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Theoretical study of anticancer drug trans-[Pd(dmnp)2Cl2] binding to DNA purine bases, phosphate group and amino acid residues

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Abstract

The reaction mechanism of the binding of the completely hydrolyzed trans-[Pd(dmnp)2Cl2] (dmnp = 2,6-dimethyl-4-nitropyridine) complexes to DNA and peptides was investigated computationally using model molecules and density functional theory calculations at the B3LYP level. To test the solvent effect, single-point energy calculations for the structures optimized in all reactions were conducted by employing the polarizable continuum model (IEF-PCM). The pentammineruthenium fragment had been intensively studied and also constituted a good model for antitumor trans-[Pd(dmnp)2Cl2], while the considered bases/ligands had been chosen as models for the main binding sites of DNA, nucleobases, and phosphate backbone and proteins, nitrogen-containing histidyl, and sulfur-containing residue such as methionine or cysteine. The activation free energies had been calculated for all the considered metal binding sites both in the gas phase and in solution and allowed building a binding affinity order for the considered nucleic acid or protein binding sites. Additionally, to better understand the interactions between the compounds and binding sites, the natural orbital population analysis (NPA) was adopted for every stationary point to employ the mutative trend of the net charge on the three important atoms which directly related to the reactions.

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References

  1. Rosenberg B, Van Camp L, Krigas T (1965) Nature 205:698

    Article  CAS  Google Scholar 

  2. Wong E, Giandomenico CM (1999) Chem Rev 99:2451

    Article  CAS  Google Scholar 

  3. Gianomenico C, Christen M (2000) U.S. Patent 6413953

  4. Lippert B (1999) Cisplatin: chemistry and biochemistry of a leading anticancer drug. Wiley-VCH, Weinheim

  5. Lippard SJ (1995) Progress in inorganic chemistry: bioinorganic chemistry, vol 48. Wiley, Sydney

  6. Clarke MJ, Zhu F, Frasca DR (1999) Chem Rev 99:2511

    Article  CAS  Google Scholar 

  7. Bear JL, Gray HB, Rainen L, Chang IM, Howard R, Serio G, Kimball AP (1975) Cancer Chemother Rep 1(59):611

    Google Scholar 

  8. Giraldi S, Sava G, Bertoli G, Mestroni G, Zassinovich G (1977) Cancer Res 37:2662

    CAS  Google Scholar 

  9. Graham RD, Williams DR (1979) J Inorg Nucl Chem 41:1245

    Article  CAS  Google Scholar 

  10. Quiroga AG, Perez JM, Montero EI, West DX, Alonso C, Navarro-Ranninger C (1999) J Inorg Biochem 75:293

    Article  CAS  Google Scholar 

  11. Matesanz AI, Perez JM, Navarro P, Moreno JM, Colacio E, Souza P (1999) J Inorg Biochem 76:29

    Article  CAS  Google Scholar 

  12. Kovala-Demertzi D, Domopoulou A, Demertzis MA, Valle G, Papageorgiu A (1997) J Inorg Biochem 68:147

    Article  CAS  Google Scholar 

  13. Al-Allaf TAK, Rashan LJ (2001) Boll Chim Farm 140(3):205

    CAS  Google Scholar 

  14. Natile G, Coluccia M (2001) Coord Chem Rev 216–217:383

    Article  Google Scholar 

  15. Farrell N, Ha TTB, Souchard JP, Wimmer FL, Cross S, Johnson NP (1989) J Med Chem 32:2240

    Article  CAS  Google Scholar 

  16. Collucia M, Nassi A, Loseto F, Boccarelli A, Mariggio MA, Giordano D, Intini FP, Caputo P, Natile G (1993) J Med Chem 36:510

    Article  Google Scholar 

  17. Montero EI, Diaz S, Gonzales-Vadillo A, Perez JM, Alonso C, Navarro-Ranninger C (1999) J Med Chem 42:4264

    Article  CAS  Google Scholar 

  18. Livingstone SE (1978) Cancer Forum 15:144

    CAS  Google Scholar 

  19. Bunger J, Stork J, Stalder K (1996) Int Arch Occup Environ Health 69:33

    Article  CAS  Google Scholar 

  20. Farrell N (1989) In: James BR, Ugo R (eds) Catalysis by metal complexes. Reidel-Kluwer, Dordrecht, The Netherlands, pp 183–207 (Chapter 8)

    Google Scholar 

  21. Farrell N, Gomes Carneiro TM, Einstein FWB, Jones T, Skov KA (1984) Inorg Chim Acta 92:61

    Article  CAS  Google Scholar 

  22. Farrell N, Gomes de Carneiro TM (1987) Inorg Chim Acta 126:137

    Article  CAS  Google Scholar 

  23. Kuduk-Jaworska J, Puszko A, Kubiak M, Pelczynska M (2004) J Inorg Biochem 98:1447

    Article  CAS  Google Scholar 

  24. Opolski A, Kuduk-Jaworska J, Wietrzyk J, Wojdat E, Waszkiewicz K, Romaniewska A, Radzikowski Cz (2000) Anti-Cancer Drugs 11:363

    Article  CAS  Google Scholar 

  25. Neva B, Cecilia C, Alessandro M, Nazzareno R (2007) J Phys Chem B 111:9955

    Article  Google Scholar 

  26. Christian G, Ivano T, Ursula R (2009) J Phys Chem A 113:11888

    Article  Google Scholar 

  27. Fuertes MA, Alonso C, Perez JM (2003) Chem Rev 103:645

    Article  CAS  Google Scholar 

  28. Fregona D, Giovagnini L, Ronconi L, Marzano C, Trevisan A, Sitran S, Biondi B, Bordin F (2003) J Inorg Biochem 93:181

