Józef S. Kwiatkowski

An ab initio quantum-mechanical study of tautomerism of purine, adenine and guanine

Abstract The stabilities of several isolated tautomers of purine, adenine and guanine are discussed by considering their relative internal energies at 0 K predicted by ab initio quantum-mechanical calculations which include relative electronic energies at the SCF level (in a few cases corrected for electron correlation) and zero-point vibrational energies. The stabilities of the guanine tautomers are compared with the results from similar calculations on isocytosine tautomers. The calculations predict the following tautomers to be most stable: in purine N(9)H; in adenine N(9)H; in guanine three tautomers of similar energy, amino-oxo N(9)H and N(7)H, and amino-hydroxy N(9)H, with the latter slightly predominating; in isocytosine amino-oxo and amino-hydroxy forms with the latter predominating. The predicted relative stabilities of the tautomers in question are in agreement with recent experimental findings for the stabilities of the molecules based on the analysis of their infrared spectra in inert-gas low-temperature matrices. The effect of the environment on the relative stabilities of several tautomers is also discussed briefly.

Molecular structure and infrared spectra of furan, thiophene, selenophene and their 2,5-N and 3,4-N derivatives: density functional theory and conventional post-Hartree-Fock MP2 studies

Abstract Molecular parameters (bond lengths and bond angles, rotational constants, dipole moments) and vibrational IR spectra (harmonic wavenumbers, absolute intensities) of furan, thiophene, selenophene and their 2,5-N and 3,4-N derivatives have been predicted by density functional theory with the combined Becke3-LYP gradient exchange-corrected functional (DFT(B3LYP)) and the conventional ab initio MP2(full) approach. The standard 6–31G(d,p) basis set was used for all atoms except selenium for which a partially uncontracted Huzinaga basis set supplemented with a set of d-polarization functions was employed. Results are compared with the available experimental data. The molecular parameters computed by means of the DFT method are in a good agreement with those predicted by the MP2 approach and with the experimental data. The calculated data suggest verification of the experimental data for the bond angles of selenophene. Very good agreement between the calculated IR wavenumbers and absorption IR intensities of the molecules studied and their deuterated species by the DFT method and the experimental data was found.

Experimental matrix isolation and theoretical ab initio HF/6-31G(d, p) studies of infrared spectra of purine, adenine and 2-chloroadenine

Abstract The results of ab initio calculations at the Hartree—Fock level with the 6-31G( d , p ) basis set are reported for the harmonic vibrational infrared spectra of purine, adenine and 2-chloroadenine. These were compared with the experimental IR spectra of the compounds isolated in low-temperature matrices. The experimental spectra of 2-chloroadenine are reported for the first time. In the case of purine this comparison resulted in the complete assignment of the experimental IR spectrum. The proposed assignments of both the adenines studied are still incomplete.

Tautomerism of nucleic acid bases and the effect of molecular interactions on tautomeric equilibria

Abstract The change in tautomeric equilibria of purine and pyrimidine bases which may occur as a result of changes from an inert to polar environment of the base is examined in a general way. The contributions to the interaction energy between two molecules of 2-oxo-5-chloro-pyrimidine are compared specifically with those for 2-hydroxy-5-chloropyrimidine to show the influence of such an interaction on the relative stability of the oxo and hydroxy tautomeric forms. Similar effects are expected to change the relative order of stabilities of tautomers of purines and pyrimidine bases as a result of their interactions with their environment. The advantages of infrared studies of these equilibria for matrix isolated bases to provide information about the isolated bases, are discussed, and the extensive results from such studies over the past 14 years are reviewed. This review concentrates on studies of the biologically significant nucleic acid bases (1-methyluracil, 1-methylcytosine, 9-methyladenine and 9-methylguanine (9-MG) and several related model compounds). The technique for these studies is reviewed and illustrated with specific examples. For all of these bases except the guanosine analog 9-MG, only one tautomeric form is found to occur in the inert matrix environment, and it is the same form found for the base in polar solutions. However, for 9-MG the normal “oxo” tautomer (G) is found to be in approximately 1:1 equilibrium with the rare “hydroxy” tautomer (G*) in the inert (Ar or N2) gas matrix. These results contrast sharply with the studies of guanine residue in more polar environments where only the oxo form is found. The possible biological significance of this finding may be considerable, since G* will form a base pair with thymine rather than cytosine, possibly leading to spontaneous mutation. Finally, recent results from theoretical ab initio calculations of relative stabilities of the nucleic acid bases are reviewed and summarized. These results show the importance of making such calculations with large enough basis sets and estimate the effects of including electron correlation and correcting for zero point vibrational energies.

An infrared matrix isolation study of tautomerism in purine and adenine

Abstract Contrary to previous interpretations of the infrared spectra of purine and adenine isolated in low-temperature argon matrices suggesting that the molecules exist as a mixture of two tautomeric forms N(9)H and N(7)H of comparable weights, reinvestigation of the vibrational spectra in inert matrices (neon, argon, nitrogen) suggests that the observed IR absorption is due to one tautomeric form of either purine or adenine. This is in agreement with ab initio quantum-mechanical calculations of the relative internal energies of purine and adenine tautomers which predict the N(9)H tautomer to be the most stable form in both cases.

