Relative stability of cytosine tautomers with the coupled cluster method

May 1, 1989 - Carlo Adamo, Marie Heitzmann, Flora Meilleur, Nadia Rega, Giovanni Scalmani, Andre Grand, Jean Cadet, and Vincenzo Barone. Journal of ...
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J . Phys. Chem. 1989, 93, 4001-4005

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Relative Stability of Cytosine Tautomers with the Coupled Cluster Method and First-Order Correlation Orbitals Andrzej Le&+Ludwik Adamowicz,* Department of Chemistry, University of Arizona, Tucson, Arizona 85721

and Rodney J. Bartlett Quantum Theory Project, University of Florida, Gainesville. Florida 3261 1 (Received: November 21, 1988)

Three tautomeric forms of cytosine molecule have been studied by the coupled cluster method with single, double, and triple excitations using first-order correlation orbitals and Gaussian DZP basic sets. The zero-point nuclear energy has been estimated by the SCF 3-21G method with analytical first and second derivatives of the total energy. The hydroxy-amino tautomer has been predicted to predominate in the gas phase in agreement with recent experimental data. The oxcamino and oxo-imino forms are less stable than the hydroxy-amino tautomer by 4 . 2 and 6 . 4 kJ mol-I, respectively. The pertinence of the present results to the interpretation of the experimental IR spectra is discussed.

Introduction I . Biological Importance of Cytosine. Cytosine occurs naturally in all nucleic acids. It is chemically bound to the sugar moiety and interacts via hydrogen bonds with other nucleic acid bases, most frequently with guanine.' Cytosine is also a parent compound of various modified nucleosides and nucleotides. Some of them occur naturally, as methyl-, 5-aza, or thio derivative^;^.^ others are products of chemical reactions of nucleic acids with various mutagenic agents, for example, the N4-hydroxy- or N4-methoxycytosine or 5-halogeno derivative^.^,^ The modified nucleosides (arabino- or xylofuranosyl, modified in some other way, sugar moiety) of cytosine are potential antiviral and antitumor agentsG8 A detailed knowledge of the structure of cytosine and its nucleosides is an important prerequisite in understanding the molecular basis underlying their biological and medicinal functions. 2. Experimental and Theoretical Studies of Cytosine. Cytosine itself, its nucleosides, nucleotides, and many other derivatives have been intensively studied by using a wide variety of experimental techniques9 Recently, NMR,I0 IR, and Raman"J2 spectroscopies have been frequently exploited. Complementary studies have been performed by means of theoretical methods involving quantum13J4 and tati is tical'^ mechanics. 3. why Tautomers Warrant Investigation? Cytosine may exist in various tautomeric forms differing by the position of the proton, which is bound to either the ring nitrogen atoms, the exocyclic oxygen, or the amino group (Figure 1). There is also a possibility that two protons simultaneously change their positions, but such a transformation is energetically rather unfavorab1e.l6 The fidelity of the genetic code can be affected by the tautomers which can be recognized as other nucleic acid bases (i.e,, uracil or thymine); in particular, rare tautomers can be responsible for the formation of mismatches1J3which, in consequence, may lead to errors in the genetic code. It has recently been discovered that several derivatives of cytosine can adopt rare tautomeric forms whose populations strongly depend upon the environment (e.g., solvent, crystal forces) (ref 12, 13, and 17 and references therein). The N(3)methylcytosine exists mainly as the oxc-imino form;'* the same form is predominant for the N4-hydroxycytosine;4 the 5-fluorocytosine exists mainly as the hydroxy-amino form.18-20,29 The interpretation of absorption spectroscopy experimental data usually reveals different tautomeric forms because they have considerably different spectra.12 In some cases, however, it is difficult to detect the rare tautomers when a single form dominates. It has been pointed out that spectroscopic methods are incapable *Author to whom correspondence should be addressed. Permanent address: Department of Chemistry, University of Warsaw, Pasteura 1, 02-093 Warsaw, Poland.

