6286
J. Phys. Chem. 1984,88,6286-6290
While the activation energies and polarizabilities do follow an empirical correlation, a more fundamental relationship appears when the energetics of the reactive process are considered at a molecular level. As the reactants, R and XY, approach to pass over an energy barrier defining the transition state, a new bond between the radical and molecule is formed: R-XY. Electronic charge from XY can be envisioned to move between R and X, creating, for a time, a charge imbalance among the atoms -R-(XY)+ or -R-X+-Y The ability to stabilize the initial charge imbalance increases-that is, the transition state complex is stabilized-with the increasing electron affinity of R and the decreasing ionization potential of XY (particularly of X). The dependence of the activation energy on the electron affinities of the terminal radicals or atoms has been noted by Benson.' Since the correlation depends more on the electron affinity and the ionization potential than on the overall reaction exothermicity, as is evidenced by the 0 and O H F2 reactions, the reaction barrier likely occurs before the X-Y bond is significantly altered. This agrees well with the inference from molecular beams experiments of a stable RXY intermediate, in which the X-Y bond is not yet broken. The rapidity of the H X, reactions can be explained in part by their different mechanisms: the absence of a stable intermediate means that the HX bond is formed and X-X bond broken to a much larger extent in the transition state, overcoming the dependence on the electron affinity of the radical. It is unlikely that a temperature-dependent study will be carried out for reaction 3, due to the equilibrium of Br2, C4, and BrCl that complicates the analysis. In light of the evidence that the ionization potential is a factor determining the activation energy, and considering the large magnitude of k2,we hypothesize that E, = 0, where E, is the activation energy of reaction i. If the frequency factors, A,, in the Arrhenius expressions, A , exp(-E,/RT), for reactions 2 and 3 are equal, the difference between k2 and k3 can be attributed to E3. On this basis we suggest that
+
+
E3 = 2.1 kcal mol-'. If the same conditions apply to reaction 1, then ,E, = 3.4 kcal mol-'. Wb are interested in extending our work on OH-halogen reactiohs to include I*, IC1, and IBr. We expect these reactions to be at least as rapid as OH + Br,. The electron affinity of SH is larger than that of either OH or S; provided that the halogen reactions with SH are exothermic, we expect that the as yet unexplored SH-halogen reactions will test the effects of a radical's electron affinity on its reactivity. Acknowledgment. We thank Dr. Glenn D. Graham for his help in the early phases of this work and Dr. James J. Schwab for providing us with a chlorine lamp. This work has been supported by the National Science Foundation under Grant ATM-8115112,
Appendix Simulations are performed by using the Runge-Kutta algorithm.45 The substantial reaction set includes 57 bimolecular reactions-representing the radical-radical and radical-molecular reactions of the various species present (including H, H,, OH, C1, C10, Cl,, HOCl, Br, BrO, Br2, HBr, HOBr, NO, and NO,); 15 termolecular reactions-representing various radical recombination steps, at the low-pressure limit-forming species such as H N 0 3 , ClNO, C1N02, ClN03, BrNO, BrNO,, and BrNO,; and 5 unimolecular reactions-accobnting for the loss of radicals at the reactor wall. The rate constants of these reactions are largely obtained from ref 10. Registry No. OH, 3352-57-6; C12,7782-50-5; Br2, 7726-95-6; BrC1, 13863-41-7.
Supplementary Material Available: A description of the computational scheme employed and a listing of all the reactions and rate constants used in it (5 pages). Ordering information is given on any current masthead page. (45) Milne, W. E. 'Numerical Solution of Differential Equations"; Dover: New York,1970.
Adduct Formation and Absolute Rate Constants in the Displacement Reaction of Thiyi Radicals with Dlsulfides M. BonifaEiC and K.-D. Asmus* Hahn-Meitner-Institut fur Kernforschung Berlin, Bereich Strahlenchemie, D- 1000 West Berlin 39, Federal Republic of Germany (Received: June 5, 1984)
The displacement reaction of thiyl radicals with disulfides is shown to proceed via a transient adduct radical by using time-resolved pulse radiolysis techniques. The relatively long-lived adduct ( t l l z > 100 ps) formed in the forward reaction of the equilibrium RS. RSSR * (RSS(R)SR]-is suggested to be a sulfuranyl radical with the unpaired electron located in an antibonding o* orbital within a trisulfide bridge. These species exhibit optical absorptions in the UV, e.g., A,, = 375 10 nm and e = (3.4 f 0.4) X lo3 M-' cm-l for the all-methylated radical, and have been identified in aqueous and methanolic solutions. Equilibrium constants of K = 180 f 30 and 60 & 20 M-' have been evaluated for the systems with R = CH3 and cysteine residue, respectively, via two different methods. The corresponding forwdrd reactions occur with k(RS- + RSSR) = 3.8 X lo6 and 7.7 X lo5 M-'s-I, respectively.
