Shinagawa, Shinagawa
/ M O Studies of Radicals f r o m Hydroxybenzenes
(13) For example, the stabilization of water dimer is calculated to be only about 1 kcal/mol. The problem may be associated with the core-core repulsion function used in MNDO, and we are currently investigating this problem. (14) See C. R. Brundle, M. B. Robin, and H. Basch, J . Chem. Phys., 53, 2196 (1970), for a more complete discussion. (15) (a) P. F. Zittel, G. B. Ellison, S. V. O'Neil, E. Herbst, W. C. Lineberger, and W. P. Reinhardt. J. Am. Chem. SOC., 98, 3731 (1976), have reported a photoelectron measurement of 19.5 kcal/mol for the ' A I / ~ B separation ~ of methylene and also a value for the electron affinity. For a recent summary of the ab initio calculations on this molecule, see A. H. Pakiari and N. C. Handy, Theor. Chim. Acta, 40, 17 (1975), and for recent experimental studies on methylene, see J. W. Simons and R . Curry, Chem. Phys. Lett., 38, 171 (1976). (b) J. H.Meadows and H. F. Schaefer, J . Am. Chem. SOC., 98, 4383 (1976), have recently reassessed their calculations in view of the result reported by Lineberger. By calculating the 3B7/'B1 separation and combining this with an experimental determination of the lA1/'B1 separation, they obtain a 3B1/1A,separation of 19.7 kcal/mol. This compares with the value of 14.1 kcal/mol previously reported by these authors.
67
(16) V. Staemmler, Theor. Chim. Acta, 35, 309 (1974). (17) R. Ditchfield, J. Del Bene, and J. A. Pople, J . Am. Chem. SOC.,94, 4806 (1972). (18) W. Thiel, unpublished result. (19) An extensive review and discussion of the recent literature is given by A. Yokozeki and S. H.Bauer, Top. Curr. Chem., 53, 71 (1975). (20) L. S. Cederbaum, Chem. Phys. Lett., 25, 562 (1974). (21) A. B. Cornford. D. C. Frost, C. A. McDowell, J. L. Ragle, and I. A. Stenhouse, J . Chem. Phys., 54, 2651 (1971). (22) D. P. Chong, F. G. Herring, and D. McWilliams, J. Electron Spectrosc. Relat. Phenom., 7, 445 (1975). (23) W. J. Hehre and J. A. Pople, J. Am. Chem. Soc., 92, 2191 (1970). (24) See M. J. S.Dewar, Chem. Br.. 11, 97 (1975); Discuss. Faraday Soc., 62, 197 (1977). (25) By the method of J. Mclver and A. Komornicki, J. Am. Chem. SOC.,94,2625 (1972); J. Mclver and A. Komornicki, Chem. Phys. Lett., I O , 303 (1971). (26) See M. J. S. Dewar, "The Molecular Orbital Theory of Organic Chemistry", McGraw-Hill, New York, N.Y., 1969. (27) M. J. S. Dewar and G. Ford, J . Am. Chem. SOC.,99, 1685 (1977).
Molecular Orbital Studies of the Radicals of Hydroxybenzenes and Epinephrine Yasuko Shinagawa* and Yoshiya Shinagawa Contributionf r o m the Department of Physiology, Kyoto University, Medical School, Kyoto 606, Japan. Received February 25, I977
Abstract: When calculations of proton hyperfine coupling constants of free radicals from hydroxybenzenes (phenol, 1,2- and 1,4-dihydroxybenzene, 1,2,3- and 1,2,4-trihydroxybenzene)and epinephrine were done using the l N D O (intermediate neglect of differential overlap) method, experimental data for 1,2-dihydroxybenzene, 1,4-dihydroxybenzene,and 1,2,4-trihydroxybenzene were exactly reproduced. Calculations for the remaining hydroxybenzenes served to explain the experimental data qualitatively. The hyperfine coupling constants of the radical from epinephrine could be assigned from the present calculations. AIthough past calculations were done to determine structures of a quinol type, we found in the INDO calculations that semiquinone radicals have a quinoidlike structure. In these radicals, the C - 0 bond lengths are fairly short, the adjacent C-C bond lengths relatively long, and the next C-C bond lengths in the rings relatively short. The proton hyperfine coupling constants of the radical formed by the oxidation of epinephrine in alkaline ethanol media were measured by electron spin resonance absorption spectroscopy and the magnitudes were 1.28, 2.61, and 0.59 G . The splitting constants calculated by means of the INDO method were consistent with the observed values.