0022-3654/89/2093-4001$01.50/0

of detecting less than 0.1-1.0% of a minor tautomer.21 Thus, the theoretical prediction of various physicochemical properties of different tautomeric forms is essential for understanding the behavior of cytosine itself and can be a useful guide for studying its numerous derivatives. 4 . Purpose o f t h e Present Study. Very recent advanced a b initio studies reveal an extreme sensitivity of the calculated relative stability of cytosine tautomers to the level of the theoretical approximation assumed in the calculational method.I2 This includes such factors as the quality of the basis set, the level of evaluating electron correlation effects, the way the nuclear vibrations are taken into account, etc. In order to elucidate these problems in the present study, we performed quantum mechanical calculations of the three lowest energy tautomers of cytosine a t the highest possible levels of theory. These 58 electron calculations are among the largest electron correlation calculations with the coupled cluster method with single, double, and triple excitations that have been reported. The goal of the present study is to establish the relative

(1) Saenger, W. Principles of Nucleic Acid Structure; Springer-Verlag: New York, 1983. (2) Singer, B.; KuSmierek, J. T. Annu. Reu. Biochem. 1982, 52, 655. (3) Burger, A . A Guide to the Chemical Basis of Drug Design; Wiley: New York, 1983. (4) Shugar, D.; Kierdanszuk, B. J . Biosci. 1985, 8, 657. (5) Drach, J. C. Annu. Rep. Med. Chem. 1980, 15, 149. (6) Gosselin, G.; Bergogne, M. C.; de Rudder, J.; de Clercq, E.; Imbach, J. L. J . Med. Chem. 1986, 29, 203. (7) Bodor, N.; Kaminski, J. J. Annu. Rep. Med. Chem. 1987, 22, 303. (8) Webb, T. R.; Mitsuya, H.; Broder, S. J . Med. Chem. 1988,31, 1475. (9) Physic@ chemical Properties of Nucleic Acids; Duchesne, J., Ed.; Academic Press: New York, 1973. (IO) Wiithrich, K. N M R of Proteins and Nucleic Acids; Wiley: New York, 1986. ( 1 1) Tsuboi, M.; Nishimura, Y.; Hirakawa, A . Y.; Peticolas, W. L. Resonance Raman Spectroscopy and Normal Modes of the Nucleic Acid Bases; Wiley: New York, 1987. (12) SzczqSniak, M.; Szczepaniak, K.; Kwiatkowski, J . S.; Ku Bulat, K.; Person, W. J . Am. Chem. SOC.1988, 110, 8319. (13) Kwiatkowski, J. S.; Zielinski, T. J.; Rein, R. Adu. Quanfum Chem. 1986, 18, 85. (14) Ladik, J. Quantum Theory of Polymers as Solids; Plenum Press: New York, 1988. (1 5) Structure and Dynamics: Nucleic Acids and Proteins; Clementi, E.; Sarma, R. H., Eds.; Adenine Press: New York, 1983. (16) Scanlan, M. J.; Hillier, I. H . J . Am. Chem. SOC.1984, 106, 3737. (17) Cieplak, P.; Bash, P.; Chandra Singh, U.;Kollman, P. A. J . Am. Chem. SOC.1987, 109, 6283. (18) SzczGSniak, M.; Nowak, M. J.; Szczepaniak, K. J . Mol Struct. 1984, 115, 221. (19) C,zermiiski, R.; Kuczera, K.; Rostkowska, H.; Nowak, M. J.; Szczepaniak, K. J . Mol. Struct. 1986, 140, 235. (20) Adamowicz, L. Chem. Phys. Lett. 1988, 153, 147. (21) Shugar, D.; Szczepaniak, K. Int J Quantum Chem. 1981,20, 573.

0 1989 American Chemical Society

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The Journal of Physical Chemistry, Vol. 93, No. 10, 1989

&H %

& H o

N

& oH

C

H

H

H

H 2

1

N

H

H 3

Figure 1. The oxo-amino ( I ) , oxo-imino (2), and hydroxy-amino ( 3 )

tautomers of cytosine. concentration of different tautomeric forms of cytosine in the gas phase at different temperatures. The impact of the results obtained in this paper on the interpretation of the IR spectra will also be discussed.

Methodology This study involves the highest computationally implemented levels of theory for calculating the electron structure of molecular systems. It includes for fourth order of many-body perturbation theory (MBPT) and the coupled cluster (CC) method with single and double excitations (CCSD) and with a noniterative inclusion of triple excitations ( C C S D T(CCSD)).22 Both approaches have been routinely used for some time for smaller molecular systems. It was demonstrated on several numerical examples23 that the CCSD T(CCSD) method provides the total electronic energies for closed-shell systems at equilibrium geometries in good agreement as the full C I method. The application of the C C method or any high-level correlation method for larger systems has been limited by an unfavorable dependence of the computational time on the number of basis functions. It has become increasingly obvious that in order to perform such correlated calculations on a system with more than 50 electrons, the number of correlation orbitals involved has to be significantly reduced. However, this reduction should not compromise the quality of the basis set. A scheme which allows for a n effective reduction of the S C F virtual orbital space was recently proposed and implemented by us24,25and recently used to perform a CC calculation with single and double excitations (CCSD)*O for the 5-fluorocytosine molecule, a system with 66 electrons. The scheme utilizes the second-order Hylleraas functional, which constitutes an upper bound to the second-order correlation energy, E,