    Article  CAS  Google Scholar 

  29. Zhu SR, Matilla A, Tercero JM, Vijayaragavan V, Walmsley JA (2004) Inorg Chim Acta 357:411

    Article  CAS  Google Scholar 

  30. Akdi K, Vilaplana RA, Kamah S, Gonzalez-Vilchez F (2005) J Inorg Biochem 99:1360

    Article  CAS  Google Scholar 

  31. Reedijk J (2003) Pro Natl Acad Sci USA 100:3611

    Article  CAS  Google Scholar 

  32. Lim MC, Martin RB (1976) J Inorg Nucl Chem 38:1911

    Article  CAS  Google Scholar 

  33. Nelson DJ, Yeagle PL, Miller TL, Martin RB (1976) Bioinorg Chem 5:353

    Article  CAS  Google Scholar 

  34. Burda JV, Zeizinger M, Sponer J, Leszczynski J (2000) J Chem Phys 113:2224

    Article  CAS  Google Scholar 

  35. Zeizinger M, Burda JV, Sponer J, Kapsa V, Leszczynski J (2001) J Phys Chem A 105:8086

    Article  CAS  Google Scholar 

  36. Burda JV, Zeizinger M, Leszczynski J (2004) J Chem Phys 120:1253

    Article  CAS  Google Scholar 

  37. Deubel DV (2002) J Am Chem Soc 124:5834

    Article  CAS  Google Scholar 

  38. Deng C, Zhou L (2010) Struct Chem 21:735

    Article  CAS  Google Scholar 

  39. Kohn W, Sham LJ (1965) Phys Rev 140:A1133

    Article  Google Scholar 

  40. Hohenberg P, Kohn W (1964) Phys Rev 136:B864

    Article  Google Scholar 

  41. Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Montgomery JA Jr, Vreven T, Kudin KN, Burant JC, Millam JM, Iyengar SS, Tomasi J, Barone V, Mennucci B, Cossi M, Scalmani G, Rega N, Petersson GA, Nakatsuji H, Hada M, Ehara M, Toyota K, Fukuda R, Hasegawa J, Ishida M, Nakajima T, Honda Y, Kitao O, Nakai H, Klene M, Li X, Knox JE, Hratchian HP, Cross JB, Adamo C, Jaramillo J, Gomperts R, Stratmann RE, Yazyev O, Austin AJ, Cammi R, Pomelli C, Ochterski JW, Ayala PY, Morokuma K, Voth GA, Salvador P, Dannenberg JJ, Zakrzewski VG, Dapprich S, Daniels AD, Strain MC, Farkas O, Malick DK, Rabuck AD, Raghavachari K, Foresman JB, Ortiz JV, Cui Q, Baboul AG, Clifford S, Cioslowski J, Stefanov BB, Liu G, Liashenko A, Piskorz P, Komaromi I, Martin RL, Fox DJ, Keith T, Al-Laham MA, Peng CY, Nanayakkara A, Challacombe M, Gill PMW, Johnson B, Chen W, Wong MW, Gonzalez C, Pople JA (2004) Gaussian 03. Gaussian Inc, Wallingford, CT

    Google Scholar 

  42. Becke AD (1993) J Chem Phys 98:5648

    Article  CAS  Google Scholar 

  43. Lee C, Yang W, Parr RG (1988) Phys Rev 37:785

    Article  CAS  Google Scholar 

  44. Willard RW, Hay PJ (1985) J Chem Phys 82:284

    Article  Google Scholar 

  45. Hay PJ, Willard RW (1985) J Chem Phys 82:299

    Article  CAS  Google Scholar 

  46. Hay PJ, Willard RW (1985) J Chem Phys 82:270

    Article  CAS  Google Scholar 

  47. Gonzalez C, Schlegel HB (1989) J Chem Phys 90:2154

    Article  CAS  Google Scholar 

  48. Gonzalez C, Schlegel HB (1990) J Chem Phys 94:5523

    Article  CAS  Google Scholar 

  49. Ehlers AW, Bohme M, Dapprich S, Gobbi A, Hollwarth A, Jonas V, Kohler KF, Stegmann R, Veldkamp A, Frenking G (1993) Chem Phys Lett 208:111

    Article  CAS  Google Scholar 

  50. Mennucci B, Cances E, Tomasi J (1997) J Phys Chem B 101:10506

    Article  CAS  Google Scholar 

  51. Mennucci B, Tomasi J (1997) J Chem Phys 106:5151

    Article  CAS  Google Scholar 

  52. Tomasi J, Mennucci B, Cances E (1999) J Mol Struct (THEOCHEM) 464:211

    Article  CAS  Google Scholar 

  53. Zhao YL, Wu YD (2002) J Am Chem Soc 124:1570

    Article  CAS  Google Scholar 

  54. DeChancie J, Houk KN (2007) J Am Chem Soc 129:5419

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This work was carried out with financial support from the National Natural Science Foundation of China (Grant No. 20971056).

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Authors and Affiliations

  1. Department of Chemistry, Jinan University, Guangzhou, Guangdong, 510632, People’s Republic of China

    Bo Jiang & Lixin Zhou

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  1. Bo Jiang
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  2. Lixin Zhou
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Correspondence to Lixin Zhou.

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11224_2011_9833_MOESM1_ESM.doc

Supplementary Data Available: Figures of trans-[Pd(dmnp)2Cl2] in all studied reactions, coordinates for optimized geometries of all calculations reported herein, and calculated vibrational frequencies of all systems. This material is available free of charge.(DOC 311 kb)

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Jiang, B., Zhou, L. Theoretical study of anticancer drug trans-[Pd(dmnp)2Cl2] binding to DNA purine bases, phosphate group and amino acid residues. Struct Chem 22, 1353–1364 (2011). https://doi.org/10.1007/s11224-011-9833-9

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