J. Phys. Chem. 1988, 92, 111-118
111
One-Electron Reduction of Nitrobenzenes by OH and H Radical Adducts to 6-Methyluracil and 6-Methylisocytosine via Electron Transfer and AdditiodElimination. Effect of Substituents on Rates and Activation Parameters for Formation and Heterolysis of Nitroxyl-Type Tetrahedral Intermediates V. Jagannadham’ and S. Steenken* Max- Planck- Institut fur Strahlenchemie. 0-4330 Miilheim. West Germany (Received: March 16, 1987; In Final Form: July 10, 1987)
The radicals formed by OH radical addition to C-5 of 6-methyluracil or of 6-methylisocytosine, Le., 5-hydroxy-5,6-dihydro-6-methyluracil-6-yl or 5-hydroxy-5,6-dihydro-6-methylisocytosin-6-yl, or that produced by H addition to C-5 of 6-methyluracil (or by H abstraction from C-6 of 5,6-dihydro-6-methyluracil), Le., 5,6-dihydro-6-methyluracil-6-yl, reacts in aqueous solution with para-substituted nitrobenzenes to give both nitrobenzene radical anions and nitroxyl-type radicals with rate constants that vary from =7 X lo7 to (2-5) X lo9 M-’ 8,depending on the pyrimidine radical and on the nitrobenzene. The nitroxyl radicals undergo a spontaneous unimolecular heterolysis to yield (additional) nitrobenzene radical anion and oxidized pyrimidine with rate constants of lo3 to 5 X lo5 s-l depending on the structure of the pyrimidine and of the nitrobenzene. This reaction is characterized by activation enthalpies of 30-40 kJ mo1-I and by activation entropies of -7 to -89 J mol-’ K-’ (entropy control). The addition/elimination sequence constitutes a case of inner-sphereelectron transfer. The rate constants radicals. On this for the heterolysis reaction are a measure of the reducing power of 5,6-dihydro-6-methylpyrimidin-6-yl basis, the cytosine radicals are better reductants than the corresponding uracil radicals, and the radicals derived by hydrogen atom addition to pyrimidines are stronger reductants than those formed by OH radical addition.
Introduction The reactions of nitroaromatics with carbon-centered radicals substituted at C, by a heteroatom Y (these radicals can easily be produced by photolysis, radiolysis, or chemical initiation) frequently lead to the one-electron reduction of the nitro compound. These reactions have received considerable attention2 due to their relevance to the understanding of the mechanism of action of nitroaromatics as sensitizers in the radiotherapy of cancer.24 It has been recognized as early as 19687 that the interaction in aqueous solution of these radicals with nitroaromatics can lead to two types of (transient) product: (1) a-alkoxynitroxyl radicals (produced by addition to the nitro group), and (2) nitro radical anions; cf. eq 1 and 2. It was suggested that the tendency to react
p’
VI I
R, -C,-0I
VI R,-bi I
+
p
O=N-Ar
R2
/” \
H
0
N -Ar
11@ Rq-C,
I R2
(1)
)
R2
v
+
carbocations7 and on the oxidizing power (redox potential) of the nitro compounds.2e~8It is obvious that it should also depend on solvent, with more polar solvents favoring the ionic path (2).9 It has recently been shown9that in aqueous solution the addition product (via eq 1) and the electron-transfer product (via eq 2 ) do not exclude each other and that (1) and (2) can occur simultaneously. This has been explained in terms of an electrontransfer/addition mechanism involving an ion pair type transition state with subsequent competition between combination (to give addition) and separation by solvent (leading to electron transfer).1° The further fate of the adduct can be heterolysis of the C-O bond between the (former) radical and the nitro compound, e.g., in the case of Y = OH:
I R2 khs
e 0;NAr
R,-b,a-NAr
(2)
V = helero atom
according to (1) or (2) depends on the stability of the (incipient) (1) Department of Chemistry, Nizam College, Osmania University Hyderabad-500001, India. (2) For reviews see (a) Adams, G. E. Ado. Radiat. Chem. 1972, 3, 125. (b) Greenstock, C. L. In The Chemistry of Amino, Nitroso and Nitro Compounds and their Derivatives; Patai, S . , Ed.; Wiley: New York, 1982; p 291. (c) Willson, R. L. In Free Radicals, Lipid Peroxidation and Cancer; McBrien, D. C. H.; Slater, T. F., Eds.; Academic: New York, 1982; p. 275. (d) Wardman, P. In Advanced Topics on Radiosensitizers of Hypoxic Cells; Breccia, A.; Rimondi, C.; Adams, G. E., Eds.; Plenum: New York, 1982; p 49. ( e ) Wardman, P.; Clarke, E. D. In New Chemo and Radiosensitizing Drugs; Breccia, A,; Fowler, J. F.; Eds.; Edizione Scientifiche: Lo Scarabeo, 1985; p 21. (3) Raleigh, J. A.; Chapman, J. D.; Borsa, J.; Kremers, W.; Reuvers, A. P. Int. J . Radiat. Bioi. 1973, 23, 311. (4) Wardman, P.; Clarke, E. D.; Flockhart, I. R.; Wallace, R. G. Br. J . Cancer 1978, 37, Suppl. III, 1. ( 5 ) Adams, G. E.; Clarke, E. D.; Jacobs, R. S.; Stratford, I. J.; Wallace, R.G.; Wardman, P.; Watts, M. E. Biochem. Biophys. Res. Commun. 1976, 72,824. Adams, G. E.; Clarke, E. D.; Flockhart, I. R.; Jacobs, R. S.;Sehmi, D. S.; Stratford, I . J.; Wardman, P.; Watts, M. E.; Parrick, J.; Wallace, R. G.; Smithen, C. E. Int. J . Radiat. Bioi. 1979, 35, 133. (6) Adams, G. E.; Willson, R. L. J . Chem. SOC.,Faraday Trans. 2 1973, 69, 719. (7) McMillan, M.; Norman, R. 0. C. J . Chem. Sot. B 1968, 590.