+

+

where the zero-order Hamiltonian, Ho, is a sum of the Fock operators, a, is the first-order correlation function, and the sum Eo E , is equal to the total S C F energy. Active correlation orbitals, which contribute to the @,, are optimized via an unitary rectangular transformation of all SCF virtual orbitals. The unitary transformation matrix, U, is assumed as an exponent of an antisymmetric matrix R:

+

U(R) = exp(R)

(2)

This approach is similar to the technique used in MCSCF orbital optimizations. The essential feature, which makes the minimization of the second-order functional feasible for multielectron polyatomic systems, is that only a small subset of all two-electron integrals is involved in the procedure. Those are the exchange integrals with two occupied and two virtua! indices, which can be easily generated from atomic integrals by a selective four-index transformation. In essence, our procedure generates the first-order (22) Bartlett, R. J. Annu. Rec. Phys. Chem. 1981, 32, 359. (23) Noga, J.; Bartlett, R. J. J . Chem. Phys. 1987, 86, 7041. (24) Adamowicz, L.; Bartlett, R. J. J . Chem. Phys. 1987, 86, 6314. The procedure was there termed OVOS, which stands for the optimized virtual orbital space. (25) Adamowicz. L . J . Phys. Chem. 1989, 93. 1780.

Lei et al. TABLE I: Various Contributions (in nu) to the Total Energy of the Oxo-Amino (l), Oxo-Imino (2), and Hydroxy-Amino (3) Tautomers of Cytosine, with the DZP Basis Set" and with the 3-21G Optimized Geometry 1 2 3 SCF -392.695022 -392.693390 -392.695897 0.108280 ZPEb 0.107565 0.106622 -0.873848 M BPT( 2)c -0.8 7 5693 -0.8741 81 -0.013749 MBPT(3)' -0.011612 -0.0 1275 3 -0.007306 M BPT( 4,)e -0.007718 -0.006 190 -0.019602 MBPT(4,)' -0.01 8984 -0.018602 MBPT(4$ 0.01 1761 0.012322 0.013349 -0.902745 M BPT( 2+ 3+4,dq) -0.90 1685 -0.8 9 8 3 76 CCSD' -0.90253 1 -0.901 564 -0.899634 -0.923230 -0.923480 -0.921630 CCSD + T(CCSD)' -1. I68758 -1,1701 55 -1.169883 E,d " D Z P basis set (153 basis functions) of Dunningz8composed of 9s5p primitive Gaussians contracted to 4s2p and augmented by one d-function on carbon, nitrogen, and oxygen atoms; js contracted to 2s and augmented by one p-function on hydrogen atoms. Zero-point energy calculated with 3-21G basis set and analytical first and second derivatives of energy. 'The MBPT and coupled cluster calculations have been performed with the 42 FOCO's. The frozen-core approximation was assumed. MBPT(4X), x = s, d, q, denote the fourth-order contributions to the correlation energy calculated with the single, double, and quadruple excitations, respectively. MBPT(2+3+4&,,) is the sum of he second-, third- and fourth-order terms which do not take into account the triple excitations. The latter are incorporated within the CCSD + T(CCSD) method. dThe second-order correlation energy calculated with the DZP basis set (124 virtual and 21 occupied orbitals). The frozen-core approximation was assumed (8 core orbitals not correlated). 300

240

I

180 0 C

fl

-

500 K

-

300 K

-

200 K

v)

n o 12c

6C

C

I

IO

3475

I '

- T=100 K

,

1850

1600

1350

wavenumbers

Figure 2. The cumulative vibrational spectra of a cytosine sample containing three tautomers in proportions resulting from the following tem-

perature-dependent ratio hydroxy-amino:oxo-amino:oxo-imino = l:exp(-4.2/kr):exp(-6,4/kT),k = 8.31451 X kJ mol-' K-'. The wavenumbers in cm-', the absorbance in arbitrary units (cf. Appendix). The arrows denote the peaks characteristic for the oxo-imino (2) tautomer. correlation orbitals (FOCO). These orbitals can be transformed to a S C F canonical set by diagonalizing the virtual block of the Fock matrix. Then a subsequent utilization of the set in MBPT and C C calculations becomes straightforward. Results Our primary focus is the calculation of the electron correlation contribution to the total energy a t the highest implemented level of theory. The FOCO procedure enables us to calculate a majority of the higher order contributions to the electron correlation energy, in a way similar to simple polyatomic system^.^^^^^ Our results are presented in Tables I-IV and Figures 1 and 2. In Table I we gathered the contributions to the total energy of cytosine tautomers. Figure 1, arising from the electronic ( S C F