Introduction Most radicals from hydroxybenzenes can be easily produced in alkaline ethanol solution and there are numerous reports1-'I concerning experimental proton hyperfine coupling constants. Geometries which reproduce the experimental data exactly have apparently not been documented. As stated by Pople,I2 the calculated results in the INDO method for the semiquinones were not supported. The a b initio calculations do not reproduce the observed data. In all these calculations or othe r ~ , the ~ ~geometries - ~ ~ of the semiquinone radicals were considered to be hexagons or a close resemblance and the C - 0 bond lengths were estimated to be those of a quinol type. The calculated results by Pople also can be reproduced in the geometries of a quinol type. I n the present INDO calculations, we found that these semiquinone anion radicals have a quinoidlike structure, with the rings which are fairly distorted from regular hexagons and the short C-0 bond lengths. Lack of success with past calculations may be due to lack of adequate consideration that the molecular geometries of these radicals are distorted as compared to a regular hexagon; i.e., they are of quinoidlike structures. The INDO method has been widely used in studies of radicals and the sigmatropic shift^.'^-^^ The INDO calculations in studies of proton hyperfine splitting constants of 0002-7863/78/1500-0067$01.00/0
semiquinones have not been successful; however, this method may still be used providing that the geometries of quinone type are reinvestigated. Pyrocatechol, epinephrine, and related compounds are substrates for the C O M T (cathechol-0-methyltransferase) and the relationship between their biological activities and chemical structures has not been well determined. The authors have reported that the diuretic actions of triazine derivatives26 principally depend upon the force of the charge transfer a t their active centers, and that the carbonic anhydrase inhibitory actions of sulfonamide derivatives2' parallel the formal charge of the sulfonamide groups. Information on molecular geometries of the radicals from hydroxybenzenes and epinephrine is required to determine the structure selectivity by the C O M T or the meta/para ratios of the 0-methylated products. In the present work, calculations of the proton hyperfine coupling constants of semiquinone anion radicals and epinephrine anion radical were made using the INDO method as well a s the H M O and the McLachlan methods. W e measured the ESR spectra of epinephrine radical, calculated its proton hyperfine coupling constants, and made assignments. Molecular geometry which well explains the observed proton hyperfine splitting constants of epinephrine radical was obtained.
0 1978 American Chemical Society
68
Journal of the American Chemical Society
/ 1OO:l / January
4, 1978
1 gauss
Figure 1. ESR spectrum of the radical from epinephrine in 0.02 mol of NaOH per liter of ethanol.