0022-3654/88/2092-0111$01.50/0
hS
R,-C
:+ I R2
@ OiNAr
+
H@
(3)
Together with eq 1, this reaction constitutes an example for organic “inner-sphere” electron transfer.’’ It was found that in aqueous solution the rate constant for the (spontaneous) heterolysis, khs, increases with increasing electron-donating power of Y, R,, and R2 and with increasing electron-withdrawing power of Ar.9 For example, for Y = OH and Ar = para-substituted benzene (eq 3), spontaneous heterolysis was not observed (khs I lo2 s-I) if R, = R2 = H. However, replacing only one hydrogen at C, by methyl makes the heterolysis observable and the k h s values are now in the 102-104-s-’ range. If R I = R2 = CH3, heterolysis is very rapid (khs I lo6 s-’) unless the electron-withdrawing power of the nitrobenzene is decreased as with 4-nitroaniline or unless the solvent is less polar than water.9 Pyrimidin-6-yl radicals, formed by, e.g., O H radical addition to C-5 of naturally occurring nucleobases, nucleosides, or nucleotides, react with nitrobenzenes exclusively by addition to give nitroxyl radicals.I2 In this respect, the 6-yl radicals are similar to CH20H. Replacement of H by methyl at C-6 in the pyrimidine series leads to 6:methylpyrimidin-6-y1 radicals which can be compared to CH,CHOH. On the basis of this analogy the nitroxyl (8) Wardman, P. Int. J . Radiat. Bioi. 1975, 28, 585. (9) Jagannadham, V.; Steenken, S. J . A m . Chem. SOC.1984, 106,6542. (10) Jagannadham, V.; Steenken, S. J . Am. Chem. S o t . , in press. (1 1) Reduction of tetranitromethane by a-alkoxyalkyl radicals also proceeds by an “inner-sphere” electron-transfer route (Eibenberger, J.; SchulteFrohlinde, D.; Steenken, S. J . Phys. Chem. 1980, 84, 704). (12) Steenken, S.; Jagannadham, V. J . Am. Chem. SOC.1985, 107,6818.
0 1988 American Chemical Society
112 The Journal of P h y s i c a l Chemistry, Vol. 92, No. 1 , 1988
Jagannadham and Steenken
20 000
15000
? .
E
;10000
7
/---
I
\
w
5 000
300
3 50
400
450
550
500
600
h/nm Figure 1. Time-resolved absorption spectra observed on reaction of O H at pH 6 with 2 mM 6-Me-i-C. (a) In the absence of 4-NAP. The c scale has been expanded by a factor of 2. (b and c) In the presence of 0.5 m M 4-NAP. The times indicated are those after the end of the 100-ns pulse. Spectrum e is that of the nitroxyl. It was obtained by substracting from spectrum c 80% of spectrum d. All spectra have been corrected for depletion of 6-Me-i-C and 4-NAP (based on G(OH + H ) = 6.6). The c values are based on G(radica1) = 5.1. Insets 1 and 2 show the rise of optical density due to formation of nitroxyl (330 nm) and of radical anion (350 nm). In (1) the two different smooth lines through the experimental points are computer fits showing monoexponential behavior. Inset 3 shows the corresponding decrease of OD due to depletion of 5-OH-6-Me-i-C' (410 nm). Inset 4 shows the rise of dc conductance of p H 4.85. A fast component and a slower component are visible. The decrease in the plateau region is due to buffering and to electrolysis. In insets 5 and 6 are seen the depletion of nitroxyl and the formation of radical anion, respectively, due to the heterolysis. Inset 7 shows the corresponding rise of conductance at pH 5.95 (0.5 mM 6-Me-i-C; 0.125 mM 4-NAP).
radicals derived from the 6-methyl-6-yl radicals are expected to undergo spontaneous heterolysis with rate constants ?lo2 s-l. In the following it is shown that this is indeed the case and that the khsvalues are a measure of the electron-donating ability of 6-yl radicals from different pyrimidines.
Experimental Section The compounds were all commercially available from Aldrich, Eastman, Fluka, Pfaltz and Bauer, or Sigma. The aqueous solutions (using water purified with a Millipore-Milli-Q system) typically contained 2 m M of the pyrimidine and 0.1-1 mM of the nitrobenzene, and they were saturated with N 2 0 in order to convert eaq-into OH. Pulse radiolysis was performed with 0.10.4-ps pulses from a 3-MeV van de Graaff accelerator using doses such that 0.5-2 p M radicals were produced. The reactions were monitored by optical or conductance (ac and dc) methods. Dosimetry was carried out with (a) N20saturated 10 mM KSCN, taking t((SCN),'-) = 7600 M-' cm-' a t 480 nm and G(OH)I3 = 6.0,14or with (b) N20-saturated 0.1 M propanol-2 solutions containing 0.2-0.5 m M nitro compound, taking G(nitro radical anion) = G(H+) = 0.85(G(OH) G(H))I5 = 5.9. With both the optical and the conductance cells the temperature of the solutions could be kept constant to f O . l OC with cells that are an integral part of a heat exchanger. The temperature was varied in 5 OC steps between 0 and 20 O C and in 10-20 OC steps between 20 and 80 OC. A r r h e n i u s plots were constructed f r o m measurements a t at least five temperatures.
+
Results and Discussion I . Reactions of 6-Methyl-5,4-dihydropyrimidin-6-y1 Radicals with P a r a - S u b s t i t u t e d Nitrobenzenes. 5-Hydroxy-6-methyl5,6-dihydropyrimidin-6-~1 radicals were produced at pH 5-6 by the selective (290%)'6J7 addition of OH to the C-5/C-6 double (13) The radiation-chemicalG-value is defined as the number of molecules removed or produced per 100 eV of absorbed radiation. (14) Schuler, R. H.; Hartzell, A. L.; Behar, B. J . Phys. Chem. 1981, 85, 192. (15) Asmus, K.-D.; Mockel, G.; Henglein, A. J . Phys. Chem. 1973, 77, 1218.
bond of 6-methyluracil (6-MeU) or 6-methylisocytosine (6-Mei-C)(see eq 4),18and 6-methyl-5,6-dihydrouracil-6-yl radical was generated by the equally selective H - a b s t r a ~ t i o n by ' ~ OH from C-6 of 6-methyl-5,6-dihydrouracil.The pyrimidin-6-yl radicals will subsequently be termed and abbreviated by using an "addition" nomenclature20 as shown by
a
r-
.4,
H2N&
OH
4 h
H
0
0
H
H
5-OH- 6 -Me U'
5
5-H-6-MeU'
a. E x p e r i m e n t s with Optical Detection. T h e pyrimidine
radicals have broad absorption bands in the region 300-500 nm and extinction coefficients 51500 M-' cm-I (see Figure la). In the presence of 0.1-0.5 mM para-substituted nitrobenzene in the (16) Fujita, S.; Steenken, S. J . Am. Chem. SOC.1981, 103, 2540. (17) Hazra, D. K.; Steenken, S. J . Am. Chem. SOC.1983, 105, 4380. ( 1 8 ) The rate constant for reaction of OH with 6-MeU and 6-Me-i-C was determined to be 5.7 X IO9 and 6.0 X lo9 M-' s-', respectively (X(observation) = 420 nm). (19) Schuchmann, M. N.; Steenken, S.; Wroblewski, 3.; von Sonntag, C. I n t . J . Radiat. Biol. 1984, 46, 225. (20) By use of acronyms based on the "abstraction" nomenclature (vide supra) recommended by IUPAC, the emphasis cannot easily be placed on the substitution at C-5 (=C,), which strongly influences the behavior of the 6-yl (=C,) radicals.
