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Interactions of the 5-fluorouracil anticancer drug with DNA pyrimidine bases: a detailed computational approach

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Abstract

The H-bonded complexes formed from interaction between 5-fluorouracil (FU) and DNA pyrimidine bases have been investigated by B3LYP method using 6-311++G** basis set in the gas phase and the water solution. Vibrational frequencies and physical properties such as dipole moment, chemical potential, and chemical hardness of these compounds have been systematically explored. The natural bond orbital analysis and the Bader’s quantum theory of atoms in molecules are also used to elucidate the interaction characteristics of the investigated complexes. The aromaticity is measured using several well-established indices of aromaticity such as NICS, HOMA, PDI, ATI, and FLU. The MEP is given the visual representation of the chemically active sites and comparative reactivity of atoms. Furthermore, the effects of interactions on NMR data have been used for further investigation of the studied compounds.

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References

  1. Cameron JS, Moro F, Simmonds HA (1993) Pediatric Nephrology 7:105–118

    Article  CAS  Google Scholar 

  2. Gennip AHV (1999) Nederlands Tijdschrift voor Klinische Chemie 2:171–175

    Google Scholar 

  3. Loeffler M, Fairbanks LD, Zameitat E, Marinaki AM, Simmonds HA (2005) Trends Mol Med 11:430–437

    Article  CAS  Google Scholar 

  4. Loeffler M, Zameitat E (2004) Encycl Biol Chem 3:600–605

    Article  CAS  Google Scholar 

  5. Pang D, Abruna HD (1998) Anal Chem 70:3162

    Article  CAS  Google Scholar 

  6. Fritzsche H, Akhebat A, Taillandier E, Rippe K, Jovin TM (1993) Nucleic Acids Res 21:5085

    Article  CAS  Google Scholar 

  7. Gane PJ, Dean PM (2000) Curr Opin Struc Biol 10:401

    Article  CAS  Google Scholar 

  8. Graves DE, Velea LM (2000) Curr Org Chem 4:915

    Article  CAS  Google Scholar 

  9. Braga SF, de Melo LC, Barone PMVB (2004) J Mol Struct THEOCHEM 710:51–59

    Article  CAS  Google Scholar 

  10. Wanga W, Collie-Duguida E, Cassidy J (2002) FEBS Lett 531:415–420

    Article  Google Scholar 

  11. Andre T, Boni C, Mounedji-Boudiaf L, Navarro M, Tabernero JT, Hickish T, Topham C, Zaninelli M, Philipalingam Bridgewater J, Tabah-Fisch I (2004) N Engl J Med 350:2343–2351

    Article  CAS  Google Scholar 

  12. Carethers JM, Chauhan DP, Fink D, Nebel S, Bresalier RS, Howell SB, Boland CR (1999) Gastroenterology 117:123–131

    Article  CAS  Google Scholar 

  13. Longley DB, Harkin DP, Johnston PG (2003) Cancer 3:330–338

    CAS  Google Scholar 

  14. Ribic CM, Sargent DJ, Moore MJ, Thibodeau SN, French AJ, Goldberg RM, Hamilton SR, Puig PL, Gryfe R, Shepherd LE, Tu D, Redston M, Gallinger S (2003) N Engl J Med 349:247–257

    Article  CAS  Google Scholar 

  15. Carethers JM, Smith EJ, Behling CA, Nguyen L, Tajima A, Doctolero RT, Cabrera BL, Tajima A, Doctolero RT, Cabrera BL, Goel A, Arnold CA, Miyai K, Boland CR (2004) Gastroenterology 126:394–401

    Article  CAS  Google Scholar 

  16. de Vos tot Nederveen Cappel WH, Meulenbeld HJ, Kleibeuker JH, Nagengast FM, Menko FH, Griffioen G, Cats A, Morreau H, Gelderblom H, Vasen HFA (2004) Int J Cancer 109:468–471

    Article  Google Scholar 

  17. Reni M, Cereda S, Galli L (2007) Cancer Lett 256:25–28

    Article  CAS  Google Scholar 

  18. Warner E, Jensen JL, Cripps C, Khoo KE, Goel R, Kerr IA, Bjarnason GA, Fields AL, Hrincu A (1999) Acta Oncol 38:255–259

