J. WYS.Chem. 1982, 86, 1341-1347
1341
Molecular Orbital Theory of the Hydrogen Bond. 28. Water-5-Fluorouracil Complexes Janet E. Del Bene o e p e m n t of Chemkriry, Ymwstown Sfate LWersIfy, Youngstown, Ohb 44555 (Rece~ved:Ju3/ 13, 1981)
Ab initio SCF and SCF-CI calculations with the STO-3Gbasis set have been performed to investigate the structures and the energies of water-5-fluorouracil (water-FU) complexes and the intermolecular water-FU surface. Although there are eight nominal hydrogen-bonding sites in the FU molecular plane, there are only four water-FU dimers which are distinguishable in the ground state. These are an amide wobble dimer in the N1-H and O2 region, a dimer at Ns-H in which the water molecule may move between Ns-H and O2 hydrogen-bonding sites and also interact with 04,a dimer with water a double proton donor to FU at O4 and F, and an open dimer with water hydrogen-bonded to F on the C6 side of C5-F. The amide wobble dimer at N1-H and O2has a stabilization energy of 10 kcal/mol. The dimer at Ns-H is 2 kcal/mol leas stable, while the remaining two dimers are only weakly bound with stabilization energies of 4 and 3 kcal/mol, respectively. Substitution of fluorine for hydrogen in the 5 position of uracil makes FU a better proton donor to water than uracil, especially through the Ns-H group, but a poorer proton acceptor at 04.It does not alter significantly the intermolecular surface in the N1-H and O2region but does change the surface around the Ns-H group, particularly near 04, and introduces an additional shallow minimum on the Ce side of C5-F. Absorption of energy by the C4=0 group of FU leads to the first excited n r* state, in which hydrogen bonds at O4are broken and the dimer at O4 and F dissociates. When the C2=0 group is the chromophore, hydrogen bonds at O2 are broken in the second n r* state, but all four water-FU dimers remain bound.
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Introduction Substituent effects on base properties are major factors determining the behavior of compounds in important chemical and biochemical processes and have therefore been a subject of interest and investigation in modern chemistry. The results of both theoretical and experimental studies have led to new insights into substituent effects on basicity.’ As part of a continuing study in this laboratory of substituent effects on the properties of hydrogen-bonded complexes, ab initio molecular orbital calculations have been performed to investigate the effect of fluorine substitution on the hydrogen-bonding properties of uracil, the simplest of the biologically important pyrimidine bases. Experimental data demonstrate that substitution of fluorine for hydrogen in the 5 position of uracil alters the chemical reactivity of the ring, although 5-fluorouracil behaves as uracil with respect to several enzymes.2 A recent molecular orbital study of 5-flUOrO(1)(a) R. W. Taft in ”Proton Transfer Reactions”, E. F. Caldin and V. Gold, E&., Wiley, New York, 1975,pp 31-77; E.M. Amett, ibid., pp 79-101; (b) D. H. Aue, H. M. Webb, and M. T. Bowers, J. Am. Chem. Soc., 98,311(1976);(c) J. F.Wolf, R. H. Staley, I. Koppel, M. Taagepera, R T. McIver, Jr., J. L. Beauchamp, and R W. Taft, ibid., 99,5417(1977); (d) R. H. Staley and J. L. Beauchamp, ibid., 97,5920(1975);(e) D.H. Aue, H. M.Webb, and M.T. Bowers, ibid., 98,318 (1976); (f) E. M. Amett, B. Cbwla, L. Bell, M.Taagepera, W. J. Hehre, and R. W. Taft, ibid., 99,5729 (1977); (9) W. L. Davidson, J. Sunner, and P. Kebarle, ibid., 101,1675(1979); (h) A. C. Hopkinson and I. G.Csizmadia, Can. J. Chem., 52,546(1974);(i)L. Radom, A u t . J. Chem., 28,l (1975); (j) H. Umeyama and K. Morokuma, J. Am. Chem. SOC., 98,4400(1976);(k) A. Pullman and P. Brochen, Chem. Phys. Lett., 34,7 (1975); (1) P.A. Kollman and S.Rothenberg, J. Am. Chem. SOC.,99,1333 (1977);(m) I. G.John,G.L. D. Ritchie, and L. Radom, J. Chem. SOC.,Perkin Trans. 2, 1601 (1977); (n) W. F. Reynolds, P. G. Mezey, W. J. Hehre, R. D. Topeom, and R. W. Taft, J. Am. Chem. Soc., 99,5821(1977);( 0 ) J. E. Del Bene, J. Chem. Phys., 63,4666(1975);J. Am. Chem. SOC.,100,1673, 1387 (1978); (p) R. L. Woodin and J. L. Beauchamp, ibid., 100,501 (1978); (9) D. H. Aue and M. T. Bowers in ‘Gas-Phase Ion chemistry“, Vol. 2,M.T. Bowers, Ed., Academic Press, New York, 1979,pp 1-51; (r) Y. C. Tee, M.D. Newton, and L. C. Allen, Chem. Phys. Lett., 76, 350 (1980); ( 8 ) A. Prose and L. Radom, J. Comput. Chem., 1,295(1980); (t) W. J. Hehre, M.Taagepera, R. W. Taft,and R.D. Topeom, J.Am. Chem. Soc., 103,1344(1981);(u) H. Berthod and A. Pullman, Zsr. J. Chem., 19, 299 (1980); (v) J. E.Del Bene, J. Am. Chem. SOC.,101,7146(1979);102, 5191 (1980);J. Comput. Chem., 2,422 (1981). (2)P. Calabreei and R. E. Parks, Jr., in “The Pharmacological Basis of Therapeutics”, A. G . G h a n , L. S. Goodman, and A. Gilman, Eds., Macmillan, New York, 1980,pp 1256-314. 00 22-3654/82/ 2088- 134 7 $0 1.2510
uracil has been published in which some of the chemical properties of 5-fluorouracil have been discussed in relationship to the computed properties of the isolated molecule.s As a means of investigating similarities and differences in the interactions of uracil and 5-fluorouracil, the structures and the energies of hydrogen-bonded water-5fluorouracil complexes have now been determined, and the intermolecular potential surface in the hydrogen-bonding regions of the 5-fluorouracil molecular plane has been described. Hydrogen bonding between water and 5fluorouracil in two low-energy n ?F* excited states has also been examined. In this paper, the results of this study are presented and compared with corresponding data for the water-uracil system.
