6674
J. Phys. Chem. 1992,96,6674-6679
fluorescence. This implies that [HC*(Tl)] should always be less than [NO+*)], as required to reconcile the proposed mechanism with the observed power dependence of the chemiluminescence rate. Enhancement Trends. Finally we address the question as to why the benzene/N02 system yields such a low NO(A2Z+) chemiluminescence yield in relation to the acetylene compounds. Some evidence may come from the study of heterogeneous phenylacetyleneclusters. Stanley and CastlemanZ2noted that NH3 is centered above the benzene ring in benzenwNH3 clusters, whereas NH3occupies a site between the ring and acetylenic group in phenylacetylene-NH3 clusters. They postulate that the aelectron density of the acetylenic group attracts NH, more strongly than benzene. The implications for this work is that the acetylene derivatives possibly may form complexes with NOz more readily than benzene, a key step in the proposed mechanism. In the above argument we have merely focused on one point (complex formation). However it should be noted that a number of other factors affect the efficiency of NO(AzZ+)production such as the ability of HC*(TI) to be deactivated by NOz and the ability of N0#B2) to be deactivated by hydrocarbons.
Conclusions In this experiment we determined the relative efficiency of NO(A2Z?) production from a mixture of NOz and hydrocarbons containing a low-lying triplet state. The trend of NO(A2Z+) production in order of decreasing efficiency is HCCH > CH3CCH > CzHsCCH > C&CCH > C&. On the basis Of the laser power dependence on NO(A2Z+)chemiluminescence, the pressure-dependent variation, and energetic considerations, a triplet mechanism for chemiluminescenceis suggested. To reconcile the present investigation with the triplet mechanism, we concluded that a significant fraction of excited NOz molecules must remain in a nonradiative collision-resistant excited state for a significant period of time.
Acknowledgment. This work was partly supported by the Grant-in-Aid for Scientific Research (No. 03453019) from the Ministry of Education, Science, and Culture. We are grateful to the Japan Society for the Promotion of Science (JSPS). The assistance and advice of Mr. Masayuki Arai, Dr. Yoshihisa Matsushita, and Dr.Masaru Fukushima were greatly appreciated.
References and Notes (1) Matsumi, Y.; Murasawa, Y.; Obi, K.; Tanaka, I. Laser Chem. 1983, 1, 113. (2) Nagai, H.; Kusumoto, T.; Shibuya, K.; Tanaka, I. J . Chem. Phys. 1986, 85, 5061. (3) Jusinski, L. E.; Sharpless, R. L.; Slanger, T. G. J. Chem. Phys. 1987, 86, 5509. (4) Fujimura, Y.; Homma, K.; Kajimoto, 0. Chem. Phys. Lett. 1987,140,
320. ( 5 ) Engleman, R., Jr.; Rouse, P. E. J . Mol. Spectrosc. 1971, 37, 240. (6) Flicker, W. M.; Mosher, 0.;Kupperman, A. J . Chem. Phys. 1978,69,
--..
3 511. .~~~
(7) Duncan, D. A.; Dietz, T. G.; Liverman, M. G.; Smalley, R. E. J. Phys. Chem. 1981,85, 7. (8) Chia, L.; Goodman, L. J. Chem. Phys. 1982, 76, 4745. 19) Nicholls. R. W. J. Res. Notl. Bur. Stond. Sect. A 1964. 68. 535. (IO) McDerkid, S.; Laudenslager, J. B. J . Quont. Spectrosc. Rbdiat. Tromfer 1982, 27, 1. (11) Greenblatt, G.D.; Ravishankara, A. R. Chem. Phys. Lett. 1987,136, 501. (12) Asscher, M.; Haas, Y. J. Chem. Phys. 1982, 76, 2115. (13) Broida, H. P.; Carrington, T. J. Chem. Phys. 1963, 38, 136. (14) Shaub, W. M.; Burks, T. L.; Lin, M. C. J. Phys. Chem. 1982,86,757. (15) Schofield, K. J. Photochem. 1978, 9, 55. (16) Miller, R. G.;Lee,E. K. C. Chem. Phys. Lett. 1974, 27,475. (17) Musahid, A.; Callear, A. B. Chem. Phys. Lett. 1989, 156, 35. (18) Dulccy, C. S.;McGee, T. J.; McIlrath, T. J. Chem. Phys. Lett. 1980, 76, 80.
(19) McAndrew, J. J. F.; Preses, J. M.;Weston, R. E., Jr.; Flynn, G.W. J. Chem. Phys. 1989, 90,4772. (20) Weaver, A.; Metz, R. B.; Bradforth, S. E.; Neumark, D. M. J. Chem. Phys. 1989, 90, 2070. (21) Barin, I. Thermodynamical Data of Pure Substances; VCH: Weinheim, Germany, 1989. (22) Stanley, R. J.; Castleman, A. W., Jr. J . Chem. Phys. 1990,92, 5770.