Experimental Section The ESR spectra of the free radical from epinephrine were obtained by autoxidation of L-epinephrine in alkaline ethanol solution. The ESR spectra of this compound have often been reported;6.28however, no data are available on the quantitative proton hyperfine coupling constants. We reinvestigated this radical and determined the hyperfine coupling constants. L-Epinephrine (commercial) was dissolved in ethanol containing 0-1.6% sodium hydroxide. The spectra were recorded at a room temperature of 25 OC on a Japan Electron Optics Laboratory JEX-3BX spectrometer and a Hitachi MES-4001 spectrometer with a 100 kHz modulation. Calculations of Spin Densities. The INDO method and its applications to the hyperfine coupling constants have been described by ~ ~ ~ . *this ~ method we investigated the Pople and ~ o l l e a g u e s . ’ * Using geometries of the radicals from phenol, 1.2- and 1,4-dihydroxybenzene, 1,2,3- and 1,2,4-trihydroxybenzene,and epinephrine.The INDO computer program was provided by the Quantum Chemistry Program Exchange, Indiana University, and translated into FACOM 230-75 F O R T R A N of Kyoto University Data Processing Center. The Cartesian coordinates necessary for the calculations were obtained from the program termed X Y Z D R , which was coded by the authors and contains the drawing program with the XY plotter, CALCOMP 770-763.The digital computer FACOM 230-75 is based on binary inner memories and 72 bits in a double precision. The digital computer M 190 of Kyoto university Data Processing Center as well as FACOM 230-75 was used. The computer M 190 is 64 bits in a double precision. The covergence was judged at Results and Discussion Hyperfine Coupling Constants of the Radical from Epinephrine. The ESR spectrum of the radical from epinephrine in 0.02 mol of NaOH per liter of ethanol is presented in Figure I . These are eight spectral components (2 X 2 X 2). When measurements were carried out in 0.02-0.1 mol of N a O H per liter of ethanol, those eight lines of the spectrum were observed to be stable. In 0.4 mol of N a O H per liter of ethanol, the stable spectrum as shown in Figure 2a was observed. In 0.2 mol of N a O H per liter of ethanol, the spectrum gradually changed from the type in Figure 1 to the type of Figure 2a. In ethanol saturated with N a O H , the spectrum shown in Figure 2b was observed a t about 10 min after the preparation. Figure 2a appears to be similar to the ESR spectrum of the radical from epinephrine in acid solution as reported by Borg28 (1965), and Figure 2b to be similar to that from adrenochrome in 0.1 N N a O H also reported by this author. The spectrum consisting of eight clear lines shown in Figure 1 was observed to be stable in alkaline ethanol solution containing N a O H in low concentration (e.g., 0.02 mol/L,). Such spectrum was not stable or was not detected in alkaline ethanol solution with a high concentration (e.g., 0.4 mol/L) of N a O H (Figure 2a). Even in ethanol solution with a low concentration of NaOH, the spectrum of epinephrine radical varies from the pattern in Figure 1 to that in Figure 2b via that in Figure 2a with passage of time. These variations of the ESR spectra are considered to correspond to the stages of the autoxidation of epinephrine; the chemical structure of epinephrine radical is considered to vary with the stage of autoxidation. The measured values of splitting constants of the radical from epinephrine were 1.28 ( A 3 ) ,0.59 ( A S ) and , 2.61 ( A 6 ) G. The as-
(b)
Figure 2. ESR spectra of the radical from epinephrine in 0.4 mol of NaOH per liter of ethanol and ethanol saturated with NaOH.
signment of splittings was done from the I N D O calculations in this report. The results of the present I N D O calculations validate that the radical corresponding to the spectrum in Figure 1 is the epinephrine radical. Calculation of Splitting Constants by Hiickel Molecular Orbital Method (HMO) and McLachlan Method. Electronic structures of hydroxybenzenes (phenol, 1,4- and 1,2-dihydroxybenzene, 1,2,3-, 1,3,5-, and 1,2,4-trihydroxybenzene)and epinephrine were calculated by means of the w technique of the H M O method. The slightly modified w technique reported by Ettinger30 was used. The Coulomb integrals so's were in the proximity of (Y 2@a t convergence in the iteration of w technique. The resonance integrals @c-o’s were calculated by the iterative method using the relationship between bond order and bond length, and these values were in the proximity of 0.6p when the iterative calculations converged. The electronic structure of epinephrine was calculated containing O H of the position in the form of the hyperconjugated structure. The values of parameters O(OH’S and p c - 0 ~for ’ ~ this structure were N 0.6p and 0.6p, respectively. The splitting constants by the H M O method as well as by the McLachlan method were calculated (Table I). The relation proposed by McConnell was used in the calculations of the splitting constants. The magnitude of Q was 22.5 G. The calculated splitting constants qualitatively agree with those observed. According to the assignment by the INDO calculations, the calculated splitting constants of the radical from epinephrine as determined by the H M O method were not in agreement with the observed values. These H M O calculations were unsuccessful as estimation of the values of parameters of the @-hydroxylgroup was difficult. The calculated splitting constants of p-semiquinone anion radical by the McLachlan method and of pyrogallol semiquinone anion radical by the H M O method are quantitatively in good agreement with the observed values while the values of semiquinone anion radical from 1,2,4-trihydroxybenzene appear to favor the assignment by Lott and co-workers.’ I The calculated values of pyrogallol semiquinone anion radical were in good agreement with the observed values, reported herein for the first time. The calculated splitting constants of o-semiquinone anion radical by the H M O method did not fit the experimental constants. These results suggest that conformations of the aromatic rings of these radicals are not the regular hexagon type, and that parametrization corresponding with the geometries is difficult.