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Method of Calculation Single determinant ground-state wave functions and energies for 5-fluorouracil (FU) and water-FU complexes have been determined by solving the Roothaan equations: using the STO-3Gbasis set with standard scale factors5 for the molecular orbital expansions. The geometry of FU was first optimized by using gradient optimization techniques?*’ At convergence, bond distances and angles from successive cycles were identical to f0.001A and f O . l O , respectively. With the structures of water and FU held rigid? the structures of various complexes in which water is hydrogen bonded to FU in the FU molecular plane were optimized subject to certain constraints. Structures involving hydrogen bonding at an 0 or F atom of FU were optimized with respect to three coordinates: R, the intermolecular 0-0 or 0-F distance; e,’, the angle between the 0-H bond of water and the intermolecular 0-0or 0-F line; and B2, the angle between the intermolecular line and the C 2 4 , C4=0, and C5-F bonds. Structures A” and B”, C” and D, and G and H are the most stable (3)J. Lin, P. R. LeBreton, and L. L. Shipman, J.Phys. Chem., 84,431 (1980). (4)C . C. J. Roothaan, Rev. Mod. Phys., 23,69 (1951). (5)W. J. Hehre, R. F. Stewart, and J. A. Pople, J. Chem. Phys., 51, 2657 (1969). (6)J. 5.Binkley, J. Chem. Phys., 64,5142 (1976). (7)R. Fletcher and M.J. D. Powell, Comput. J.,6,163 (1973). (8)J. E.Del Bene, J. Chem. Phys., 62,1961 (1975).
0 1982 American Chemical Society
1342
The Journal of Physical Chemisby, Vol. 86, No. 8, 1982
Del Bene
0
i c" O
I
H
\1.219
/
H
AN-112
H-
H-N,
\
7
I 278'"\
-0
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D
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o&-
H \H Flgurs 1. Water-5-fluorouracil structures A", B",
C", D, and H.
F
\
1.358
F
Figure 3. Optimized geometry of 5-fluorouracil.
bond and the N-O line, and the angle O2 between the N-0 line and the C2 symmetry axis of water. Structures E' and F', which are related to E and F but which have the external 0-H bonds of water trans to O2and O,,respectively, were also optimized. In all cases, gradient optimization techniques were employed, and at convergence intermolecular distances and angles at successive cycles were identical to 10.01 A and *lo,respectively. Additional calculations were performed on various water-FU complexes to estimate rotational and translational barriers.', Energies and wave functions for excited n T* states of FU and the water-FU complexes were determined from configuration interaction (CI) calculations. All singly excited configurations arising from electron excitation from occupied valence orbitals to virtual orbitals were included in the CI expansions. Hence, the CI results are essentially full first-order CI results. The CI calculations were performed at the ground-state geometries of FU and the complexes D through H which have C, symmetry. To evaluate the effect of excitation on A", B", and C", CI calculations were performed on structures with the same intermolecular coordinates R, el', and 02, but with C, symmetry. Since these calculations have been performed at the ground-state geometries, the CI energies are vertical excitation energies. All calculations were performed in double precision on an AMDAHL 47O/V5computer. The gradient optimization calculations were done with a version of the Gaussian 80 system of programs.l0
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Figuro 2. Water-Cfluorouracil structures E, F, and G. I f Flgures 1 and 2 were combined, Structures A" and E, C", and F, and D and G would overlap.
