J. Phys. Chem. 1990, 94, 1887-1894
1887
Electron Spin Resonance and Pulse Radiolysis Studies on the Reaction of OH' and SOiwith Five-Membered Heterocyclic Compounds in Aqueous Solution I.
Dogan,*9la
S. Steenken,* D . Schulte-Frohlinde, and S.
Max-Planck-Institut fur Strahlenchemie, 0-4330 Miilheim, Federal Republic of Germany (Received: June 26, 19891
The reactions of several five-memberedoxygen and nitrogen heterocyclics with OH' and SO4'- radicals have been investigated in aqueous solution using in-situ radiolysis and photolysis ESR, and optical and conductometric pulse radiolysis techniques for detection. OH' reacts with (the saturated) oxazolidone, imidazolidinone,hydantoin, and oxazoline derivatives by hydrogen abstraction, preferentially from the carbon adjacent to the nitrogen atom. With (the unsaturated) oxazoles and isoxazoles, OH' reacts by addition to the carbon at the 5-position of the ring to produce allylic radicals. In basic and acidic solutions of oxazole a ring opening process follows the OH' addition. SO4'- reacts with oxazoles and isoxazoles by addition to C5 yielding SO4- adducts, whereas with imidazole, pyrazole, and pyrrole derivatives,SO-; gives rise to neutral, conjugated radicals with the unpaired electron delocalized over the entire ring, which are derived from the parent compounds by one-electron oxidation followed by deprotonation. In the case of N-methylimidazole, the radical cation is obtained. The absolute rate constants determined for the reaction of SO4'- with the five-membered heteroaromatics (k = 3 X lo8 to 8 X lo9 M-' s-I 1 reflect the electrophilicity of the SO4'- radical.
introduction The reactions of the hydroxyl radical, OH', with heterocyclic compounds have attracted considerable attention, due to the relevance to the radical chemistry of the nucleic acid bases. These reactions have been studied by using ESR2-5 and pulse radiolysis6-13 methods. The OH' radical reacts with heterocyclic compounds containing double bonds by adding to an unsaturated carbon atom,2~3~5-12 and with saturated heterocyclics by abstracting hydrogen from a carbon.4~~~ The hydroxyl radical has been shown to be very selective in both and H - a b ~ t r a c t i o n re'~ actions with six-membered heterocyclic compounds such as pyridine and pyrimidine derivatives. A similar selectivity may be expected in its reactions withfiue-membered heterocyclic rings. An electron spin resonance (ESR) study of the furans,3 for example, has shown that OH' adds almost exclusively to positions adjacent to the oxygen. However, with respect to addition to five-membered N heterocyclics and to H-abstraction reactions, the question of selectivity has not yet been addressed. The sulfate radical anion, SO4'-, reacts with several aromatic compounds to give hydroxycyclohexadienyl radicals (L(OH adducts") whose formation can be explained by either addition of SO4'- to the ring, followed by hydrolysis, or by a direct electron transfer from the ring to SO4'-, followed by hydroxylation of the resulting radical cation.14 Reaction of furans with SO4'- similarly results in the formation of OH adduct radi~a1s.I~In order to get more mechanistic information, we studied the reactions of these oxidizing radicals with five-membered heterocyclic compounds containing oxygen and nitrogen, such as oxazole, isoxazole, imidazole, pyrrole, and pyrazole derivatives. Both ESR and pulse radiolysis techniques with optical and conductance detection were ( I ) (a) Present address: Bogazici University, Department of Chemistry, Istanbul, Turkey. (b) Present address: Egean University, Department of Chemistry, Bornova, Izmir, Turkey. (2) Samuni, A.; Neta, P. J . Phys. Chem. 1973, 77, 1629. (3) Schuler, R. H.; Laroff, G.P.; Fessenden, R. W. J . Phys. Chem. 1973, 77, 456. (4) Taniguchi, H.; Kirino, Y. J . Am. Chem. SOC.1977, 99, 3625. (5) Steenken, S.; ONeill, P. J . Phys. Chem. 1978, 82, 372. (6) Steenken, S.; O'Neill, P. J . Phys. Chem. 1979, 83, 2407. (7) Fujita, S.; Steenken, S. J . Am. Chem. SOC.1981, 103, 2540. (8) Hazra, D. K.; Steenken, S. J . Am. Chem. Soc. 1983, 10.5, 4380. (9) Novais, H. M.: Steenken, S. J . Phys. Chem. 1987, 91, 426. (IO) Lilie, J. Z . Naturforsch. 1971, 266, 197. (11) Rao, P. S.; Simic, M.; Hayon, E. J . Phys. Chem. 1975, 79, 1260. (12) Bansal, K. M.; Sellers, R. M. J . Phys. Chem. 1975, 79, 1775. (13) Schuchmann, M. N.; Steenken, S.; Wroblewski, J.; von Sonntag, C. Int. J . Radiat. Biol. 1984, 46, 225. ( 1 4) See: Steenken, S. In Free Radicals in Synrhesis and Biology; Minisci, F., Ed.; Nato AS1 Series C260; Kluwer Academic: Dordrecht, 1989; p 213, and the related references given there. ( 1 5 ) Steenken, S. Unpublished results.