Infrared matrix isolation and ab initio quantum mechanical studies of purine and adenine

Abstract Results are presented from ab initio SCF (3-21G) calculations for the geometries of the N(9)H and N(7)H tautomers of purine and adenine and vibrational spectra (wavenumbers and intensities) of the N(9)H forms. All these results are compared with available geometries from crystallographic studies and with reported infrared spectra of the molecules isolated in inert gas low-temperature matrices. The N(9)⇌N(7)H tautomerism of the molecules in question is also briefly discussed.

Infrared spectra of thiouracils: experimental matrix isolation and ab initio Hartree-Fock, post-Hartree-Fock and density functional theory studies

Abstract The experimental infrared absorption spectra of 2-thiouracil, 4-thiouracil and 2,4-dithiouracil isolated in low-temperature argon matrices are compared with the spectra of these compounds computed by the density functional theory with the combined Becke3-LYP exchange-correlation energy functional (DFT(B3-LYP)) and conventional ab initio methods (Hartree-Fock (HF), MP2) using the standard 6-31G(d,p) basis set. The vibrational spectra computed at the DFT(B3-LYP)/6-31G(d,p) and HF/6-31G(d,p) levels of theory were found to reproduce well the experimental IR spectra. The results of MP2/6-31G(d,p) calculations predicted the normal modes due to out-of-plane vibrations somewhat less accurately. An assignment of the bands observed in the infrared spectra of the three thiouracils was performed, based on the comparison with the spectra calculated at the DFT(B3-LYP)/6-31G(d,p) level.

MOLECULAR AND ELECTROSTATIC PROPERTIES OF THE N-METHYLATED NUCLEIC ACID BASES BY DENSITY FUNCTIONAL THEORY

Abstract Complete geometry optimizations using a density functional theory (DFT) with the combined Becke3 and LYP functional potentials (B3-LYP) and the conventional ab initio Hartree-Fock (HF) method with the 6-31G(d,p) basis set were carried out for the fundamental tautomeric forms of nucleic acid bases (cytosine, thymine, guanine and adenine) and their derivatives methylated at the N1 (pyrimidines) or N9 (purines) positions. At the HF/6-31G(d,p) geometries, the dipole moments, electronic densities and molecular electrostatic potentials (MEPs) were computed using the HF/6-31G(d,p), MP2(fc)/6-31G(d,p), DFT(B3-LYP)/6-31G(d,p), DFT(B3-LYP)/6-31 + + G(d,p) methods and DFT with inclusion of Becke nonlocal, gradient-corrected exchange energy terms (DFT(NLE) method) with the numerical DNP basis set. The same properties were also computed using the DFT(B3-LYP)/6-31G(d,p) method for the corresponding optimized geometries of the molecules. The charges that reproduce the MEP maps from the ab initio (HF, MP2) and DFT calculations were fitted and compared. The ground state molecular parameters (rotational constants, dipole moments) of the methylated bases are compared with the molecular parameters calculated at the same level for the nonmethylated DNA bases and with available experimental data. The results show that the DFT calculations reproduce well the MP2 results for the MEPs, the ESP charges and the dipole moments of the DNA bases and their N-methylated derivatives.

Molecular structure and vibrational IR spectrum of formamide revisited: ab initio post-Hartree—Fock study

Abstract The results of high-level ab initio calculations using a 6-311G(3df,2p) basis set with electron correlation included at the second-order Moller—Plesset perturbation theory are reported for molecular parameters (geometry, dipole moment, rotational constants) and the vibrational IR spectrum (harmonic wavenumbers, absolute intensities) of formamide. The present calculations predict such a small deviation from the planarity of the molecule that it should be considered as a planar system. Computed dipole moment, rotational constants and the vibrational IR spectra of formamide and its deuterated species agree very well with the available experimental data.

Infrared experimental and ab initio quantum mechanical studies of 2-mercaptopyrimidine tautomers

Abstract Results are presented from ab initio SCF(3-21G*) calculations for the geometries and vibrational spectra (wavenumbers and absolute intensifies) of the thiol and thione tautomers of 2-mercaptopyrimidine. The results of calculations are compared with available experimental data, particularly with the reported vibrational spectra of the molecule isolated in inert gas matrices (Ar, N 2 ) and in crystalline state. The calculations of the normal modes predicted the experimental spectrum close enough to allow reliable assignment of most of the bands. The thiol⇌⇌thione tautomerism of the molecule is discussed. Matrix isolated monomers were observed in the thiol form only. That agrees with the results of ab initio calculations of internal energies of the tautomers [SCF(6-31Gu*) + MBPT(2)(6-31G*) + vib(0)(3-21G*); at the SCF(3-21G*) geometries] which predict the energy of thiol form to be ≈33 kJ mol −1 lower than that of thione form. In the crystalline state the hydrogen-bonded associations in the thione form dominate while in disordered amorphous layers, in matrices with a high guest-to-host ratio and in annealed matrices the associations both in thiol and thione form were observed.