structures found at 02, 04,and F hydrogen-bonding sites, respectively, and are shown in Figures 1and 2. Of these structures, D, G, and H were constrained to have C, symmetry, while A", B", and C" are asymmetric, with the constraint that the extemal0-H bond of water be rotated 60' out of the plane defined by the hydrogen-bonded 0, H, and 0 atoms. This constraint was imposed in view of the results obtained in the study of water-uracil comp l e x e ~which , ~ showed that a 60° rotation of the external 0-H bond of water about the hydrogen-bonded 0-H bond leads to the most stable cyclic structures. Structures E and F, shown in Figure 2, have FU as the proton donor through an N-H group. They were constrained to have C, symmetry and were optimized with respect to the intermolecular N-O distance, the angle B{ between the N-H (9) J. E. Del Bene, J. Comput. Chem., 2, 188 (1981). (10) J. S. Bmkley, R. A. Whiteside, R. Kriahnan, R. Seeger, I). J. DeFrees, H. B. Schlegel, S. Topiol, L. R. Kahn, and J. A. Pople, Carnegie-Mellon University, Pittsburgh, PA 16213. (11) T. J. Zielineki,M. Shibata, and R. Rein, Znt. J. Qwntum Chem., 19, 171 (1981). (12) W. Gwhlbauer, 'Nucleic Acid Structure",Springer-Verlng,New York, 1976. (13) J. E. Del Bene, J. Comput. Chem., 2, 200 (1981).
Results and Discussion The results of this study will be presented in five sections. The fmt deals with the structure and the properties of 5-fluorouracil, while the second is concerned with the structures and the stabilization energies of the locally (14) It may be questioned whether it would be informative to investigate further the energies of the water-6-fluorouracil complexes by performing single-point calculationson these complexeswith the larger split-valence 4-31G basis set. However, since the computed 4-31G energies would not refer to optimized 4-31G structures, compariwnsof the relative stabilities of them structures would not be very meaningful, nor would comparisons of the energies of related structures on different intermolecular surfaces. Although S M 3 G is a minimal basis set,it does give reasonable energies for hydrogen bonds to lone pairs involving fmt-row atoms. The larger 431G basis set tends to overestimate severely these energies.
The Journal of Physical Chemistry, Vol. 86, No. 8, 1982 1343
Molecular Orbital Theory of the Hydrogen Bond
TABLE I: Mulliken Population Data for 5-Fluorouracil total total electron n electron electron n electron atom density density atom density density H, 0.775 N, 7.355 1.772 C,
N, C, C, C,
5.583 7.377 5.701 5.919 5.955
0.907 1.769 0.915 1.118 1.003
0,
H, 0,
F, H,
8.287 0.780 8.250 9.119 0.901
1.331 1.245 1.940
optimized complexes A”, B”, C”, D, E, E’, F, F’, G, and H. In the third section, the intermolecular water-FU surface is described, and that surface is compared with the water-uracil surface in section four. In the fifth section, the fates of the water-FU dimers in excited n A* states are discussed and analyzed. 5-Fluorouracil. The computed equilibrium geometry of FU is shown in Figure 3. A comparison with a fully optimized geometry of uracil also obtained by gradient optimization techniquesll shows that fluorine substitution in the 5 position does not lead to large structural changes. The largest change in bond distances is an 0.020-A lengthening of the C4-C5 bond, which indicates a weakening of this bond. The largest angular change is an increase of 1.1’ in the N3-C4-0 angle. In FU, the highest occupied molecular orbital is predicted to be a A orbital, as in uracil. From Koopmans’ theorem, the computed fmt ionization potential is 7.14 eV. The nonbonding n orbitals of FU have energies of -9.21, -10.00, and -12.92 eV and are associated primarily with 04,02,and F, respectively. A comparison of corresponding n and A orbital energies with those of uracil shows that the effect of the fluorine atom is to destabilize A and stabilize n orbitals, consistent with the primary electronic effects of a A-electron-donating and u-electronwithdrawing group. The computed dipole moment of FU is 2.70 D, which is smaller than that of uracil. The dipole moment vector makes an angle of 5’ with the N1-N3 line in the direction N1(+)N3(-), with the negative end displaced toward Cq. Mulliken population data for the ground state of FU are reported in Table I. Fluorine substitution in uracil leads to only small changes in the total and A electron populations of most atoms. However, there is a large decrease in thee total electron density of C5owing to a large decrease in u electron density. A loas of A electron density also leads to a smaller decrease in the total density of Ob In contrast, the total electron density of c6 is increased in FU compared to uracil as a result of a A-electron-density gain. Water-5-Fluorouracil Complexes. There are eight nominal hydrogen-bonding sites in the FU molecular plane. At six of these, FU is a proton acceptor with hydrogen bonding occurring at O2 on the N1 and N3 sides of the Cz=O group, at O4 on the N3 and C5 sides of the C4=0 group, and at F on the C4 and c6 sides of C5-F. Structures A” and B”, C” and D, and G and H, respectively, are the locally optimized structures found at these sites. At the remaining two sites FU is the proton donor through the N1-H and N3-H groups. Structures E and F, respectively, are the preferred structures at these two sites. These structures are described in Table I1 and illustrated in Figures 1 and 2. The most stable water-FU complex is E, with a stabilization energy of 10.2 kcal/mol. It is characterized by a nearly linear N1-H.. -0hydrogen bond, an attractive interaction between the hydrogens of water and Oz, and a favorable alignment of molecular dipole moment vectors. Structure E is 1.9 kcal/mol more stable than a conformation E’, in which the water molecule is rotated by 180’
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TABLE 11: Ground-State Structures and Stabilization Energies of Water-5-Fluorouracil Complexesa AE,
structure A‘‘ 30 B‘ 31
kcal/mol A E , au 90 2.82 -0.01554 -9.8 91 2.82 -0.01336 -8.4 61 84 3.34 -0.01358 C‘ -8.5 C,“ 30 90 2.82 -0.01249 -7.8 D -6’ 128 2.84 -0.00626 -3.9 E 5 118 2.64 -0.01620 -10.2 E’ 0 141 2.67 -0.01318 -8.3 F 6 118 2.67 -0.01337 -8.4 F’ 6 118 2.67 -0.01325 -8.3 Gd 32 118 2.96 -0.00650 -4.1 H 20 103 2.76 -0.00496 -3.1 a Structures are shown in Figures 1 and 2. The intermolecular coordinates are measured with reference to the dashed lines. A nonoptimized asymmetric cyclic structure in the N,-H and 0, region. The hydrogen-bonded 0-H is cis to C,=O with respect to the 0-0,line. In G, the 0-0,distance is 2.87 A , the angle between the 0-H bond and the 0-0,line is lo”,and the angle between the 0-0,line and the C,=O bond is 121”.
