RESUMEN
Protonation of nucleobases in anions of canonical 2'-deoxyribonucleotides has been investigated by the DFT computational study at the B3LYP/aug-cc-pvdz level of theory. It is demonstrated that the protonation leads to a significant decrease of conformational space of purine nucleotides while almost all conformers found for non-protonated molecules correspond to minima of the potential energy surface for protonated mdTMP and mdCMP. However, in all nucleotides, only one conformer is populated. This applies to all tautomers of protonated molecules except the mdTMP and mdCMP with the proton attached to the carbonyl group where a minor population of second conformer is observed. Protonation of nucleobase leads to significant elongation of the N-glycosidic bond. These findings agree well with suggestions that protonation of nucleobase is a first step in cleavage of the glycosidic bond. The oxygen atoms of both carbonyl groups of thymine and the N3 atom of the pyrimidine ring of cytosine, guanine, and adenine represent the most preferable sites for protonation of anions of 2'-deoxyrobonucleotides. The highest proton affinity is observed for the base in mdGMP and the lowest for the thymine moiety in mdTMP. It should be noted that calculated values of the proton affinities in anionic nucleotides are significantly higher (by 2-3 eV) than for nucleosides and neutral nucleotides. This allows assuming that the proton affinity of the base in DNA macromolecule may be tuned by changing the extent of shielding or neutralization of negative charge of the phosphate group.
Asunto(s)
Desoxirribonucleótidos/química , Protones , Isomerismo , Modelos Moleculares , Conformación Molecular , Teoría Cuántica , TermodinámicaRESUMEN
The molecular structure and deformability (with respect to average geometry) of methyl ethers of canonical 2'-deoxyribonucleotides thymidine-5'-phosphate (mTMP), 2-deoxycytidine-5'-phosphate (mCMP), 2-deoxyadenosine-5'-phosphate (mAMP) and 2'-deoxyguanosine-5'-phosphate (mGMP) in different types of DNA have been calculated using B3LYP/cc-pvdz method. Comparison of energy at equilibrium conformations of nucleotides and conformations with torsion angles of backbone fixed to average values for different types of DNA reveals that incorporation of nucleotides to A-DNA macromolecules requires the minimum amount of deformation energy. Therefore, this type of DNA should be the least strained from viewpoint of intramolecular deformations of monomers. Modeling of environmental effects within the PCM approach reveals that the immersion of nucleotides in polar medium results in significant decrease of energy differences between anti conformers of all DNTs and syn conformers of mGMP. This also leads to reduction by almost a half nucleotides' deformation energy facilitating formation of DNA macromolecule. Change of DNTs conformation causes switch between different types of intramolecular H bonds. Every type of DNA possesses unique set of intramolecular hydrogen bonds in nucleotides.
Asunto(s)
Desoxirribonucleótidos/química , Conformación de Ácido Nucleico , Simulación por Computador , Desoxirribonucleótidos/clasificación , Enlace de Hidrógeno , Estructura MolecularRESUMEN
The molecular structure and relative stability of different conformers of isolated canonical 2'-deoxyribonucleotides thymidine-5'-phosphate (pdT), 2-deoxycytidine-5'-phosphate (pdC), 2-deoxyadenosine-5'-phosphate (pdA), and 2'-deoxyguanosine-5'-phosphate (pdG) were calculated using the B3LYP/6-31++G(d,p) level of theory. The results of the calculations reveal that, for all nucleotides except pdG, conformers with a syn orientation of the base do not correspond to a minimum on the potential energy surface. In the case of pdA and pdC, conformers with an orthogonal orientation of the nucleobase are located instead, north/syn conformers. These conformers as well as syn conformers of pdG are stabilized by intramolecular N-H...O hydrogen bonds. Analysis of the electron density distribution within the atoms in molecules theory reveals the presence of numerous C-H...O hydrogen bonds in the nucleotides. However, a more detailed consideration of the properties of these bonds demonstrates that many of them should be considered as strong attractive electrostatic interactions rather than true hydrogen bonds. True hydrogen bonds are represented mainly by C6/ C8-H...O5'/O-P in anti conformers and the N-H...O-P bonds in syn conformers. It is demonstrated that the values of ellipticity of the electron density at the bond critical point (BCP) and the distance between BCP and ring critical point are the most reliable indicators for determining the true intramolecular hydrogen bonds.