+
*
Introduction Chemical systems containing different disulfides or disulfidethiol mixtures are known to undergo relatively rapid exchange of thiyl groups resulting in the formation of mixed disulfides',2 as outlined in the general equilibria 1 and 2. Since disulfides
+ R2SSR2* 2R1SSRZ + R'SH * R'SH + R'SSR'
R'SSRl R'SSR'
reactions have always found particular interest in biological science^.^ It is now well established that these processes involve thiyl radicals which act via an overall substitution mechanism, e.g.
(1)
(1) Gupta, D.; Knight, A. R. Can. J . Chem. 1980, 58, 1350. (2) Owen, T. C.; Ellis, D. R. Radiat. Res. 1973,53,24 and references cited
(2)
therein. (3) Friedman, M. "The Chemistry and Biochemistry of the Sulfhydryl Group in Amino Acids, Peptides and Proteins"; Pergamon Press: Oxford, 1973.
and thiols serve important biochemical functions, these exchange 0022-3654/84/2088-6286$01.50/0
0 1984 American Chemical Society
The Journal of Physical Chemistry, Vol. 88, No. 25, 1984 6287
Reaction of Thiyl Radicals with Disulfides R’SSR’
+ RZS*
-+
R’SSR’
+ R’.
(3)
Accordingly, these exchange reactions could be studied particularly well by using photolysis’ and radiolysis,2 both of which are convenient methods of generating free radicals, although the mere presence of molecular oxygen in the disulfide/thiol-containing systems is often sufficient for radical f ~ r m a t i o n . ~As may be anticipated, the exchange reactions occur irrespective of the nature of the solvent, e.g., in aqueous, or hydrocarbon solutions5or within neat disulfides and disulfide-thiol mixtures.l Although reaction 3 may be considered a straightforward one-step displacement reaction, the exact mechanism is still under discussion. On the basis of several arguments Pryor and Smith6 have, in fact, suggested that this reaction may proceed via an addition-elimination sequence, without being able, however, to provide positive experimental evidence for a transient intermediate. This idea is nevertheless most reasonable in view of the increasing frequency with which radical adducts in general are being identified particularly with time-resolved spectroscopic method^.^ In a most recent pulse radiolysis investigationa on the reaction of disulfide radical cations, RSSR’., with thiolates, RS-,we found the first direct evidence for a transient (RSS(R)SR]- radical exaround 380 nm. hibiting an optical absorption band with A, Such a radical may also be viewed as a thiyl radical adduct to a disulfide molecule and should therefore be expected as an intermediate also in reaction 3. Hardly any data were available up to now on absolute rate constants for these displacement and possible addition processes. An estimate of ca. 2 X lo6 M-’ s-’ has been made by Pryorg for the general displacement reaction 3 in analogy to the reaction of a polysulfenyl radical with molecular sulfur, S8,and k < lo7 M-’ s-l has been found by Hoffman and Hayonlo for the reaction of the penicillamine thiyl radical with the disulfide cystamine. The present investigation is concerned with a pulse radiolysis study on the reaction of thiyl radicals with disulfides and will provide direct evidence for an intermediate adduct radical as well as absolute rate constants of the elementary reactions involved.