The Journal of Physical Chemistry, Vol. 92, No. 1, 1988 113
One-Electron Reduction of Nitrobenzenes
TABLE I: Bimolecular Rate Constants k, for Reaction of 5-OH-6-MeU' with p-RC6H4N02and Rate Constants klnand Activation Parameters for Nitroxvl Heterolvsis' init yield of ~~
radical k,/M-' s-I compd
R
o/
at 20
3.0 3.2 9.4 4.4 4.2
1
SOSCH,
0.90
2 3
NO2 CN
0.8 1 0.70
OCC
lo8 108g x 108 x 108 X 108g X X
aniond
opt
cond
51
53
83 44
56
in D20 4
S02NH2
0.58
5
COCH,
0.47
4.1 3.6 3.2 2.7
X X X X
lo8 108g losh 108g
47
54
69
60
in DzO 6
CO2CH3
0.44
I
CONHz
0.31
9
so3-
0.10
10 11 14 15
CH=NOH
cor
CH3 OCH3
0.10 0.1 1 -0.14 -0.28
3.1 X 3.4 x 2.2 x 1.5 X 2.1 x 1.2 x
lo8 1088 108 108g 108 1088
3.3 x 1088 8.5 x 107' 6.9 x 107'
48
84
50
88
47
43 60
khs/S-l
at 30 O C ' 6.1 X 6.0 X 2.8 X 6.1 X 4.4 x 5.5 x 3.7 x 4.0 X 3.9 x 5.3 x 3.4 3.0 4.1 2.7 2.7 2.3 1.2 1.8 1.9
103 103g 104 103 103g 103 103 103g 103 1038
x 103 103 103g 103 10'g 103 x 103g X 103 X 103g X X X X X
AH*//
AS/J
kJ mo1-I
mol-' K-'
* 18.8
39.8 f 5.7
-42.5
31.5 f 1.2 36.5 f 1.3
-55.4 f 3.7 -52.6 f 4.2
29.1 f 3.1 32.9 f 5.8
-77.5 f 10.3 -67.5 f 19.2
38.8 f 1.5
-47.3 f 4.8
27.6 f 8.5 31.8 f 4.5
-86.3 f 27.5 -73.2 f 15.2
37.4 f 6.2
-56.3
27.8 f 8.9
-89.4 f 29.2
37.5 f 2.2
-58.6 f 6.7
notes
k h ~ ( ~ 2 0 ) / ~ h s ( ~= 2 01.2 )
khs(H20)/khs(D20)
= 1.3
* 20
ndi nd,
aN20-saturated aqueous solutions. [Nitrobenzene] = 0.2-1 mM; [pyrimidine = 2 mM; pH 4.5-6.5. *From Exner, 0. In Correlation Analysis in Chemistry; Chapman, N. B.; Shorter, J., Eds.; Plenum: New York, 1978. CDeterminedby monitoring the OD buildup 10-20 nm below A,, of radial anion. The k , values refer to the slower component (see text). percent of total anion formation. The optical values were determined at A,, of radical anion. The values measured by conductance showed some dependence on pH, indicative of buffering (due to impurities). CThe optically determined values are from the buildup of [radical anion] and, in the case of 4-NBN and 4-NAP, from the decay of [nitroxyl] at 310 and 330 nm, respectively. (For 298 K. The activation parameters are from optical experiments. The r values for the Arrhenius plots were usually >0.99; in a few cases they were >0.98. gFrom conductance detection. "From ref 12. 'These numbers were obtained by monitoring the OD for depletion of [5-OH-6-MeUe]at 400 nm and for formation of adduct at its second A,, at 480 nm. Jnd, not determinable. 2 mM pyrimidine solutions (pH 5-6) these absorptions were replaced by much stronger ones in the regions 300-390 and 520-600 nm (see Figure lb,c and insets 1 and 2 for the system 4-nitroacetophenone (4-NAP)). For this 5-OH-6-Me-i-C' system, the rates of increase of optical density (OD) at 300-390 or 520-600 nm or those of the decrease (see inset 3) at 410-470 nm (where 5-OH-6-Me-i-C' absorbs stronger than its reaction product) increased with increasing nitrobenzene concentrations. However, close inspection of the shapes of the OD buildups reveals that these are not purely monoexponential but contain two components (see insets 1 and 2). The rates of both components increased with increasing nitrobenzene concentration, whereby the reaction period of the faster component appeared to be about 2 times shorter than that of the slower component, indicating that the rate constant for the faster process is twice that of the slower one. However, due to the difficulty in identifying a plateau value which defines the completion of the fast process estimates of its rate constant are rather inaccurate. The situation is more favorable with respect to the kinetic analysis of the slower component, due to the presence of a well-defined plateau. (The rate of the slower component was found to be dependent on the concentration of 4-NAP in a satisfactory fashion in the range 0.2-1 mM). For this reason, the value given in Table I1 for the rate constant for reaction of 4-NAP with 5-OH-6-Me-i-C' is that for the slower component. It was measured 20 nm below A,, of radical anion, because at this wavelength the slower component was influenced less by the fast one. Analogous observations were made on reaction of OH with 6-methylisocytosine in the presence of other para-substituted nitrobenzenes. When 6-methylisocytosine was replaced by 6methyluracil (which gives 5-OH-6-MeU0),the situation was again similar with respect to the presence of two components.21
+
(21) The proportion of the two components depended on the nitrobenzene, on the nature of the pyrimidine radical, and also on X (observation). In some cases the slower component was more pronounced and therefore easier to measure at 15-25 nm below the A,, of the radical anion (ref 22).
