Skip to main content
SpringerLink
Log in

Synthesis, substitution kinetics, DNA/BSA binding and cytotoxicity of tridentate N^E^N (E = NH, O, S) pyrazolyl palladium(II) complexes

  • Original Paper
  • Published:
JBIC Journal of Biological Inorganic Chemistry Aims and scope Submit manuscript

Abstract

The pincer complexes, [Pd(L1)Cl]BF4 (PdL1), [Pd(L2)Cl]BF4 (PdL2), [Pd(L3)Cl]BF4 (PdL3), [Pd(L4)Cl]BF4 (PdL4) were prepared by reacting the corresponding ligands, 2,6-bis[(1H-pyrazol-1-yl)methyl]pyridine (L1), bis[2-(1H-pyrazol-1-yl)ethyl]amine (L2), bis[2-(1H-pyrazol-1-yl)ethyl]ether (L3), and bis[2-(1H-prazol-1-yl)ethyl]sulphide (L4) with [PdCl2(NCMe)]2 in the presence NaBF4. The solid‐state structures of complexes PdL1–PdL4 confirmed a tridentate coordination mode, with one chloro ligand completing the coordination sphere to afford square-planar complexes. Chemical behaviour of the complexes in solution confirms their stability in both aqueous and DMSO stock media. The electrochemical properties of the compounds showed irreversible two-electron reduction process. Kinetic reactivity of Pd complexes with the biological nucleophiles viz, thiourea (Tu), L-methionine (L-Met) and guanosine 5′-diphosphate disodium salt (5’-GMP) followed the order: PdL2 < PdL3 < PdL4, and PdL2 < PdL1. The kinetic reactivity is subject to the electronic effects of the spectator ligand(s), and the trend was supported by the DFT computed results. The palladium complexes PdL1–PdL4 bind to calf thymus (CT-DNA) via intercalation mode. In addition, the bovine serum albumin (BSA) showed good binding affinity to the complexes. The mode of quenching mechanism of the intrinsic fluorescence of CT-DNA and BSA by the complexes was found to be static. The order of interactions of the complexes with DNA and BSA was in tandem with the rate of substitution kinetics. The complexes, however, displayed relatively low cytotoxicity (IC50 > 100 µM) when tested against the human cervical adenocarcinoma (HeLa) cell line and the transformed human lung fibroblast cell line (MRC-5 SV2).

Graphical abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Scheme 1
Fig. 1
Fig. 2
Chart 3

Similar content being viewed by others

References

  1. Joksimović N, Janković N, Petronijević J, Baskić D, Popovic S, Todorović D, Zarić M, Klisurić O, Vraneš M, Tot A (2020) Med Chem 16:78–92

    Article  PubMed  Google Scholar 

  2. Wei X, Yang Y, Ge J, Lin X, Liu D, Wang S, Zhang J, Zhou G, Li S (2020) J Inorg Biochem 202:110857

    Article  CAS  PubMed  Google Scholar 

  3. Franich AA, Živković MD, Ćoćić D, Petrović B, Milovanović M, Arsenijević A, Milovanović J, Arsenijević D, Stojanović B, Djuran MI (2019) J Biol Inorg Chem 24:1009–1022

    Article  CAS  PubMed  Google Scholar 

  4. Lima MA, Costa VA, Franco MA, de Oliveira GP, Deflon VM, Rocha FV (2020) Inorg Chem Commun 112:107708

    Article  CAS  Google Scholar 

  5. Divsalar A, Saboury AA, Mansoori-Torshizi H, Ahmad F (2010) J Phys Chem B 114:3639–3647

    Article  CAS  PubMed  Google Scholar 

  6. Jahromi EZ, Divsalar A, Saboury AA, Khaleghizadeh S, Mansouri-Torshizi H, Kostova I (2016) J Iran Chem Soc 13:967–989

    Article  CAS  Google Scholar 

  7. Darabi F, Hadadzadeh H, Simpson J, Shahpiri A (2016) New J Chem 40:9081–9097

    Article  CAS  Google Scholar 

  8. Churusova SG, Aleksanyan DV, Rybalkina EY, Susova OY, Brunova VV, Aysin RR, Nelyubina YV, Peregudov AS, Gutsul EI, Klemenkova ZS (2017) Inorg Chem 56:9834–9850

