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Solvation of the tautomeric forms of 2-oxopyrimidine in chloroform solution: a Monte Carlo simulation
Journal of Molecular Structure (Theochem), 184 (1989) 221-230
221
Elsevier Science Publishers B.V., Amsterdam - Printed in The Netherlands
SOLVATION OF THE TAUTOMERIC FORMS OF 2-OXOPYRIMIDINE IN CHLOROFORM SOLUTION: A MONTE CARLO SIMULATION
PIOTR CIEPLAK* Quantum Chemistry Laboratory, University of Warsaw, Pasteura 1,02-093 Warsaw (Poland)
MACIEJ GELLER Department of Biophysics, Institute of Experimental Physics, University of Warsaw, Zwirki i Wigury 93,02-089 Warsaw (Poland)
(Received 15 December 1987; in final form 6 May 1988)
ABSTRACT Solvation of both tautomeric forms of 2-oxopyrimidine by chloroform has been investigated using the Monte Carlo method for a cluster consisting of 50 solvent molecules at T=300 K. The results indicate that, in agreement with experiment, this solvation shifts the tautomeric equilibrium only a little towards the lactam form. This is an opposite effect to that occurring in the case of solvation by CC&. These calculations, together with two previous ones, indicate that solvent molecules tend to minimize the energy of their interactions, whereas the solute molecule tends to locate itself in such an orientation towards the surrounding molecules as to minimize its energy of interaction with the solvent. This conclusion seems to be independent of the solvent polarity.
INTRODUCTION
In our two previous studies [ 1,2] the hydration and solvation in Ccl, solution of the two tautomeric forms of 2-oxopyrimidine, shown below (Scheme 1) , have been theoretically investigated. ( lactim 1
(lactam 1 K_
[bxtpml [lactlm
1
A Scheme
1
The results, in accord with experiment, indicated that hydration significantly *Author to whom correspondence should be addressed.
0166-1280/89/$03.50
0 1989 Elsevier Science Publishers B.V.
222
shifts the tautomeric equilibrium towards the lactam (keto) form, while solvation by carbon tetrachloride shifts this equilibrium slightly towards the lactim (enol) one, i.e. towards the form which prevails in the vapour phase. Water and carbon tetrachloride are examples of a high polar and a non-polar solvent, respectively. In the case of chloroform, an “intermediate” solvent, the experimental data [ 31 suggest that the tautomeric equilibrium is shifted a little towards the lactam form. The aim of this study was to check this fact by means of theoretical methods using the Monte Carlo simulation technique. The three studies together enable us to draw some general conclusions about the influence of solvation phenomena on the properties of the solvated molecules. METHOD
As described previously [ 2 1, solvation of the tautomeric forms was studied by the Monte Carlo simulation [4,5] using the Metropolis sampling method applied to a cluster consisting of n= 50 CHC& molecules and appropriate solute at temperature of T= 300 K. To calculate the energy of interaction between molecules A and B the following atom-atom potentials of Pohorille et al. [ 61, successfully used to study the solvation effects on the association of nucleic bases, were applied
Ey
qiqj
cij -r6_+Dij
exp (-aij’ii) 41 v where qi are the atomic net charges from CNDO/B calculations. The same atomic charges for 2-oxopyrimidine were employed as in the previous study of Ccl, solvation. For CHC& qc = O.l20e, qcl = - 0.065e and qH= 0.075e were used. Equilibrium in the Monte Carlo process was achieved after 100 000 configurations and an additional 100 000 configurations were generated to obtain the final results. The optimized geometry of the tautomeric forms obtained by the MIND0/3 method was used [ 71. Because of the symmetry to rotation, the rigid form of the OH group was assumed. zy
RESULTS AND DISCUSSION
Salvation of tautomeric form of 2-oxypyrimidine (n = 50, T =300 K)
Mean energies of the interactions for both tautomeric forms are listed in Table 1. The results point to a small shift in the tautomeric equilibrium in CHC& solution towards the lactam (keto) form.