However, when 5-H-6-MeV was produced (by H-abstraction from C-6 of 5,6-dihydro-6-methyluracil) in the presence of the nitrobenzenes, only one component was discernible in the buildup of OD, the rate of which was proportional to [nitrobenzene] in the range 0.2-1 mM and independent of wavelength. b. Conductance Experiments. The reaction between 6methylpyrimidin-6-yl radicals and nitrobenzenes leads to increases of the conductance of the solutions, if performed at pH 7. This shows that the conductance change is caused predominantly by the production of H+, which, at pH >7, removes an equivalent of OH- thereby leading to a conductance decrease. The conductance increase was found to consist of two nitrobenzene concentration dependent components with essentially the same characteristics as the OD increase (see inset 4 of Figure 1). This indicates that with the two detection methods the same reactions are being monitored. With optical detection at A,, of radical anion,22it is essentially the radical anion that is seen, while with conductance the production of H+ is measured. The fact that the production rates of H+ and of radical anion are the same thus means that the two are products of the same rcaction(s). After completion of these reactions their yields were determined (after 10-50 ~s at [nitrobenzene] I 0.5 mM) by both detection techniques to correspond to only 40-90% of the 6-yl radicals produced by OH. The individual values depend on the pyrimidine radical and on the nitrobenzene (see Tables 1-111). In Tables 1-111 are also collected the rate constants k , for formation of product via the s l o w e r path, as obtained from optical and conductance experiments. The two methods yield k, values equal within 20%. c. Structure-Activity Relationsfor k,. For 5-OH-6-MeU' the rate constants vary from 7 X lo7 to 9 X lo8 M-' s-l, depending on the nature of the substituent on the nitrobenzene (Table I). For 5-OH-6-Me-i-C' the rate constants are somewhat larger, Le., ( 2 2 ) For the A,,
values of the radical anions see ref 9.
114
Jagannadham and Steenken
The Journal of Physical Chemistry, Vol. 92, No. 1, 1988
TABLE 11: Bimolecular Rate Constants k , for Reaction of 5-OH-6-Me-i-C' with p-RC6H4NO2and k , Values and Activation Parameters for Nitroxvl Heterolvsis' k,/M-'s-I init yield of khs/s-l AH*/kJ As/J at 20 O C at 30 "C mol-' mol-] K-' notes compd R radical anionb UP 9.0 X IO' 1.6 X IO4 40.0 f 3.5 -32.2 f 11.7 1 SO3CH3 0.90 81 1.8 x 109 6.2 X I O 4 43.8 f 1.7 -7.1 f 5.6 2 NO, 0.81 87 1.2 x 109 1.2 X IO4 36.2 f 3.6 -46 f 12 72 0.70 3 CN khs(H@)/kha(D20) = 1.4 34.2 f 3.7 -56 f 12.5 in D,O 8.8 X IO3 44.7 i 3.5 -16.9 f 11.9 1.0 x 109 77 1.5 x 104 4 SOZNH, 0.58 -45.3 f 8.7 7.7 x 108 1.2 X lo4 36.7 f 2.6 0.47 81 5 COCH3 7.6 X lo8' 83C3d -41.5 f 12.3 38.2 i 3.7 1.2 x 109 77 1.2 x 104 0.44 6 COZCH, 7.1 X IO' 37.0 f 3.7 -46.7 f 12.5 8.8 X IO3 82 7 CONH, 0.31 7.7 X IO' 40.1 f 4.0 -39 f 13.4 0.10 6.0 X IO' 85 9 so,2.9 X 10sc~' -0.14 nd 14 CH3 2.7 X -0.28 nd 15 OCH, "The conditions and definitions are as described in Table I . bFrom optical measurements. cFrom conductance. d p H 6.0. 'Determined at 400 nm (depletion of 4-OH-6-Me-i-C') and at 480 nm (formation of adduct).
TABLE 111: Bimolecular Rate Constants k , for Reaction of 5-H-6-Me-U with p-RC6H4NOZand k , Values and Activation Parameters for Nitroxyl Heterolysis",b init yield of radical k , / W 1 s-' anion khs/s-' AH*/kJ AS/J compd R up at 20 "C opt cond at 20 "C mol-' mo1-l K-' notes
1
SO1CHq ~~
0.90
2 3
CN
0.81 0.70
4
in D,O SO,NH,
0.58
5
COCH,
0.47
6 7 8 9 10
12 13 14 15 16
NO,
in D 2 0 COZCHI CONH, CI SO3CH=NOH CH20H H CH3 OCH, NH,
0.44 0.31 0.24 0.10 0.10 0.01 0.00 -0.14 -0.28 -0.57
2.7 2.3 2.2 2.1 2.2
X
IO9
84
51
x 109' IO9 IO9 x 109'
90 61
51
1.2 X IO9 1.3 x 109~ 1.7 X 1.4 x 109c
63
52
69
74
1.8 X IO9 2.0 x 109 nd -6 X IO' nd nd
56 59
X
X
45
1.3 X IO9' 9.8 X IOse nd
"The conditions and definitions are as described in Table I. and 480 nm
58 50 59 76 72 49 55
6.0 x 104
5.5 x 4.6 x 1.2 x 1.2 x 4.8 x 6.1 x 7.6 x 7.3 x 8.0 x 4.3 x 6.4 x 4.8 x 2.2 x 3.9 x 3.3 x 1.4 x 1.2 x 8.9 x 7.0 x 2.1 x
29.1 f 4.6
-54 f 15.7
105 105 105~
34.6 f 4.0 37.1 f 2.5
-19.1 f 13.4 -21.8 f 8.8
104 104 104' 104 104'
41 f 4.7 42.5 f 2.1
-15.2 f 16 -7.5 f 7.0
38.6 f 2.0
-19.7 f 6.9
104~
34.9 f 1.6 36.6 f 2.0 40.8 f 4.7 104c 40.5 f 3.3 36.6 f 2.2 104 1 0 4 ~ 40.3 f 3.1 43 f 3.2 104' 104~ 38.3 f 3.2 103' 40.9 f 3.4 1 0 3 ~ 45.5 f 3.1 103~ 104
104 104
kh,(H,0)/khs(D20) = 2.3
khr(H20)/khs(D20) = 1.7
-36.6 f 5.5 -27.5 f 7.0 -16.2 f 16.1 -24.3 f 11.3 -32.4 f 7.4 -20.8 f 10.7 -19.3 f 1 1 -36.3 f 11.1 -30 f 11.6 -16.8 f 10.9
[Nitrobenzene] = 0.1-1 mM. 'From conductance. dFrom ref IO. 'Measured at 400
3 X lo8 to 2 X lo9 M-' s-', again increasing with the electron deficiency of the nitrobenzene (Table 11). In the case of 5-H6-MeU' the k , values are ( ~ 1 - 3 ) X lo9 M-I s-', suggesting that this radical is the most powerful reductant of the pyrimidin-6-yl radicals (Table H I ) . The rate constants for reaction of the 6methyl-6-yl radicals may be compared with those12 for the nonmethylated 6-yl radicals: the methyl group at C-6 leads to an increase in the rate constant by a factor of 5-8, attesting to the increased reducing power due to the electron-donating methyl group at the reaction site (C-6). The same phenomenon is observed in going from C H 2 0 H to the better reductant CH,CHOH.6,9,23 The increase in k , in going from the 5-hydroxyuracil to the 5-hydroxycytosine to the 5-hydrouracil system was observed also with the 6-yl radicals unmethylated at C-6.12 The higher reducing strength of the 5-hydroxycytosine radicals compared to the 5hydroxyuracil radicals, which is in agreement with the lower ionization potential of cytosine (8.9 eV) compared to that of uracil (9.8 eV), is probably caused by the replacement of an electronwithdrawing carbonyl oxygen by an amino group. The difference in k , between 5-hydroxy- and 5-hydrouracil-6-yl radicals is due (23) Asmus, K.-D.; Wigger, A.; Henglein, A. Ber. Bunsen-Ges. Phys. Chem. 1966, 70. 8 6 2 .
