Radical cations in the OH-radical-induced oxidation of thiourea and tetramethylthiourea in aqueous solution

Article abstract of DOI:10.1021/ja983275b

Hydroxyl radicals were generated radiolytically in N₂O-saturated aqueous solutions of thiourea and tetramethylthiourea. The rate constant of the reaction of OH radicals with thiourea (tetramethylthiourea) has been determined using 2-propanol as well as NaN₃ as competitors to be 1.2 x 10¹⁰ dm³ mol^-1 s^-1 (8.0 x 10⁹ dm³ mol^-1 s^-1). A transient appears after a short induction period and shows a well-defined absorption spectrum with λ(max) = 400 nm (ε = 7400 dm³ mol^-1 cm^-1); that of tetramethylthiourea has λ(max) = 450 nm (ε = 6560 dm³ mol^-1 cm^-1). Using conductometric detection, it has been shown that, in both cases, OH^- and a positively charged species are produced. These results indicate that a radical cation is formed. These intermediates with λ(max) = 400 nm (450 nm) are not the primary radical cations, since the intensity of the absorbance depends on the substrate concentration. The absorbance build-up follows a complex kinetics best described by the reversible formation of a dimeric radical cation by addition of a primary radical cation to a molecule of thiourea. The equilibrium constant for this addition has been determined by competition kinetics to be 5.5 x 10⁵ dm³ mol^-1 for thiourea (7.6 x 10⁴ dm³ mol^-1 for tetramethylthiourea). In the bimolecular decay of the dimeric radical cation (thiourea, 2k = 9.0 x 10⁸ dm³ mol^-1 s^-1; tetramethylthiourea, 1.3 x 10⁹ dm³ mol^-1 s^-1), formamidine (tetramethylformamidine) disulfide is formed. In basic solutions of thiourea, the absorbance at 400 nm of the dimeric radical cation decays rapidly, giving rise (5.9 x 10⁷ dm³ mol^-1 s^-1) to a new intermediate with a broad maximum at 510 nm (ε = 750 dm³ mol^-1 cm^-1). This reaction is not observed in tetramethylthiourea. The absorption at 510 nm is attributed to the formation of a dimeric radical anion, via neutralization of the dimeric radical cation and subsequent deprotonation of the neutral dimeric radical. The primary radical cation of thiourea is deprotonated by OH^- (2.8 x 10⁹ dm³ mol^-1 s^-1) to give a neutral thiyl radical. The latter reacts rapidly with thiourea, yielding a dimeric radical, which is identical to the species from the reaction of OH^- with the dimeric radical cation. The dimeric radical cations of thiourea and tetramethylthiourea are strong oxidants and readily oxidize the superoxide radical (4.5 x 10⁹ dm³ mol^-1 s^-1 for thiourea and 3.8 x 10⁹ dm³ mol^-1 s^-1 for tetramethylthiourea), phenolate ion (3 x 10⁸ dm³ mol^-1 s^-1 for tetramethylthiourea), and even azide ion (4 x 10⁶ dm³ mol^-1 s^-1 for thiourea and ~10⁶ dm³ mol^-1 s^-1 for tetramethylthiourea). With O₂, the dimeric radical cation of thiourea reacts relatively slowly (1.2 x 10⁷ dm³ mol^-1 s^-1) and reversibly (2 x 10³ s^-1).