    Article  CAS  Google Scholar 

  19. Li VS, Choi D, Wang Z, Jimenez LS, Tang MS, Kohn H (1996) J Am Chem Soc 118:2326–2331

    Article  CAS  Google Scholar 

  20. Tomasz M, Lipman R, Chowdary D, Pawlak J, Verdine GL, Nakanishi K (1987) Science 235:1204–1208

    Article  CAS  Google Scholar 

  21. Hecht SM (2000) J Nat Prod 63:158–168

    Article  CAS  Google Scholar 

  22. Zuber G, Quada JC, Hecht SM (1998) J Am Chem Soc 120:9368–9369

    Article  CAS  Google Scholar 

  23. Jeffry GA (1991) SaengerW. Springer, Berlin

    Google Scholar 

  24. Scheiner S (1997) Hydrogen bonding. Oxford University Press, New York

    Google Scholar 

  25. Desiraju GR, Steiner T (1999) The Weak Hydrogen Bond in Structural Chemistry and Biology. Oxford University Press, New York

    Google Scholar 

  26. Perrin CL, Nielson JB (1997) Annu Rev Phys Chem 48:511–544

    Article  CAS  Google Scholar 

  27. Del Bene JE, Jordan MJT (2001) J Mol Struct: THEOCHEM 573: 11–23

  28. Hobza P, Havlas Z (2000) Chem Rev 100:4253–4264

    Article  CAS  Google Scholar 

  29. Desfrançois C, Carles S, Schermann JP (2000) Chem Rev 100:3943–3962

    Article  Google Scholar 

  30. Buckingham AD, Del Bene JE, McDowell SAC (2008) Chem Phys Lett 463:1–10

    Article  CAS  Google Scholar 

  31. Sum AK, Sandler SI (2000) J Phys Chem A 104:1121–1129

    Article  CAS  Google Scholar 

  32. Robertson EG, Simons JP (2001) Phys Chem Chem Phys 3:1–18

    Article  CAS  Google Scholar 

  33. Scheiner LS (1994) Acc Chem Res 27:402–408

    Article  CAS  Google Scholar 

  34. Han D, Wang H, Ren N (2004) J Mol Model 10:216–222

    Article  CAS  Google Scholar 

  35. Priem D, Ha TK, Bauder A (2000) J Chem Phys 113:169–175

    Article  CAS  Google Scholar 

  36. Sponer J, Leszcynski J, Hobza P (2001) J Mol Struct 573:43–53

    Article  CAS  Google Scholar 

  37. Hobza P, Sponer J (1999) Chem Rev 99:3247–3276

    Article  CAS  Google Scholar 

  38. Dolenc J, Borstnik U, Hodoscek M, Koller J, Janezic D (2005) J Mol Struct 718:77–85

    Article  CAS  Google Scholar 

  39. Gaussian 03, Revision A7, Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Zakrzewski VG, Montgomery JA, Stratmann JRE, Burant JC, Dapprich S, Millam JM, Daniels AD, Kudin KN, Strain MC, Farkas O, Tomasi J, Barone V, Cossi M, Cammi R, Mennucci B, Pomelli C, Adamo C, Clifford S, Ochterski J, Petersson GA, Ayala PY, Cui Q, Morokuma K, Malick DK, Rabuck AD, Raghavachari K, Foresman JB, Cioslowski J, Ortiz JV, Stefanov BB, Liu G, Liashenko A, Piskorz P, Komaromi I, Gomperts R, Martin RL, Fox DJ, Keith T, Al-Laham MA, Peng CY, Nanayakkara A, Gonzalez C, Challacombe M, Gill PMW, Johnson B, Chen W, Wong MW, Andres JL, Gonzalez C, Head-Gordon M, Replogle ES, Pople JA, Gaussian, Inc., Pittsburgh, PA, 2003

  40. Miertus S, Tomasi J (1982) Chem Phys 65:239–245

    Article  CAS  Google Scholar 

  41. Boys SF, Bernardi F (1970) MolPhys 19:553

    CAS  Google Scholar 

  42. Glendening DE, Reed AE, Carpenter JE, Weinhold F NBO, Version 3.1

  43. Paul BK, Mahanta S, Singh RB, Guchhait N (2010) J Phys Chem A 114:2618

    Article  CAS  Google Scholar 

  44. Bader RFW (1990) Atoms in molecules. A quantum theory. Oxford University Press, New York

    Google Scholar 

  45. Bader RFW (1985) Acc Chem Res 18:9

    Article  CAS  Google Scholar 

  46. Bader RFW (1991) Chem Rev 91:893

    Article  CAS  Google Scholar 

  47. Pulay P, Hinton JF, Wolinski K (1993) Tossel JA (ed) Nuclear magneticshieldings and molecular structure, vol 386 of NATO ASI Series C. Kluwer, Dordrecht