Experimental Section All chemicals were of the purest grade commercially available (Merck, Fluka, Aldrich) and used as received. Solutions were prepared from deionized Millipore-filtered water the quality of which corresponds to triply distilled water. The pH of the solutions was generally adjusted with N a O H or HC104 solutions. Deoxygenation was achieved by bubbling with N, for ca. 1 h per dm3 of solution. For the study of -OH radical induced processes the solutions were subsequently saturated with N 2 0 (which converts hydrated electrons via N 2 0 + eaq -OH + OH- + N,). Generation of radicals was achieved by exposing the aqueous solutions to short pulses (typically 0.5-6-1s duration) of highenergy electrons from a 1.55-MeV Van de Graaff accelerator. Dosimetry was based on the .OH radical induced oxidation of thiocyanate to the (SCN),. radical anion.” The absorbed doses per pulse were generally in the range of 1-10 Gy (1 Gy = 1 J kg-’ = 100 rd) yielding an .OH radical concentration of (0.6-6) X 10” M in the N,O-saturated systems. In N,-bubbled systems the main radical species available for reaction with substrates are -OHand eq- both formed at half these concentrations. Calculation of the above concentrations is based on G(.OH) = G(e,,-) = 3
-
(4) Fava, A.; Reichenbach, G.; Peron, U. J . Am. Chem. SOC.1967, 89, 6696. ( 5 ) Stone, J. A.; Esser, J. Can. J . Chem. 1973, 52, 1253. (6) Pryor, W. A.; Smith, K. J. Am. Chem. SOC.1970, 92, 2731. (7) (a) Asmus, K.-D.; Gobl, M.; Hiller, K.-0.; Mahling, S.; Monig, J. J . Chem. SOC., Perkin Trans. 2, in press. (b) Monig, J.; Gobl, M.; Asmus, K.-D. J . Chem. SOC.,Perkin Trans. 2, in press. (8) BonifaEiE, M.; Asmus, K.-D. Int. J . Radial. Biol. 1984, 46, 35. (9) Pryor, W. “Mechanisms of Sulfur Reactions”; McGraw-Hill: New York, 1962; p 42. (10) Hoffman, M. 2.;Hayon, E. J . Phys. Chem. 1973, 77, 990. (11) Adams, G. E.; Boag, J. W.; Currant, J.; Michael, B. D. “Pulse Radiolysis”; Ebert, M., Keene, J. P., Swallow, A. J., Baxendale, J. H., Eds.; Academic Press: London, 1965; p 117.
8
w
6
X
L3
x 4 m
9 2 0
I
300
I
I
I
340
A,
I
I
380 nm
I
I
420
I
460
Figure 1. Optical absorption spectrum obtained in pulse-irradiated, deoxygenated, aqueous solution containing 2 X lo-* M CH3SSCH3 and 2 M (CH3)2CHOH pH 4.6 measured ca. 50 ps after a 0.3-ps pulse. Insert: Optical absorption as a function of time recorded at 380 nm.
species per 100-eV absorbed energy (equivalent to ca. 3 X mol J-l) in the radiolysis of water. The transient species and their kinetics were directly observed by recording the optical densities of the pulsed solutions as a function of wavelength and time. Details of the pulse radiolysis technique and the evaluation of data from the individual signals have already been described.l2-l4 The experimental error limit of all pulse radiolysis data is generally estimated to f10% unless specifically noted. All experiments were carried out at room temperature.
Results and Discussion Formation of a Transient Adduct Radical. The simplest reaction according to eq 3, which could possibly provide an adduct radical intermediate, namely CH3S. + CH3SSCH3
-+
[adduct].
-
products
(4)
was studied by pulse radiolysis of various solutions containing dimethyl disulfide. In deaerated aqueous systems containing 2 X lo-’ M CH3SSCH3 plus 2 M (CH3)*CHOH at pH 4.6, for example, a strong transient optical absorption is observed, the spectrum of which is shown in Figure 1. It exhibits a maximum a t A,, = 375 f 10 nm and grows exponentially with a half-life of 10 I S . The corresponding absorption-time curve is given in the insert of Figure 1. The underlying primary reactions in such solutions are scavenging of .OH radicals and Ha atoms (the latter are formed with G = 0.6) by the alcohol, yielding mainly a-hydroxyl radicals (with 85% efficiency)15 via .OH/H.
+ (CH3)ZCHOH
-
(CH3)zCOH
+ H20/H2
(5)
The hydrated electrons react with the disulfide to form a threeelectron-bonded radical anion16J7
-
eaq- + CH3SSCH3
(CH3S:.SCH3)-
(6)
In the absence of thiolate anions which stabilize this anion radical in the equilibrium
(12) Matheson, M. S.; Dorfman, L. M. “Pulse Radiolysis”;M. I. T. Press: Cambridge, MA, 1969. (13) Baxendale, J. H., Busi, F., Eds. “The Study of Fast Processes and Transient Species by Electron Pulse Radiolysis”; Reidel: Dordrecht, 1982; NATO Advanced Study Institute Series. (14) Asmus, K.-D. “Methods in Enzymology”;Packer, L., Ed.; Academic Press: New York, 1984; p 167. (15) Asmus, K.-D.; Mockel, H.; Henglein, A. J . Phys. Chem. 1973, 77, 1218. (16) Adams, G. E.; McNaughton, G. S.; Michael, B. D. “The Chemistry of Ionization and Excitation”; Johnson, G. R. A,, Scholes, G., Eds.; Taylor and Francis: London, 1967; p 281. (17) Gobl, M.; BonifaEiE, M.; Asmus, K.-D. J . Am. Chem. SOC.,in press.