+
+
Shinagawa, Shinagawa
1 M O Studies of Radicals f r o m Hydroxybenzenes Total energ
-61.910
(
-3,78 )
( -6.94)
( 1.95 )
(a )
69
1[
Ratio of
-2
-61,920
-1
- 61.930
-0
( 4.18)
( b )
Figure 3. Calculated splitting constants of phenoxy radical (parenthesized) and its geometries. Table I. Calculated Splitting Constants of Radicals from Hydroxybenzenes and Epinephrine by HMO and McLachlan Methods Splitting constants, G Radicals Phenoxy radical p-Semiquinone anion radical o-Semiquinone anion radical Pyragallol semiquinone anion radical Semiquinone anion radical from 1,2,4-trihydroxybenzene Anion radical from epinephrine
Position
c
McLachlan technique method
Obsd
2 3 4 2
6.6 1.96 10.4 2.31
2.43 1.305 6.615 1.845
2.7675 2.61 4.635 2.565
3 4 4 5
3.65 0.95 9.96 5.41
0.135 4.1625 0.9 5.3775
1.8 3.5775 2.115 3.96
0.27 3.465 0.6525
1.6875 3.1725 2.0925
0.18 2.0925 0.405
1.35 2.1375 1.26
3 5 6 3 5 6
1.10
w
1.3 4.8 0.6
0.65 4.80 1.35 1.28 0.59 2.61
Because the ESR spectrum of m-semiquinone anion radical in alkaline ethanol solution in our experiments consisted of 15- 17 lines and was unresolved, the spin densities of this radical could not be calculated. The proton hyperfine splitting constants of this radical have been reported,25 and its spin densities have not been calculated. The calculations of its spin densities will be reported by our group after the spectrum has been confirmed. INDO Calculations. Phenoxy Radical. The observed splitting have been reported to be 6.6 ( A 2 ) , 1.96 (A3), and 10.4 (A4) G. In spite of many calculation^'^^'^ including a b initio, there are apparently no reports which explain the observed splitting constants even qualitatively. The calculated values reported by Pople and his co-workers15 were -4.1 (A2), 2.2 (A3), and -3.4 ( A d ) ,and were similar to the values (3.78, - 1.95, 3.1 I ) calculated for the geometry of the hexagonal ring in Figure 3a. Both calculated values show the reverse trend to the observed ones. The values obtained from the geometry in Figure 3b, however, show a similar trend to the observed ones, that is, A2, A3, and A4 are -6.94, 4.18, and -10.37 G, respectively. The fairly good agreement between the calculated values and the observed ones is due to the calculations for a quinoidlike structure. The molecular geometry of phenoxy radical is considered to be of a quinoidlike structure. The relationship between some bond lengths and the total energies, metalortho or paralortho ratios of the calculated splitting constants of phenoxy radical are shown in Figure 4. The bond lengths C2-C3, Ol-Ci, and C3-C4varied from 1.30 8,to 1.42 A, from I . I O A to 1.22 A, and from 1.40 8,to 1.50 A, respec-
1.15
1.20
I
1.25
( b )
r (A)
A
1.40 1.42 1.44 1.46 1.48 1.50
Figure 4. Total energies, meta/ortho and para/ortho ratios of calculated splitting constants of phenoxy radical as functions of bond lengths. Total energy, meta/ortho and para/ortho ratios of calculated splitting constants as a function of (a) C Z - C bond ~ length (in the range from 1.30 A to 1.42 A), (b) O I - C I bond length (in the range from 1.10 A to 1.22 A), (c) C ~ - C I bond length (in! the range from 1.40 A to 1.50 A). 0-0, calculated obmeta/ortho ratio; 0 - 0 , calculated para/ortho ratio; served meta/ortho ratio; - - - - -, observed para/ortho ratio; 0-0, total energy.
