Regular Article

Theoretical Chemistry Accounts

, Volume 117, Issue 2, pp 323-332

First online:

Natural resonance structures and aromaticity of the nucleobases

  • Guangyu SunAffiliated withLaboratory of Medicinal Chemistry, Center for Cancer Research, NCI, NIH, DHHS, NCI-FrederickLeadscope Inc.
  • , Marc C. NicklausAffiliated withLaboratory of Medicinal Chemistry, Center for Cancer Research, NCI, NIH, DHHS, NCI-Frederick Email author 

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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)