6288
The Journal of Physical Chemistry, Vol. 88, No. 25, 1984
BonifaEiC and Asmus
it dissociates practically instantaneously to the free C H 3 S thiyl radical, while the thiolate is neutralized to CH3SH.'6,18 All these reactions are completed within less than 1 ps.19820 Furthermore, none of the radical species formed in reactions 5-7 exhibits an absorption with A,, = 375 nm; Le., for both reasons the spectrum shown in Figure 1 must be attributed to yet another species. Formation of the new transient requires the presence of both thiyl radicals and disulfide. Thus, no 375-nm absorption is observable in deaerated solution of disulfide, alcohol, and acetone, Le., where all eaq-are eventually converted to (CH3)2COH(via eaq- CH3COCH3 H + / H 2 0 ) rather than to C H 3 S radicals via reaqtions 6 and 7. (This result, incidentally, shows that (CH3)2COHradicals, which are known to be quite good reductants, are not able to transfer an electron to dimethyl disu!fide; only lipoic acid and its derivatives can be reduced by (CH3)2COH radicals21*22 but even this may possibly not be a straightforward electron transfer.) The same negative result is obtained if the thiyl radicals are formed from reaction of the corresponding thiol with -OH or (CH3)2COH and no disulfide is present in the solution. Furthermore, in our systems the rate of formation of the 375-nm absorption increases linearly with increasing disulfide concentration. All these considerations and experimental findings identify this new species as an immediate product of the thiyl radical reaction with the disulfide, and we assign it to the radical adduct formed in the reaction CH3S* CH3SSCH3 {CH,SS(CH3)SCH3}. (8)
urable yield of the adduct is however lower than in the aqueous system, and at M CH3SSCH3amounts only to about onequarter of the yield in the aqueous solution at the same disulfide concentration. One of the reasons (in addition to possible kinetic differences) is considered to be the generally lower yield of free solvated electrons in less polar media.13 Similar results as for CH3SSCH3 have been obtained with pulse-irradiated solutions of various other disulfides, e.g., (HOOCCH2CH2S)2,penicillamine disulfide (PenSSPen), cystine (CysSSCys), and cystamine (CyaSSCya). In the case of the latter a 380-nm adduct absorption was observable only at high pH, i.e., 59.5, and at a yield considerably lower than for the other disulfides. No adduct was observed from the reactions C2HSS. C2HSSSC2H, and (CH3)2CHS. + (CH3)2CHSSCH(CH3)2in neutral solutions containing diethyl and diisopropyl disulfide, respectively, in either aqueous or methanolic solutions. We presume comparatively slower kinetics to be the main reason that no adducts can be detected in these latter systems. Addition of even small amounts of thiols to the disulfide solutions results in an increase of the adduct radical yield by a factor of about 2. For example, G E = 1650 (at 380 nm) has been measured for pulseirradiated aqueous solutions (pH 7) containing M (HOOCCH2CH2S)2and 2 M propan-2-01, In the 2X M HOOCCHzCH2SHGE= 3550 presence of additional 1 X was measured ( G = species per 100 eV of absorbed energy, E in M-' cm-I). This finding is quantitatively explained by the formation of additional thiyl radicals in the reaction
Two other alternative radical structures, which have not yet been excluded as possible intermediates, would be a (CH3SSCH3)+.radical anion and a CH3SS. perthiyl radical. The former could be envisaged because of the known, although relatively weak, oxidizing properties of thiyl radicals.23 The (CH3SSCH3)+.radical cation absorbs, however, at 440 nm24and must therefore be rejected. Arguing against the perthiyl radical is more difficult since corresponding species with Amx around 380 nm have been suggested from pulse radiolysis studies on the oxidation of various amino-group-containing disulfides, e.g., peni~illamine.~~ Perthiyl-derived combination products, namely, trisulfides, have also been identified in y-irradiated solutions of some of these compounds.26 In the oxidation of simple aliphatic disulfides, RSSR, such trisulfide products have, however, only been found for R = tert-butyl and not for methyl and other alkyl groups.27 Perthiyl radicals with absorptions around 380 nm have also been suggested as being formed in direct photolysis of various disulfides.2E But again no such species was detectable in the case of dimethyl disulfide. All this clearly speaks against a CH3SS. radical and we are therefore indeed left with a radical adduct as the only reasonable cause of our 375-nm absorption. The same transient absorption spectrum as shown in Figure 1 is obtained irrespective of pH (Le., 5 3 ) or the nature of the alcohol used as an .OH/H. scavenger in the aqueous solution. Since reactions analogous to reactions 6-8 are also expected to occur in other solvents, it is not surprising that the 375-nm adduct is formed, for example, also in methanol as solvent. The meas-
(CH3),C0H
+
+
+
+
(18) Hoffman, M. Z.; Hayon, E. J . Am. Chem. SOC.1972 94, 7950. (19) DraganiE, I. G.; DraganiE, Z. D. "The Radiation Chemistry of Water"; Academic Press: New York, 1971. (20) Dissociation of the (CH,S.:SCH,)- anion radical proceeds in aqueous solution at pH 1 1 with k = 5.2 X lo6 s-l. Schenck, H.-P. Diploma Thesis, Technical University, Berlin, 1982. Schenck, H.-P.; Asmus, K.-D., unpublished results. (21) Willson, R. L.J . Chem. SOC.D 1970, 1425. (22) Wu, Z.; Ahmad, R.; Armstrong, D. A. Radiat. Phys. Chem. 1984, *>
*e.