Substltuent Effects on the Spectral, Acid-Base, and Redox Properties of Indolyl Radlcals: A Pulse Radiolysis Study Slobodan V. Jovanovic*lt and Steen Steenkent Laboratory 030, The Boris Kidric Institute, P.O. Box 522, 11001 Beograd, Yugoslavia, and Max-Planck-Institut ftir Strahlenchemie, Stifstrasse 34-36, 0-4330 Mtilheim a.d. Ruhr 1, Germany (Received: March 2, 1992)
Spectral and acid-base properties and reduction potentials of various substituted indolyl radicals were studied by pulse radiolysis in aqueous solutions at 20 O C . Except for the 5-methoxyindolyland 5-carboxyindolyl radicals, the spectra of the substituted indolyl radicals resemble the previously published 320- and 520-nm spectra of the neutral and 330- and 580-nm spectra of the cation indolyl and tryptophan radicals. The substitution of indolyl radical cation by electron-attracting groups (positive a') results in a blue shift of the 580-nm band by -30 nm, whereas the spectra of methylindolyl (a' = -0.31) are similar to those of unsubstituted indolyl radicals. The 430- and 455-nm bands appearing in the spectra of the 5-carboxyindolyl and 5-methoxyindolyl radical cations, respectively, indicate even stronger interaction of the unpaired electron with the 5-substituent. The radical cations of various indole-3-acetic acids decarboxylate at pH values below their pK, to produce allyl radicals. The 5-bromoindolyl radical undergoes solvolysis to 5-hydroxyindolyl radical in acidic and alkaline media. The dissociation constants and reduction potentials of the substituted indolyl radicals correlate with the Brown substituent constants: pK, = 4.14 - 2.1321~+, correlation coefficient 0.987, and E0/0.059 = 22.29 + 3.52a', correlation coefficient 0.980. The p values from these correlations (-2.13 and 3.5) are similar to that of the Hammett correlatirm of the dissociation constants of the protonated indole nitrogen in various substituted indoles, p = -2.49, but smaller than the p value of the dependence on the substituent of the reduction potentials of phenoxy1 radicals, p = 5.4.
Introduction The free radical chemistry of methylindoles,l,zdimethoxy-, dihydroxy-, and (methoxyhydroxy)indoles,3 and hydroxyindoles,4" The Boris Kidric Institute.
* Max-Planck-Institut fiir Strahlenchemie.
as well as tryptophan and its derivatives,'3*610has been extensively studid However, the effect of substitution On the Physicochemical characteristics of indoie radicals has remained unclear. For example, it was reported'J that methyl substitution at positions 2 and 3 of the indole ring influenced considerably the pK, values of indolyl radicals, whereas the effect on their reduction potentials
0022-365419212096-6674$03.00/0 0 1992 American Chemical Society
Substituent Effects on Indolyl Radicals
The Journal of Physical Chemistry, Vol. 96,No. 16,I992 6675
was minimal. This is a surprising result since one excepts a substituent to influence not only the acidity but also the redox properties of a molecule. Ofinterest would be a better understanding of the effects of the substitution in the side chain of 3-substituted indole radicals, which should aid the general understanding of the transmission of substituent effects in heterocyclic free radicals. In this study various substituted indole derivatives were oxidized to indolyl radicals by strong transient oxidants, such as Br2'- and (SCN)iradicals, and TI(I1) ions. The spectral and acid-base properties of the indolyl radicals in aqueous solutions at 20 "C were determined by pulse radiolysis with optical detection. From the equilibrium kinetics of the electron-transfer reactions of the indolyl radicals with the redox standards quanosine (E7 = 1.17 V)," NOT (E = 1.03 V),I2 promethazine (E = 0.98 V)," and tyrosine (E13 = 0.76 V),S the reduction potentials vs normal hydrogen electrode (NHE) were determined. The dissociation constants and reduction potentials of substituted indolyl radicals were correlated with the Brown substituent constants, d .
Materials and Metbods The chemicals were of the highest purity available, and were used without purification. Indole, 5-nitroindole, 5-cyanoindole, 5-methoxyindole, 5-methoxytryptophan, 5-methoxyindole-3-acetic acid, S-methoxy-2-methylindole,5-methoxyindole-2-carboxylic acid, 5-methoxy-2-methylindole3-acetic acid, indble3-acetic acid, and 5,6-dimethoxyindole were obtained from Aldrich; 5methylindole, tyrosine, promethazine hydrochloride, guanosine, 5-methyltryptophan, 5-methyltryptamine, indoleS-carboxylic acid, 5-bromoindole, and 5-bromoindole-3-aceticacid were obtained from Sigma; sodium nitrite, perchloric acid, potassium bromide, thallium sulfate, potassium hydroxide, and phosphate buffer were the products of Merck. Dehydrostobadine hydrochloride was a generous gift from L. Horakova of the Institute of Organic Chemistry and Biochemistry, Czechoslovak