[Complete conformational family of 2',3'-didehydro-2',3'-dideoxyguanosine: quantum chemical and electron density topological study].

Comprehensive conformational analysis of the biologically active nucleoside 2',3'-didehydro-2',3'-dideoxyaguanosine (d4G) has been performed at the MP2/6-311++G(d,p)//DFT B3LYP/6-31G(d,p) level of theory. The energetic, geometrical and polar characteristics of twenty d4G conformers as well as their conformational equilibrium were investigated. The electron density topological analysis allowed us to establish that the d4G molecule is stabilized by nine types of intramolecular interactions: O5'H...N3, O5'H...C8, C8H...O5', C2'H...N3, C5'H1...N3, C5'H2...N3, C8H...H1C5', C8H...H2'C5' and N2H1...O5'. The obtained results of conformational analysis permit us to think that d4G may be a terminator of the DNA chain synthesis in the 5'-3' direction. Thus it can be inferred that d4G competes with canonical 2'-deoxyaguanosine in binding an active site of the corresponding enzyme.

[The 5'-deoxyadenylic acid molecule conformational capacity: quantum-mechanical investigation using density functional theory (DFT)].

Exhaustive conformational analysis of the 5'-deoxyadenylic acid molecule, has been carried out by the quantum-mechanical density functional theory method at the MP2/6-311++G(d,p)//DFT B3LYP/6-31G(d,p) theory level. As many as 726 of its conformations have been revealed with the relative gas phase Gibbs energies under standard conditions from 0 to 12.1 kcal/mole. It has been shown, that the energetically most favorable conformation has north sugar puckering and synorientation of the nitrogenous base and is stabilized by intramolecular O(p1)H(p1)-N3 and O3'H-O(p) hydrogen bonds. Four conformations have been shown to have their geometry similar to that of AI-DNA and four - of BI-DNA. One conformer of the 5'-deoxyadenylic acid molecule is similar to its sodium salt hexahydrate structure in crystalline state resolved by the X-ray diffraction method and taken from literature. It is shown that effective charges of C4' and C5' atoms are the most sensitive to the molecule conformation ones. The role of the intramolecular OH-N hydrogen bonds in formation of the 5'-deoxyadenylic acid molecule structure has been demonstrated.

[The simplest molecular model of 2'-deoxyribopolinucleotides sugar-phosphate backbone: quantum-chemical adequacy check].

The physical adequacy of the simplest molecular model "sugar residue (SR)--phosphate group (PG)--SR" of 2'-deoxyribopolinucleotides sugar-phosphate backbone is confirmed at DFT B3LYP/6-31++G(d,p) and DFT B3LYP/6-31G(d,p) of quantum-chemical methods. It is proved that complicacy of the model to the "SR-PG-SR-PG-SR" and higher levels does not noticeably change the numerical values of torsion angles. Also these angles depend negligibly on counterion nature (e.g. Na+ to Li+, K+ or Cs+ change) and transition from vacuum to continuum approximation with medium dielectrical values of 1.4, 24.9, and 78.4. It is shown that model loses its adequacy when PG is the end link.

[Structural flexibility of canonical 2'-deoxyribonucleotides in DNA-like conformations].

Quantitative characteristics of structural flexibility of the DNA elementary monomer units -5'-deoxycytidylic, 5'-thymidylic, 5'-deoxyadenylic and 5'-deoxyguanylic acid molecules--have been calculated with original methods. Root-mean-square deviations from equilibrium for all conformational parameters, caused by nuclei thermal or quantum zero-point vibrations, have been found to lie within 4 degrees divided by 25 degrees at 0 K and 7 degrees divided by 50 degrees at 298 K and corresponding relaxed force constants--within 1 divided by 35 kcal/mol x rad(-2). Their values have been found to be sensitive to the molecule's conformation. It has been proven, that the torsion angle gamma is the most rigid one whereas relaxed force constants for all other conformational variables are lower and comparable to each other. The data obtained could serve for development of structural-dynamical models of the DNA.

[Molecular mechanisms of transitions induced by cytosine analogue: comparative quantum-chemical study].

Using the simplest molecular models at the MP2/6-311++G(2df,pd)//B3LYP/6-311++G(d,p) level of the theory it has been shown for the first time that in addition to traditional incorporational errors caused by facilitated (compared with the canonical DNA bases cytosine (Cyt)) tautomerization of 6-(2-deoxy-beta-D-ribofuranosyl)-3,4-dihydro-6H,8H-pyrimido[4,5-c][1,2]oxazin-7-one (DCyt), this mutagen causes the replication errors, increasing one million times the population of mispair Gua.DCyt* (asterisk marked mutagenic tautomer) as compared with mispair Gua.Cyt*. It is also proved that DCyt in addition to traditional incorporational errors also induces similar errors by an additional mechanism - due to a facilitated tautomerization of the wobble base pair Ade.DCyt (compared to the same pair Ade.Cyt) to a mispair Ade.DCyt* which is quasirisomorphic Watson-Crick base pair. Moreover, the obtained results allowed interpreting non-inconsistently the existing experimental NMR data.

[Quantum-mechanical conformational analysis of the 5'-thymidilic acid molecule].

The conformational analysis of the DNA structural unit--the nucleotide with thymine base and electroneutral phosphate group at 5'-position-has been carried out with the applied quantum mechanics methods at the MP2/6-311++G(d,p) // B3LYP/6-31G(d,p) theory level. As many as 660 conformations with relative Gibbs energies under standard conditions from 0 to 11.1 kcal/mole have been found. Among them, six conformations are similar to the structure of the nucleotide of AI-DNA, one--to AII- and seven--to the DNA in BI-form. The lowest Gibbs energy among the DNA-like conformations (deltaG = 2.7 kcal/mole) belongs to BI-DNA-like structure. It is shown that the glycoside chemical bond is the most labile one. The role of intramolecular CH...O hydrogen bonds in formation of the 5'-thymidilic acid molecule structure is demonstrated.