LJ, LJI.
(23) Forni, L. G.; Monig, J.; Mora-Arellano, V. 0.; Willson, R. L. J . Chem. Soc., Perkin Trans. 2 1983, 961. (24) BonifaEiE, M.; Schafer, K.; Mijckel, H.; Asmus, K.-D. J. Phys. Chem. 1975, 79, 1496. (25) (a) Elliot, A. J.; McEachern, R. J.; Armstrong, D. A. J. Phys. Chem. 1981,85,68. (b) Wu, Z.; Back, T. G.; Ahmad, R.; Yamdagni, R.; Armstrong, D. A. J. Phys. Chem. 1982,86, 4417. (26) Purdie, J. W. Can. J . Chem. 1969, 47, 1029, 1037. (27) Weiss, J. Ph.D. Thesis, Technical University, Berlin, 1982, D83. (28) Morine, G. H.; Kuntz, R. R. Photochem. Photobiol. 1981, 33, 1 .
+
+ HOOCCH2CH2SH
-+
HOOCCH2CH2S.
(CH3)2CHOH (9)
This reaction is commonly known as a "repair" r e a c t i ~ n ~ ~ . ~ ~ -C*
I + I
RSH
-
I I
-C-H
t RS.
(10)
which for (CH3)2COH occurs with rate constants of (2-6) X loE M-' s-1.29,31 It is, of course, not required that the thiol added is complementary to the disulfide. Adduct formation has thus also been observed in N20-saturated solutions containing CH3SSCH3 as disulfide and either cysteine (CysSH), penicillamine (PenSH), or cysteamine (CyaSH) as thiol. The absorptions of the transient adduct radicals are very similar and peak at 375-380 11311.~~
As shown in our previous publicationE it is also possible to form the adduct radical as a result of disulfide radical cation-thiolate neutralization in the general reaction sequence
(to some extent possibly even via direct association of the thiolate and disulfide radical cation8). Adduct radicals with A,, = 380-390 nm have been found, for example, in solutions containing cysteamine (CyaS-) or penicillamine (Pens-) as thiolate and CH3SSCH3 or lipoic acid as disulfide. In this respect it was interesting to note that disulfide radical cations could only oxidize thiolate and not the undissociated thioL8 Another radical which is able to oxidize thiolate is the (SCN),-. radical anion33 (SCN)2-* + RS-
-
RS.
+ 2SCN-
(13)
(29) Adams, G. E.; McNaughton, G. S.; Michael, B. D. Trans. Faraday SOC.1968, 64, 902.
(30) Redpath, J. L. Radiat. Res. 1973, 54, 364. (31) Wolfenden, B. S.; Willson, R. L.J. Chem. SOC.,Perkin Trans. 2 1982, 805. (32) The optical transitions of (R2S:.SR2)+, (RS.:SR)- and other threeelectron-bonded, two-center species have been found to depend on the nature of the substituents R," with electron induction resulting in a bond weakening and red shift in X., Any corresponding interpretation of the present absorptions is, however, not warranted since owing to the various equilibria involved in the mixed systems several individual spectra may superimpose. In addition the overall electronic situation is quite different in the trisulfide type radical species.