223 TABLE 1 Mean interaction energies (in kJ mol-‘) between CHCl, and pyrimidine and in pure CHC&“: n&O, T=300 K Form
E tot
Lactim
- 686.3 k 31.8 - 707.3 f 26.9 - 629.3 f 30.1
LtlCtAUll
Pure CHC&
- 626.0 + 30.1 -631.9 f 27.0
J&Hc~,P
E&n
-60.3 AI 5.4 - 75.4 f 4.8
- 13.7 - 14.1 - 12.6
where ~CHC~.CHC~ is the sum of the interaction energies between CHC& molecules, and ECHCI,,Pis the sum of the interaction energies between CHCl, and pyrimidine. 'E,,=EcHc~,.cHc~+EcHc~~.P
AJLv =Etit (lactam) -Etit (lactim) = -21 kJ mol-’ For comparison, the following are the results obtained previously [ 1,2] for water and Ccl, solution simulations with n = 50 solvent molecules
AEmlv (H, 0) = Etit (lactam ) -E,,
(lactim) = - 55.5 kJ mol-’
AESolv(CCL) = Ebt (lactam ) - Ebt (lactim) = 14.9 kJ mol-l In the above, only the energies of solvation were taken into account. To estimate the total tautomerisation energy in solution the internal energy difference between both tautomers should be added to the AE,,,. According to experimental [8] and theoretical [9] estimates, the gas-phase value for the tautomerisation of 2-oxopyrimidine is approximately 10 kJ mol-l. Thus, the overall picture of the tautomeric equilibria in different solvents will be preserved even if this value is added to the calculated data.
Interaction among CHCls molecules The radial distribution functions (RDFs ) for the CHC& cluster at T= 300 K for the lactam form are shown in Fig. 1. Appropriate RDFs for the lactim form are nearly identical. The strong similarity of these functions indicates the resemblance of the CHC$ structure in both cases. The gee RDFs reach maxim-a at 5.4 A, the gccl at 5 A, and the g CHexhibits two maxima at 4.5 A and 6.0 A. The gclcl and gHC1 RDFs exhibit two maxima: 3.8 A and 6.2 A, and 3.3 A and 5.6 A, respectively. The gnn RDFs reach maxima at 5.2 A. To study the solvent structure in detail, the stable configurations of the CHC& dimer have been determined. Moreover, a similar Monte Carlo simulation for a cluster consisting of pure CHC& (n = 50, T= 300 K) has been performed. It
224
Fig. 1. Radial distribution functions for CHC13 molecules in the presence of the la&am forms of 2-oxopyrimidine. (a) (-1 gee; (---I gee,; (*****I &!HCl. (b) (-1 &la; (----I gHH; (****I gHCl*
is of interest that all RDFs for the pure solvent are nearly identical to those for both the solvent structures discussed above. The stable configurations of the dimer are presented in Fig. 2 and contributions to the total energy of their interactions are listed in Table 2. The most stable configuration of the dimer corresponds to the staggered “head-to-head” type (I&= - 11.4 kJ mol-‘), whereas the eclipsed “head-to-head” and the two “head-to-tail” configurations have an energy about 2.5 kJ mol-’ higher than the previous one. The most stable configuration of the dimer and its energy corresponds exactly to the most stable configuration and the energy of the Ccl, dimer [ 21. The attractive contribution to the interaction energies are entirely due to the dispersion terms. Both molecules in the most stable configuration are oriented in such a way as to minimize the Cl***Cldistance which results in lowering the dispersion attraction. The distance between the closest chlorine nuclei is about 3.8 A which is somewhat greater than the corresponding sum of the van der Waals radii (3.6 A). This distance corresponds exactly to the first peak of the gcIcl. The rcc distance in this configuration of the dimer is, however, about 4.5 A which is significantly shorter than the position of the first peak of the gee (5.4 A). Hence, this type of configuration rarely seems to be realized in the solvent. To make this analysis more quantitative, the percentages of the various types of CHC&. - - CHC&, configurations from all three Monte Carlo simulations has
C’ -.p
P’
H-C
Cl
C-H
Cl’ I-
4.5A-l A
/’
H-C.,
'\C-H CO Cl
b&CL
I4.0i-4 B
CI
CL
\
CL
\
L-H CC&
/f-H
C’Cl
c4.3Lj
\
C!, \’ S-H
;C-H
CC/,
L4.3f1-I
C
D
CI \
,C-H Cl';{
/“
H--C,,
h$l
c_
4.9i-I E Fig. 2. Stable configurations of the CHCl, dimer. TABLE 2 Stable configurations of the CHCl, dime+ (in kJ mol-‘) Configurations
E to*
:
- 8.9 -11.4
: e
-
8.5 1.4
Edstat
Edisp
0.3 0.2
- 20.8 15.5
9.2 6.3
-0.4 1.6
- 14.8 14.5 - 3.9
6.4 6.7 0.9
“For notation of the configurations see Fig. 2.
