44. 44.
    Dorcier A, Dyson PJ, Gossens C, Rothlisberger U, Scopelliti R, Tavernelli I (2005) Organometallics 24:2114–2123CrossRefGoogle Scholar
  45. 45.
    Reedijk I (2009) Eur J Inorg Chem 2009:1303–1312CrossRefGoogle Scholar

Copyright information

© SBIC 2018

Authors and Affiliations

  • Irwin Cassells
    • 1
  • Tameryn Stringer
    • 1
  • Alan T. Hutton
    • 1
  • Sharon Prince
    • 2
  • Gregory S. Smith
    • 1
  1. 1.Department of ChemistryUniversity of Cape TownRondeboschSouth Africa
  2. 2.Department of Human BiologyUniversity of Cape Town, Medical SchoolObservatorySouth Africa

Personalised recommendations