Journal of Molecular Structure (Theochem), 121(1985) 133-136 Elsevier Science Publishers B-V., Amsterdam - Printed in The Netherlands

MNDO STUDY OF THE TAUTOMERS OF NUCLEIC BASES

Part ID. Reinvestigation of the amino-type tautomers structure

ANDRZEJ SYGULA and ANDRZEJ BUDA

Institute of Chemistry. Jagiellonian University, Karasia 3, 30-OS0 Krakbw (Poland)

(Received 12 June 1984)

ABSTRACT

MNDO recalculations with full geometry optimization for the amino-type tautomers of cytosine, adenine and gnanine predict noncoplanarity of the amino nitrogen atom with heteroaromatic rings. These molecular structures are about 2.1 kJ mol-* more stable in comparison with “coplanar” structures. Bond lengths, valence angles, dipole moments and ionization potentials of the “coplanar” and “noncoplanar” forms do not differ significantly.

INTRODUCTION

Until now it has been assumed that the nitrogen atom of the amino group attached to the aromatic or heteroaromatic system is coplanar with the ring plane. This assumption has been made on the basis of the microwave experi- ment showing that the aniline molecule (in the gas phase) forms basically two intersecting planes, one containing the CsHSN moiety and the other the NH2 group Cl]. In preceding papers of this series 12, 31, we published the results of MNDO calculations of nucleic basis structures assuming such coplanar geometry for the amino-type tautomers. However, recent theoretical and experimental results clearly show that this assumption cannot be sus- tained [4-6]. X-Ray crystal-structure determinations of aniline show that the amino-nitrogen atom is out of the phenyl ring plane [4]. Very recent MNDO calculations also predict the noncoplanarity of the nitrogen atom with the aromatic ring in the aniline molecule [ 51. Ab initio calculations as well as our MNDO studies on cytosine carried out with full geometry optimization predict a similar conformation of the amino group to be the most stable 163. It seems therefore necessary to reinvestigate the problem of the preferred structures of the amino-type tautomers of the nucleic bases without any geometry restrictions.

CALCULATIONS

The MNDO method [7] (modified neglect of diatomic overlap) with the Dawidon-Fletcher-Powell 181 optimization routine was used throughout

0166-1280/85/$03.30 0 1985 Elsevier Science Publishers B.V.

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this study. The starting geometries of the amino-type tautomers (Cl-C3, Al-A4, Gl-G8)* were taken from refs. 2 and 3. Any assumption about planarity was made during geometry optimization procedure. In some cases it was necessary to change the starting geometries slightly by squeezing out the amino nitrogen atom from the aromatic ring planes in order to reach a global potential energy minimum.

All calculations were performed on the CDC CYBER 72 computer of the Regional Computational Center “CYFRONET” in Krakow.

RESULTS AND DISCUSSION

The MNDO full geometry optimization for the amino-type tautomers of the nucleic bases lead to significant changes in some torsional angles as compared to the calculations carried out with assumption about molecular skeleton planarity. Figure 1 shows the non-zero Z-coordinates for the most important amino-type tautomers* of cytosine (Cl), adenine (Al) and guanine (Gl). It can be seen from Fig. 1 that the amino nitrogen atoms are slightly, but significantly, noncoplanar with the aromatic rings. The standard deviations from the least-square planes defined by the ring atoms are 0.13, 0.15 and 0.13 A for Cl, Al and Gl respectively. A similar situation is observed in all other amino-type tautomers of nucleic bases. We found the value of the angles between the aromatic ring plane and the CU-N,mti bond to be ca. 5.5” in all considered cases. In our opinion, it is not an artifact of the MNDO method; recently published results of ab initio calculations carried out with full geometry optimization for cytosine and N-hydroxycytosine also predict a noncoplanarity of the amino nitrogen atom with the ring planes and the deviation is 0.11 A for cytosine Cl [6]. It seems that the noncoplanarity considered is a common feature of the NH2 substituted aromatics: X-ray structure determination [4] and MNDO calculations [5] show that the amino nitrogen atom is noncoplanar with the phenyl ring in the most stable

&X~Ao -.0132

I

0116

Cl H - 0026

Fig. 1. The non-zero Z-coordinates (A) for the tautomers Cl, Al and 01.

*The symbols of the tautomers used throughout this study are the same as used previousiy in refs. 2 and 3.

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conf&mation of aniline; the deviation of the nitrogen atom from the best ring plane being very close to that calculated for the nucleic basis tautomers (0.12 143 and 0.11 A [S] ).

On the other hand, full geometry optimization does not lead to substan- tial changes in bond lengths and bond angles. For example, for Cl, Al and Gl these differences do not exceed 0.001 W and 0.1” for bond lengths and valence angles, respectively.

As expected, the aromatic rings are essentially planar in most of the examples considered. The standard deviation of the ring atoms from theleast- square plane is smaller than 0.02 A. Only in the case of 67 is a significant deviation (0.07 A) of the N3 atom from the best ring plane found. For other tautomers, the maximum deviations of the ring atoms from the planarity do not exceed 0.03 A.

Heats of formation, dipole moments and ionization potentials

The heats of formation, relative stabilities, dipole moments and ionization potentials calculated by the MNDO method for 15 amino-type i%utomers of cytosine, adenine and guanine are given in Table 1, Comparison of the data with the results of our earlier calculations [2, 3] shows that heats of formation for the “noncoplanar” conformations are lower, as a rule, by about 2.1 kJ mol-l except for G5 and G7, for which decreases in the heats of

TABLE 1

Heats of formation, relative stabilities, dipole moments and first ionization potentials calculated by MNDO for “noncoplanar” amino-type tautomers of cytosine, adenine and guanine

Tautomer AH* (kJ mol-’ )

Relative stabilities (kJ mol-l)

P (D) L

c3

-54.49 41.44 5.58 9.53 -40.59 55.34 6.11 9.30 -95.93 0.00 3.32 9.55

Al 226.43 0.00 2.49 9.10 A2 251.76 25.33 5.30 9.48 A3 308.57 62.14 6.65 9.25 A4 275.96 49.53 4.43 6.62

Gl 32.35 30.34 5.29 8.65 G2 43.26 41.25 1.53 9.06 G3 2.01 0.00 2.41 6.93 G4 19.94 17.93 4.31 9.02 65 87.32 85.31 5.34 9.22 G6 65.68 63.87 6.40 6.91 G7 66.26 66.27 6.39 9.23 as 63.56 61.57 3.51 9.17

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formation are 0.25 and 4.35 kJ mar’, respectively. It seems that the main contribution to the gain in energy should be related to the loss of the am-m0 nitrogen atom coplanarity with the aromatic ring plane. This conclusion is further supported by the results of MNDO calculations for aniline: the “noncoplanar” form is more stable by 1.25 kJ mol-’ than the “coplanar” form 151 I

The differences in the ionization potentials and dipole moments between “coplanar” 12, S] and “noncoplanar” forms (Table 1) are negligible, the averaging differences being 0.03 eV and 0.09 D respectively. Therefore, in- significant differences in calculated heats of formation and dipole moments when going from “coplanar” to “noncoplanar” form means that our previous conclusions 12, 3) about relative stabilities of the nucleic bases tautomers still remain valid both for the gas and condensed phases.

ACKNOWLEDGEMENTS

The authors are indebkd to Prof. J. S. Kwiatkowski (N. Copernicus University, Toruii, Poland) for suggestions and discussions. Thanks are also due to the Regional Computational Center “CYFRONET” in Krakow for allocation of computer time.

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