The Journal of Physical Chemistry, Vol. 93, No. 10, 1989 4003

Relative Stability of Cytosine Tautomers TABLE 11: Correlation Energy Contributions to the Total Energy" of Cytosine Tautomers

1

-0.875693 -1.169883 74.85 -0.02587 1 -0.047787 A + T(CCSD) -1.195754 /?,(a) = E2 + A -1.204445 EJb) = E2 + A/{ E,(c) = &(a) + T(CCSD) -1.217670 E,(d) = E,(b) + T(CCSD) -1.226361

MBPT(2)

E2 { = MBPT(2)/E2, 56 A = CCSD-MBPT(2)

2

3

-0.873848 -1.168758 74.77 -0.028683 -0.049382 -1,197441 -1.207 121 -1.2 18 140 -1.227820

-0.8741 8 1 -1.170155 74.71 -0.025453 -0.047449 -1.195608 -1.204226 -1.2 17604 -1.226222

"See footnotes to Table 1.

+ electronic correlation)

and nuclear'(zer0-point vibrations) motions. The electronic part has been obtained with double-[ basis set augmented with polarization functions (DZP). The zero-point energy (ZPE) of the nuclear vibrational motion was obtained with the 3-21G basis set by means of SCF analytical derivative methods.26 W e applied a scaling factor of 0.91 to the final result, which is a commonly accepted c o r r e c t i ~ n . ' ~ ~ ~ ~ In Table I1 we present electronic correlation energies obtained by simple extrapolation formulas applied to higher order correlation corrections, which were evaluated with FOCO's. The purpose of these extrapolations is to estimate the electronic correlation energy, which one should obtain with all virtual orbitals employed in the calculations. The extrapolation procedure is justified by two observations. First, the MBPT(2) method with 42 FOCO's consistently reproduces about 74.8% of the secondorder correlation energy obtained with the nonreduced virtual space, Le., with the 124 virtual orbitals, for all three tautomers considered. The second observation is based on our previous C C S D calculations on small polyatomic systems performed with FOCO's which indicate that the decrease of the higher order correlation contribution calculated a t the C C S D level of theory is almost exactly proportional to the decrease of the second-order energy, which results from using a reduced virtual space.zs This suggests that the higher order correlation energy for the nonreduced virtual space can be estimated by multiplying the FOCO C C S D result by the ration of the second-order full-space and reduced-space energies. This procedure gives rise to the quantity EJb) in Table 11. E,(b) is composed of the second-order correlation energy calculated with 124 virtual orbitals and the scaled higher order terms calculated with the reduced virtual orbital space. The E,(b) estimation of the electron correlation energy can be further improved by adding the unscaled triple excitation contribution obtained within the CCSD T(CCSD) method (the E,(d) entry in Table 11) since the triple excitation effects do not scale as do the other C C S D terms. W e believe that the E,(d) value is our best estimation of the total electron correlation energy in the full D Z P basis and this result is used to predict the tautomeric equilibrium. The resulting relative stability of the cytosine tautomers is presented in Table 111. The oxc-amino tautomer has been chosen as the reference form because in this form cytosine predominantly exists in biological systems. From Table I11 it is clear that the qualitatively correct order of relative stabilities of the three tautomers can already be obtained a t the S C F level. It is essential, however, to use a DZ-quality basis set with polarization functions centered a t each atom. The contributions to the relative stability arising from the nuclear vibrations and electronic correlation are far from being negligible and have to be included. One can make an interesting observation upon examining the resulting CC wave functions of different tautomeric forms. The

+

(26) Binkley, J. S.; Frisch, M.; Raghavachari, K.; DeFrees, D.; Schlegel, H. B.; Whiteside, R.; Fluder, E.; Seeger, R.; Fox, D. J.; Head-Gordon, M.; POpk, J. A. GAUSSIAN 86; release c, Carnegie Mellon University, Pittsburgh. (27) Hess, B. A. Jr.; Schaad, L. L.; Cdrsky, P.; Zahradnik, R. Chem. Rev. 1986, 86.709. (28) Dunning, Th. H. Jr. J . Chem. Phys. 1970, 53, 2823. (29) Kwiatkowski, J. S.; Person, W. B.; Szczepaniak, K.; SzczqSniak, M. Acta Eiochim. Polon. 1987, 34, 165.