  48. Hehre WJ, Radom L, Schleyer PR, Pople JA (1986) Ab initio molecular orbital theory. Wiley, New York

    Google Scholar 

  49. Cyranski MK, Krygowski TM, Katritzky AL, Schleyer PvR (2002) J Org Chem 67:1333–1338

  50. Krygowski TM (1993) J Chem Inf Comput Sci 33:70–78

    Article  CAS  Google Scholar 

  51. Poater J, Duran M, Sola M, Silvi B (2005) Chem Rev 105:3911–3947

    Article  CAS  Google Scholar 

  52. Bultinck P, Ponec R, Van Damme S (2005) J Phys Org Chem 18:706

    Article  CAS  Google Scholar 

  53. Matito E, Duran M (2005) Sola‘M. J ChemPhys 122:014109–014117

    Google Scholar 

  54. Diederichsen U (1997) Angew Chem Int Ed Engl 36:2317

    Article  CAS  Google Scholar 

  55. Chaires JB (1990) BiophysChem 35:191

    CAS  Google Scholar 

  56. Colson P, Bailly C, Houssier C (1996) BiophysChem 58:125

    CAS  Google Scholar 

  57. AliakbarTehrani Z, Fattahi A (2009) THEOCHEM 913:277–283

    Article  Google Scholar 

  58. Liu M, Tingting L, Amegayibor S, Cardoso DS, Jeehiun YK (2008) J Org Chem 73:9283

    Article  CAS  Google Scholar 

  59. Koch U, Popelier PLA (1995) J Phys Chem 99:9747

    Article  CAS  Google Scholar 

  60. Popelier PLA (1998) J Phys Chem A 102:1873

    Article  CAS  Google Scholar 

  61. Parra RD, Ohlssen J (2008) J Phys Chem A 112:3492

    Article  CAS  Google Scholar 

  62. Zió1kowski M, Grabowski SJ, Leszczynski J (2006) J Phys Chem A, 110: 6514

  63. Roohi H, Nowroozi AR, Anjomshoa E (2011) Comput and Theor Chem 965:211–220

    Article  CAS  Google Scholar 

  64. Raissi H, Jalbout AF, Nasseri MA, Yoosefian M, Ghassi H, Hameed A (2008) Inter. J Quant Chem 108:444

    Article  Google Scholar 

  65. Espinosa E, Molins E (2000) J Chem Phys 113:5686–5694

    Article  CAS  Google Scholar 

  66. Reed AE, Curtiss LA, Weinhold F (1988) Chem Rev 88:899

    Article  CAS  Google Scholar 

  67. Hobza P, Havlas Z, Chem Rev 100 (2000) 4253. and references cited therein

  68. Hobza P, Spirko V, Selzle HL, Schlag EW (1998) J Phys Chem A 102:2501

    Article  CAS  Google Scholar 

  69. Durig JR, Little TS, Gounev TK, Gardner JK, Sullivan JF (1996) J Mol Struct 375:83–94

    CAS  Google Scholar 

  70. Liu JN, Chen ZR, Yuan SF (2005) J Zhejiang Univ Sci B 6:584–589

    Article  Google Scholar 

  71. Sajan D, Lakshmi KU, Erdogdu Y, Joe IH (2011) Spectrochim Acta A 78:113–121

    Article  CAS  Google Scholar 

  72. Ibrahim M, Mahmoud AA (2009) J Comput Theor Nanosci 6:1523–1526

    Article  CAS  Google Scholar 

  73. Koopmans TA (1933) Physics 1:104–113

    CAS  Google Scholar 

  74. Gogary TM, Koehler G (2007) J Mol Struct: THEOCHEM 808:97–109

    Article  Google Scholar 

  75. Onsager L (1936) Electric moments of molecules in liquids. J Am Chem Soc 58:1486–1493

    Article  CAS  Google Scholar 

  76. Lippert B (1999) Cisplatin: chemistry and biochemistry of a leading anticancer drug. Verlag Helvetica Chimica Acta, Zurich

    Book  Google Scholar 

  77. Deepa P, Kolandaivel P, Senthilkumar K (2012) Mater Sci Eng, C 32:423–431

    Article  CAS  Google Scholar 

  78. Murray JS, Sen K (1996) Molecular electrostatic potentials, concepts and applications. Elsevier, Amsterdam

    Google Scholar 

  79. Scrocco E, Tomasi J (1978) In: Lowdin P (ed) Advances in quantum chemistry, vol II. Academic Press, New York

    Google Scholar 

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Correspondence to Leila Hokmabady.

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Hokmabady, L., Raissi, H. & Khanmohammadi, A. Interactions of the 5-fluorouracil anticancer drug with DNA pyrimidine bases: a detailed computational approach. Struct Chem 27, 487–504 (2016). https://doi.org/10.1007/s11224-015-0578-8

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