Full text of DOI:10.1021/ja983275b

238
J. Am. Chem. Soc. 1999, 121, 238-245
Radical Cations in the OH-Radical-Induced Oxidation of Thiourea
and Tetramethylthiourea in Aqueous Solution
Wen-feng Wang,†,§ Man Nien Schuchmann,† Heinz-Peter Schuchmann,† Wolfgang Knolle,‡
Justus von Sonntag,‡ and Clemens von Sonntag*,†
Contribution from the Max-Planck-Institut fu¨r Strahlenchemie, Stiftstrasse 34-36, P.O. Box 101365,
D-45413 Mu¨lheim an der Ruhr, Germany, Institut fu¨r Oberfla¨chenmodifizierung, Permoserstrasse 15,
D-04303 Leipzig, Germany, and Shanghai Institute for Nuclear Research, P.O. Box 800-204,
Shanghai 201800, China
ReceiVed September 14, 1998
Abstract: Hydroxyl radicals were generated radiolytically in N2O-saturated aqueous solutions of thiourea and
tetramethylthiourea. The rate constant of the reaction of OH radicals with thiourea (tetramethylthiourea) has
been determined using 2-propanol as well as NaN3 as competitors to be 1.2 × 1010 dm3 mol-1 s-1 (8.0 × 109
dm3 mol-1 s-1). A transient appears after a short induction period and shows a well-defined absorption spectrum
with λmax ) 400 nm (ꢀ ) 7400 dm3 mol-1 cm-1); that of tetramethylthiourea has λmax ) 450 nm (ꢀ ) 6560
dm3 mol-1 cm-1). Using conductometric detection, it has been shown that, in both cases, OH- and a positively
charged species are produced. These results indicate that a radical cation is formed. These intermediates with
λmax ) 400 nm (450 nm) are not the primary radical cations, since the intensity of the absorbance depends on
the substrate concentration. The absorbance build-up follows a complex kinetics best described by the reversible
formation of a dimeric radical cation by addition of a primary radical cation to a molecule of thiourea. The
equilibrium constant for this addition has been determined by competition kinetics to be 5.5 × 105 dm3 mol-1
for thiourea (7.6 × 104 dm3 mol-1 for tetramethylthiourea). In the bimolecular decay of the dimeric radical
cation (thiourea, 2k ) 9.0 × 108 dm3 mol-1 s-1; tetramethylthiourea, 1.3 × 109 dm3 mol-1 s-1), formamidine
(tetramethylformamidine) disulfide is formed. In basic solutions of thiourea, the absorbance at 400 nm of the
dimeric radical cation decays rapidly, giving rise (5.9 × 107 dm3 mol-1 s-1) to a new intermediate with a
broad maximum at 510 nm (ꢀ ) 750 dm3 mol-1 cm-1). This reaction is not observed in tetramethylthiourea.
The absorption at 510 nm is attributed to the formation of a dimeric radical anion, via neutralization of the di-
meric radical cation and subsequent deprotonation of the neutral dimeric radical. The primary radical cation
of thiourea is deprotonated by OH- (2.8 × 109 dm3 mol-1 s-1) to give a neutral thiyl radical. The latter reacts
rapidly with thiourea, yielding a dimeric radical, which is identical to the species from the reaction of OH-
with the dimeric radical cation. The dimeric radical cations of thiourea and tetramethylthiourea are strong
oxidants and readily oxidize the superoxide radical (4.5 × 109 dm3 mol-1 s-1 for thiourea and 3.8 × 109
dm3 mol-1 s-1 for tetramethylthiourea), phenolate ion (3 × 108 dm3 mol-1 s-1 for tetramethylthiourea), and
even azide ion (4 × 106 dm3 mol-1 s-1 for thiourea and ∼106 dm3 mol-1 s-1 for tetramethylthiourea). With
O2, the dimeric radical cation of thiourea reacts relatively slowly (1.2 × 107 dm3 mol-1 s-1) and reversibly
(2 × 103 s-1).
Introduction
a radioprotectant. Formamidine disulfide appears to be a primary
product; several sulfur-free nitrogen-containing compounds,
sulfate ion, and elemental sulfur have also been observed. These
Sulfur-containing compounds show a complex free-radical
chemistry which is very different from that exhibited by carbon-
centered free radicals (for reviews see refs 1-4). For example,
sulfur-centered radicals are able to form three-electron-bonded
intermediates such as RSSR•-, R2SSR2•+, or R2SOH•.5 The
radiation-induced chemistry of thiourea in aqueous solution has
been studied6-13 with a view toward its potential application as
(5) Asmus, K.-D. In Sulfur-Centered ReactiVe Intermediates in Chemistry
and Biology; Chatgilialoglu, C., Asmus, K.-D., Eds.; Plenum: New York,
1990; pp 155-172.