Academy of Sciences, Prague, Czechoslovakia. Water was purified with a Millipore MilliQ system. Because of the relatively low solubility of indoles in cold water, the solutions were gently heated to dissolve them. Indoles with carboxylic groups were dissolved as potassium salts. The pH of the solutions, which was adjusted with NaOH and HC104,was measured with the Radiometer PHM 83 Autocal pH meter with a glass combination electrode. The solutions were saturated with high-purity N 2 0 (1 atm; [O,] I 3 ppm) to convert hydrated electrons to 'OH radicals. The 3-MeV Van de Graaff pulse radiolysis set up at the Max-Planck-Institut fiir Strahlen~hemie'~ with optical detection was used for the pulse radiolysis studies. The absorbed doses were in the range from 2 to 3 Gy when the indolyl spectra were being recorded and for pK determinations, and from 0.8 to 1.5 Gy in the measurements of electron-transfer rates and equilibrium absorbances. The absorbed doses were measured with reference to the absorbance at 480 nm of the thiocyanate radical (E = 7600 M-l cm-I; G = 6.0)14 generated by the *OH radical oxidation of SCN- in N20-saturated aqueous solution of 10 mM KSCN. The following well-known 'OH radical reactions produce transient oxidants used for the generation of the indolyl radicals: 'OH
+ Tl(1) 'OH
-
(TIOH)' + Tl(I1)
+
+ Br-
Br'
Br-
Br'
+ OH-
+ OH-
* Br2*-
-
k = 1.1 X 1O'O M-l s-Il6
+ SCN- SCN' + OHSCN' + SCN- =+(SCN)2'-
'OH
The rate constants for reaction of the transient oxidants with
TABLE I: Rates of Geaerrition of Various sllbatitatedMoly1 Radicals Mewred by Pnbe Radiolysis in Aqueous Solutioas at 20 O C indole, R-Ind indole 5-cyanoindole 5-nitroindole 5-bromoindole 5-methylindole indole-5-carboxylate 5-methoxyindole 5,6-dimethoxyindole
5-methoxyindole-2-carboxylic
k [ X t R-Ind1.O M-I s-l Br2*-b Tl(I1)' (SCN);-' 8.5 X lo8 0.9 X lo9 4.2 X lo8 3.2 X lo8 6.7 x io8 1.1 x 109 8.0 X lo8 4.1 X lo8 5.1 X lo8 1.4 x 109 1.8 X lo8
acid 1.0 x 109 2.0 x 109 5.3 x io8 4.6 X lo8 9.7 x 108
5-mcthoxy-2-methylindole 5-methoxytryptophan
5-methoxyindole-3-aceticacid 5-methoxy-2-methylindole-3acetic acid 5-bromoindole-3-acetic acid tryptophan 5-methyltryptophan dehydrostobadine indole-3-acetic acid
1.4 x 109 7.7 x i08d 1.1 x 109 1 x 8 X lo8 2.0 X lo9 1.5 x 109 6.4 X lo8
io8d
"Estimated to be accurate to alO%.bDetermined in the pH range from 2.5 to 13.5. cMeasured at pH 3 and 7. dFrom ref 7.
-E ?W
250
350
450
550
650
750
Alnm Figure 1. Transient absorption spectra obtained upon Br;- oxidation of indole in N20-saturated aqueous solution of 1 mM indole at 20 OC,D = 3 Gy/pulse: ( 0 )indolyl cation at pH 3; ( 0 )neutral indolyl radical at pH 7. The inset shows variation of absorbance at 590 nm with the PH.
indoles were determined from the effect of an indole derivative at appropriate concentration (in the range from 0.05 to 1 mM) on the rate of an oxidant decay. The reactions were monitored at the following wavelengths: & = 360 nm, t = lo00 M-l cm-I, for Tl(II),15& = 355 nm, E = loo00 M-' cm-',for Br2+,16and A, = 480 nm, t = 7600 M-' cm-I, for (SCN)2*-.14 ReSultS Acid-Base and Spectral Properties. The indolyl radicals were generated in aqueous solutions by one-electron oxidation of the corresponding indole derivative by strong transient oxidants, X' [X' = (SCN);-, Br2', and TI(II)], as indicated by the following reaction:
X' + R-Ind-R'
-
R-Indo+-R'
+ X-
(1)
The rate constants of reaction 1 were found to be close to diffusion controlled, k = lo9 M-' s-l, for the stronger oxidants, Tl(I1) (E, = 2 V)I5 and Br2.- (E = 1.8 V)," whereas somewhat lower rates, k = l@ M-I s-l were measured for (SCN)2'- (E = 1.29 V).18 The rate constants were found to be independent of pH in the range from 3 to 7 for Tl(I1) and (SCN)2*, and from 2 to 13.5 for Br2*-. The results are summarized in Table I. The resulting indolyl radicals exhibited pronounced absorbances in the UV-vis region (see Figure 1 and Table 11) as already reported for radicals from methylindoles,'S2 tryptophan,68 5,6-
Jovanovic and Steenken
6616 The Journal of Physical Chemistry, Vol. 96, No. 16, 1992 TABLE II: Speetrcll Ropertier, of W y l Radicals R-Indo(-H) R-Ind'+ indolyl from X,nm P X,nm P 320 4000 330 5000 indole 2000 580 3000 520 4Ooo 4800 335 325 5-methylindole 1900 1800 580 530 3400 2500 335 320 5- bromoindole 1400 1600 555 510 2300 1500 335 335 5-cyanoindole 1400 1250 550 495 5400 1800 555 520 5-nitroindole 3000 2500 330 320 indole-5-carboxylicacid 1600 430 510 2000 570 1800 3800 3600 330 330 5-methoxyindole 4500 2100 445 530 520 shb 1700 3000 330 2600 335 5-bromoindole-3-aceticacid 1600 575 2900 520 4700 3500 335 330 5-methyltryptamine 2900 1600 575 520 7000 5000 340 325 dehydrostobadine 2900 540 2000 560 590 sh 2500 4700 3800 330 325 indole-3-acetic acid 2800 2000 560 515 #Apparent molar absorbances (M-I cm-I), accurate to &lo%. Shoulder.