to withdrawal of electron density from C, by fhe O H group at C, (-I effect).I2 For the same reason HOCH2CHOH is usually a weaker reductant than CH3CHOH.9~24~25 The difference in the rate constants between the 5-hydroxy- and the 5-hydrouracil systems is larger than that between the 5-hydroxyuracil and 5hydroxyisocytosine ones. This shows that the reducing power of the 6-yl radicalI2 is influenced by the substituent (OH or H ) at C-5 (+) more than by that (0or NH2) at C-2 or at C-4 (=C7). 2. Unimolecular Production of Radical Anion. After completion of the "fast" reactions described in section 1 (reaction period 150 ks at [nitrobenzene] L 0.5 mM), changes of OD and conductance were observed (at pH 4-7) that occurred on a longer timescale (milliseconds). The type of OD change was found.to be dependent on wavelength. With, e.g., the 5-OH-6-Me-i-Cl 4-NAP system the OD increased in an exponential way at 350 or 550 nm, whereas at 1 3 4 0 nm it decreased with the same rate as the increase at 1 3 4 5 nm (see insets 5 and 6 in Figure 1). Parallel to the OD changes, the conductance increased (at pH 5-6) in an exponential fashion with the same rate (see inset 7, (24) Ross, A. B.; Neta, P.Natl. Stand. Ref.Data Ser. ( U S . , Natl. Bur. Stand.) 1982, Report No. 70. ( 2 5 ) Steenken, S . ; Davies, M. J ; Gilbert, B. C. J. Chem. Soc., Perkin Trans. 2, 1986, 1003
The Journal of Physical Chemistry, Vol. 92, No. I , 1988 115
One-Electron Reduction of Nitrobenzenes SCHEME I
0
5.5
5.0
---
L.5
r v1
Y
-g
L.0
3.5
3.0 2.6
28
30
32
3L
36
1000/K
Figure 2. Arrhenius plot of the khsvalues (determined optically) for the nitroxyl from 5-OH-6-MeU’ and 4-nitrobenzonitrile (4-NBN) ( r = 0.998). [6-MeU] = 2 mM; [4-NBN] = 0.5-1 mM; pH 6.4.
Figure 1). At pH ~ 8 . the 5 conductance decreased with the same rate as that of the increase at acid pH. This OH--induced inversion of the polarity of the conductance signal shows that it is due to the production of H+. In contrast to the OD and conductance changes occurring on the fast time scale as described in section 1, the rate of the “slow” changes was found to be independent of [4-NAP] (within 0.05-1 mM), from which it is concluded that the changes are due to a unimolecular reaction. The rates of change are also independent of the initial concentration of the radicals (in the range 0.5-5 MM),and of pH (4-6.5). The rates are, however, dependent on temperature (varied from Oo to 80’; see, e.g., Figure 2), and above pH 7 they increase with increasing pH according to the equation kobsd= khs koH- [OH-] where khs is the rate constant measured at acid pH.26 In no instance was there evidence for a second component in the unimolecular production of radical anion (cf., e.g., Figure 3, in which clean monoexponential buildups are seen). After completion of the slow, unimolecular reaction the absorption spectrum measured (see Figure Id) was found to be identical with that6z9J2of the 4-NAP radical anion. The G value13 for formation of the radical anion was found to be 5.1. This value corresponds to quantitative conversion of 5-OH-6-Me-i-C’ into
+
(26) From the slopes of these plots koK values of (3-5) X lo9 M-’ s-’ were
obtained for the OH--catalyzed path. The values are similar to those mea-
sured’* for the corresponding systems nonmethylated at C-6. The catalysis by OH- involves deprotonation from N-1 followed by rapid heterolysis.’* In agreement with this is the fact that the nitroxyl derived from the OH adduct to C-5 of 1,3,6-trimethyluraciI (see Table IV) is resistant to catalysis by OH-.
4-NAP- if it is taken into account that the 6-yl radical is formed to only 95% by reaction of the parent pyrimidine with OH” and that O H is scavenged to a small extent (assumed to be 10%) by reaction with 4-NAP. On that basis, the production of H+ is also quantitative, as was shown by time-resolved conductance titration at pH 4 . 5 (where buffering due to parent (pK = 4.5) is negligible). Results analogous to those described for 5-OH-6-Me-i-C’ and 4-NAP were observed for the other pyrimidin-6-yl radicals and the other 4-substituted nitrobenzenes. The rate constants for the unimolecular production of radical anion and of H+ are collected in Tables 1-111. The formation of radical anions by reaction at pH 4-6 of any of the 6-methyl-pyrimidin-6-yl radicals with the substituted nitrobenzenes listed in Tables 1-111 was demonstrated also by in situ radiolysis ESR measurements. The ESR parameters observed were identical with those9 described earlier. 3. Formation of Radical Anion and Nitroxyl. The results presented are explained in terms of reaction of the pyrimidin-6-yl radicals with the nitrobenzenes to give two products: the nitroxyl, formed by addition to the nitro group, and the radical anion, as the electron-transfer product from the pyrimidine radical to the nitrobenzene. These products result from an ion pair type transition state that can lead to combination or, if solvent intrusion takes place, to electron transfer.I0 The nitroxyl is suggested in analogy to the behavior of pyrimidin-6-yl radicals nonmethylated at C-6 where these radicals are the exclusive reaction products.I2 This assignment is supported by the absorption spectrum of the nitroxyl (obtained by difference; see Figure le) which has a peak at 325 nm (=25 nm below A,, of radical anion9), in agreement with corresponding spectra from other nitroxyl~.~J* The other product is the nitrobenzene radical anion. As seen in Tables 1-111, the “initial” yield of radical anion (and of H+), Le., that produced in the fast steps whose rates are dependent on nitrobenzene concentration, varies from 40% to 90% with an average value of 50-60%. As reported in section 1, with 5-OH-6-MeU’ and 5-OH-6Me-i-C’ two components were seen in the concentration-dependent “fast” buildup of radical anion at its A,, and also at the A,, of the nitroxyl. In contrast, on reaction of 5-H-6-MeU’ with any of the nitrobenzenes only one component was discernible in the buildup of radical anion, nitroxyl, or H+. The latter radical is symmetrically substituted at C-5. If the radical center (at C-6) is to a certain degree pyrimidal, two diastereomeric radicals exist in the case of the OH-substituted radicals, but not with 5-H-6-Me’. These radical forms should have a different rea~tivity.~’It is
116 The Journal of Physical Chemistry, Vol. 92, No. 1, 1988
'i
I
bl
I
k300P54
I -.