    Article  CAS  PubMed  Google Scholar 

  9. Muralisankar M, Basheer SM, Haribabu J, Bhuvanesh NS, Karvembu R, Sreekanth A (2017) Inorg Chim Acta 466:61–70

    Article  CAS  Google Scholar 

  10. Fong TTH, Lok CN, Chung CYS, Fung YME, Chow PK, Wan PK, Che CM (1939) Angew Chem Int Ed 55(2016):11935–11941

    Google Scholar 

  11. Ž.D. Bugarčić, G. Liehr, R. van Eldik, J. Chem. Soc., Dalton Trans. (2002) 951–956.

  12. Bogojeski J, Jelić R, Petrović D, Herdtweck E, Jones PG, Tamm M, Bugarčić ŽD (2011) Dalton Trans 40:6515–6523

    Article  CAS  PubMed  Google Scholar 

  13. Bugarčić ŽD, Petrović B, Zangrando E (2004) Inorg Chim Acta 357:2650–2656

    Article  Google Scholar 

  14. Soldatović T, Shoukry M, Puchta R, Bugarčić ŽD, van Eldik R (2009) Eur J Inorg Chem 2009:2261–2270

    Article  Google Scholar 

  15. D. Jaganyi, F. Tiba, O.Q. Munro, B. Petrović, Ž.D. Bugarčić, Dalton Trans. (2006) 2943–2949.

  16. D.O. Onunga, D. Jaganyi, A. Mambanda, J Coord Chem. (2019) 1–17.

  17. Ćoćić D, Jovanović S, Radisavljević S, Korzekwa J, Scheurer A, Puchta R, Baskić D, Todorović D, Popović S, Matić S (2018) J Inorg Biochem 189:91–102

    Article  PubMed  Google Scholar 

  18. R.O. Omondi, R. Bellam, S.O. Ojwach, D. Jaganyi, A.A. Fatokun, J. Inorg. Biochem. (2020) 111156.

  19. Sorrell TN, Malachowski MR (1983) Inorg Chem 22:1883–1887

    Article  CAS  Google Scholar 

  20. García-Antón J, Pons J, Solans X, Font-Bardia M, Ros J (2003) Eur J Inorg Chem 2003:3952–3957

    Article  Google Scholar 

  21. Ojwach SO, Guzei IA, Darkwa J, Mapolie SF (2007) Polyhedron 26:851–861

    Article  CAS  Google Scholar 

  22. A.S. Potapov, E.A. Nudnova, G.A. Domina, L.N. Kirpotina, M.T. Quinn, A.I. Khlebnikov, I.A. Schepetkin, Dalton Trans. (2009) 4488–4498.

  23. Cooper SRI (2020) CrystEngComm 22:7186

    Article  Google Scholar 

  24. Allen FH (2002) Crystallogr B58:380

    CAS  Google Scholar 

  25. Zhao J, Xu Z, Lin J, Gou S (2017) Inorg Chem 56:9851–9859

    Article  CAS  PubMed  Google Scholar 

  26. Tan C, Liu J, Li H, Zheng W, Shi S, Chen L, Ji L (2008) J Inorg Biochem 102:347–358

    Article  CAS  PubMed  Google Scholar 

  27. Hall MD, Telma KA, Chang K-E, Lee TD, Madigan JP, Lloyd JR, Goldlust IS, Hoeschele JD, Gottesman MM (2014) Cancer Res 74:3913–3922

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Moon S, Hanif M, Kubanik M, Holtkamp H, Söhnel T, Jamieson SM, Hartinger CG (2015) ChemPlusChem 80:231–236

    Article  CAS  Google Scholar 

  29. Shabbir M, Akhter Z, Ahmad I, Ahmed S, Shafiq M, Mirza B, McKee V, Munawar KS, Ashraf AR (2016) J Mol Struct 1118:250–258