tively. The calculated splitting constants for the geometry in Figure 3b were the closest to the observed values among the 60 or so geometries we calculated. p-Semiquinone Anion Radical. Some of the calculated splitting constants by the empirical5 or semiempirical methods using some sets of parameters were reported to agree with the observed values of 2.37 G for p-semiquinone anion radical. These parameters in the empirical method, however, were not applicable to the splitting constants of other semiquinone radicals. The necessity of different parameters for different semiquinones reflects the variety of the molecular geometries of semiquinones. The calculated value by the INDO method was reported by Pople and his co-workers to be 0.9 G and we found the splitting constant calculated for the geometry of regular hexagon to have a similar value to that reported by Pople et aI.I5 In the present calculations, relationships as shown in Figure 5 were found between bond lengths (or bond angles) and the total energies (or the splitting constants) of p-semiquinone anion radical. Figure 6 shows five geometries which are likely for the p-semiquinone anion radical. The calculated splitting constants for these five geometries are in good agreement with the observed ones. The total energy of the radical shown in Figure 6 differs and the radical of Figure 6a gives a minimum energy among the five geometries. Therefore, the geometry in Figure 6a is the most likely for the p-semiquinone anion radical. The calculated value of ''0 hyperfine coupling constant i n this work is 7.6 and those of I3C are -2.85 ( A I ) and 3.1 (A2)
G. o-Semiquinone Anion Radical. C a l c u l a t i o n ~ l ~were ~ ' made
70
Journal of the American Chemical Society
/
Splitting constant ( a . u.
-78.4880
-784900 -78.4959 -784970
t
2.40
I
2.20
2.30
/
January 4, 1978
Splittin
(gauss)
Total energy
1OO:l
(gauss) -78.750 2.30 2.20
1
2.10
1.40
1.45
1.50
r (A) Witting
1
-78,4900
-78.5100
constant
(gauss)
2.90 2.70
2.32 127
128 129
130
(degree) Splitting constant
( b )
1.30
1.35 ( C )
1.40 r (A)
(gauss)
230 2.20 -7860 1.10 1.11
1.12
1.13
r (A)
( c )
Figure 5. Total energies and the calculated splitting constants ofp-semiquinone anion radical as functions of bond lengths or bond angles. Total energy C S angle (in the range and the calculated splitting constant as a function of (a) C3-H3 bond length (in the range from I .08 A to I .I4 A), (b) C ~ C ~ bond from 127O to 129.5O), (c) C4-O4 bond length (in the range from 1.10 A to 1.13 A), (d) C3-C4 bond length (in the range from 1.43 8, to 1.50 A), (e) C2-C3 bond length (in the range from 1.30 8, to 1.40 A). 0-0, calculated splitting constant; 0-0, total energy; - - - -, observed splitting constant.
(-0.9524)
Figure 7. Resulting geometry of o-semiquinone anion radical and its calculated splitting constants (parenthesized). The total energy is -78.872 039 au.
124.75'
129.006 +
-
/
(c 1
\
/
( e )
Figure 6. Resulting geometries of p-semiquinone anion radical. Their total energies (au) are (a) -78.661 789, (b) -78.665 968, (c) -78.499 030, (d) -78.495 808, (e) - 78.501 978. Their calculated splitting constants (C) are (a) -2.3706, (b) -2.3682, (c) -2.3710, (d) -2.3742, (e) -2.3724.