TABLE III: Various Contributions to the Relative Stability of Cvtosine Tautomers"

3- 1

2-1

SCF ZPE

4.3 1.9

-2.3 -2.5

Various Approximations to the Correlation Energy Contributionb E2 3.0 -0.7 &(a) -4.4 0.4 EJb) -7.0 0.6 EJc) -1.2 0.2 E,(d) -3.8 0.4 SCF + 0.91ZPE + E,(d)' 2.2 -4.2 a Zero energy corresponds to the oxo-amino tautomer. Negative energy values denote a stabilizing effect, while positive energy values denote a destabilizing effect with respect to the oxo-amino form. Energies in kJ mol-'. bSee footnotes to Table I. E,(x), x = a, b, c, d, defined in Table 11. 'This is our best estimation of the relative stability of the cytosine tautomers. We adopted the 0.91 scale factor for the ZPE c ~ n t r i b u t i o n . ' ~ . ~ ~

TABLE I V Contributions to the Relative Stability" of Cytosine Tautomers Calculated at Different Levels of Theory

SCF

ZPE E2

DZP (present work) 6-31G* (ref 30) 3-21G (ref 16) A31 (pseudopot.) (ref 31) 3-21G (present work) 3-21G (ref 12, 29)b MIND0/3 (ref 17) DZP (present work) 6-31G* (ref 30)

2-1

3-1

4.3 2.7 1.7 9.2 1.9

-2.3 2.5 15.9 -2.5 -2.0

2.4 3.0

-0.7

3.1

-1.5

Cumulative Relative Energy SCF + 0.91ZPE + E2 DZP (present work) 9.0 6-31G* (ref 30) 5.8c SCF + 0.91ZPE + E,(d) DZP (present work) 2.2

-5.3 -1.0

-4.2

"See footnotes to Table I. Zero energy corresponds to the oxoamino tautomer. Negative energy values denote a stabilizing effect, while positive energy values denote a destabilizing effect with respect to the oxo-amino form. Energies in kJ mol-'. bAlthough not explicitely stated, the ZPE energy reported by Kwiatkowski et al.29includes the 0.91 scale factor, also used in their subsequent paper.I2 cThis value does not take into account the ZPE contribution. If the latter is added the corrected value should approach about 8 kJ mol-'. nature of the correlation effect seems to be somewhat different for the oxo-imino and oxo-amino or hydroxy-amino tautomers. For the oxeimino form, the contribution from some doubly excited determinants is more pronounced than for the oxo-amino or hydroxy-amino forms, suggesting a stronger multireference character of the wave function. In consequence, one may expect a slower convergence of a single determinant based perturbation theory for the oxo-imino form. Therefore, it seems likely that, in order to assess the difference in energy between oxc-imino and oxo-amino tautomers, one has to include even higher order corrections of the perturbation theory, such as offered by the infinite order CC approach. The comparison of the results obtained in this paper with recent calculations of other authors is given in the Table IV. It is seen that the quality of the basis set, especially the use of the polarization functions located at the hydrogen atoms, is a crucial factor determining the accuracy of the final results, both a t the S C F and correlated levels. This is not surprising considering that the tautomerization involves relocations of hydrogen atoms and a significant alternation of the molecular bond structure. One notices that without polarization functions on the hydrogens (the 6-3 1G* basis set), Kwiatkowski et aL30 predicts the oxo-amino (30) Kwiatkowski, J. S.; Bartlett, R. J.; Person, W. B. J . Am. Chem. SOC. 1988, 110, 2353.

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The Journal of Physical Chemistry, Vol. 93, No. 10, 1989