(6) Dale, W. M. Nature 1956, 177, 531.
(7) Dale, W. M.; Davies, J. V. Progress in Radiobiology, Proceedings,
4th Int. Conf., Cambridge, 1955; pp 119-127.
(8) Dale, W. M.; Davies, J. V. Radiat. Res. 1957, 7, 35-46.
(9) Dale, W. M.; Davies, J. V. Int. J. Radiat. Biol. 1959, 1, 189-195.
(10) Charlesby, A.; Kopp, P. M.; Read, J. F. Proc. R. Soc. A 1966, 292,
122-133.
* To whom correspondence should be addressed. Fax: (Germany) 208
306 3951. Phone: (Germany) 208 306 3529. E-mail: vonsonntag@
mpi-muelheim.mpg.de.
† Max-Planck-Institut fu¨r Strahlenchemie.
(11) Nanobashvili, E. M.; Chirakadse, G. G.; Gvilava, S. E.; Mosashvili,
G. A.; Katsadse, D. V. VI. Thiourea, urea and their deriVatiVes; Izdatel’stvo
“Metsniereba”: Tbilisi, 1980; pp 113-136.
‡ Institut fu¨r Oberfla¨chenmodifizierung.
§ Shanghai Institut for Nuclear Research.
(1) Asmus, K.-D. Acc. Chem. Res. 1979, 12, 436-442.
(2) von Sonntag, C.; Schuchmann, H.-P. In The Chemistry of Functional
Groups. Supplement E: The Chemistry of Ethers, Crown Ethers, Hydroxyl
Groups and Their Sulphur Analogues. Part 2; Patai, S., Ed.; Wiley: New
York, 1980; pp 971-993.
(3) Asmus, K.-D. Methods Enzymol. 1990, 186, 168-180.
(4) Wardman, P.; von Sonntag, C. Methods Enzymol. 1995, 251, 31-45.
(12) Natsvlishvili, S. E.; Nanobashvili, H. M.; Ignatashvili, S. H.;
Panchvidze, M. V. In Proceedings of the 5th Tihany Symp. Radiation
Chemistry; Dobo, J., Hedvig, P., Schiller, R., Eds.; Akademiai Kiado:
Budapest, 1983; pp 589-593.
(13) Charlesby, A.; Fydelor, P. J.; Kopp, P. M.; Keene, J. P.; Swallow,
A. J. In Pulse Radiolysis; Ebert, M., Keene, J. P., Swallow, A. J., Baxendale,
J. H. Eds.; Academic Press: London, 1965; pp 193-201.
10.1021/ja983275b CCC: $18.00 © 1999 American Chemical Society
Published on Web 12/19/1998

OH-Radical-Induced Oxidation of Thiourea
J. Am. Chem. Soc., Vol. 121, No. 1, 1999 239
latter products are probably, in most cases, largely hydrolysis
products of the disulfide (cf. ref 14), but there are also
indications that, in the presence of oxygen, a chain process may
give rise to the production of elemental sulfur under certain
conditions.8 Recently, the radiolysis of thiourea derivatives has
been studied in connection with their use as corrosion inhibitors
in nuclear reactors.15,16
The reactions of OH radicals with thiourea derivatives give
rise to an intermediate which exhibits a characteristic absorption
near 400 nm.13,15,16 While this intermediate has, in the past, been
thought to be a neutral radical, the present work will show that,
with thiourea and N,N,N′,N′-tetramethylthiourea, the intermedi-
ate in question is, in fact, a dimeric radical cation.