0022-3654/90/2094-1887$02.50/0
employed in order to clarify the reaction mechanism, to investigate (pH dependent) transformation reactions, and to determine the selectivities of OH' and SO4'- in their reactions with the heterocyclics.
Experimental Section The experimental methods for the in situ radiolysis ESR16 and for the optical and conductometric pulse radiolysis1' systems have been previously described. The chemicals were obtained from commercial sources and were used as received, except for pyrrole which was purified by fractional distillation before use. In the case of the ESR studies concerning the reactions with OH', the concentrations of the heterocyclics were 1-2 mM, and the solutions were N 2 0 saturated. The g factors of the radicals were calculated with reference to the peak from the quartz cell (g = 2.000 44).16 The SO4'- radicals were generated either from the reaction of ea; with K2S208,or by in-situ photolysis of K2S2O8 in the presence of 1% acetone as a sensitizer. In the first case the concentrations of the heterocyclics were 0.2-1 mM, those of S20a2-were 2-5 mM, and the solutions contained ca. 20 mM tert-butyl alcohol to scavenge OH'. In-situ photolysis experiments were carried out with argon-saturated solutions containing 5-10 mM of heterocyclic compound, 2C-40 mM K2S20a,and 1% (v/v) acetone. The g factors were determined by simultaneous measurements of field and microwave frequencies. In all cases appropriate corrections for second-order effectsI8 were made. For the experiments with time-resolved conductance detection, solutions saturated with argon were irradiated with electron pulses of 0.4 ws duration. The solutions contained 2-10 mM K2SZOa, 0.2 mM heterocyclic, and ca. 60 mM tert-butyl alcohol. The yields in the conductivity experiments were calculated with reference to the signal obtained with a 0.2 M solution of methanol containing the same amount of K2S2O8, as described by Bansal and Fessenden.19 The KSCN dosimeter was used in the optical pulse radiolysis experiments, using G((SCN),'-) = G(0H) = 6.0 and c((SCN),'- at 480 nm to be 7600 M-I cm-I.
-
Results and Discussion I . Reactions of OH'. The ESR spectrum recorded on reaction of OH' with 2-oxazolidinone at pH 5 showed the presence of two radicals with a concentration ratio of -6:l (see Figure 1). At pH 5-10 the spectrum of the higher intensity radical (1) is characterized by a doublet (a = 1.59 G) of doublets (a = 13.81 G) of a triplet (35.09 G, further split by second order). The 1.59-G (16) Eiben, K.; Fessenden, R. W. J . Phys. Chem. 1971, 75, 1186. (17) Jagannadham, V.; Steenken, S. J . Am. Chem. SOC.1984, 106,6542. (18) Fessenden, R. W. J . Chem. Phys. 1962, 37, 747. (19) Bansal, K. M.; Fessenden, R. W . Radiaf. Res. 1978, 7.5, 497.
0 1990 American Chemical Society
1888 The Journal of Physical Chemistry, Vol. 94, No. 5, 1990
Dogan et al.
Figure 1. (Highly polarized) ESR spectrum recorded on reaction of OH' with 2 mM 2-oxazolidinone at pH 5 and -5 "C. Q denotes the quartz signal. The inset shows the change of the a-coupling constant of the 5-yI radical with pH. The computer-simulated spectra are shown below the experimental.