    Article  CAS  Google Scholar 

  30. Brinck T, Borrfors AN (2019) J Mol Model 25:125

    Article  PubMed  Google Scholar 

  31. Nkabinde SV, Kinunda G, Jaganyi D (2017) Inorg Chim Acta 466:298–307

    Article  CAS  Google Scholar 

  32. Pitteri B, Bortoluzzi M, Marangoni G (2005) Transition Met Chem 30:1008–1013

    Article  CAS  Google Scholar 

  33. Miller TM, Bederson B (1978) Adv At Mol Opt Phys 13:1–55

    Article  Google Scholar 

  34. Ghahremanpour MM, van Maaren PJ, Caleman C, Hutchison GR, Van der Spoel D (2018) J Chem Theory Comput 14:5553–5566

    Article  CAS  PubMed  Google Scholar 

  35. Kosović M, Jovanović S, Bogdanović GA, Giester G, Jaćimović Ž, Bugarčić ŽD, Petrović B (2016) J Coord Chem 69:2819–2831

    Article  Google Scholar 

  36. Kosović M, Jaćimović Ž, Bugarčić ŽD, Petrović B (2015) J Coord Chem 68:3003–3012

    Article  Google Scholar 

  37. Jaganyi D, Hofmann A, van Eldik R (2001) Angew Chem Int Ed 40:1680–1683

    Article  CAS  Google Scholar 

  38. Ćoćić D, Jovanović S, Nišavić M, Baskić D, Todorović D, Popović S, Bugarčić ŽD, Petrović B (2017) J Inorg Biochem 175:67–79

    Article  PubMed  Google Scholar 

  39. Jovanović S, Obrenčević K, Bugarčić ŽD, Popović I, Žakula J, Petrović B (2016) Dalton Trans 45:12444–12457

    Article  PubMed  Google Scholar 

  40. J.D. Atwood Journal (1997). Inorganic and organometallic reaction mechanisms. John Wiley & Sons

  41. Bellam R, Jaganyi D, Mambanda A, Robinson R (2018) New J Chem 42:12557–12569

    Article  CAS  Google Scholar 

  42. Bellam R, Jaganyi D, Mambanda A, Robinson R, BalaKumaran MD (1894) RSC Adv 9(2019):31877–31883

    Google Scholar 

  43. Zhou X-Q, Sun Q, Jiang L, Li S-T, Gu W, Tian J-L, Liu X, Yan S-P (2015) Dalton Trans 44:9516–9527

    Article  CAS  PubMed  Google Scholar 

  44. Vuradi RK, Dandu K, Yata PK, Mallepally RR, Chintakuntla N, Ch R, Thakur SS, Rao CM, Satyanarayana S (2018) New J Chem 42:846–859

    Article  CAS  Google Scholar 

  45. Omondi RO, Bellam R, Ojwach SO, Jaganyi D, Fatokun AA (2020) J Inorg Biochem 210:111156

    Article  CAS  PubMed  Google Scholar 

  46. Onunga DO, Bellam R, Mutua GK, Sitati M, BalaKumaran MD, Jaganyi D, Mambanda A (2020) J Inorg Biochem 213:111261

    Article  CAS  PubMed  Google Scholar 

  47. Mukherjee S, Mitra I, Fouzder C, Mukherjee S, Ghosh S, Chatterji U, Moi SC (2017) J Mol Liq 247:126–140

    Article  CAS  Google Scholar 

  48. Karami K, Alinaghi M, Amirghofran Z, Lipkowski J (2018) Inorg Chim Acta 471:797–807

    Article  CAS  Google Scholar 

  49. İnci D, Aydın R, Zorlu Y (2021) Eur Biophys J 50:771–785

    Article  PubMed  Google Scholar 

  50. Cory M, McKee DD, Kagan J, Henry D, Miller JA (1985) J Am Chem Soc 107:2528–2536

    Article  CAS  Google Scholar 

  51. Mitra I, Mukherjee S, Misini B, Das P, Dasgupta S, Linert W, Moi SC (2018) New J Chem 42:2574–2589

    Article  CAS  Google Scholar 

  52. Milutinović MM, Rilak A, Bratsos I, Klisurić O, Vraneš M, Gligorijević N, Radulović S, Bugarčić ŽD (2017) J Inorg Biochem 169:1–12