to determine the splitting constants of the o-semiquinone anion radical yet none have explained the geometry of this radical. The calculated splitting constants by the INDO method reported by Pople and his c o - w o r k e r ~were ' ~ -1.9 ( A 3 ) and 0.2 ( A d ) G. The splitting constants calculated by us for the ge-
ometry with the regular hexagon showed a trend similar to data in Pople's report, that is, -1.91 (A3) and -0.3 ( A d ) G. The geometry in Figure 7 , however, gives the splitting constants -3.65 (A3) and -0.95 (Ad) G, which are in perfect agreement with the experimental data. This geometry should be the most likely conformation of o-semiquinone anion radical. Pyrogallol Semiquinone Radical, The observed splitting constants of pyrogallol semiquinone radical are 5.66 ( A S )and 0.99 (Ad, A6) G. Values of the calculated splitting constants of this radical differ from the observed ones. The magnitude of the splitting constants calculated by us suggests that this radical has no hydroxyl group. Among the splitting constants of various conformations, those of monoanion radical (Figure 8b) showed a reverse trend to the experimental splitting constants, and those of dianion radical (Figure 8a) showed a trend similar to the observed ones. According to the present calculations, the bond lengths of three C - 0 bonds were not equivalent. The inside C - 0 bond was shorter than two outside C - 0 bonds. The outside C - 0 bond was equivalent from the symmetry of the radical. Semiquinone Anion Radical of 1,2,4-Trihydroxybenzene. The observed splitting constants of 1,2,4-trihydroxybenzene were reported by Stone and Waters3 to be 1.3 ( A 3 ) ,4.8 ( A S ) ,
Shinagawa, Shinagawa
/ M O Studies of Radicals f r o m Hydroxybenzenes
71 Total ener
(a.
"3
3 -133,866
i ,
-133.868 1
0
(a)
I
(b)
Figure 8. Resulting geometry of pyrogallol semiquinone radical and calculated splitting constants (parenthesized). (
0.6209 1
( 1.2583)
1 -133.873 Splitting constant (gauss) ( a 6 )2.61 _D
( - 0 7353 I
(-1.35421
(a
1
(-4.7713
2'o
1
Figure 9. Resulting geometries of semiquinone anion radical from I ,2,4-trihydroxybenzene and calculated splitting constants (parenthesized).
(a,
11.28
I
11.0
and 0.6 ( A 6 ) Oe. Lott and his colleagues" reinvestigated this radical and proposed another assignment, 0.62 (A3),4.80 ( A S ) , and 1.35 ( A 6 ) Oe, with the aid of Huckel M O and McLachlan methods. According to the present I N D O calculations, the assignment by Lott and his co-workers was preferred. The calculated splitting constants for the geometry in Figure 9a were 0.62 ( A 3 ) ,4.80 ( A s ) ,and 1.35 ( A 6 ) G. Thesevalues are in better agreement with the observed ones than the calculated constants for the geometry in Figure 9b. The calculated splitting constants for the geometry in Figure 9b were 1.3 (A3), -4.8 ( A S ) and , -0.7 (A6) G. The total energy for the geometry in Figure 9a, -95.544 689 au, was lower than that for the geometry in Figure 9b, -95.472 866 au. In the geometry in Figure 9a, the C4-04 bond length was larger than the two C - 0 bond lengths, and one of these was equivalent to the other. Semiquinone Anion Radical of Epinephrine. The observed splitting constants of semiquinone anion radical of epinephrine were 1.28 ( A 3 ) ,0.59 ( A S ) and , 2.61 ( A 6 ) G. The assignment of the splittings was determined with the aid of the present calculations. Epinephrine contains the side chain connecting to the fourth atom of the catechol ring. The calculated splitting constants of this radical vary corresponding to the geometry of the catechol ring or the conformation of the side chain. The assignment, however, was not so applicable to the variation of geometries or the conformations of this radical. In Figure 10, the splitting constants and the total energies of different geometries and conformations of semiquinone anion radical of epinephrine are plotted. From this figure and unpublished data the observed splitting constant 2.61 G corresponds to the position of the sixth hydrogen atom, 1.28 G to the position of the third hydrogen atom, and 0.59 G to the position of the fifth hydrogen atom. Both the calculated splitting constant and the total energy were applicable to the variation of geometries of the catechol ring and not so applicable to that of conformations of the side chain of this radical. The geometry of the catechol ring of the semiquinone anion radical of epinephrine is presumably quite similar to that in Figure 11 (geometry (a)). The splitting constants calculated from the conformation containing the geometry (a) of the catechol ring and the side chain 111 are -1.5230 (A3), 0.81 82 ( A S ) and , -2.5598 (A6) G. Those calculated from the conformation containing the geometry (a) and the side chain IV are -1.3563 (A3), 0.9037 ( A S ) ,and -2.6103 ( A 6 ) G. The actual conformation of semiquinone
t j
(b)
(
I
a5 0.59-
I
1
I
II
Ill
IV
V
Figure 10. Calculated splitting constants for some conformations of epinephrine anion radical and their total energies. -, splitting constant at the position of the third hydrogen atom; - - -, splitting constant at the position of the fifth hydrogen atom; - - - -, splitting constant at the position total energy. 0 ,geometry of the of the sixth hydrogen atom; ring HB shown in Figure 1 la;t), geometry of the ring HB shown in Figure 1 1 b; 0,geometry of the ring HB shown in Figure I IC; 0,geometry of the ring HB shown in Figure 1 Id; A,geometry of the ring HB shown in Figure I le; I, conformation of the side chain R shown in Figure 1 1 I; 11, conformation of the side chain R shown in Figure 1 1 11; 111, conformation of the side chain R shown in Figure I I 111; IV,conformation of the side chain R shown in Figure 11 IV;V, conformation of the side chain R shown in Figure 1 I V.