form to be the most stable at the S C F level, contrary to the present D Z P calculations, which result in the lowest S C F energy for the hydroxy-amino tautomer. The use of the D Z P basis set also produces a noticeable difference in the second-order correlation energy. These are the primary reasons why the presently evaluated stabilization energy for the hydroxy-amino form in relation to the oxo-amino form (1-3) is significantly different from the earlier result,30 even when the same correlation method is used ( S C F + 0.91ZPE + E 2 ) . The Z P E values were evaluated in both Kwiatkowski’s et al. and our present work at the same level of theory, producing, however, slightly different results. Having access to Kwiatkowski’s et al. computer outputs, we noticed that his 3-21G S C F energy is slightly higher than ours (-390.416 201 vs -390.416 205) for the oxo-amino tautomer, indicating that his molecular geometry is less optimal. The difference in the Z P E values can be caused by the resulting insignificant differences in structural parameters. The results collected in Table I11 enable us to estimate the percentage of constituents of the cytosine sample a t different temperatures. Assuming that only three tautomers are present in the sample and adopting the equilibrium rate constant between tautomers in the exponential form, we obtain the following relative concentration of hydroxy-amino (3):oxo-amino (1):oxo-imino (2) = 1:exp(-4.2/kr):exp(-6.4/kT) where k = 8.31451 X kJ mol-’ K-’ and T i s the temperature. It is clear that a t temperatures below 100 K the hydroxy-amino tautomer (3) should not be contaminated by any other forms. However, in gas phase at T = 500 K, the contribution of all three forms will be present with a noticeable concentration and the ratio of hydroxy-amino:oxo-amino:oxo-imino forms will equal to 1 4 5 3 . This will have an immediate impact on the IR spectra. W e calculated simplified IR spectra a t different temperatures using the scaled 3-21G S C F frequencies and the absorbancies multiplied by a factor corresponding to the concentration of each tautomer (see Figure 2). The broadening of the absorption peaks has been achieved by means of simple Gaussian functions with the halfwidth of 1 cm-’ and the altitude proportional to the absorbances. W e did not consider the second hydroxy-amino tautomer ( 0 - H directed to the N(3) ring atom) which, according to Szczqiniak et a1.,I2 can be responsible for the splitting of some absorption bands. From the 3-21G S C F calculation for the oxo-imino tautomer (2), we can expect the appearance of strong absorption bands a t 3483,3456, 1768, 1728, 1397, 1 1 19,905, 887, and 632 cm-’ (cf. Appendix). These bands are visible in our simulated IR spectra, as indicated by the arrows in Figure 2. The figure comprises only regions near the 3450 cm-’ (N(I)-H and NH2 modes) and 1720 cm-’ ( C - 0 modes) wavenumbers which are particularly interesting for cytosine. Our conclusion as to the appearance of the bands of the oxoimino tautomer in the IR absorption spectra of cytosine does not disagree with the experimental data. Upon careful examination of the argon matrix spectra of Szczqiniak et al.,12 one can identify certain peaks which can be attributed to the oxo-imino form. However, one needs data for experiments performed a t different temperatures to make a positive assignment. Conclusions On the basis of the present theoretical study, we may confirm the conclusions based on the recent matrix-isolation data and theoretical a b initio calculations12 that in gas phase the cytosine molecules exist predominantly in the hydroxy-amino (3) form. We obtained the improved values of the relative stability of three tautomers of cytosine: the most stable is the hydroxy-amino form (3), followed by the oxo-amino form (1) (4.2 kJ mol-’ above 3) and the oxo-imino form (2) (6.4 kJ mol-’ above 3). Our investigation has been performed a t the highest implemented levels of theory. The results indicate that the relative stability order 3 < 1 < 2 can be obtained at the S C F level with ( 3 1 ) LeS. 4 , Ortega Blake. I Int J Quamum Chem 1986, 30. 2 2 5

Lei et al. TABLE V: Wavenumbers (v, em-’) and Integrated Intensities ( A , km mol-’) Calculated with the 3-21G Basis Set for Oxo-Amino (l), Oxo-Imino (2), and Hydroxy-Amino (3) Tautomers of Cytosine”

2

1

*

3

U

A

U

A

U

A

3559 3465 3440 3120 3084 1772 1663 1644 1544 1483 1419 1357 1237 1207 1107 I077 1073 97 1 89 1 882 861 765 744 692 605 581 538 525 463 446 351 216 166

67 104 106 2 3 677 622 99 27 1 130 125 137 77 21 7 12 80 0 3 316 20 4 2 46 42 3 5 4 68 3 3 11 4

3483 3456 3336 31 I5 3090 1768 1728 1658 1478 1423 1418 1397 1294 1223 1119 1075 1054 99 1 927 905 887 827 747 740 708 632 562 529 515 426 373 I89 158

133 89 4 3 2 704 575 6 53 0 0 270 32 56 294 7 5 8 12 309 162 8 0 6 57 122 9 2 38 11 I1 0 0

3562 3552 3444 3108 3077 1647 1602 1548 1529 1462 1389 1313 I237 1 I54 1125 1086 1062 974 953 910 845 778 76 1 596 570 563 517 483 48 1 462 331 233 214

67 119 100 5 15 173 480 365 16 399 58 193 198 2 29 4 114 9 24 228 19 12 0 0 258 3 97 4 59 139 13 17 0