    Article  PubMed  Google Scholar 

  53. Poloni DM, Dangles O, Vinson JA (2019) J Agric Food Chem 67:9139–9147

    Article  CAS  PubMed  Google Scholar 

  54. Fetzer L, Boff B, Ali M, Xiangjun M, Collin J-P, Sirlin C, Gaiddon C, Pfeffer M (2011) Dalton Trans 40:8869–8878

    Article  CAS  PubMed  Google Scholar 

  55. Cheng Z-J, Zhao H-M, Xu Q-Y, Liu R (2013) J Pharm Anal 3:257–269

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Schmidt C, Robinson CV (2014) FEBS J 281:1950–1964

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Zhou X-Q, Li Y, Zhang D-Y, Nie Y, Li Z-J, Gu W, Liu X, Tian J-L, Yan S-P (2016) Eur J Med Chem 114:244–256

    Article  CAS  PubMed  Google Scholar 

  58. G. Ayyannan, M. Mohanraj, M. Gopiraman, R. Uthayamalar, G. Raja, N. Bhuvanesh, R. Nandhakumar, C. Jayabalakrishnan, Inorg. Chim. Acta. (2020) 119868.

  59. Karami K, Hosseini-Kharat M, Sadeghi-Aliabadi H, Lipkowski J, Mirian M (2014) Eur J Med Chem 73:8–17

    Article  CAS  PubMed  Google Scholar 

  60. R.O. Omondi, S.O. Ojwach, D. Jaganyi, Inorg. Chim. Acta. (2020) 119883.

  61. R.O. Omondi, N.R. Sibuyi, A.O. Fadaka, M. Meyer, D. Jaganyi, S.O. Ojwach, Dalton Trans. (2021).

Download references

Acknowledgements

We are grateful for financial assistance from the University of KwaZulu-Natal, National Research Foundation (NRF-South Africa, CPRR-98938) and Liverpool John Moores University, UK (2017 Seed Corn Grant to AAF). Mr Sizwe Zamisa is also acknowledged for refining the structures of complexes PdL1–PdL4. The authors would like to thank the National Integrated Cyber Infrastructure System, Centre for High Performance Computing (CHPC), Department of Science and Technology, Republic of South Africa for software license.

Author information

Author notes

  1. Reinner O. Omondi

    Present address: Department of Chemistry, University of Cape Town, Rondebosch, 7701, South Africa

Authors and Affiliations

  1. School of Chemistry and Physics, University of KwaZulu-Natal, Private Bag X01, Scottsville, Pietermaritzburg, 3209, South Africa

    Reinner O. Omondi & Stephen O. Ojwach

  2. Department of Biotechnology, University of the Western Cape, Private Bag X17, Bellville, Cape Town, 7535, South Africa

    Adewale O. Fadaka

  3. Department of Anesthesia, Division of Pain Management, Cincinnati Children’s Hospital, Medical Center, Burnet 3322, Avenue, Cincinnati, OH, 45229, USA

    Adewale O. Fadaka

  4. Centre for Natural Products Discovery (CNPD), School of Pharmacy and Biomolecular Sciences, Faculty of Science, Liverpool John Moores University, Liverpool, L3 3AF, UK

    Amos A. Fatokun

  5. School of Pure and Applied Sciences, Mount Kenya University, P.O. Box 342-01000, Thika, Kenya

    Deogratius Jaganyi

  6. Department of Chemistry, Faculty of Applied Sciences, Durban University of Technology, P.O. Box 1334, Durban, 4000, South Africa

    Deogratius Jaganyi

Authors
  1. Reinner O. Omondi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Adewale O. Fadaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Amos A. Fatokun
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Deogratius Jaganyi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Stephen O. Ojwach
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Stephen O. Ojwach.

Ethics declarations

Conflict of interest

The authors declare no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (PDF 4006 kb)

Rights and permissions

Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Omondi, R.O., Fadaka, A.O., Fatokun, A.A. et al. Synthesis, substitution kinetics, DNA/BSA binding and cytotoxicity of tridentate N^E^N (E = NH, O, S) pyrazolyl palladium(II) complexes. J Biol Inorg Chem 27, 653–664 (2022). https://doi.org/10.1007/s00775-022-01959-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00775-022-01959-y

Keyword

Search

Navigation