I
t
Jagannadham and Steenken
i
t
time
pulse
, ,
1
time
pulse
Figure 3. Conductance traces showing ion production via a fast (bimolecular) and a slow (unimolecular) step. The latter is due to the heterolysis shown in the formulas. (a) and (b) differ with respect to the substituent on the electron acceptor. In (c) also the electron donor is changed. The curves through the experimental points are from computer fits based on a monoexponential rise. [Nitro-cpd] = 0.5 mM; [pyrimidine] = 2 mM; 20 OC;pH 5.9.
SCHEME 11
%-EH O
-I
hs d
f
N
@NO?
TABLE I V Comparison of Rate Constants k , and k , and Activation Parameters for the System 4-NAP and Various 6-Methylpyrimidin-6-yl Radicalso k,JM-' S-I khsls-' AH'lkJ AS/J init yield of radical at 20 OC at 20 "C molv1 mol-I K-I radical anion ~~~~
~
5-OH-6-MeU' 5-OH-6-Me-i-C' 5-H-6-MeU' 5-hydroxy- 1,3,6-trimethyluracil-6-yl
3.1 X lo8 7.7 x 108 1.7 x 109 5.2 x 108 4.8 X lo8'
2-amino-5-hydroxy-4,6-dimethylpyrimidin-6~yl 7.5 X 10' 1.0 x 109' 1.4 x io7d.h
2.5 X lo3 7.9 X lo3 7.3 X I O 4 1 . 1 x 104 1.4 x 1046 9.7 X 2 8 X IO5 26 X IO5' 2 2 x 104d.b
38.8 f 36.7 f 38.6 f 26.4
1.5 2.6 2.0 2.2
36.2 f 1.9'
-47.3 f 4.8 -45.3 & 8.7 -19.7 f 7 -79 f 7.7
69; 60b 81: 83b 69; 14b 60; 676
-53 f 6.3'
4 5C.b e e e
"The conditions and definitions are as described in Table 1. bFrom conductance detection. 'The number is for reaction with 4-NBN. dThe number is for reaction with 4-nitroaniline. 'There is no step visible, even at 0 OC.
therefore suggested that the two components observed with the 5-hydroxy-6-yl radicals arise via the cis and trans paths depicted in Scheme I. It is assumed that along both paths branching occurs to yield addition or oxidation/reduction products. Branching possibly proceeds via a (T or CT) complex analogous to that p r o p o ~ e d ~in. ' the ~ reaction of a-hydoxyethyl radical with nitrobenzenes.28 According to Scheme I, the product distribution is determined by the rate constants for production and decomposition of the (CT) complexes.29 (27) We thank referee 2 for pointing this out. It has been shown by ESR that radicals substituted at C , by a heteroatom are not planar (Fessenden, R. W. J . Phys. Chem. 1967, 71.74; Livingston, R.; Dohrmann, J. K.: ?eldes, H. J . Chem. Phys. 1970, 53,2448; Dobbs, A. J.; Gilbert, B. C.: Norman, R. 0. C. J . Chem. SOC.,Perkin Trans. 2, 1972, 786). However, in order to see under these conditions the two-component kinetics, it is necessary that the inversion period of pyramidal C-6 be greater than or equal to the reaction period of the diastereomeric radicals with the nitrobenzene microsecond range). The nitrobenzene concentration does in fact influence the "composition" of the OD buildup kinetics in a way that qualitatively supports this picture. (28) The formation of complex from the reactants is likely to be reversible'O (see Scheme I). A search was made for a charge-transfer complex between (the parent compound) 6-Me-i-C and 4-NAP in aqueous solution, using 2 mM 6-Me-i-C and 0.5 mM 4-NAP. If such a complex exists, its OD/cm is 50.002 at X 2 300 nm. (29) A situation where k , is negligible compared to k, (or vice versa) leads to only one component in the formation of nitroxyl, while two components are still possible for the production of radical anion.
In contrast to the "fast" and bimolecular formation, the "slow" and unimolecular production of radical anion and of H+ as observed on the 0.1-4-111s time scale was found to be analyzable in terms of only one component (see, e.g., Figures 1 and 3), which means that the cis and trans nitroxyls decompose with rates equal within 520%. On the basis of the existing data a distinction between the cis and trans isomers is not possible. Therefore, in the following discussion the term nitroxyl will be used without specifying its isomeric structure. 4 . Heterolysis of the Nitroxyls. The heterolysis reaction (rate constant khs),which proceeds by cleavage of the C(6)-0 bond, gives rise to the nitrobenzene radical anion and H+. The remaining product is necessarily an oxidized pyrimidine. In the case of uracil, one-electron oxidation of its OH adduct has been shown to lead to isobarbituric acid and to 5,6-dihydroxy-5,6-dihydrouracil(uracil glyc01).~~-~' Glycols have also been found as oxidation products of OH adducts of thymine.32 Isobarbituric acids and glycols both originate from the same precursor, the (incipient) carbocation at (30) (a) AI-Yamoor, K. Y . ;Garner, A,; Idriss Ali, K. M.; Scholes, G. Proceedings ofthe 4th Tihany Symposium on Radiation Chemistry; Hedvig, P.; Schiller, R., Eds.; Akademiai Kiado: Budapest, 1977; p 845. (b) Schuchmann, M . N.; von Sonntag, C. J . Chem. SOC.,Perkin Trans. 2 1983, 1525. (c) Jovanovic, S . V.; Simic, M. G . J . Am. Chem. Sac. 1986, 108,5968. (31) See also ref 12. (32) Nishimoto, S.: Ide. H.; Wada, T.; Kagiya, T. Int. J . Radiat. Biol. 1983, 4 4 , 585.