TABLE IIk Acid-Base Properties of Indolyl Radicals in Aqueow S d U 8t ~20 O C EU+b indolyl from PK,o indole (1) 4.6e 0 4.1 -0.02 indole-5-carboxylicacid (2) -0.31 5-methylindole (3) 5.0 -0.78 5-methoxyindole (4) 6.1 3.1 0.15 5-bromoindole (5) 0.66 2.8 5-cyanoindole (6) 0.79 5-nitroindole (7) 2.1 5,6-dimethoxyindole (8) 7.36 -1.56 -1.09 5-methoxy-2-methylindole( 9 ) 6.2 -0.87 5-methoxyindole-3-aceticacid (10) 5.4 -0.80 5-methoxyindole-2-carboxylicacid (11) 6.3 -1.18 5-methoxy-2-methylindole-3-acetic acid (12) 6.2 -0.09 5.1 indole-3-acetic acid (13) tryptophan (14) 4.3e 5-methoxytryptophan (15) 5 .o 5-methyltryptophan (16) 4.6 4.1 5-methyltryptamine (17) 3.1 dehydrostobadine (18)
*
dimeth~xyindole,~ and 5,6-dihydroxyindole.I9 The absorption spectra of indolyl radicals changed with the pH of the solution in a manner characteristic for the acid-base equilibria, i.e.
+ H+
390
480
570
660
750
llnm
m e 2. Absorption spectrum of the 5-methoxyindolylradical cation obtained upon (SCN);- oxidation of 5-methoxyindole at pH 3.0 in N20-saturated aqueous solution of 1 mM S-MeO(Ind), 25 mM KSCN at 20 O C , D = 3 Gyfpulse.
the determination of redox potentials of free radicals has been well documented,2O so only the highlights of the procedure will be presented. The indolyl radicals were generated by one-electron oxidation of the corresponding indole derivative (reaction 1) and reacted with a selected electron donor, D. The establishment of the redox equilibrium R-Ind'+
+ D * R-Ind + Do+
(3)
Diecaapion
a Estimated to be accurate to AO.1. From ref 22. Assignment of ut values from refs 23 and 27. value is 0.3 pH units lower than the previously published 4.9.' The reason for this discrepancy is not known. value is 1.2 pH units higher than previously published pK, = 6.0.' We believe that our value is more accurate since it was obtained in independent experiments using Br2*-, 'N3. and (SCN),'- as oxidants. 'From refs 7 and 8.
R-Ind'(-H)
0
was verified from the kinetics, and, whenever possible, from the absorbamxp of the radicals, R-Ind'+ and D'+, at equilibrium. The results are summarized in Tables IV and V.
~~~
R-Ind"
""i,
(2)
The pranounced differences in the spectral properties of the neutral and cation indolyl radicals enabled accurate determination of the dissociation constants (see Table 111). An example is illustrated in Figure 1. OneEkd" Reductkm Potenti& The one-electron reduction potentials of selected indolyl radicals were determined with reference to the guanosine(-H)' (E7= 1.17 V)," promethazine'+ (E = 0.98 V ): tyrosine(-H)' (El3 = 0.76 V): and NOz' (E = 1.03 V)'* systems. The use of the pulse radiolysis technique for
Spectral churreteristics. As seen from Table 11, the spectra of the indolyl radicals are only moderately influenced by the substituent at the 5-position, with the exception of methoxy and carboxy. For example, the longer wavelength band of the spectra of 5-bromo, 5-cyano-, and 5-nitroindolyl cation radicals (electron-withdrawing substituents) is blue-shifted by -30 nm as compared to the spectra of unsubstituted indolyl, whereas those of indolyl radicals substituted with the electron-donating methyl group are similar to the spectrum of unsubstituted inddyl radicals. The spectrum of the 5-methoxyindolylradical cation exhibits a strong absorption at 450 nm (Figure 2) in addition to the typical bands at 330 and 520 nm. The 450-nm band is indicative of localization of positive charge at the electron-rich methoxy group as reported for radical cations of methoxybenzoic acids.21 It is interesting that an additional methoxy group at C6, as in 5.6dimethoxyindolyl radicals, results in the disappearance of the 450-nm band from the spectrum of the corresponding indolyl cation radicaL3 The spectrum of the 5-carboxyindole "radical cation" also contains the 430-nm band. The overall charge of this radical is zero at pH 3. This is concluded from the lack of effect of the ionic strength varied from I = 13 mM to 1 M on the rate of decay of this radical at pH 3. Consequently, it is concluded that the carboxy group of the 5-carboxyindole radical cation is deprotonated; i.e., this radical is a zwitterion. On the other hand, there was a clearly obsemable ionic strength effect on the decay of the N 1-deprotonated 5-carboxyindolyl at pH 9. On deprotonation from N 1. the overall charge becomes negative; Le., a radical anion is formed. (4)
F h t m T d o m " The spectra of the indolyl radicals generated from Sbromoindole, 5-bromoindole-3-acetic acid, and indole-3-acetic acid exhibited pH-dependent first-order transformations.