splitting is assigned to the N-H proton based on its exchange by D in D,O as a solvent. This radical has also been observed by Taniguchi and K i r i n ~ .With ~ the other radical (2, characterized by a 1 :1 : 1 triplet of 0.35 G,a 0.65-Gdoublet, a 14.50-Gdoublet, and a 1 :2:1 triplet of 38.13 G,further split by second order) only a part of the spectrum was visible due to CIDEP effects and to partial overlap of some of its lines with signals from the first radical. Around pH I O the intensities of the signals of both 1 and 2 decreased, and 2 could not be detected. However, with the addition of 0.2M phosphate buffer, the lines of 2 became observable again. In the pH range 10.5-12.7the lines of 2 were not seen even with the buffer. Above pH 12.7the spectral lines reappeared; however, the N-H proton coupling was gone and a decrease of the a - H coupling constant was observed. From the dependence of the a - H coupling constant on pH (see inset of Figure I), the pK, of 2 was found to be 12.91,using Yagil's H-acidity function?O as previously d e ~ c r i b e d .The ~ pK, value of the higher intensity radical 1 has been determined as 10.90.4 These two radicals are identified in terms of structures 1 and 2 which are produced by H abstraction by OH' from C4 or C5 of the ring. Radical 1 is expected to have a higher acidity than O A , ,0-5 )'
e
H
O
L
T
H
*
O
LO $ ;N 1 H
3 1
H
H
2
1 pK,=1090
H*jl+H+
H+dl+H+
p~,=iz91
(1)
in ref 4, where only the higher intensity radical was observed and assigned to structure 2. From the reaction of OH' with N-methyl-2-oxazolidinone,two radicals were observed. The spectra of the radicals remained the same in the pH range 6-13 with concentration ratios 3/4 6:l. By comparing the coupling constants of these radicals with those of 1 and 2, the radicals are assigned the structures 3 and 4, respectively (Table I). 5,5-Dimethyloxazolidinedione.Only above pH 6 was a radical observable. In the pH range 6-13 the spectrum remained the same and consisted of a 0.41-G quartet of a 22.26-Gtriplet. The radical is assigned to structure 5 which is produced by H abstraction from
-
,$c - OA,pO CP2
H3C
H3C
\
-~i,
0-f-CH3
OAN/+O \+H. pK,=63
H
O
7CH3
(2)
5
one of the 5-methyl groups of the compound. Since the pK, of it is likely that also the radical is the parent compound is 6.3,22 present in the anionic form above pH 6. 2-Imidazolidinone. The ESR spectrum obtained at pH 2-9 showed the presence of one radical with two nonequivalent nitrogens (0.60and 0.65G),three nonequivalent hydrogens (0.85, 1SO, and 13.60G),and two equivalent hydrogens (38.85 G). The spectrum contained second-order lines, and the low-field lines were not observable due to polarization (CIDEP). The spectrum is assigned to radical 6, formed by H abstraction from the 4-position of the ring. H
H
dTHH
O +
O A N 3 p H
1'
2'
2 because it has the unpaired electron adjacent to the deprotonation site.21 On this basis, the more acidic radical (whose intensity is higher) is assigned to structure 1 and the less acidic and lower intensity radical to 2. This assignment disagrees with the one made (20) Yagil, G.J . Phys. Chem. 1967, 71, 1034. (21) Neta, P. Ado. Phys. Org. Chem. 1976, 12, 223
02> HI
+OH',
.HZ0
pH-2-9
(3)
t
0 HI
6
Above pH 9 another spectrum appeared which consisted of two equal nitrogen (0.52G) and two equal hydrogen (8.35 G) splittings. At pH 12 this was the only observable spectrum. This radical (7)is suggested to be formed from the radical 6 by dis( 2 2 ) Nuhn, P.; Woitkowitz, P. Pharmazie 1977, 32, 727.
The Journal of Physical Chemistry, Vol. 94, No. 5, 1990 1889
Reaction of OH’ and SO4’- with Heterocyclic Compounds
TABLE I: ESR Parameters of the Radicals Obtained on Reaction of OH’ with Oxazolidinone, Imidazolidinone, and Hydantoin and Derivatives”
0
g, E
1381
H 159
-
I H 0.65
0 52 g = 2.00425
g = 2 00359
g = 2 00293
g 2.00287
1
2
0
74 9 42
250
0
0
39 10
I
H
-
0 15
g = 2 00303
2 00306
g = 2.00378
g = 2 00381
2’
1’
9’
9
F iH ,
0
H 3960
13.15
H3C
CH3
-
965
065
1.90
g 2.00297
g
4
3
=
2 00318
330
1735
g = 2 00291
10
11
0 85
02g ,
0
1320
H
H3C < O
1
i
S
1360
0 70
H Q
-
2 00253
6
-
H
H44 94
H
1 50 Q = 2 00302
g 2 00284
12
6
Q = 2 00278
13
3w
,
0
H 850 140
CH3 3 09
g = 2 00344
24’
‘The coupling constants are in gauss. The g factors were determined with respect to the quartz signal (g = 2.00044), and are corrected for second-ordereffects. Nuclei with no number given have splittings