about the N1-0 line. The complex E’ has the water hydrogens cis to C6-H and is not stable with respect to rotation of water about the N1-0 line. The second most stable structure is A”, a cyclic structure with the water molecule bridging adjacent N1-H and O2 hydrogen-bonding sites. Structure A”, which is stabilized and N1-H* -0hydrogen bonds, is by distorted 0-He -02 only 0.4 kcal/mol less stable than E. On the N3 side of the C d group another cyclic structure, B”, is found. In B”,the water molecule bridges adjacent N3-H and O2 hydrogen-bonding sites, and the complex is stabilized by distorted 0-H. -.02and N3-H-. a 0 hydrogen bonds. Structure B” is, however, 1.4 kcal/mol less stable than A”. At the N3-N group, the preferred C, structure is F, which is stabilized by a nearly linear N3-H.. .O hydrogen bond and favorable long-range interactions between the hydrogens of water and Ob Structure F has a stabilization energy of 8.4 kcal/mol and is 0.1 kcal/mol more stable than conformation F’, in which the water molecule is rotated 180’ about the N3-O line so that the hydrogens of water interact with OF Since the potential curve for this rotation is quite flat, there is essentially free rotation of the water molecule about the N3-O line. Although the water-FU complex at N3-H is quite stable, FU is a weaker proton donor to water through N3-H than through N1-H. This is due at least in part to a reduced positive charge on H3 compared to H1, and to the relationship between the N3-H bond dipole moment vector and the molecular dipole moment vector of FU. Although a cyclic water-FU structure in the N3-H and O4 region might have been anticipated, optimization of a complex in this region leads to structure C”, which is shown in Figure 1. This structure is quite different from cyclic structures A” and B”, as evident from the long 0-04 distance of 3.34 A and the 61’ angle between the 0-H bond of water and the 0-04line. In C , the N3-0 distance is 2.65 A and the angle between the N3-H bond and the N3-O line is 6’, which indicates that the position of the water oxygen is practically superimposable on the oxygen position in structure F. Thus, C” is appropriately described as a point on the potential curve for rotation of water about the N3-0 line and not as a bridging structure in the sense of A” and B”. Structure C” is stabilized by a nearly linear N3-H. -0hydrogen bond and a favorable long-range interaction between O4and the water hydrogen which lies in the FU molecular plane. The 8.5kcal/mol
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The Journal of Physical Chemistry, Voi. 86,No. 8, 1982
7344
Del Bene
C
-1 I
I I
I
f I
‘-1
H
-4
I I
--
-t
m
I
0
Y
e
W
d -e
-io
H
0
F
Flfpe 4. schematic d&gram of the water-5-fiwrowacii Memdecular surface in the h y d r w regions of the 5-fluorouracil mdecular plane.
