Local aromaticity in natural nucleobases and their size-expanded benzo-fused derivatives.
The influence of the insertion/addition of a benzene ring to the natural nucleic acid bases on the local aromaticity of the so-called size-expanded (xN, with N being adenine, guanine, cytosine, and thymine) bases is examined. To this end, the local aromaticity of the six- and five-membered rings in both the natural bases and their benzoderivatives is determined using HOMA, NICS, aromatic fluctuation index (FLU), and para-delocalization index (PDI) descriptors. In general, there is a good correspondence between the different indices, so that ring moieties with more negative NICS values also have larger HOMA and PDI measures and lower FLU indices. The results also point out notable differences in the aromatic character of the natural and size-expanded bases, which generally are hardly affected upon hydrogen bonding. The differences in the highest occupied molecular orbital-lowest unoccupied molecular orbital (HOMO-LUMO) gap determined for the size-expanded nucleobases show an inverse correlation with the aromaticity of the fused benzene ring, so that the larger the HOMO-LUMO gap is, the lower the destabilization experienced by the benzene upon insertion/addition to the natural bases. This finding suggests that the introduction of suitable chemical modifications in the benzene ring might be useful to modulate the HOMO-LUMO gap while enabling the design of modified DNA duplexes that are able to act as molecular wires.
Huertas
Oscar
O
Departament de Fisicoquímica, Facultat de Farmàcia, Universitat de Barcelona, Avenida Diagonal 643, 08028, Barcelona, Spain.
Poater
Jordi
J
Fuentes-Cabrera
Miguel
M
Orozco
Modesto
M
Solà
Miquel
M
Luque
F Javier
FJ
D000225:Adenine / Q000737:chemistry*; D001554:Benzene / Q000737:chemistry*; D003596:Cytosine / Q000737:chemistry*; D006147:Guanine / Q000737:chemistry*; D006860:Hydrogen Bonding; D015394:Molecular Structure; D009696:Nucleic Acids / Q000737:chemistry*; D011084:Polycyclic Aromatic Hydrocarbons / Q000737:chemistry*; D013941:Thymine / Q000737:chemistry*
D009696:Nucleic Acids; D011084:Polycyclic Aromatic Hydrocarbons; D006147:Guanine; D003596:Cytosine; D001554:Benzene; D000225:Adenine; D013941:Thymine