Substituent Effects on Indolyl Radicals
The Journal of Physical Chemistry, Vol. 96, No. 16, 1992 6677
TABLE Iv: OlleEkctron Transfer Reactions of W y l Radiuls Determined by Pulse Radiolysis of Aqueous Solutions at 20 O C
acceptor, A'+ from indole 5-methylindole 5-cyanoindole 5-nitroindole indole-5-carboxylate guanosine 5-methoxyindole 5- bromoindole indole-3-aceticacid (IAA) tyrosine dehydrostobadine
5-methoxy-2-methylindole-3-acetic acid (MMIA) NO,
donor, D tyrosine tyrosine promethazine tyrosine promethazine promethazine tyrosine 5-methoxyindole tyrosine promethazine promethazine promethazine IAA promethazine promethazine MMIA
pH 13.1 13.1 6.0 12.5 6.5 6.5 13.1 7.0 13.0 6.0 6.5 6.5 13.1 6.4 3.0 9.1
kf,"M-l s-' 6.1
k,," M-I
lPd 5.0 losd 3.5 lo8 1.2 x 109 2.7 X lo9 2.7 X lo8 3.8 X lo7 7.0 X lo8 8.8 X lo6 1.5 X lo9 2.0 X lo8 2.3 X lo8 7.0 X los 1.0 x 108 3.3 X lo9 2.2 X lo7 X X X
nm nm 3X 4x 3X 1X 2X 4X 2X 2X 3X 2X 2X 7x nm nm
s-]
los 106
Kki,b
1200 300
lo6 lo6 lo6 lo7 lo6 lo6 lo6 lo6 lo5 105
19 17 4
Kabb
v
MpH:
3 1.4 1000 380 4000 lo00 21 nm 4 1050 1050 300 8 590 80 20
0.03 0.01 0.18 0.15 0.21 0.18 0.08 0.07 0.05 0.18 0.18 0.15 0.05 0.16 0.11 0.08
"Estimated to be accurate to *lo% for reactions in the favorable direction, and *20% for the others. bEquilibrium constants derivd from the kinetics, Kbn = kf/k,,and equilibrium absorbances of the radicals, Knb = [D'+][A]/[A'+][D]. CTheredox potential difference calculated from the arithmetic mean of the equilibrium constants by the Nemst equation AE [RT/nFl In K = 0.059 log K. In most cases, however, the accuracy of the determination of Ktin suffered from the fast decay rates of the indolyl radicals (typically 2k = lo9 M-' d). Consequently, more weight was given to the more accurate K.lx
TABLE V Ow-Electron Reduction Potentials of Indolyl Radicals vs NHE at 20 'C indolyl radical from PKr Eo," V indole (1) indole-5-carboxylate (2) 5-methylindole (3) 5-methoxyindole (4) 5-bromoindole (5) 5-cyanoindole (6) 5-nitroindole (7) 5-methoxy-2-methylindole3-aceticacid (12) indole-3-acetic acid (13) tryptophan (14) tryptamine dehydrostobadine (18)
4.6 4.1 5.0
6.1 3.7 2.8 2.1 6.2 5.1 4.3 4.3 3.7
xu+, v
E13," v 0.8P 0.82c 0.77 0.77 0.77 0.88
E7,O V
1.29b 1 3 1.24 1.18 1.32 1.48 1.49 1.09 1.20 1.21d 1.21c 1.30
1.15b 1.17c 1.12 1.12 1.12 1.23 1.20 1.04 1.09 1.OSd 1. O S 1.10
0 -0.02 -0.31 -0.78 0.15 0.66 0.79 -1.18 -0.09
0.85
0.69 0.73 0.7od 0.7ff 0.75
"The redox potentials at pH 0 are calculated as the mean values from the redox potential differences given in Table IV. The values are estimated to bc accurate to k0.02 V. The pH dependence of the reduction potentials of the indolyl radicals is evaluated from the formula E , = Eo 0.059 X log ([H+]/([H+] K,)], where [H+] and K,are the concentration of Ht ions and the dissociation constant of the indolyl radical, respectively. value is 0.05 V higher than that given in ref 2. For discussion, see text. CThisvalue was calculated from the formula EPH= Eo + 0.059 log ([H+](K, [Ht])/(K, [H+])], where K, is the dissociation constant of the carboxylic group in the parent compound, pK, = 4.60 0.05. dThe mean of recently published values 1.19:' 1.21: and 1.24 V.* CFromrefs 8 and 10.
