Theoretical Chemistry Accounts

, Volume 117, Issue 2, pp 323–332 | Cite as

Natural resonance structures and aromaticity of the nucleobases

Regular Article


Natural resonance theory (NRT) and nucleus- independent chemical shift (NICS) analyses have been applied to the standard nucleobases adenine, guanine, cytosine, uracil, and thymine. The molecular electron densities were obtained from density functional theory calculations at the B3LYP level and ab initio calculations at the HF, MP2, and CCD levels. Compared with the dominance of the two Kekulé structures in benzene, the structural modifications in the forms of endocyclic heteroatoms and exocyclic substituents introduce various degrees of charge separation in nucleobases. As a result, the leading resonance structures for cytosine, uracil, and thymine are found to be covalent structures, but their weightings decrease to ~30% in the NRT expansion. For adenine and guanine, the covalent structures have weightings of ~20%, and the leading ionic resonance structures have weightings of as high as about 8%. Methods that include electron correlation effects, B3LYP, MP2, and CCD, give smaller weightings for the covalent structures than HF. However, MP2 and CCD results often include “strange” resonance structures with connections between unbonded vicinal atoms, making DFT at the B3LYP level the better choice for calculating these molecules’ electron density. The NICS at the ring center shows that the six-membered rings in cytosine, uracil, thymine, and guanine are nonaromatic with NICS within  − 3 to  − 1 ppm, while it is  − 7.3 ppm for the six-membered ring in adenine. The NICS of the five-membered rings of adenine and guanine is around  − 12 ppm, a slight decrease from the value of  − 15.0 ppm for pyrrole.


Nucleobase DFT Natural bond orbital Natural resonance theory Quantum chemical calculations Aromaticity Nucleus-independent chemical shift (NICS) 


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  1. 1.
    Saenger W (1984) Principles of nucleic acid structure. Springer, Berlin Heidelberg New YorkGoogle Scholar
  2. 2.
    Weinhold F (1998) In: Schleyer PV, Allinger NL, Clark T, Gasteiger J, Kollman PA, Schaefer HF (eds) Encyclopedia of computational chemistry. John Wiley, New York, pp 1792–12Google Scholar
  3. 3.
    Glendening ED, Weinhold F (1998). J Comput Chem 19:593CrossRefGoogle Scholar
  4. 4.
    Glendening ED, Weinhold F (1998). J Comput Chem 19:610CrossRefGoogle Scholar
  5. 5.
    Glendening ED, Badenhoop JK, Weinhold F (1998). J Comput Chem 19:628CrossRefGoogle Scholar
  6. 6.
    Schleyer PV, Maerker C, Dransfeld A, Jiao HJ, Hommes N (1996). J Am Chem Soc 118:6317CrossRefGoogle Scholar
  7. 7.
    Schleyer PV, Jiao HJ, Hommes N, Malkin VG, Malkina OL (1997). J Am Chem Soc 119:12669CrossRefGoogle Scholar
  8. 8.
    Becke AD (1993). J Chem Phys 98:5648CrossRefGoogle Scholar
  9. 9.
    Lee CT, Yang WT, Parr RG (1988). Phys Rev B 37:785CrossRefGoogle Scholar
  10. 10.
    Binkley JS, Pople JA, Hehre WJ (1980). J Am Chem Soc 102:939CrossRefGoogle Scholar
  11. 11.
    Roothan CCJ (1957). Rev Mod Phys 23:69CrossRefGoogle Scholar
  12. 12.
    Moller C, Plesset MS (1934). Phys Rev 46:618CrossRefGoogle Scholar
  13. 13.
    Pople JA, Krishnan R, Schlegel HB, Binkley JS (1978). Int J Quant Chem 14:545CrossRefGoogle Scholar
  14. 14.
    Glendening ED, Badenhoop JK, Reed AE, Carpenter JE, Bohmann JA, Morales CM, Weinhold F (2001). NBO 5.0 Theoretical Chemistry Institute. University of Wisconsin, MadisonGoogle Scholar
  15. 15.
    Wolinski K, Hinton JF, Pulay P (1990). J Am Chem Soc 112:8251CrossRefGoogle Scholar
  16. 16.
    Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Zakrzewski VG, Montgomery JJA, Stratmann RE, 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, Rega N, Salvador P, Dannenberg JJ, Malick DK, Rabuck AD, Raghavachari K, Foresman JB, Cioslowski J, Ortiz JV, Baboul AG, 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, Challacombe M, Gill PMW, Johnson B, Chen W, Wong MW, Andres JL, Gonzalez C, Head-Gordon M, Replogle ES, Pople JA (1998). Gaussian 98 (Rev A.11.3). Gaussian Inc., PittsburghGoogle Scholar
  17. 17.
    Weinhold FA Private communicationGoogle Scholar

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  1. 1.Laboratory of Medicinal ChemistryCenter for Cancer Research, NCI, NIH, DHHS, NCI-FrederickFrederickUSA
  2. 2.Leadscope Inc.ColumbusUSA

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