Figure 1. Spectrum (2 µs after the pulse) obtained in the pulse
radiolysis of N2O-saturated solutions of thiourea (O, 2 × 10-3 mol
dm-3) and tetramethylthiourea (9, 10-3 mol dm-3) at natural pH (6.8);
3 Gy/pulse. Inset: Pulse radiolysis (5 ns, 17 Gy/pulse) of N2O-saturated
solution of thiourea (10-2 mol dm-3) at pH 6.5. Absorption build-up
monitored at 400 nm (4). The solid line is the result of computational
modeling of the reactions 3-5 (see text).
Experimental Section
Pulse radiolysis of millimolar solutions of thiourea (Merck) and
N,N,N′,N′-tetramethyl thiourea (Fluka) in Milli-Q-filtered (Millipore)
water saturated with either N2O or with N2O/O2 was carried out (in
Mu¨lheim) with a 2.8-MeV Van-de-Graaff generator delivering electron
pulses of 0.4-2 µs. Intermediates were monitored by optical and
conductometric detection. The pulse radiolysis setup has been described
previously.17 Nanosecond-pulse experiments were carried out (in
Leipzig) with an 11 MeV linear accelerator, with 17-Gy pulses of 5-ns
duration. For dosimetry, N2O-saturated thiocyanate solution was used
for optical detection,18 and dimethyl sulfoxide solution was used for
conductometric detection.19 A series of pulse radiolysis experiments
was also carried out in the presence of varying concentrations of the
competitors 2-propanol and sodium azide.
thiourea), 3.9 × 109 dm3 mol-1 s-1, obtained by monitoring
the build-up kinetics of the intermediate at 400 nm, is too low,
as will be shown below).
Reaction of the OH Radical with Thiourea and Tetra-
methylthiourea. Pulse radiolysis of N2O-saturated solution of
thiourea yields an intermediate which exhibits a strong absorp-
tion with λmax ) 400 nm (Figure 1). Taking G(•OH) ) 5.96 ×
10-7 mol J-1, ꢀ(400 nm) ) 7400 dm3 mol-1 cm-1 is calculated.
The spectrum of the intermediate derived from tetramethyl-
thiourea has its maximum at a longer wavelength [ꢀ(450 nm)
) 6560 dm3 mol-1 cm-1, Figure 1]. This is comparable to the
case of N,N′-diethylthiourea [ꢀ(425 nm) ) 5250 dm3 mol-1
cm-1].16 The similarity that is observed in the behavior of
thiourea and tetramethylthiourea toward the OH radical indicates
that this reaction is not an H atom abstraction. (Thiourea had
formerly often been thought to exist in the iso, i.e., iminothiol,
form, cf. ref 25, but this view has since been refuted.26)
A complexity is apparent in the way the absorption builds
up at 400 nm. While its rate increases at higher thiourea concen-
trations, the build-up shows a lag period of several nanoseconds
before it takes on first-order characteristics (Figure 1, inset).
The build-up kinetics as shown in Figure 1 (inset) and the
other findings described below are in accordance with the
sequence of reactions 3-5 (Scheme 1; R ) H, thiourea; R )
CH3, tetramethylthiourea).
As the expected10,20 primary oxidation products of the radiolysis of
the thioureas, the formamidine and tetramethylformamidine disulfides
were synthesized21,22 from the corresponding thioureas through oxidation
with H2O2, to be used as reference material. This procedure yields the
formamidinium disulfides, which are stable under acidic conditions.
Their spectra turn out to be quite similar to those of their parent
thioureas. The fact that we have not succeeded in separating these
disulfides from their parent thioureas by HPLC has, however, precluded
their direct identification and quantitative determination as products in
the present case.