The Journal of Physical Chemistry, Vol. 88, No. 25, 1984 6289
Reaction of Thiyl Radicals with Disulfides 10
t
t
9t
7
0
15
3
s
C
0'
I
I
# I 1 4 1 1 1
I
I
1 1 1 1 1 1
I , , ,
I
-
10-~ lo-* 10-1 [RSSR], M Figure 2. Yields of adduct radical in terms of Gc (at 380 nm) as a function of disulfide concentration in pulse-irradiated, deoxygenated, aqueous solutions containing 2-5 M (CH,),CHOH plus CH3SSCH3, (neutral) (O),or cystine, pH 10 ( 0 ) . 10-4
The thiyl radical could then add to a disulfide to form the adduct radical via reaction 12. (Direct oxidation of a disulfide by (SCN ) p does not take place.) As an example, N20-saturated aqueous M CH3SSCH3,2 X M penisolutions containing 2 X cillamine, and lo-' M SCN- at pH 9.6 were studied by means of pulse radiolysis. Upon irradiation hydrated electrons were converted by N 2 0 into .OH, and all .OH by reaction with SCNthen into (SCN)1., followed finally by reactions 13 and 12. The adduct radical yield generated in the reaction sequence amounts to GE= 3300 M-' cm-I, which is in good agreement with GE= 3000 M-I cm-I (ref 8) obtained in a corresponding solution, where the thiolate was oxidized by (CH3SSCH3)+.radical cations instead Of by (SCN)2-*. Oxidation of undissociated thiol, RSH, by ( S C N ) p is much slower.33 In solutions of pH < pK(RSH) thiyl radicals may, however, conveniently be generated via direct reaction with *OH radicals RSH *OH RS. HzO (14)
+
-
+
For comparison, the adduct radical yield (measured at 380 nm) in pulse-irradiated, N,O-saturated solutions containing 2 X lo-' M PenSH and 2 X M CH3SSCH3at pH 5 amounted to Ge = 3300 M-' cm-l. This is practically the same yield as in the above-mentioned solutions, where oxidation was initiated by (SCN)2-. or (CH3SSCH3)+-instead of by .OH radicals. In all solutions containing thiolate ions a competing process for adduct formation is in principle complexation of the thiyl radical to the (RS:.SR)- radical anion (e.g., reverse reaction of equilibrium 7). It has been shown, however, that this latter route is of significanceat the applied RS-concentration only for a limited number of cases, Le., when the disulfide radical anion is particularly stable, as for cystamine and lipoic acid.8*10*16 The kinetic stability of all adduct radicals is rather high and typically greater than 100 ps under our pulse radiolysis conditions. Measured first half-lives are, for example, 250 and 440 p s for (CH3SS(CH3)SCH3}.and (CysSS(Cys)SCys}., respectively (applied dose: 2 Gy per pulse). The decay of the species occurred almost exponentially but second-order contributions were indicated by a slight dose dependence. N o attempt has, however, been made at this stage to analyze the decay kinetics more quantitatively. Yields and Formation Kinetics. The yield of the (RSS(R)SR)* adduct radical is strongly dependent on the disulfide concentration. Figure 2 shows, for example, the measured Gc at 380 nm as a function of disulfide concentration in pulse-irradiated, deoxy~~~~~
(33) Adams, G. E.; Aldrich, J . E.; Bisby, R. H.; Cundall, R. B.; Redpath, J. L.; Willson, R. L. Radiat. Res. 1972, 49, 218.
5
[ RSSRl ,
1V2M
Figure 3. Plots of first-order rate constants k = In 2/t,12 for the formation of the adduct radical absorption at 380 nm vs. disulfide concentration. Solutions and symbols as for Figure 2.
genated, aqueous solutions of up to 5 M propan-2-01 (usually 2 M) and various concentrations of either dimethyl disulfide (pH neutral) or cystine ( p H 10) (ensuring always [(CH3),CHOH] / [RSSR] 1 100). The S-shaped curves obtained suggest that the radical adduct formation may be a reversible process and reaction 12 in its general form should rather be formulated as an equilibrium RS.