+
+
+
+
The spectrum of the 5-bromoindolyl radical cation delayed with to a spectrum with the maximum at 420 nm at pH 2.5 (Figure 3). This decay was independent of the 5bromoindole concentration and the dose rate. On the basis of the similarity of the spectrum produced upon the decay of 5bromoindolyl radical cation with the spectrum of the 5-indoxyl (neutral 5-hydroxyindolyl) r a d i ~ a l ,it~ is suggested that 5bromoindole radical cation undergoes solvolysis and subsequent Br- elimination, to yield the 5-hydroxyindole radical, as indicated below in eq 5. A similar reaction occurs in alkaline media, pH
k = 8 X lo3
> 12.5, where the neutral 5-bromoindole radical reacts with the hydroxide ion. The 5-hydroxyindolyl radical produced in this reaction deprotonates from N1 at pH > 12.2: which is the pK, of this radical, to the corresponding radical anion. Hydrolytic debromination was not observed in neutral media (k < lo3 s-l at pH 7), which indicates that this reaction is acid-base catalyzed. The yield of hydrolytic debromination is -50% in both acidic and alkaline media, as deduced from the comparison of an a p parent molar absorbance of 5-indoxyl upon transformation of the 5-bromoindolyl radical with that of 5-indoxyl generated by Br2'--induced one-electron oxidation of 5-hydroxyindole at a p
0
350
450
550
650
750
Alnm
Figure 3. Transient absorption spectra obtained upon Br2'- oxidation of
-
5-bromoindole in N20-saturated aqueous solution of 0.6 mM 5-bromoindole, 20 mM KBr at pH 2.5,20 OC, 1 Gy/pulse: (m) 40 ps after the pulse, (e) 1 ms after the pulse (upon the completion of the monomolecular transformation of 5-bromoindolyl radical cation).
propriate pH (e&, 2400 vs 5000 M-l s - ~ at pH 2.5). The radical cations from 5-bromoindole-3-acetic acid and indole-3-acetic acid undergo faster first-order transformations, k
6678 The Journal of Physical Chemistry, Vol. 96, No. 16, 1992
dissociation constant is higher than expected from 2 6 = -0.78 - 0.02 = -0.80. In the case of the radicals from indole-3-acetic acids, the dissociation constants deviate (Figure 4a) in an inconsistent manner. For example, pK, = 5.1 of indole-3-acetate is higher, whereas pK, = 5.4 of 5-methoxyindole-3-aceticacid is lower than predicted from the Hammett correlation. Similar deviations from the Hammett correlation were reported25for ionization of indole-3-acetic acids. The acidities of 5-substituted tryptophyl radicals are higher than those of 5-substituted indoles, which may be explained by the transmission of the inductive effect of the side-chain NHs+ group through the side chain. The efficiency of the transmission (-4095, taking ai(NH3+) = 0.92) is high, considering that the charged amino group is separated from the ring by two methylene groups. The transmission of the inductive effect of the >NH(CH,)+ ~ f o u p through one methylene group in the dehydrostobadine radicals is expected to be of at least comparable efficiency.
sigma+
,,
26.00
1 9
p5
0 22 00
2 1 2o O0
1
Dehydrostobodine. pH=7
3 ' . 4
Jovanovic and Steenken
d '
(b) Reduction Potenti.ls. Similar to the dissociation constants, the reduction potentials of 5-substituted indolyl radicals were found to correlate reasonably well with the Brown substituent constants (Figure 4b):
9
Eo/0.059 = 22.29 + 3.52a+, correlation coefficient O.98O3l (8) EJ0.059= 22.29 + 3.5.0'
Linear free energy correlation of (a) dissociation constantsand (b) reduction potentials of indolyl radicals with u+. Numbers above data points correspond to those given in Tabla 111and V. Unfilled symbols in (a) designate data points excluded from the correlation (for discussion, see text). Figure 4.
= los M-' s-I, to a featureless spectrum. This is suggested to be due to decarboxylation reactions, yielding allyl-type radicals.
The first-order transformations of the indolyl radicals of 5bromoindole-3-acetic acid and indole-3-acetic acid were not observed in neutral and alkaline media, where the radicals are neutral, except for the COO- group. This is presumably due to the lower electron-deficiency of the neutral as compared to the cation radicals, as a result of which there is less driving force for the side-chain fragmentation reaction (decarboxylation). Iinear Free Eaergy Relatiom. (a) Dhociation Constants. The pK, values of indolyl radical cations, pK,, may be correlated with the Brown u+ values (Figure 4a), correlation coefficient 0.987: pK, = 4.14 - 2.132~'
(7)
Electrondeficient substituents such as NOz destabilize the indolyl cation through an increase in positive charge at the site of protonation. Conversely, electron-rich substituents have a stabilizing effect, as in 5-methoxyindolyl (ApK, = lS), because of the partial delocalizationof the positive charge at C5 and increased electron density of N1. However, the slope of the correlation, p = -2.13, indicates an only moderately strong influence of the substituents on the acidity of indolyl radical cations. A relatively poor correlation is obtained if indolyl radicals with charged groups at C2 and C3 are included. The deviation from the linear free energy correlation for the radicals derived from indole-2-carboxylic acids may be explained by the formation of hydrogen bonds between the charged carboxyl group in the side chain and the indolyl N-H. For example, in the case of the radicals derived from 5-methoxy-indole-2-carboxylicacid, the