been determined. The results are listed in Table 3. It is seen that the solvent molecules are only rarely located in the positions corresponding to the minima of the interaction energy for the CHCl, dimer. This is probably due to: (i) the
226 TABLE 3 Percentage of the various types of mutual configuration of the CHCl, molecules in pure CHC& cluster and in the solvent shells around the tautomeric forma of 2-oxopyrimidine” obtained from Monte Carlo simulations Solvent
Configuration
Lactam Lactim
a+b
c+d
e
others
2.9
7.2 7.1 6.4
3.8 3.6 3.8
86.1 86.3 86.9
3.0 2.9
“Fornotation of the configurations see Fig. 2.
-20
-10
0
10
BlCHCl3,CHCl31
Fig. 3. Quasi-component distribution function for binding energy of the CHCl, in the presence of the lactam form of 2-oxopyrimidine. xe denotes the mole fraction of CHCl, molecuke with binding energy between B and B + dB, where B is the mean energy of interaction between a CHCl, molecule and any other molecule of the solvent.
energy of interaction for the dimers is rather small; and (ii) the differences between them are comparable to the energy of the thermal motions. Finally, the quasi-component distribution functions (QCDFs ) [lo] for binding energy among the solvent molecules have been calculated. The results, presented in Fig. 3, are nearly identical for both tautomeric forms. All these results indicate that the structure of the CHC& solvation shell is not much perturbed by the solute. Interactions between CHCl, and pyrimidine
The radial distribution functions g,_,, gx_cl, and g&n, where X denotes an atom of the pyrimidine molecule, for both tautomeric forms, are shown in Fig. 4. The most pronounced differences between both forms are seen near the nitrogen atom, Ni, in the region of proton displacement. The gNl_n exhibits a sharp peak at 3.0 A for the lactim form while there is not such a peak for the lactam one. It suggests that near the N1 atom of the lactim form the configurations of the solvent molecules correspond mainly to the “tail-to-N,” type while the configuration of the “head-to-N,” dominates for the la&am form.
227
g
e
g
f
3i
3 2
, ,,..... _._:: *y"-<, 2; ,.,.j ,' ' i 3 5 7'
1
Fig.4. Radialdistribution functionsfor chloroformmolecules vs. atomiccentersX of 2-oxopyrimidine(r in A). (a-d) Lactam;(e-h) lactim;(a,e) X=N,; (b,f) X=N,; (c,g) X=C5; (d-h) X=0’. (-)&_C; (----) &_a; (““) &?x_,. Comparison of the radial distributions [Fig. 4 (b ),(f) ] shows that the opposite is true for the N3 atom. It is worth noting that even g,,_, RDFs exhibit differences between both tautomeric forms, although this region of the pyrimidine seems to be similar in both cases. The size of the CHC13 molecule, however, is quite large and, therefore, the differences in packing of these molecules near the N, or 0’ atoms can influence the properties of the solvation shell in other parts of the pyrimidine molecule. The QCDFs for binding energy B (CP-CHCl,), i.e. the mean energy of the interaction between the pyrimidine molecule and a solvent, are presented in Fig. 5. It is seen that the solvent favours somewhat the la&am form. To answer the question of whether there are preferable stable configurations of the solvent molecules around tautomers, additional calculations have been performed with n = 1 and n = 2 CHCl, molecules. Results of the calculations
228
0.05. 0.04.