Results and Discussion
Radical-Generating System. Hydroxyl radicals are generated
in the radiolysis of water (reaction 1). The radiation chemical
yields (G values) of the primary radicals are G(•OH) ≈ G(eaq
)
-
) 2.9 × 10-7 mol J-1 and G(H•) ) 0.6 × 10-7 mol J-1. N2O
•
is used to convert the solvated electron into OH (reaction 2)
so that a total hydroxyl radical yield of 5.8 × 10-7 mol J-1 is
achieved in a 10-3 mol dm-3 thiourea solution. G(•OH) increases
with increasing substrate concentration.23
OH radical addition could occur initially at the carbon-sulfur
double bond (reaction 3). The short-lived adduct could then
decay into a radical cation and a hydroxide ion (reaction 4).
The existence of the lag phase in the absorbance build-up (Figure
1, inset) indicates an initial reaction which gives rise to an
intermediate which does not absorb at 400 nm.
H2O ionizing8 eaq-, •OH, H•, H+, H2O2, H2
(1)
(2)
radiation
eaq- + N2O + H2O f •OH + OH- + N2
The reaction rates of the OH radical, the solvated electron,
and the H atom with thiourea are close to the diffusion-
controlled limit24 (the value reported in ref 24 for k(•OH +
At the same time, conductance measurements show that, with
both thiourea and tetramethylthiourea, a positively charged
(20) Simonet, J. In The Chemistry of Sulfur-Containing Functional
Groups; Patai, S., Rappoport, Z., Eds.; Wiley: New York, 1993; Suppl.
S., pp 440-492.
(14) Rio, L. G.; Munkley, C. G.; Stedman, G. J. Chem. Soc., Perkin
Trans. 2, 1996, 159-162.
(15) Dey, G. R.; Naik, D. B.; Kishore, K.; Moorthy, P. N. Radiat. Phys.
Chem. 1994, 43, 365-369.
(21) Preisler, P. W.; Berger, L. J. Am. Chem. Soc. 1947, 69, 322-325.
(22) Foss, O.; Johnsen, J.; Tvedten, O. Acta Chem. Scand. 1958, 12,
1782-1798.
(16) Dey, G. R.; Naik, D. B.; Kishore, K.; Moorthy, P. N. J. Chem.
Soc., Perkin Trans. 2 1994, 1625-1629.
(23) Schuler, R. H.; Hartzell, A. L.; Behar, B. J. Phys. Chem. 1981, 85,
192-199.
(17) von Sonntag, C.; Schuchmann, H.-P. Methods Enzymol. 1994, 233,
3-20.
(24) Buxton, G. V.; Greenstock, C. L.; Helman, W. P.; Ross, A. B. J.
Phys. Chem. Ref. Data 1988, 17, 513-886.
(18) Schuler, R. H.; Patterson, L. K.; Janata, E. J. Phys. Chem. 1980,
84, 2088-2089.
(25) Werner, E. A. J. Chem. Soc. 1912, 2180-2191.
(26) Duus, F. In ComprehensiVe Organic Chemistry; Neville Jones, D.,
Ed.; Pergamon Press: Oxford, 1979; pp 373-487.
(19) Schuchmann, H.-P.; Deeble, D. J.; Phillips, G. O.; von Sonntag, C.
Radiat. Phys. Chem. 1991, 37, 157-160.

240 J. Am. Chem. Soc., Vol. 121, No. 1, 1999
Wang et al.
Figure 3. Competition plot of hydroxyl radical reactions with thiourea
(4 × 10-4-5 × 10-3 mol dm-3) and with 2-propanol (0.05 mol dm-3).
Inset: Competition plot of hydroxyl radical reactions with thiourea (10-3
mol dm-3) and with NaN3 (2 × 10-4-8 × 10-3 mol dm-3).
Figure 2. Conductance change observed in N2O-saturated solution of
thiourea (10-3 mol dm-3) at pH 3.5 and at pH 10 (inset); 0.4-µs pulses
of ∼4 Gy/pulse. The initial jump at e10 µs is due to the formation
and subsequent neutralization of H+ within the pulse (reaction 1).
Scheme 1
experiments ensured (see below) that equilibrium 5/-5 lay
practically completely on the side of 2.