The slope of the correlation, p = 3.5, is smaller than that for substituted phenoxyl radicals, p = 5.426(p = 7*' was also reported for phenoxyl radicals at pH 7), which means that the reduction potentials of indolyl radicals are less sensitive to para subtitution than their phenoxyl counterparts. This difference may be explained by the higher resonance energy of the unpaired electron in the indolyl as compared with the phenoxyl radicals due to a higher ?r electron density on C atoms of the indole ring.28 The reduction potential of 5-carboxyindolylradicals at pH 0, deviates considerably from the above correlation (Eo= 1.55 V for 6= -0.02), whereas the dissociation constant of the radical cation conforms with the u+. This deviation is probably due to neglect of protonation of the carboxyl group in the calculation of the pH dependence of the reduction potential. For example, it is difficult to determine the pK of this radical for protonation of the carboxy group if below pH 2. However, if this pK exists, the reduction potential would be lower by 0.06-0.12 V, and the a+ value higher (up to 0.45 for the fully protonated carboxy group). The radicals derived from 5-hydroxyindole, with pK,, (cation) C 0, pKI2(neutral) = 12.1, and Eo = 1.04 V,4 and 5,6-dihydroxyindole, with pK,,(cation) C 0 and p&(neutral) = 6.8,19 were excluded from the above considerations because of appreciable deviations from eqs 7 and 8. In fact, physicochemical characteristicsof indoxyl radicals are more closely related to those of phenoxyl-type radicals. The redox potentials of various substituted indolyl radicals are also correlated with their dissociation constants (Figure 5, data from Table V). A moderately good correlation EO/O.O59 = 28.35 - 1.5pK, (9) correlation coefficient 0.94, indicates that the substitution influence reduction potentials and dissociation constants in a similar manner, but in opposite directions. For example, electrondonating substituents increase electron density in the pyrrole part of the indole ring, which results in increased stability (higher pK,) and decreased electron deficiency (lower Eo) of indolyl radical cations. In spite of the relatively low correlation coefficient, the quality of the correlation is satisfactory, considering uncertainties in the redox potentials. The slope of the line, -0.09 V/+1 pH unit difference in pK,, is similar to -0.1 12 V/pK for phenoxyl radicals in acet~nitrile.~~
The Journal of Physical Chemistry, Vol. 96, No. 16, 1992 6679
Substituent Effects on Indolyl Radicals
16\ 18
\
3
\
w
20.00
0
12
18.00
1600
PKr E10.069= 28.36 - l.SpK,
Figwe 5. correlation of reduction potentials (E0/0.059) with dissociation constants (pKr) of indolyl radicals. Numbers above data points correspond to those given in Tables 111 and V. Data point number 2 was excluded from the correlation.
The correlation of pKr with the reduction potentials of the indolyl radicals allows the calculation and/or prediction of less aaxaPble reduction potentials. For example, 5,6-dimethoxyindole is rather insoluble in water, which precludes accurate measurement of its oxidation potential by pulse radiolysis. However, from the measured pKr = 7.3 (seeTable 111) of the 5,64imethoxyindolyl radicals, the reduction potentials are Eo = 1.08 V, E7 = 1.07 V, and El3 = 0.74 V. Similar values may be obtained from the correlation of the reduction potentials with Za+; Le., EO= 1.06 V, E, = 1.05 V, and E13 = 0.72 V. The somewhat "symmetrical" substituent effect on the dissociation constants and the reduction potentials of indolyl radicals leads to a gradual decrease in the reduction potential differences with pH (see Table V). For example, the standard potentials, Eo, of 5-bromo- and 5-methoxyindole differ by hE = 0.14 V, whereas at pH 13, this difference is close to 0 V. F d y , a few commentsmay be made on the data on reduction potentials and dissociation constants of 2-methyl-,3-methyl-,and 2,3-dimethylindolyl radicals.'S2 Eo = 1.1 V2 of 2-methylindole is higher than Eo = 1.07 V2 of 3-methylindole, whereas pKr = 5.0' of 3-methylindole is lower than pKr = 5.7l of 2-methylindole. This is at variance with the general direction of the substituent effect in phen0xy1~~ and indolyl radicals; i.e., the radicals with lower pK, should have higher reduction potentials. In addition, our values for reduction potentials of various indolyl and tryptophyl radicals were found to differ significantly from the data reported in ref 2. In that study2the reduction potentials of tryptophan and indole radicals were equal. In light of their ability to oxidize tyrosine in alkaline media (Table IV), indolyl radicals have more and tryptophan radicals have leas positive reduction potential than tyrosine phenoxyl. Consequently, the reduction potentials of indolyl and tryptophyl radicals must be different, as indicated in Table V. Spmmuy and Conclusions
Acid-base properties and reduction potentials of substituted indolyl radicals were found to be influenced by the substitution at C2, C3, C5, and C6. However, the p values from the Hammett correlations of dissociation constants ( p = -2.13) and standard potentials ( p = 3.5) are smaller than p = 5.4 of the dependence on the substituent of reduction potentials of phenoxyl radicals. This difference may be explained by the higher degree of delocalization of the unpaired electron in the indolyl as compared with the phenoxyl radicals.