0.02. O.Ol-5
4
-3
-2
L. 0 1
-1
2 Lap-cm3
I
Fig. 5. Quasi-component distribution functions for the binding energy B(CP-CHC&). Xn is the mole fraction of the solvent molecules; B (CP-CHCl,) is the mean energy of the interaction between the P-oxopyrimidine molecule and a solvent. (----I La&m form; (-) la&am form.
b-
)_
H
H
H
Fig. 6. Global minimum of the interaction between one CHC& molecule and 2-oxopyrimidine: (a) lactim; (b) la&am. Chloroform molecules are projected into the XY plane at the top of figure and into the X2 plane at the bottom. Fig. 7. Global minimum of the interaction of two CHC& molecules and 2-oxopyrimidine: (a) lactim, (b) la&am.
TABLE 4 Global minima (kJ mol- * ) of interaction energy for the system: nCHCIs + pyrimidine at T= 0 K”
1 2
La&am Lactim La&am Lactim
-16.8 - 15.2 -35.2 -31.0
-7.1 -8.0
“Notation as in Table 1.
3.1 0.8
-13.6 -16.4
6.2 7.6
- 16.8 - 15.2 -28.1 -23.0
-2.6 -0.6 -5.1 0.2
-26.8 -26.5 -41.2 -40.1
12.5 12.0 18.2 16.9
229
are presented in Figs. 6 and 7 and in Table 4. Each figure shows configurations corresponding to the calculated minimum of the interaction energy. To determine the local minima the previously described procedure, which involves gradually decreasing the temperature during Monte Carlo simulations, has been applied [ 11. n=l The final configurations, corresponding to the global minimum of the interaction energy for the lactam and the lactim form are shown in Fig. 6 (a) and (b), respectively. Of course, because of the planar symmetry of pyrimidine there are two identical minima above and below the plane of the molecule. Contrary to the case of solvation by CCL these configurations are not the “headto-plane” type. It is seen from the Table 4 that it is due to the electrostatic interaction resulting from the presence of the positively charged H-C group of the CHC& molecule. The energy of the “head-to-plane” configuration (similar to that of the Ccl,) is, however, only slightly higher (E= -12.1 kJ mol-‘). n=2 The global minima, shown in Fig. 7, do not correspond to the location of each CHC& molecule in the corresponding minimum (shown in Fig. 6) above and below the plane of pyrimidine, as for the CC& molecules. It is seen from Table 5 that this configuration is determined by both dispersion and electrostatic energies. It is also seen that none of these molecules is located in the minimum corresponding to the case n = 1. CONCLUSIONS
It follows from these simulations that, in agreement with experiment, the solvation of pyrimidine by CHC13shifts the tautomeric equilibrium only a little towards the lactam form. This is an opposite shift to that occurring in the case of solvation by Ccl, [ 21. This effect is mainly due to the small difference in the energies of interaction between the solvent and the solute molecule in the two cases. The results presented both in this work and in the two previous ones [ 1,2] indicate that the structure of the solvent is only little disturbed by the solute molecule. This conclusion seems to be independent of the polarity of the solvent. These calculations indicate that solvent molecules tend to minimize the energy of their interactions, whereas the solute molecule tends to locate itself in such an orientation towards the surrounding molecules as to minimize (algebraically) its energy of interaction with the solvent.
To obtain more precise results it would be necessary to perform simulations with a much larger number of solvent molecules and to use proper boundary conditions. Also, the three-body effects should be taken into account. ACKNOWLEDGMENT
This work was supported by the Polish Academy of Sciences within the project C.P.B.P. 01.12.