+ RSSR
(RSS(R)SR)-
(15)
For dimethyl disulfide the curve levels off at [CH3SSCH3]2 2 X M with G E= 9400 M-' cm-I. Assuming that the radical yield formed via reactions 6, 7, and 15 is equal to the initial yield of hydrated electrons, Le., G = 2.8, the extinction coefficient of the (CH3SS(CH3)SCH3].radical is calculated to be 3360 M-' cm-' . For the cystine system the corresponding yield-concentration plot does not lead to a plateau value in the experimentally accessible concentration range. This finds its plausible explanation in a different stability constant of the {CysSS(Cys)SCys). radical adduct as indicated by the shift of the corresponding curve to higher concentrations in comparison with the ICH3SS(CH3)SCH3)radical curve. The half-values of the two curves in Figure 2 are located at 5.2 X M CH3SSCH3and 1.4 X M CysSSCys (based on the same maximum GEas in the dimethyl disulfide system). Assuming that these curves truly reflect only equilibrium 15, stability constants of K I 5= (1.9 f 0.2) X lo2 M-' and (0.7 A 0.2) X lo2 M-' are derived for the two corresponding adduct radicals, respectively. It has not been attempted to evaluate further stability constants in particular for the mixed (RISS(R1)SRZ). radicals in this investigation. From the present result it is evident, however, that the respective stability constants are likely to vary to an appreciable extent. Therefore, it is not feasible to compare numerically the measured GEvalues for the various radical adducts, even at a given disulfide concentration. An alternative method of determining equilibrium constants is analysis of the associated kinetic processes. As mentioned already, the absorption of the radical adduct grows exponentially, with the rate becoming faster with increasing disulfide concentration. A plot of the measured first-order rate constants ( k , = In 2/tl12) for these processes as a function of disulfide concentration is shown in Figure 3. The data refer to the formation of (CH3SS(CH3)SCH3J.and (CysSS(Cys)SCys). radicals in pulse-irradiated, deoxygenated, aqueous solution of 2-5 M propan-2-01 plus various concentrations of dimethyl disulfide (pH 7) or cystine (pH lo), respectively. The data yield straight lines with intercepts. Such kinetic behavior is compatible with equilibrium conditions. Accordingly, the second-order rate constants for the forward reactions, klS,can be evaluated from the slopes of the curves, while the intercepts represent the first-order rate constants, k-,,, for the back-reaction of equilibrium 15. The results obtained for the two
6290
The Journal of Physical Chemistry, Vol. 88, No. 25, 1984
TABLE I: Rate Constants of Forward Reaction and Back-Reaction and Equilibrium Constants for Reaction 15 KI5IM-I substitu-
kI5/(M-l
from
ent R 5-I) av k15/k-l5 from yield k-l5/S-' CH3" 3.8 X IO6 2.3 X lo4 165 f 15 190 f 20 180 f 30 cysteine 7.7 X lo5 1.5 X IO4 50 f 10 70 f 20 60 f 20 residueb
BonifaEiE: and Asmus bonds will be weakened by at least one-quarter as compared to a normal S-S a-bond and thus provide a rationale for the establishment of an equilibrium between the adduct radical and its thiyl radical and disulfide constituents. This concept is also in accord with the observed formation of high yields of mixed disulfides,'*2since an R'S. adduct to an R2SSRZdisulfide could suffer breakage of both sulfur-sulfur bonds, thereby establishing two equilibria
., p S - R 2
"Neutral solution. bpH 10.
RI-sZ'S
species are listed in Table I together with the equilibrium constants K I 5 evaluated from the kinetic data ( k l S / k - l sand ) from the yield-concentration plots of Figure 2. Very good agreement is found for K I Sbetween both methods, indicating that these values do indeed represent the thermodynamic stability constants of the (RSS(R)SR)-radical adducts. The rate constants k I 5are the first absolute and directly measured values for the reaction of thiyl radicals with disulfides. They agree well with the previous est i m a t e ~ ~and - ' ~further show that the thiyl radical addition to a disulfide is not a diffusion-controlled process. In fact, it appears that this radical addition is also the rate-determining step in the overall displacement reaction formulated in eq 3. An instructive kinetic example is finally provided in a mixed system with the initial thiyl radical being different from the disulfide constituents. The reaction of Pens. radicals with dimethyl M PenSH, disulfide (2 M propan-2-01, 1 M CH3COCH3,5 X pH 4.6, various CH3SSCH3concentrations) can best be followed via the decay of the Pens. absorption at 330 nm.lo A bimolecular rate constant of k16 = 2.7 X lo7 M-' s-' is derived from the forward reaction of the equilibrium Pens.
+ CH3SSCH3+ (CH3SS(CH3)SPen).
(16)
Evaluation of k-16 and K16 from the intercept and slope of the corresponding graph as in Figure 3, or evaluation of all the kinetic data from the formation kinetics of the adduct radical absorption is, however, not feasible since they include not only the reactions involved in equilibrium 16 but also dissociation of the adduct via (CH3SS(CH3)SPen)+ CH3SSPen
+ CH3S.
(17)
and equilibrium CH3S. + CH3SSCH3+ (CH3SS(CH3)SCH3).