stabilization energy of this structure, which is similar to the stabilization energies of F and F’, is consistent with this description. On the C5side of the C4=0 group, two stable structures D and G are found, which are shown in Figures 1 and 2. Structure D is an open structure stabilized by a slightly nonlinear 0-H.. e o 4 hydrogen bond. With a stabilization energy of 3.9 kcal/mol, it is 0.2 kcal/mol less stable than G, in which the water molecule is a double proton donor, forming distorted O-H-..04 and 0-H.0 SFhydrogen bonds. Structurm D and G are found at local minima with respect to rotation and translation of water in the FU molecular plane, with an in-plane rotational-translational barrier of 0.9 kcal/mol for converting D to G. An out-of-plane rotation-translation of water converts D to G with a reduced barrier of only 0.4 kcal/mol. When the water molecule is on the C6 side of C5-F, structure H is formed, which is stabilized by a nonlinear O-H...F hydrogen bond. With a stabilization energy of only 3.1 kcal/mol, this is the least stable water-FU complex. Water-5-Fluorouracil Intermolecular Surface. The data for the locally optimized structures A” through H may be used to construct a schematic diagram of the water-FU intermolecular surface in the hydrogen-bonding regions of the FU molecular plane. Such a diagram is shown in Figure 4. When hydrogen bonding occurs at the N1-H group, the preferred structure has the O-H bonds of water cis (E)rather than trans (E’) to C y 0 with respect to the intermolecularline. Structure E’ is converted to E without a rotational barrier, and with a 1.9 kcal/mol gain in stability. Although structure E is the most stable water-FU structure on the intermolecular surface, it is only 0.4
kcal/mol more stable than A”, in which the water molecule bridges adjacent N1-H and O2 hydrogen-bonding sites. These two structures are nearby on the intermolecular surface, which is relatively flat in this region. Thus, A” and E are not two distinguishable dimers but correspond to two forms of one water-FU amide wobble dimers in which the water molecule is relatively free to move between an open position at N1-H and a bridging position at N1-H and 02.The wobble involves not just rotation but translation of the water molecule in the FU molecular plane. While the water molecule is relatively free to move in the Nl-H and O2region, movement of water around the C2=0 group is strongly hindered by the ureide barrier.s The height of this barrier has been estimated by optimizing with respect to the 0-O2distance a structure in which the O-H bond of water was constrained to be colinear with the C2=0 bond, with an angle of 90° between the water and FU molecular planes. The barrier is indicated by L2 in Figure 4 and is 7.1 kcal/mol. On the N3 side of the C2=0 group, another water-FU amide wobble dimer is found which is described by structures B” and F’. However, because the surface for rotation of water around the N3-O line is quite flat, the water molecule is not restricted to associating with O2but can also associate with 04.Although the most stable structure for a water-FU complex in the N3-H region of the surface is C” in which the in-plane hydrogen of water interacts with 04,translation of water toward O4 results in some loss of stability. This is indicated by the line labeled C,,” in Figure 4, which represents the energy of a somewhat arbitrary, nonoptimizable water-FU structure described by the coordinates R, 8,’ and O2 found for the optimized structures A” and B”. Structure C,” lies 0.7 kcal/mol above the optimized structure C”, which indicates that the imide slide (movement of the water molecule around the N3-H group from O2to 04)’is restricted, and formation of an amide wobble dimer in the Ns-H and O4 region is inhibited. C,,” is a point on the barrier to movement of water around the C4=0 group. The barrier height is 5.7 kcal/mol, as shown by the line marked L4 in Figure 4. Thus, in the region of the water-FU surface between O2and 04,only one dimer exists which is described by structures B”, F’, F, and C”. On the C5 side of the C4=0 group, two water-FU structures exist at local minima which are separated by a very small potential barrier of no more than 0.4kcal/moL The water molecule may move between its position in structure D in which it is hydrogen bonded to 04,to a slightly more favored position in which it interacts with both O4and F in structure G. Thus,D and G are the two structures which describe the third water-FU dimer formed in the O4 and F region. A third barrier of 3.0 kcal/mol impedes the movement of water from this minimum on the surface to another on the ceside of C5-F. Here, the fourth water-FU dimer H is found, which is the most weakly bound dimer. Thus, although there are eight nominal hydrogen-bonding sites on the water-FU surface, there are only four distinguishable dimers. The most stable is the amide wobble dimer in the N1-H and O2 region, with a stabilization energy of about 10 kcal/mol. A t 2 kcal/mol higher in energy is the second dimer which forms a t N3-H. In it, the water molecule may move (wobble) between Ns-H and 02 hydrogen-bonding sites and may also interact with 04.The third dimer is one in which water is a double proton donor to O4 and F, while the fourth is an open dimer with water hydrogen-bonded to F on the C6side of C5-F. The latter two weakly bound
Molecular Orbital Theory of
the Hydrogen Bond
Ll,-ll0 C2-
-N ,
Flgure 5. Schematic diagram of the water-uracil Intermolecular svface In the hydrregbns of the uracil molecular plane.
dimers have stabilization energies of only 4 and 3 kcal/mol, respectively, and are therefore not as stable as the water dimer. In addition, dimer D-G is separated from the very stable dimer a t N3-H by a barrier of only 1 kcal/mol. Water-5-Fluorouracil and Water-Uracil Potential Surfaces. The effect of fluorine substitution on the intermolecular water-FU surface in the hydrogen-bonding regions of the molecular plane may be determined by comparing that surface with the water-uracil surface. So that direct comparisons may be made, water-uracil structures A”, B”, C”, D, E,E’,F, and F’ have been reoptimized subject to the same constraints employed for the corresponding water-FU dimers, using Rein’s optimized geometry for uracil.ls The resulting water-uracil intermolecular surface is shown in Figure 5. Although the presence of the fluorine atom in the 5 position makes FU a slightly better proton donor to water through N1-H than uracil, it does not significantly alter the intermolecular surface in the N1-H and O2 region where the amide wobble dimer exists, nor does it change the height of the ureide barrier to movement of water around the C y 0 group. It does however, have a pronounced effect on hydrogen bonding involving N3-H and Ok FU is a better proton donor through N3-H than uracil, as evident from the increased stabilities of the water-FU (15) With this uracil geometry, water-uracil interaction energies may
be altered to some exbnt, aa anticipated. See, for example: J. E. Del Bene, J. Chem. Phys., 62,1961 (1978);J. D.Dill, L.C.Allen, W. C. Topp, and J. A. Pople, J. Am. Chem. Soc., 97,7220 (1975). However, the general
characteristicsof the watepuracil intermolecular surface are unchnnged.