REFERENCES 1 2 3 4
P. Cieplak and M. Geller, J. Mol. Struct. (Theochem), 121 (1985) 247. P. Cieplak and M. Geller, J. Mol. Struct. (Theochem), 124 (1985) 249. M.J. Nowak, K. Szczepaniak, A. Bareki and D. Shugar, J. Mol. Struct., 62 (1980) 47. J.P. Valleau and S.G. Whittington, in B.J. Berne, (Ed.), Statietical Mechanics, Part A: Equilibrium Technique, Plenum Press, New York, 1977, p. 137. 5 N. Metropolis, A.W. Metropolis, M.N. Rosenbluth, A.H. Teller and E. Teller, J. Chem. Phys., 21 (1953) 1087. 6 A. Pohorille, S.K. Burt and R.D. McElroy, J. Am. Chem. Sot., 106 (1984) 402. 7 R. Czermiliski, B. Lesyng and A. Pohorille, Int. J. Quantum Chem., 16 (1979) 1141. 8 P. Beak, F.S. Fry, Jr., J.L. Lee and F. Steelem, J. Am. Chem. Sot., 98 (1976) 171. 9 P. Cieplak, U.C. Singh and P.A. Kollman, Int. J. Quantum Chem. QBS, 14 (1987) 65. 10 A. Ben-Naim, Water and Aqueous Solution, Plenum Press, New York, 1974.
221
Elsevier Science Publishers B.V., Amsterdam - Printed in The Netherlands
SOLVATION OF THE TAUTOMERIC FORMS OF 2-OXOPYRIMIDINE IN CHLOROFORM SOLUTION: A MONTE CARLO SIMULATION
PIOTR CIEPLAK* Quantum Chemistry Laboratory, University of Warsaw, Pasteura 1,02-093 Warsaw (Poland)
MACIEJ GELLER Department of Biophysics, Institute of Experimental Physics, University of Warsaw, Zwirki i Wigury 93,02-089 Warsaw (Poland)
(Received 15 December 1987; in final form 6 May 1988)
ABSTRACT Solvation of both tautomeric forms of 2-oxopyrimidine by chloroform has been investigated using the Monte Carlo method for a cluster consisting of 50 solvent molecules at T=300 K. The results indicate that, in agreement with experiment, this solvation shifts the tautomeric equilibrium only a little towards the lactam form. This is an opposite effect to that occurring in the case of solvation by CC&. These calculations, together with two previous ones, indicate that solvent molecules tend to minimize the energy of their interactions, whereas the solute molecule tends to locate itself in such an orientation towards the surrounding molecules as to minimize its energy of interaction with the solvent. This conclusion seems to be independent of the solvent polarity.
INTRODUCTION
In our two previous studies [ 1,2] the hydration and solvation in Ccl, solution of the two tautomeric forms of 2-oxopyrimidine, shown below (Scheme 1) , have been theoretically investigated. ( lactim 1
(lactam 1 K_
[bxtpml [lactlm
1
A Scheme
1
The results, in accord with experiment, indicated that hydration significantly *Author to whom correspondence should be addressed.
0166-1280/89/$03.50
0 1989 Elsevier Science Publishers B.V.
222
shifts the tautomeric equilibrium towards the lactam (keto) form, while solvation by carbon tetrachloride shifts this equilibrium slightly towards the lactim (enol) one, i.e. towards the form which prevails in the vapour phase. Water and carbon tetrachloride are examples of a high polar and a non-polar solvent, respectively. In the case of chloroform, an “intermediate” solvent, the experimental data [ 31 suggest that the tautomeric equilibrium is shifted a little towards the lactam form. The aim of this study was to check this fact by means of theoretical methods using the Monte Carlo simulation technique. The three studies together enable us to draw some general conclusions about the influence of solvation phenomena on the properties of the solvated molecules. METHOD
As described previously [ 2 1, solvation of the tautomeric forms was studied by the Monte Carlo simulation [4,5] using the Metropolis sampling method applied to a cluster consisting of n= 50 CHC& molecules and appropriate solute at temperature of T= 300 K. To calculate the energy of interaction between molecules A and B the following atom-atom potentials of Pohorille et al. [ 61, successfully used to study the solvation effects on the association of nucleic bases, were applied
Ey
qiqj
cij -r6_+Dij
exp (-aij’ii) 41 v where qi are the atomic net charges from CNDO/B calculations. The same atomic charges for 2-oxopyrimidine were employed as in the previous study of Ccl, solvation. For CHC& qc = O.l20e, qcl = - 0.065e and qH= 0.075e were used. Equilibrium in the Monte Carlo process was achieved after 100 000 configurations and an additional 100 000 configurations were generated to obtain the final results. The optimized geometry of the tautomeric forms obtained by the MIND0/3 method was used [ 71. Because of the symmetry to rotation, the rigid form of the OH group was assumed. zy
RESULTS AND DISCUSSION
Salvation of tautomeric form of 2-oxypyrimidine (n = 50, T =300 K)
Mean energies of the interactions for both tautomeric forms are listed in Table 1. The results point to a small shift in the tautomeric equilibrium in CHC& solution towards the lactam (keto) form.