The acidities of 5-substituted tryptophyl radicals are higher than those of 5-substituted indoles, which may be explained by the transmission of the inductive effect of the sidechain NH3+group through the side chain. The efficiency of the transmission (-4O%, taking q(NH3+) = 0.92) is high, considering that the charged amino group is separated from the ring by two methylene groups. The reduction potential of dehydrostobadine (as indole derivative), E, = 1.1 V, is considerably higher than E7 = 0.58 VS0of indolinedobadhe. Such an enormous difference clearly indicates that the C 2 X 3 double bond of indole is strongly electron-withdrawing. The redox potentials of various substituted indolyl radicals are also correlated with their dissociation constants, Eo/0.059 = 28.35 - 1.5pKr. This allows the calculation and/or prediction of less accessible reduction potentials from the data on dissociation constants, which are more readily obtainable. Acknowledgment. The gift of dehydrostobadinehydrochloride from Dr. L. Horakova of the Institute of Organic Chemistry and Biochemistry, Czechoslovak Academy of Sciences, Prague, is gratefully acknowledged. S.V.J. thanks the Max Planck Society for a fellowship.
References and Notes (1) Shen, X.;Lind, J.; Merlnyi, G. J . Phys. Chem. 1987, 91, 4403. (2) Merlnyi, G.; Lind, J.; Shen, X . J . Phys. Chem. 1988, 92, 134. (3) AI-Kanvini, A. T.; O"eil1, P.; Adams, G. E.; Cundall, R. B.; Jacquet, B. Lang, G.; Junino, A. J. Phys. Chem. 1990,94,6666. (4) Jovanovic, S. V.; Staenken, S.;Simic, M. G. J. Phys. Chem. 1990.94, 3583. ( 5 ) Jovanovic, S. V.;Simic, M. G. Li$e Chem. Rep. 1985, 3, 124. (6) Solar, S.; Getoff, N.; Sudhar, P. S.;Armstrong, D. A.; Singh, A. J. Phys. Chem. 1991, 95, 3639. (7) Posener, M. L.; Adams, G. E.; Wardman, P. J . Chem. Soc., Faraday Trans. 1 1976, 72, 2231. (8) Jovanovic, S. V.;Simic, M. G. J. Free Radicals Biol. Med. 1985, 1 , 125. (9) DeFelippis, M. R.; Murthy, C. P.;Faraggi, M.; Klapper, M. H. Biochemistry 1989, 28, 4847. (10) Jovanovic, S. V.; Harriman, A.; Simic, M. G. J. Phys. Chem. 1986, 90, 1935. (1 1) Jovanovic, S. V.;Simic, M. G. Biochim. Biophys. Acta 1989,1008, 39. (12) Wilmarth, W. K.;Stanbury, D. M.; Byrd, J. E.; Po, H. N.; Chua, C. P.Coord. Chem. Rev. 1983, 51, 155. (13) Jagannadham, V.;Steenken, S.J . Am. Chem. Soc. 1984,106,6542. (14) Baxendalc, J. H.; Bevan, P. L. T.; Scott, D. A. Trans. Faraday Soc. 1968,64, 2389. (15) Schwarz, H. A.; Dodson, R. W. 1.Phys. Chem. 1984, 88, 3643. (16) Zchavi, D.; Rabani, J. J. Phys. Chem. 1972, 76, 312. (17) Woodruff, W. H.; Margerum, D. W. Znorg. Chem. 1973, 12,962. (18) DeFelippis, M. R.; Faraggi, M.; Klapper, M. H. J . Phys. Chem. 1990, 94, 2420. (19) AI-Kazwini, A. T.; O'Neill, P.; Adams, G. E.; Cundall, R. B.; Lang, G.; Junino, A. J. Chem. Soc., Perkin Trans. 2, 1991, 1941. (20) Steenken, S.Lundolt-Bhsrein 1985, 13e, 147. Wardman, P. J. Phys. Chem. Ref Data 1989, 18, 1637. (21) Stccnken, S.;ONeill, P.; SchulteFrohlinde, D. J. Phys. Chem. 1977, 81, 26. (22) H a w h , C.; Leo, A. substituent Constantsfor Correlarion Analysis in Chemistry and Biologv; Wiley: New York, 1979. Hansch, C.; Leo, A.; Taft, R. W. Chem. Rev. 1991, 91, 165. (23) Aten, W.C.; Blichel, K. H. Z . Naturforsch. 1970, 256, 961. (24) Jovanovic, S. V.;Steenken, S.;Simic, M. G. J. Phys. Chem. 1991, 95, 684. (25) Bowden, K.; Parkin, D. C. Can. J . Chem. 1966,44, 1493. (26) Jovanovic, S. V.;Tosic, M.; Simic, M. G. J. Phys. Chem. 1991,95, 10824. (27) Lind, J.; Shen, X.;Eriksen, T. E.; MerEnyi, G. J . Am. Chem. Soc. 1990,112,479. (28) Remers, W. A. In Indoles; Houlihan, W. J., Ed.; Wiley-Interscience: N e w York, 1972; Part One,pp 3-226. (29) Bordwcll, F. G.; Cheng, J.-P. J . Am. Chem. Soc. 1991, 113, 1736. (30) Steenken, S.; Sundquist, A. R.; Jovanovic, S. V.; Crockett, R.; Sies,
H. Chem. Res. Toxicol., in press. (31) Eo is a classical electrochemical symbol used to denote the standard potential, which refers to the activity of H+ being equal to 1, Le., at approximately pH 0. Eo is often used in the pulse radiolysis determinations for the redox potential at pH 0. This means that the values of Eo arc equal to the values of.?' However, this does not mean that the corresponding terms are equal.