The Journal of Physical Chemistry, Vol. 86, No. 8, 1982 1345
dimers F and F’. That FU is a stronger proton donor through N3-H correlateswith the increased positive charge on H3 in FU and is consistent with experimental data which show that fluorouracil and fluorouracil-containing compounds have a much lower pK, for H3 ionization than uracil and the corresponding natural compounds.2,12 Moreover, the presence of fluorine also reduces the basicity of O4for hydrogen bonding with water, as indicated by the absence of a stable bridging structure C” on the water-FU surface. Although the water molecule hydrogen-bonded to FU at N3-H is stabilized by interaction with O4 (structures F and C”), C” is not a bridging structure in the sense of A” and B”. Translation of water toward O4 is accompanied by some loss in stability, so that formation of a wobble dimer is not favored in the N3-H and O4 region. Rather, the imide slide is restricted, and the wobble dimer is found in the N3-H and O2 region. This is in contrast to the situation which is found on the water-uracil surface, where the bridging structures between N3-H and O2 (B”) and N3-H and O4 (C”) are slightly more stable than the corresponding open structures F’ and F, respectively. The imide slide permits easy movement of water between O2 and O4 hydrogen-bonding sites, with the wobble structure in the N3-H and O4 region preferred to the one in the N3-H and O2 region. The presence of the fluorine atom produces a larger barrier to movement of the water molecule around the C4=0 group and leads to a more shallow minimum on the water-FU surface when the water molecule is hydrogen bonded to O4 on the C6 side of the C4=0 group. The potential well is also broader near the minimum, allowing for movement of water away from O4and toward F as the water molecule becomes a double proton donor. The presence of fluorine also introduces an additional minimum on the water-FU surface on the c6 side of c5-F. However, this minimum is shallow at 3.1 kcal/mol. These comparisons indicate that fluorine substitution in uracil does not significantly alter the hydrogen-bonding surface with water in the N1-H and O2region, but it does change the regions around the N3-H and C4=0 groups and introduces an additional shallow minimum on the CBside of C5-F. Excited States. In FU, two excited states with computed transition energies of 5.10 and 6.24 eV arise from r* excitations. Although the n orbitals which give n rise to the dominant configurations in these states are delocalized, each state can be associated with excitation of a particular carbonyl group. The lower-energy n u* state is associated with absorption of energy by the C4=0 group. In this state, the dominant configuration arises from electron excitation from the higher-energy n orbital to the lowest u*,which is antibonding in the C4=0 group and between c5 and c6, with a node near the C& group. In this state, a dramatic electron redistribution occurs in the C4=0 group as C4 becomes negatively charged by 0.170e and 0 becomes positively charged by 0.229e. This redistribution of electron density is also evident from the excited-state dipole moment of FU, which is reduced to 1.49 D. The dipole moment vector makes an angle of 27’ with the C2=0 bond in the direction C(+)O(-), with the negative end directed toward N1. In the second n u* state, the C2=0 group is the chromophore. The dominant configuration arises from electron excitation from the lower-energy n orbital to the second a* which is an antibonding orbital between C2 and 0. The nature of the electron redistribution is evident from the increase in the total electron density of C2which acquires a negative charge of 0.112e and the decrease in
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1346
The Journal of Physical Chemistry, Vol. 86, No. 8, 1982
TABLE 111: Blue Shifts of n + n* Bands of Water-5-Fluorouracil Comdexes teV)
structure
blue shift in first n+n* state"
Del Bene
TABLE IV: Stabilization Energies (kcal/mol) in Ground and Excited n + n * States
blue blue shift in shift in second fist n + n * struc- n + n * statea ture state"
blue shift in second n+n* state"
0.04 0.23 E' 0.05 0.01 Bb -0.03 0.22 F 0.06 0.01 Cb 0.05 0.03 F' -0.02 0.10 %b 0.21 0.00 G 0.16 -0.03 0.19 -0.02 H 0.03 -0.01 E 0.06 0.09 a A negative sign indicates a red shift, a lower transition energy in the complex than in 6-fluorouracil. Complex of C, symmetry with values of R , B ,' and e taken from the corresponding asymmetric structure.