The Journal of Physical Chemistry, Vol. 92, No. 1. 1988 117
One-Electron Reduction of Nitrobenzenes PK,
2.0
2.4
2.8
3.2
3.6
I
1
I
I
6.0
5'L
t
L.0
\-1,5
-10
-
L.5
-
LO
-
3.5
-
L Y
m
-
3.0 I
5.0
'
-0.6
*\ I
I
02
-02
I
I V
06
1.0
UP
Figure 4. Hammett and Bronsted plot for heterolysis at 20 " C of the
nitroxyls from 5-H-6-MeU' and para-substitutednitrobenzenes. The pK values for the radical anions are from ref 33. The slopes correspond to p = 1.5 and a = -1.5. C-6, by deprotonation the former and by hydration the latter (see Scheme 11). These reactions may also be concerted with the C-0 heterolysis. For systems alkylated at N-1 (as with the nucleosides and nucleotides) deprotonation is not possible so hydration is expected to occur exclusively. a. Structure-Activity Relations. The heterolysis is the reaction in which the actual electron transfer between the pyrimidine system (the electron donor) and the nitrobenzene (the electron acceptor) takes place ("inner-sphere" electron transfer). The rate of this step should therefore be sensitive to and thereby indicative of the electron-donating ability of the pyrimidine and of the electron-accepting power of the nitrobenzene. This expectation is borne out by the data collected in Tables I-IV. Concerning the effect of the nitrobenzene, the khsvalues increase with increasing electron-withdrawing power of the substituent. A Hammett relation is obeyed, as shown for the 5-H-6-MeU' system, with a slope corresponding to p = 1.5 (Figure 4). Correlating the khsvalues with the pK values33of the nitrobenzene radical anions (=Bronsted plot) also yields a straight line, with the same (but inverted) slope giving a Bronsted a = -1.5 (Figure 4). The high correlation coefficient (0.98) in the Bronsted plot indicates that the leaving group abilities of the nitrobenzene radical anions in the heterolysis reaction, as expressed in terms of khs, are well described by their pK values. There is an at least equally good criterion for predicting the rate constants for heterolysis, and that is the one-electron redox potential34E: of the nitrobenzene. In Figure 5 is shown for the 6-Me-DHU system the dependence ( r = 0.99) of log khson E: (Marcus plot). The slope corresponds to 6.2 V-' which may be compared with 6.9 V-I determined36for the heterolysis of nitroxyls produced by addition of CH,CHOH to nitrobenzenes9 and with 7-1 1 V-' p r e d i ~ t e dfor ~ ~an , ~outer-sphere ~ electron transfer. The Marcus slopes for the heterolyses of the nitroxyls from 5-OH-6MeU' and 5-OH-6-Me-i-C' are ~ 6 . and 8 6.1, V-I, respectively. Concerning the influence of the nature of the pyrimidine radical on the heterolysis rate constants, it is obvious from Tables I-IV that the khsvalues are larger for the 5-hydroxy-6-Me-iso-cytosine than for the 5-hydroxy-6-Me-uracil system. This indicates that the former is a stronger reductant than the latter. The same conclusion was reached from the rate constants for reaction k,, and the explanation is again the same (see section IC). On the (33) Reference 6. Griinbein, W.; Fojtik, A,; Henglein, A. 2.Nuturforsch. 1969, 24, 1336. Griinbein, W.; Henglein, A. Ber. Bunsen-Ges. Phys. Chem. 1969, 73, 376. (34) For a collection of one-electron redox potentials in aqueous solution see ref 35. (35) Steenken, S. Landolt-Bdmsrein 1985, 13e, 147. (36) Using the same data set of the redox potentials as that used for 5-H-6-MeU'. (37) Marcus, R. A. Annu. Rev. Phys. Chem. 1964, 15, 155.
I
- f
slope = 6.2 V-'
-/
V
-07
-06
-05
-0L
-03
-02
E I V vs N H E
Figure 5. Marcus plot for the heterolysis of the nitroxyls from 5-H-6MeU' and para-substituted nitrobenzenes. The E: (one-electron reduction potentials at pH 7 ) are from ref 35 and 43.
basis of the khsvalues, 5-H-6-MeU' is the most powerful reducing system of the three. The khs values are 10-30 times larger than those for 5-OH-6-MeU'. For an obvious explanation for the difference between the systems one can invoke the electronwithdrawing property (-I effect) of the O H group at C-5 which is adjacent to the reaction site at C-6. In this respect it is interesting to compare the activation parameters for the heterolyses for the two systems (Tables I and 111): with the activation enthalpies being the same, the larger rate constants for 5-H-6-MeU' are entirely due to the more positive activation entropies as compared to 5-OH-6-MeU'. The higher entropies for 5-H-6MeU' probably indicatelo less charge density, Le., more charge delocalization (to C-5) in the transition state of the heterolysis. b. Solvent Kinetic Isotope Effects and Activation Parameters. The heterolysis reaction was further characterized by determining its rate constant as a function of temperature (in the range 0-80') and of solvent ( H 2 0 was replaced by 99% D20). In most cases excellent Arrhenius plots (see Figure 2) were obtained ( r I0.99), from which the activation parameters with the indicated error limits as listed in Tables I-IV were obtained. As seen in the tables, for the three pyrimidine systems there is very little variation in the activation enthalpies. They all fall in the range 30-40 kJ mol-'. The differences between the individual khs values are thus essentially caused by differences between the corresponding activation entropies. This does not only refer to the effect of the structure of the pyrimidine radical (the electron donor) but also to that of the nitrobenzene (the electron acceptor). Isokinetic Hammett plots (Le., plotting AH* vs AS* for a series of nitrobenzenes) have slopes corresponding to isokinetic temperatures between 206 and 267 K, indicating entropy control of the reaction. Compensatory effects are visible with respect to the nature of the solvent: In the case of 6-MeU and 6-Me-i-C the relatively low values of 1.2-1.4 for the solvent kinetic isotope effect khs (H20)/khs(D20)result from the AH* and A S * values being moved in the same direction. The rateenhancing effect of smaller AH* in D 2 0 is thereby compensated by the rate-decreasing effect of the more negative AS*. As compared to 5-OH-6-Me-U', 5-H-6-MeU' is less susceptible to solvent-induced compensatory effects on khs. The khs (H20)/kh,(D20)value of 1.7-2.3 (Table 111) is similar .to that (2.2)9 found for the heterolysis of the nitroxyl from CH3CHOH and nitrobenzenes, whereas that (1.2-1.3) for the 5-hydroxy-6methyluracil system is comparable to that9 (1.5) for the heterolysis of nitroxyl from HOCH2CHOH and 4-nitrobenzonitrile. The couples CH3CHOH/5-H-6-MeU' and HOCH,CHOH/S-OH6-MeU' differ by the substituent (H or OH) at C,. For the former couple sufficient data is available9 to test for a free energy relationship between the hetefolysis reactions with different nitrobenzenes. The AG*(CH3CHOH) vs AGt(S-H-6-MeU') plot is shown in Figure 6 (r = 0.97). The slope of this plot, which should be equal to the ratio of the Hammett p values for the two types
J. Phys. Chem. 1988, 92, 118-122
118
525 c
-
L9.5
E"
duced on hydration of the (incipient) C-6 carbocation. An analogous effect has been observed39in the case of trialkoxymethyl carbocations. The radical from 2-amino-4,6-dimethylpyrimidine appears to react with nitrobenzenes by electron transfer: no evidence for nitroxyl-type adducts was found.