223 TABLE 1 Mean interaction energies (in kJ mol-‘) between CHCl, and pyrimidine and in pure CHC&“: n&O, T=300 K Form
E tot
Lactim
- 686.3 k 31.8 - 707.3 f 26.9 - 629.3 f 30.1
LtlCtAUll
Pure CHC&
- 626.0 + 30.1 -631.9 f 27.0
J&Hc~,P
E&n
-60.3 AI 5.4 - 75.4 f 4.8
- 13.7 - 14.1 - 12.6
where ~CHC~.CHC~ is the sum of the interaction energies between CHC& molecules, and ECHCI,,Pis the sum of the interaction energies between CHCl, and pyrimidine. 'E,,=EcHc~,.cHc~+EcHc~~.P
AJLv =Etit (lactam) -Etit (lactim) = -21 kJ mol-’ For comparison, the following are the results obtained previously [ 1,2] for water and Ccl, solution simulations with n = 50 solvent molecules
AEmlv (H, 0) = Etit (lactam ) -E,,
(lactim) = - 55.5 kJ mol-’
AESolv(CCL) = Ebt (lactam ) - Ebt (lactim) = 14.9 kJ mol-l In the above, only the energies of solvation were taken into account. To estimate the total tautomerisation energy in solution the internal energy difference between both tautomers should be added to the AE,,,. According to experimental [8] and theoretical [9] estimates, the gas-phase value for the tautomerisation of 2-oxopyrimidine is approximately 10 kJ mol-l. Thus, the overall picture of the tautomeric equilibria in different solvents will be preserved even if this value is added to the calculated data.
Interaction among CHCls molecules The radial distribution functions (RDFs ) for the CHC& cluster at T= 300 K for the lactam form are shown in Fig. 1. Appropriate RDFs for the lactim form are nearly identical. The strong similarity of these functions indicates the resemblance of the CHC$ structure in both cases. The gee RDFs reach maxim-a at 5.4 A, the gccl at 5 A, and the g CHexhibits two maxima at 4.5 A and 6.0 A. The gclcl and gHC1 RDFs exhibit two maxima: 3.8 A and 6.2 A, and 3.3 A and 5.6 A, respectively. The gnn RDFs reach maxima at 5.2 A. To study the solvent structure in detail, the stable configurations of the CHC& dimer have been determined. Moreover, a similar Monte Carlo simulation for a cluster consisting of pure CHC& (n = 50, T= 300 K) has been performed. It
224
Fig. 1. Radial distribution functions for CHC13 molecules in the presence of the la&am forms of 2-oxopyrimidine. (a) (-1 gee; (---I gee,; (*****I &!HCl. (b) (-1 &la; (----I gHH; (****I gHCl*
is of interest that all RDFs for the pure solvent are nearly identical to those for both the solvent structures discussed above. The stable configurations of the dimer are presented in Fig. 2 and contributions to the total energy of their interactions are listed in Table 2. The most stable configuration of the dimer corresponds to the staggered “head-to-head” type (I&= - 11.4 kJ mol-‘), whereas the eclipsed “head-to-head” and the two “head-to-tail” configurations have an energy about 2.5 kJ mol-’ higher than the previous one. The most stable configuration of the dimer and its energy corresponds exactly to the most stable configuration and the energy of the Ccl, dimer [ 21. The attractive contribution to the interaction energies are entirely due to the dispersion terms. Both molecules in the most stable configuration are oriented in such a way as to minimize the Cl***Cldistance which results in lowering the dispersion attraction. The distance between the closest chlorine nuclei is about 3.8 A which is somewhat greater than the corresponding sum of the van der Waals radii (3.6 A). This distance corresponds exactly to the first peak of the gcIcl. The rcc distance in this configuration of the dimer is, however, about 4.5 A which is significantly shorter than the position of the first peak of the gee (5.4 A). Hence, this type of configuration rarely seems to be realized in the solvent. To make this analysis more quantitative, the percentages of the various types of CHC&. - - CHC&, configurations from all three Monte Carlo simulations has