anion radical is presumably close to the conformation containing the geometry (a) of the catechol ring and the side chain IV.
Conclusion Theoretical spin densities obtained from molecular orbital calculations have been used to interpret the ESR spectra of radicals of hydroxybenzenes; however, the difficulties encountered may be for the most part due to their assumed conformations based on the structure of a quinol type. Using the INDO calculations for several radicals of hydroxybenzenes and epinephrine, we found conformations that may interpret the experimental hyperfine splitting constants of protons. The present I N D O calculations showed that all molecular geometries of these radicals of hydroxybenzenes are of quinoidlike conformations; therefore, the calculations of semiquinones should be done according to structures of a quinoid type. The observed value of the splitting constant for p-semiquinone anion radical, 2.37 G, was reproduced exactly by calculations which assumed that this was quinoid type of the planar aromatic ring. The most likely geometry of p-semiquinone anion radical has the minimum total energy among the geometries which have the values of the calculated splitting
72
Journal of the American Chemical Society HB
/
1OO:l
/ January 4 , 1978
R I
$ i &
.,&&. H B-"
I
d2
%A I1
IV
ill
(9 1 HBx@ V
Figure 11. Resulting geometries of the hydroxybenzene ring (HB)and conformations of the side chain
constants, 2.37 G . The I N D O calculations for the molecular geometries of a quinoid type reproduced exactly the experimental splitting constants of o-semiquinone anion radical and the semiquinone anion radical of 1,2,4-trihydroxybenzene which as well as pyrogallol semiquinone radical was suggested to be of the dianion type. In the semiquinone anion radical of 1,2,4-trihydroxybenzene, the CI-01 bond length was equivalent to the C 2 - 0 2 bond length, and the C4-O4bond was longer than the other two C-0 bonds. In the pyrogallol semiquinone radical, the C1-01 bond length was equivalent to the C3-03 bond length, and the C 2 - 0 2 bond was shorter than the other two C - 0 bonds. The I N D O calculations reproduced the experimental splitting constants of phenoxy radical except for the value of the position of the third hydrogen atom. Some C - 0 bonds of the radicals of these hydroxybenzenes were a quinoidlike type, that is, shorter than those of regular hydroxybenzenes. In conclusion, the molecular geometries of the radicals from hydroxybenzenes proved to be not of a quinol type but of a quinoid type. The present I N D O calculations showed that the C - 0 bond lengths of these radicals are, in general, fairly short, the adjacent C-C bond lengths in the rings relatively long, and the next C-C bond lengths in the rings relatively short. The proton hyperfine splitting constants of o-semiquinone, p semiquinone anion radical, and the anion radical of 1,2,4-trihydroxybenzene were explained quantitatively with the aid of the I N D O calculations. The splitting constants of the phenoxy radical and pyrogallol semiquinone anion radical were explained qualitatively. The ESR spectrum of semiquinone anion radical of epinephrine was studied and the observed splitting constants and their assignments were determined.
Acknowledgment. Gratitude is due to M. Ohara for assistance with the manuscript.
(R)o f epinephrine anion radical.
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