7
I I
r-l
Summary and Conclusions
37 5 L50
1
I
I
I
L71
192
513
53L
555
A G * I C H 3 E H O H ) I k l mol-' Figure 6. Correlation of free energies of activation for heterolysis of the nitroxyls from 5-H-6-MeU' with those (ref 9) from CH,CHOH.
of heterolysis reaction, results as 1 .O, in agreement with the individually determined p values (both 1.5). This is additional evidence for the close resemblance of the CH3CHOH and 5-H6-Me-U' systems. In contrast, when AC* values for the heterolysis of the nitroxyls from 5-OH-6-MeU' or 5-OH-6-Me-i-C' are plotted versus those for the nitroxyls from CH3CHOH, the correlation coefficients are only 0.93 and 0.92, respectively, which indicates that CH3CHOH is not a good model for the 5 hydroxy-6-yl radicals. That these belong to a class of their own is shown not only by their similar solvent kinetic isotope effect (1.2-1.4) but also by the good correlation (r = 0.98) between their corresponding AG* values. As seen in Table IV, reactions of 5-hydroxy-6-methyl-6-yl radicals from two additional pyrimidines were studied. As compared to that from 6-methyluracil, the radical from 1,3,6-trimethyluracil shows a higher reactivity with both 4-NAP and 4-NBN, as judged by both k , and khs. This demonstrates the increase in electron density resulting from the additional methyl groups at N-1 and N-3. Of particular interest are the strongly negative activation entropies. Since there is no proton at N-1 whose transfer, in the transition state, to adjacent water molecules can lead to their freezing,38the negative values probably originate from immobilization of H 2 0 molecules caused by the ions pro(38) Hydration of a proton by four water molecules leads to an entropy loss of 105 J mol-' K-' (cf. Frost, A. A,; Pearson, R. G. Kinerics and Mechanism, Wiley: New York, 1961; Buschmann, H.-J.; Dutkiewicz, E.: Knoche. W. Ber. Bunsen-Ges. Phys. Chem. 1982, 86, 129
It has been shown that the O H or H adducts to the 5-position of 6-methyluracil and of 6-methylisocytosine react with nitrobenzenes to give partly electron-transfer products (radical anions) and partly nitroxyl radicals (via addition). The nitroxyl radicals undergo a unimolecular heterolysis reaction that gives additional radical anion. The heterolysis, which is analogous to solvolysis of nonradical tetrahedral intermediate^,^^ is essentially entropy controlled. The addition/elimination sequence4' is an example for i n n e r - ~ p h e r eelectron ~~ transfer. The rate constants k, for reaction of the pyrimidin-6-yl radicals and the rate constants khsand the activation parameters for the heterolysis can be used to scale the reducing properties of these radicals. On this basis, the 5-hydroxy-6-methyl-6-yl radicals (i.e., the O H adducts) are considerably weaker reductants than the corresponding 5-hydroradicals (i.e., the H a d d ~ c t s ' ~in) , agreement with earlier results.I2 The cytosin-6-yl is a more potent electron donor than that from uracil. As compared to simple aliphatic radicals.with known redox potential,345-H-6-MeU' is very. similar to CH3CHOH, 5-OH-6-MeU' is comparable to HOCH2CHOH, and the O H adduct to uracil itself, 5-hydroxyuracil-6-y1,'* resembles C H 2 0 H . Acknowledgment. V.J. thanks the University Grants Commission, New Delhi, for providing travel grants and the MaxPlanck-Institut for supporting a 4-month stay at Miilheim. Registry No. 1, 6214-20-6;2, 100-25-4;3, 619-72-7;4, 6325-93-5;5 , 100-19-6; 6 , 619-50-1; 7, 619-80-7; 8, 100-00-5; 9, 30904-42-8; 10, 1129-37-9; 11, 2906-29-8; 12, 619-73-8; 13, 98-95-3; 14, 99-99-0; 15, 100-17-4;16, 100-01-6;D2,7782-39-0; 5-OH-6-MeU.,77802-11-0; 5OH-6-Me-i-C., 11 1349-91-8; 5-H2-6-Me-U.,20670-30-8; 5-0H-1,3,6Me3U., 1 1 1 349-92-9; 2-amino-5-hydroxy-4,6-dimethylpyrimidin-6-y1 radical, 1 1 1349-93-0. (39) Steenken, S.; Buschek, J.; McClelland, R. A. 1.Am. Chem. SOC.1986, 108, 2808.
(40) For reviews on tetrahedral intermediates see, e.g., (a) Cordes, E. H. Prog. Phys. Org. Chem. 1967,4, 1 . (b) Fife, T. H. Act. Chem. Res. 1972, 5 , 264. (c) McClelland, R. A,; Santry, L. J. Ace. Chem. Res. 1983, 16, 394. (d) Capon, B.; Dosunmu, M. I.; Sanchez, M. N. M. Adc. Phys. Org. Chem. 1985, 21, 37. (41) Steenken, S. J . Chem. SOC.,Faraday Trans. I 1987, 83, 113 (42) cf. Eberson, L. Adu. Phys. Org. Chem. 1982, 18, 79. (43) Steenken, S., unpublished material.
Rate Constants for Oxidation Reactions by Radical Cations from Methyl Iodide Hari Mohan and Klaus-Dieter Asmus* Hahn-Meitner-Institut Berlin GmbH, Bereich Strahlenchemie, Glienicker Str. 100, 0-1000 Berlin 39, Federal Republic of Germany (Received: April 2, 1987) Radical cations from methyl iodide, CH31'+, and (CH31:.ICH3)+ are shown to be excellent oxidants with a one-electron redox potential presumably 3 +2 V. Absolute rate constants in the order of lo9 M-' s-' have been determined for their reactions with various organic sulfides, disulfides, thiols, phenothiazines, and inorganic metal and halide ions. A similarly high reactivity has also been found for the hydroxyl radical adduct to methyl iodide, CH31(OH)'. The results are discussed in view of the electronic and steric structure of these oxidizing radical species and the substrates to be oxidized. nected in the equilibrium
Introduction
One-electron oxidation of alkyl iodides leads to two different kinds of radical cations.' They have been suggested to be con( 1 ) Mohan, H.; Asmus, K.-D. J . Chem. Soc., Perkin Trans. 2, in press.
0022-3654/88/2092-0118$01.50/0
RI"
+ RI z(RI:.IR)+
(1)
i.e., their actual yield is a function of the RI concentration and the equilibrium constant. For the methylated species (R = CH3)
0 1988 American Chemical Society