Wavenumbers include the scale factor of 0.91. the DZP basis set due to a fortuitous cancellation of the correlation effects and the zero-point vibrational energies. However, the zero-point nuclear vibrations and the electron correlation effects individually give rise to important contributions to the calculated relative stability. Probably the most striking result of the present paper is the stability of the oxo-imino (2) tautomer which appears to be very close to the oxo-amino (1) form. To a large extent this is due to electron correlation effects. If our estimation of the relative stability of cytosine tautomers were correct, we would expect the appearance of characteristic peaks in the IR spectra corresponding to all three tautomers. It seems clear that a more detailed revision of the experimental IR spectra, particularly in the region of 3450 and 1700 cm-I, will be necessary to confirm the presence of the oxo-imino tautomer (2). W e also suggest the examination of the temperature dependence of the IR spectra of the carefully equilibrated cytosine samples. From our calculations we may expect a fairly easy tautomerization of the oxo-amino form (1) to the rare oxo-imino form ( 2 ) . Such a process is particularly interesting from a biophysical point of view, because the most prevalent hydroxy-amino form of cytosine cannot appear in nucleosides as a result of the glycosidic bond formation. We estimate the relative total energy to be about 2.2 kJ mol-’, which gives rise to the relative concentration in the gas phase as 5:2 a t room temperature. This ratio can be strongly influenced by the environmental factors typical for biological systems, which may lead to a decrease in the population of the rare oxo-imino tautomer.

Acknowledgment. W e are greatly indebted to Drs. M. SzczqSniak, K. Szczepaniak, J. S. Kwiatkowski, K. Ku Bulat, and W. B. Person for sending us their paper‘* prior to its publication. This research was supported in part by an institutional grant from the National Cancer Institute and in part by the U S . Office of Naval Research.

J . Phys. Chem. 1989, 93, 4005-4009 Appendix We attach the wavenumbers and integrated intensities for three tautomers of cytosine calculated with the 3-21G basis set (Table V). These data are complementary to the spectra presented in Figure 2. Analogical calculations have been recently performed by SzczqSniak et a1.I2 for the oxo-amino (1) and hydroxy-amino

4005

(3) tautomers. We noticed small differences both in wavenumbers and intensities which probably come from small differences between the optimal geometries obtained in the Present Paper and the quoted work. Registry No. Cytosine, 71-30-7.

Photochemistry and Photophysics of Small Heterocyclic Molecules. 2. CW COP Laser Inducement of the Bimolecular Reaction of Thiirane John T. Campbell and Joseph J. BelBruno* Department of Chemistry, Dartmouth College, Hanouer, New Hampshire 03755 (Received: January 20, 1988; In Final Form: December 13, 1988)

The gas-phase IR laser photolysis of ethylene sulfide has been examined in the presence of SF, as a sensitizer molecule. Reaction does not occur in the absence of the sensitizing agent or at laser frequencies not absorbed by both thiirane and SF,. Surprisingly, ethylene, methane, and carbon disulfide are the resultant gaseous products. Pyrolysis and conventional UV photochemistry do not yield the latter two species, and S2, a major product in conventional photochemistry and thermochemistry, is not observed at all. The dependence of the photolysis on laser fluence, gas (total and/or sensitizer) pressure, and laser wavelength is examined. The data are consistent with a mechanism involving the reaction of highly vibrationally excited thiirane molecules (produced by a combination of collisional and radiative processes) via an intermediate S(lD) species. The thiirane system appears to be unique in that CW C 0 2 laser enhancement of bimolecular chemistry is not readily observed in organic molecules.