structure ground state E' -8.3 E 10.2 A' -9.8
-
Ab
the electron density of O2 which becomes positively charged by 0.248e. A dramatic increase in the dipole moment to 4.70 D occurs. In the second n A* state, the dipole moment vector makes an angle of 27' with the C4=0 group in the direction C(+)O(-), with the negative A* states of FU are similar to end toward Cg. The n the corresponding states of ~raci1.l~ The effect of absorption of energy by the C2=0 and C4=0 groups in the water-FU complexes may be determined from the blue shifts of the n A* bands, since these reflect a weakening or breaking of hydrogen bonds. The A* states of blue shifts in the first and second n structures A through H are reported in Table 111. In the A* state, the only appreciable blue shifts are first n found in C,, D, and G , all of which are stabilized in the ground state by interaction of water with 04. Since a positively charged O4 is not a good proton acceptor, the hydrogen blue shifts reflect the breaking of 0-Hoe bonds. Similarly, in the second n A* state, large blue shifts are found in A and B, in which water is hydrogen bonded to O2 in the ground state. Since O2 becomes positively charged in the second excited state, hydrogen bonds a t O2 are broken. In addition, smaller but appreciable blue shifts are found in E and F' in which the interactions between the hydrogens of water and O2stabilize the ground state but become repulsive in the excited state. The data for the blue shifts in Table I11 may be used to estimate the excited-state stabilities of structures A" through H on vertical excitation. These estimations are reported in Table IV and may be used to predict the excited-state fates of the four water-FU dimers. In the first n A* state, the amide wobble dimer in the N1-H and O2 region remains intact but is destabilized by about 1 kcal/mol relative to the ground state. The water-FU potential surface in this region is similar to the ground state. In contrast, that region of the surface between O2 and O4 is dramatically changed. An amide wobble dimer exists in the N3-H and O2region, and this dimer is slightly more stable in the excited state than in the ground state. However, rotation of water about the N3-0 line is not free, since the interaction between the hydrogens of water and O4 is no longer a stabilizing interaction. The surface between N3-H and O4becomes very steep, dramatically increasing in energy as the water molecule interads with and approaches 04.On the C5 side of the C4=0 group, the surface also changes, as the dimer described by structures D and G probably dissociates, since the open form D is no longer bound in the n ?r* state, and G has a stabilization energy of only 0.4kcal/mol due to a residual attractive interaction between water and F. The fourth dimer in which water is hydrogen bonded to F on the c6 side of C5-F remains bound but is even less stable than in the
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-
-
-
-
-
-
-
g o 4
first n+n* stat@ -7.1 -8.9 -8.8b
second n+n* state" -8.1 -8.1 -4.6b
B' F' F C' ' C,"
-8.4 -8.3 -8.4 -8.5 -7.8
-9.0b -8.8 -7.0 -1.3b -3.1b
- 3.4b -6.1 -8.2 -8.0b -7.8b
D G
-3.9 -4.1
+ 0.5 -0.4
-4.4 -4.8
I
H
-2.4 -3.4 -3.1 Stabilization energy on vertical excitation. b Estimated from the blue shift computed for the corresponding c, structure.
-
ground state. Hence, these data suggest that only three of the water-FU dimers remain bound in the first n A* state. Two are amide wobble dimers of comparable stabilities, one in the N1-H and O2 region and the other in the N3-H and O2 region, and the third is a very weakly bound dimer at F with the water molecule on the c6 side of C5-F. As anticipated, the intermolecular surface in the second n A* state is quite different, since hydrogen bonds at O2are broken when the C 2 4 group is the chromophore. As a result, the amide wobble dimer in the N1-H and O2 region becomes an open dimer in which FU is a proton donor to water. Since the long-range interaction between the hydrogens of water and 02 is no longer stabilizing, it would appear that the water molecule may be free to rotate about the intermolecular N1-0line in the excited state. The intermolecular surface surrounding N3-H also changes significantly. The amide wobble dimer in the N3-H and O2region collapses to an amide wobble dimer in the N3-H and O4region, and rotation of water about the N3-0 line is restricted. The water-FU dimer on the C5 side of the C4=0 group is more stable in the second n ?r* state than in the ground state, as both D and G are stabilized by excitation. Similarly, the open dimer H in which water is hydrogen bonded to F on the c6 side of C5-F is also slightly more stable in the second n A* state. Thus, these data suggest that four water-FU dimers exist in this state. These are a very stable open dimer in which FU is a proton donor to water through the Nl-H group, an amide wobble dimer of comparable stability in the N3-H and O4 region, a third dimer having water as a double proton donor to O4 and F, and an open dimer with water hydrogen-bonded to F on the c6 side of C6-F. The latter two dimers, while more stable in the second n A* state than in the ground state, are still much more weakly bound than the former. The fates of the excited water-FU dimers in the first and second n u* states are similar to the fates of the corresponding water-uracil dimers in these states.13
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Conclusions The ab initio molecular orbital calculations performed in this study of water-5-fluorouracil (watel-FU) complexes support the following statements. (1) Although there are eight nominal hydrogen-bonding sites in the FU molecular plane, there are only four water-FU dimers which are distinguishable. These are an amide wobble dimer in the N1-H and O2region, a dimer at N3-H in which the water molecule may wobble between N3-H and O2 hydrogen-