(8a)
These considerations apply in principle to all mixed systems. Structure and Stability of the Radical Adduct. It is a wellestablished fact that unpaired electrons in a sulfur-centered radical show a strong tendency to coordinate with free p-electron pairs of other sulfur or heteroatoms and stabilize in a three-electronbonded system.34 In analogy the RS. radical is expected to add to a sulfur atom of the disulfide
to form a sulfuranyl radical with one of the sulfur-sulfur bonds containing three electrons. Such a species should, of course, establish an energetically more favorable resonance structure
in which the unpaired electron is shared between the two equivalent S-S bonds. In mixed systems, the actual distribution of the electron density will, of course, be affected by different substituents R, but the basic structure of the radical adduct will remain the same. In analogy to the three-electron, two-center systems (e.g., (R2S:.SR2)+ radical cations and (RS:.SR)- radical anions) the unpaired electron is expected to be accommodated in an antibonding a* 0 r b i t a 1 . I ~As ~ ~a~consequence each of the sulfursulfur (34) Asmus, K.-D. Acc. Chem. Res. 1979, 12, 436 and references cited
therein.
'
(19)
R'
z R~St - R'SSR'
4b R ~ S S R 't R ' S .
The respective equilibrium constants are expected to depend on the nature of the substituents as has been found for the three-electron, two-center systems.17 Our species would, in fact, constitute a three-electron, three-center system, and it is interesting to note that such electronic structure has also been suggested for a number of sulfuranyl radicals, which also provide the possibility of delocalization of the a* antibonding e l e c t r ~ n . ~ ~ , ~ ~ The thermodynamic stabilities of the adduct radicals, Le., the equilibrium constants K l 5 ,are considerably smaller than those of the (R2S:.SR2)+ radical cations,37 for example. The main reason for this finding appears to be the relatively low rate constants k15for the formation of the adduct radical. By comparison, the forward reaction of the equilibrium R2S+*+ R2S + (R;?S:.SR2)+ (20) occurs at almost diffusion-controlled rates, Le., several orders of magnitude f a ~ t e r . ~The ~ . respective ~~ back-reactions, on the other hand, are about equal in rate (e.g., for the all-methylated species k-20= 1.8 X lo4 SKI (ref 38 and 39) and klS= 2.3 X lo4 s-', One reason for the differences in the rate constants for the forward reactions is most likely the presumably much smaller electrophilicity of the thiyl radicals as compared to that of the R2S+radical cations. In any case the relatively low stability constant K l 5probably also explains why several adduct radicals, e.g., with R = C2H5or (CHJ2CH, could not be stabilized. In analogy to corresponding three-electron, two-center radicals and radical ions their stability would be expected to be still smaller than for (CH3SS(CH3)SCH3].and thus require disulfide concentrations too high for experimental verification. The overall kinetic stability of the (RSS(R)SR). adduct radicals may not be regarded as a direct measure of the stability of the sulfur-sulfur bonds. As in the case of other u* radical species it possibly also reflects other side reactions such as deprotonation,
et^.^^ In conclusion, our experiments have proven the formation of an intermediate adduct radical in the overall displacement reaction of thiyl radicals with disulfides. In addition it has been possible, for the first time, to measure absolute rate constants for the reaction of thiyl radicals with disulfides, which substantiate previous estimates.
Acknowledgment. This work has been supported by the International Bureau of the KFA Jiilich within the terms of an agreement on scientific cooperation between the Federal Republic of Germany and the Socialist Federal Republic of Yugoslavia. Registry No. MeS., 7 175-75-9; CysS., 35772-84-0; MeSSMe, 62492-0; CysSSCys, 56-89-3; (H02CCH,CH2S)2,1119-62-6; PenSSPen, 20902-45-8: CvsSH. 52-90-4: CvaSSCva. 51-85-4: EtSSEt. 110-81-6: (CH3)2CHSSdH(CH3)2,4253-i9-8; Et&, 14836-22-7; (CH3)2CHS.; 25783-06-6.
(35) Perkins, C. W.; Martin, J. C.; Arduengo, A. J.; Lau, W.; Alegria, A. Kochi, J. K. J . Am. Chem. SOC.1980, 102, 7753 and references cited therein. (36) Asmus, K.-D.; Gillis, H. A,; Teather, G. G. J . Phys. Chem. 1978,82, 2677. (37) BonifaEii., M.; Mockel, H.; Bahnemann, D.; Asmus, K.-D. J. Chem. SOC.,Perkin Trans. 2 1975, 675. (38) Chaudhri, S. A,; Gobl, M.; Freyholdt, T.; Asmus, K.-D. J . Am. Chem. Soc., in press. (39) Goslich, R.; Monig, J.; Asmus, K.-D., to be submitted for publication.