C’ -.p
P’
H-C
Cl
C-H
Cl’ I-
4.5A-l A
/’
H-C.,
'\C-H CO Cl
b&CL
I4.0i-4 B
CI
CL
\
CL
\
L-H CC&
/f-H
C’Cl
c4.3Lj
\
C!, \’ S-H
;C-H
CC/,
L4.3f1-I
C
D
CI \
,C-H Cl';{
/“
H--C,,
h$l
c_
4.9i-I E Fig. 2. Stable configurations of the CHCl, dimer. TABLE 2 Stable configurations of the CHCl, dime+ (in kJ mol-‘) Configurations
E to*
:
- 8.9 -11.4
: e
-
8.5 1.4
Edstat
Edisp
0.3 0.2
- 20.8 15.5
9.2 6.3
-0.4 1.6
- 14.8 14.5 - 3.9
6.4 6.7 0.9
“For notation of the configurations see Fig. 2.
been determined. The results are listed in Table 3. It is seen that the solvent molecules are only rarely located in the positions corresponding to the minima of the interaction energy for the CHCl, dimer. This is probably due to: (i) the
226 TABLE 3 Percentage of the various types of mutual configuration of the CHCl, molecules in pure CHC& cluster and in the solvent shells around the tautomeric forma of 2-oxopyrimidine” obtained from Monte Carlo simulations Solvent
Configuration
Lactam Lactim
a+b
c+d
e
others
2.9
7.2 7.1 6.4
3.8 3.6 3.8
86.1 86.3 86.9
3.0 2.9
“Fornotation of the configurations see Fig. 2.
-20
-10
0
10
BlCHCl3,CHCl31
Fig. 3. Quasi-component distribution function for binding energy of the CHCl, in the presence of the lactam form of 2-oxopyrimidine. xe denotes the mole fraction of CHCl, molecuke with binding energy between B and B + dB, where B is the mean energy of interaction between a CHCl, molecule and any other molecule of the solvent.
energy of interaction for the dimers is rather small; and (ii) the differences between them are comparable to the energy of the thermal motions. Finally, the quasi-component distribution functions (QCDFs ) [lo] for binding energy among the solvent molecules have been calculated. The results, presented in Fig. 3, are nearly identical for both tautomeric forms. All these results indicate that the structure of the CHC& solvation shell is not much perturbed by the solute. Interactions between CHCl, and pyrimidine
The radial distribution functions g,_,, gx_cl, and g&n, where X denotes an atom of the pyrimidine molecule, for both tautomeric forms, are shown in Fig. 4. The most pronounced differences between both forms are seen near the nitrogen atom, Ni, in the region of proton displacement. The gNl_n exhibits a sharp peak at 3.0 A for the lactim form while there is not such a peak for the lactam one. It suggests that near the N1 atom of the lactim form the configurations of the solvent molecules correspond mainly to the “tail-to-N,” type while the configuration of the “head-to-N,” dominates for the la&am form.
227
g
e
g
f
3i
3 2
, ,,..... _._:: *y"-<, 2; ,.,.j ,' ' i 3 5 7'
1
Fig.4. Radialdistribution functionsfor chloroformmolecules vs. atomiccentersX of 2-oxopyrimidine(r in A). (a-d) Lactam;(e-h) lactim;(a,e) X=N,; (b,f) X=N,; (c,g) X=C5; (d-h) X=0’. (-)&_C; (----) &_a; (““) &?x_,. Comparison of the radial distributions [Fig. 4 (b ),(f) ] shows that the opposite is true for the N3 atom. It is worth noting that even g,,_, RDFs exhibit differences between both tautomeric forms, although this region of the pyrimidine seems to be similar in both cases. The size of the CHC13 molecule, however, is quite large and, therefore, the differences in packing of these molecules near the N, or 0’ atoms can influence the properties of the solvation shell in other parts of the pyrimidine molecule. The QCDFs for binding energy B (CP-CHCl,), i.e. the mean energy of the interaction between the pyrimidine molecule and a solvent, are presented in Fig. 5. It is seen that the solvent favours somewhat the la&am form. To answer the question of whether there are preferable stable configurations of the solvent molecules around tautomers, additional calculations have been performed with n = 1 and n = 2 CHCl, molecules. Results of the calculations
228
0.05. 0.04.