J. Phys. Chem. 1982, 86, 1347-1350
bonding sites and also interact with 04,a dimer with water a double proton donor to FU at O4 and F, and an open dimer with water hydrogen-bonded to F on the c6 side of C5-F. (2) The most stable water-FU dimer is the amide wobble dimer in the N1-H and O2 region with a stabilization energy of 10 kcal/mol. The dimer at N3-H is approximately 2 kcal/mol less stable. The dimers with water bound at O4 and F, and at F on the c6 side of C5-F, are only weakly bound with stabilization energies of 4 and 3 kcal/mol, respectively. (3) Substitution of fluorine for hydrogen in the 5 position of uracil makes FU a better proton donor to water than uracil, especially through the N3-H group, and a poorer proton acceptor at 04.(4) The water-FU potential surface in the N1-H and O2region is similar to the water-uracil surface. However, the presence of fluorine alters the intermolecular surface around the N3-H group, especially in the N3-H and O4 regions, and introduces an additional shallow minimum on the c6 side of C5-F. ( 5 ) The first excited n ?r* state of FU arises from absorption of energy by the C4=0 group. Hydrogen
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1347
bonds at O4are broken in this state, and only three of the water-FU dimers remain bound. These are two amide wobble dimers, one in the N1-H and O2 region and the other in the N3-H and O2 region, and a weakly bound dimer at F with water on the c6 side of C5-F. In the T* state when the C2=0 group is the chrosecond n mophore, hydrogen bonds at O2 are broken but all four dimers remain bound. The ground-state amide wobble dimer in the N1-H and O2region becomes an open dimer at N1-H, and the dimer at N3-H becomes a wobble dimer at N3-H and 04.The dimer with water a double proton donor at O4 and F, and the one with water hydrogenbonded to F on the c6 side of C5-F, remain intact with slightly increased stabilities in the second n ?r* state.
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Acknowledgment. This work was supported by NIH research grant GM27955 from the National Institute of General Medical Sciences. This support and that of the Youngstown State University Computer Center are gratefully acknowledged.
Effects of Competition for Charge Capture from the Matrix on Intermolecular Eiectron-Tunneling Reactions R. Kurt Huddlerton and John R. Miller* Chemlstrv DMsbn, A r p n e Mtbnal Laboratory, Argonne, Illlnols 60439 (Received: September 4, 1081)
A general method is presented for correcting for the direct capture of matrix charges by the acceptor in an intermolecular electron-transfer reaction in a rigid medium. The method is based on a two-step electron-tunneling model that takes into account the correlation between matrix charge capture and intermolecular electron transfer. As an experimental test of the method, electron transfer from the anion of cinnamaldehyde to neutral pyromellitic dianhydride was studied in 2-methyltetrahydrofuran glass at 77 K. Good agreement between the model and the experimental kinetic results was obtained.
I. Introduction Pulse radiolysis of matrices provides an excellent technique for the study of intermolecular electron-transfer (ET) Typically, a solute, S1,captures charge from the matrix, either trapped electrons (e;) or solvent holes (h'), and transfers the charge to a second solute, Sa However, some matrix charges will be captured directly by S2 (reaction 2). Competition between S1and S2 for
-
e; (h+) + S1
S1*
(1)
e, (h+) + S2
S2*
(2)
s1 Szf
(3)
SI* + s2
-+
capture of e, (h+) will lead to a nonrandom distribution of acceptors relative to the donor in the intermolecular reaction (3). Thus, in correcting for the charge captured directly by S2,the Sl*decay curve cannot be simply scaled by a constant equal to the fraction of charge captured initially by SI,as was done earlier.'$ In fact, the correction is typically much smaller, and it continues to decrease with time after the competing charge-capture reactions ((1)and (1) Miller, J. R. Science (Washington, D.C.) 197& 189, 221. (2) Miller, J. R.; Beitz, J. V. Proc. Int. Conf.Radiat. Res., 6th 1979, 301. (3) Kira, A.; Noaaka, Y.; Imamura, M. J. Phys. Chem. 1980,84,1882. 0022-3654/02/2086-1347801.25/0
(2)) are complete. We present here an accurate procedure for this competition correction and an experimental test of the method.
11. Correction Procedure Tachiya has considered the problem of two-step electron t~nneling.~ Here we adopt his model but generalize it to allow for different rates for the three ET processes, (1)-(3). The rate constants as a function of distance for reactions 1-3 are assumed to have the form5s6 ki(r) = vi'exp[-(r - Ro,j)/ui] i = 1, 2, 3 = vi exp(-r/ai) (4) so that vi = vi' exp(Ro,i/ai). The significance of the parameters ai, vi', and Ro!ihas been discussed previously.' Because of the strong distance dependence of the ET rate constant, the reaction probability can be described by a reaction radius such that a donor species having an acceptor within a distance R i ( t ) can be considered to have reacted by time t.6 An accurate expression for the reaction radius is5@p8 R i ( t ) = ai In gvit (5) (4) Tachiya, M. J . Chem. SOC.,Faraday Trans 11, 1979, 75, 271. (5) Miller, J. R. J. Chem. Phys. 1972,56, 5173. (6) Tachiya, M.; Mozumder, A. Chem. Phys. Lett. 1974, 28, 87. (7) Beitz, J. V.; Miller, J. R. J. Chem. Phys. 1979, 71, 4579.
0 1982 American Chemical Society