Introduction The use of pulsed C 0 2 lasers in the vibrational enhancement of unimolecular processes is well-known.' Less well studied is the application of either pulsed or C W infrared lasers to bimolecular chemistry. This is in stark contrast to much of the published work on UV/vis laser enhancement2 in which electronic excitation of one of the reactants in a bimolecular reaction is observed to greatly augment the reaction rate. One exception to this generalization is the use of C 0 2 lasers in the realm of sensitized bimolecular p h o t ~ c h e m i s t r y . ~Both *~ pulsed and C W lasers have been employed in previously reported studies, although our concern in this report is only with the C W studies. Tardieu de Maleissye et aL5 have reported on the SF6-sensitized reaction of ethane, and in a series of related experiments,b8 Pola has employed S F 6 sensitization to the decomposition of small fluoro-substituted molecules. While these experiments were successful in driving a chemical reaction, the use of sensitizers in IR laser photochemistry typically results in a loss of molecular specificity in the deposition of the laser energy. The chemistry often becomes indistinguishable from that of (homogeneous) high-temperature p y r o l y ~ i s . ~ ( I ) See, for example: Bagratashvili, V. N.; Letokhov, V. S.; Makarov, A. A.; Ryabov, E. A. Multiple Photon Infrared Laser Photophysics and Photochemistry; Harwood Academic: Amsterdam, 1985. (2) Fontijn, A., Clyne, M. A. A,, Eds. Reactions of Small Transient Species; Academic Press: London, 1983. (3) Danen, W. C.; Jang, J. C. In Laser-Induced Chemical Processes; Steinfeld, J. I., Ed.; Plenum Press: New York, 1984. (4) The use of CW lasers in IR laser induced unimolecular chemistry has been examined in a series of papers. See, for example: Zitter, R. N.; Koster, D. F.; Parvez, M. S. Opr. Commun. 1986, 59, 259. Zitter, R. N.; Koster, D. F.; Ringwelski, A,; Cantoni, A. Appl. Phys. 1983, 830, 19. Zitter, R. N.; Koster, D. F.; Ringwelski, A.; Cantoni, A. Appl. Phys. 1983, 830, 79, and references therein. (5) (a) Tardieu de Maleissye, J.; Lempereur, F.; Marsal, C.; Ben-Aim, R. I. Chem. Phys. Letr. 1976, 42, 46; (b) Tardieu de Maleissye, J.; Lalo, C.; Lempereur, F.; Masanet, J. J . Phys. Chem. 1987, 91, 5899. (6) Pola, J.; Engst, P.; Horak, M. Collect. Czech. Chem. Commun.1981, 46, 1254. (7) Pola, J. Collect. Czech. Chem. Commun. 1981, 46, 2854. ( 8 ) Pola, J. Collect. Czech. Chem. Commun. 1981, 46, 2860.

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Previous attempts to induce bimolecular reactions via IR excitation have involved both pulsed and C W C 0 2 laser systems. Birely and LymanIo were successful in their utilization of the technique, but the experiments were restricted to di- and triatomic inorganic species and pulsed lasers. The addition of vibrationally excited hydrogen halides to chloro- and fluorocarbonsI1J2was attempted with high-energy pulsed lasers, but no laser enhancement of the process was observed. The failure of these attempts at enhancement of the bimolecular chemistry was attributed to efficient energy transfer successfully competing with the reaction. The net effect was simple thermal heating of the gas sample. Lenzi et al.I3 have examined the V-T process in SF,/Ar mixtures and have shown that, with a pulsed laser, nonthermal vibrational distributions may be accessed during the laser pulse. This type of nonequilibrium reaction was employed by Mele et al. and Chin et in the pulsed laser sensitized decomposition of cyclohexene and UF,, respectively. Finally, Guckert and C a d s report on the product selectivity in the pulsed photolysis of trans-2-butene. The selectivity in this experiment was attributed to secondary photolysis of products formed from the decomposition of the initial reactant. Laser enhancement of the SN2reaction between NH, and CH,Br to produce an ion-pair product was unsuc~essful,~ but this type of product is not well characterized and the lack of detected product may be related to the chemistry rather than any competitive process. Two successes have been reported in the literature with CW excitation. Continuous-wave irradiation was employed in the addition of C1 radicals to the CH2D2molecule resulting in the formation of methylene chloride.', This process was (9) Shaub, W. M.; Bauer, S. H. Int. J . Chem. Kinet. 1975. 7, 509. (10) Birely, J. H.; Lyman, J. L. J . Photochem. 1975, 4, 269. (11) Herman, I. P.; Marling, J. B. J . Chem. Phys. 1979, 71, 643. (12) Douglas, D. J.; Moore, C . B. In Laser-Induced Processes in Molecules: Physics and Chemistry; Kompa, K. L., Smith, S . D., Eds.; SpringerVerlag: New York, 1979. (13) Lenzi, M.; Molinari, E.; Piciacchia, G.; Sessa, V.; Terranova, M. L. Chem. Phys. 1986, 108, 167. (14) Mele, A,; Salvetti, F.; Molinari, E.; Terranova, M. L. J . Phorochem. 1986, 32, 265. Chin, C.; Hou, H.; Bao. Y.; Li, T. Chem. Phys. Lett. 1983, 101, 69. (15) Guckert, J . R.; Carr, R. W. J . Phys. Chem. 1986, 90, 5679.

0 1989 American Chemical Society