0.02. O.Ol-5
4
-3
-2
L. 0 1
-1
2 Lap-cm3
I
Fig. 5. Quasi-component distribution functions for the binding energy B(CP-CHC&). Xn is the mole fraction of the solvent molecules; B (CP-CHCl,) is the mean energy of the interaction between the P-oxopyrimidine molecule and a solvent. (----I La&m form; (-) la&am form.
b-
)_
H
H
H
Fig. 6. Global minimum of the interaction between one CHC& molecule and 2-oxopyrimidine: (a) lactim; (b) la&am. Chloroform molecules are projected into the XY plane at the top of figure and into the X2 plane at the bottom. Fig. 7. Global minimum of the interaction of two CHC& molecules and 2-oxopyrimidine: (a) lactim, (b) la&am.
TABLE 4 Global minima (kJ mol- * ) of interaction energy for the system: nCHCIs + pyrimidine at T= 0 K”
1 2
La&am Lactim La&am Lactim
-16.8 - 15.2 -35.2 -31.0
-7.1 -8.0
“Notation as in Table 1.
3.1 0.8
-13.6 -16.4
6.2 7.6
- 16.8 - 15.2 -28.1 -23.0
-2.6 -0.6 -5.1 0.2
-26.8 -26.5 -41.2 -40.1
12.5 12.0 18.2 16.9
229
are presented in Figs. 6 and 7 and in Table 4. Each figure shows configurations corresponding to the calculated minimum of the interaction energy. To determine the local minima the previously described procedure, which involves gradually decreasing the temperature during Monte Carlo simulations, has been applied [ 11. n=l The final configurations, corresponding to the global minimum of the interaction energy for the lactam and the lactim form are shown in Fig. 6 (a) and (b), respectively. Of course, because of the planar symmetry of pyrimidine there are two identical minima above and below the plane of the molecule. Contrary to the case of solvation by CCL these configurations are not the “headto-plane” type. It is seen from the Table 4 that it is due to the electrostatic interaction resulting from the presence of the positively charged H-C group of the CHC& molecule. The energy of the “head-to-plane” configuration (similar to that of the Ccl,) is, however, only slightly higher (E= -12.1 kJ mol-‘). n=2 The global minima, shown in Fig. 7, do not correspond to the location of each CHC& molecule in the corresponding minimum (shown in Fig. 6) above and below the plane of pyrimidine, as for the CC& molecules. It is seen from Table 5 that this configuration is determined by both dispersion and electrostatic energies. It is also seen that none of these molecules is located in the minimum corresponding to the case n = 1. CONCLUSIONS
It follows from these simulations that, in agreement with experiment, the solvation of pyrimidine by CHC13shifts the tautomeric equilibrium only a little towards the lactam form. This is an opposite shift to that occurring in the case of solvation by Ccl, [ 21. This effect is mainly due to the small difference in the energies of interaction between the solvent and the solute molecule in the two cases. The results presented both in this work and in the two previous ones [ 1,2] indicate that the structure of the solvent is only little disturbed by the solute molecule. This conclusion seems to be independent of the polarity of the solvent. These calculations indicate that solvent molecules tend to minimize the energy of their interactions, whereas the solute molecule tends to locate itself in such an orientation towards the surrounding molecules as to minimize (algebraically) its energy of interaction with the solvent.
To obtain more precise results it would be necessary to perform simulations with a much larger number of solvent molecules and to use proper boundary conditions. Also, the three-body effects should be taken into account. ACKNOWLEDGMENT
This work was supported by the Polish Academy of Sciences within the project C.P.B.P. 01.12.
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