Benzoderivatives of nucleic acid bases as modified DNA building blocks.
The tautomeric properties of benzoderivatives of the canonical nucleic acid bases have been studied by using different computational approaches. Attention has been paid to the impact of the benzene group in altering the tautomeric preferences of the canonical bases both in the gas phase and in aqueous solution. To this end, relative solvation free energies of the tautomers determined from Self-Consistent Reaction Field continuum calculations and Monte Carlo-Free Energy Perturbation are combined with gas-phase tautomerization free energies determined from quantum mechanical calculations. The results provide a detailed picture of the tautomeric preferences of the benzoderivatives of nucleic acid bases. This information is used to examine the recognition properties of the preferred tautomers of the benzo-fused derivatives, paying particular attention to the ability to form Watson-Crick hydrogen-bonding and stacking interactions as well as to the hydrophobic nature of the modified bases. The implications of present results on the potential use of benzo-fused bases as potential building blocks in modified DNA duplexes are examined.
Huertas
Oscar
O
Departament de Fisicoquímica, Facultat de Farmacia, Universitat de Barcelona, Avgda Diagonal 643, Barcelona 08028, Spain.
Blas
José Ramón
JR
Soteras
Ignacio
I
Orozco
Modesto
M
Luque
F Javier
FJ
D001555:Benzene Derivatives / Q000737:chemistry*; D005740:Gases; D006860:Hydrogen Bonding; D007536:Isomerism; D009696:Nucleic Acids / Q000737:chemistry; D011684:Purine Nucleosides / Q000737:chemistry*; D011741:Pyrimidine Nucleosides / Q000737:chemistry*; D012996:Solutions
D001555:Benzene Derivatives; D005740:Gases; D009696:Nucleic Acids; D011684:Purine Nucleosides; D011741:Pyrimidine Nucleosides; D012996:Solutions