Taking the equivalent conductance at 20 °C of H+ (325 Ω-1
cm3 mol-1), OH- (180 Ω-1 cm3 mol-1 27
into account, and
)
assuming a value of 50 Ω-1 cm3 mol-1 for the singly charged
radical cation, one obtains G(radical cation) ) (5.8 ( 0.5) ×
10-7 mol J-1 (limit at relatively high thiourea concentrations,
e.g., 10-3 M). This confirms that the OH radical reaction leads
essentially quantitatively to radical cation formation. Additional
support for this has been obtained as follows. Oxidation of
thiourea with the strong oxidant Cl2 in 0.1 mol dm-3 NaCl
•-
and 10-3 mol dm-3 thiourea solution produces the radical cation
•-
of thiourea quantitatively since Cl2 is a poor hydrogen atom
species is generated. In acidic solutions of thiourea, a conduc-
tance decrease is observed immediately (<5 µs) after the pulse
(Figure 2), whereas in basic solution, a conductance build-up
is observed (Figure 2, inset). This indicates that the formation
of an ion pair (reaction 4) is the quasi-immediate consequence
of the reaction of the hydroxyl radical. In acidic solution, the
hydroxide anion formed in reaction 4 removes H+, which leads
to a decrease of the conductance. In basic solution, the ion pair
from reaction 4 remains unaffected, which results in a conduc-
tance increase.
abstractor. By comparing the yield of the radical cation obtained
•
in this way with that obtained by the oxidation with OH, we
found identical values. Thus, the oxidation of thiourea by •OH
produces the radical cation exclusively.
•
With tetramethylthiourea, oxidation by OH produces only
•-
85% of radical cation as compared with the oxidation by Cl2
(measured by optical detection). This implies that, in this case,
•
there may be some 15% H atom abstraction by OH at the
methyl groups. On the other hand, the conductivity measure-
ments show a quantitative yield of radical cation in both thiourea
and tetramethylthiourea. Taking into account the results of these
two independent measurements, we conclude that H atom
As the bimolecular rate constant of reaction 3 cannot be
determined directly from the build-up kinetics at 400 nm (as
has been attempted elsewhere),15,16,24 we have determined it by
competition with 2-propanol. In N2O-saturated solutions of
2-propanol containing various concentrations of thiourea (4 ×
10-4-5 × 10-3 mol dm-3), the absorbance (A) at 400 nm, 10
µs after the pulse, was determined at each thiourea concentration
(Ao is the absorbance of the thiourea solution at the same
wavelength in the absence of 2-propanol). Taking k(•OH +
•
abstraction at the methyl groups by OH is less than 10%.
Assignment of the Intermediate λmax 400 nm. The maxi-
mum value of the 400-nm absorbance is dependent on the
substrate concentration. When this is reduced from 10-3 mol
dm-3 to 6 × 10-6 mol dm-3, Gꢀ decreases from 4.5 to 3.2 cm-1
kGy-1 (values corrected for the loss by bimolecular decay). This
reduction cannot be accounted for by the decrease in G(OH)
due to the lower solute concentration23 but rather points to the
existence of an equilibrium situation where a dimeric radical
cation is formed (reactions 5/-5) which is responsible for the
strong absorption observed at 400 nm. A structure with a
disulfidic linkage is preferred since formamidinium disulfides
are produced in the oxidation of aliphatic thioureas (cf. ref 22).
Other canonical structures of the adduct 2 exist, apart from the
disulfide radical anionic form, e.g., those that involve the
materialization of the radical function on the carbon atom or a
form reminiscent of a dimeric sulfide radical cation. The latter
form represents the oxidative nature (see below) of 2 particularly
well. The equilibrium constant K5 ) k5/k-5 can be obtained from
2-propanol) ) 1.9 × 109 dm3 mol-1 s-1 24
,
k3(•OH + thiourea)
) 1.0 × 1010 dm3 mol-1 s-1 is obtained from the slope of the
plot Ao/A shown in Figure 3. Similarly, k3(•OH + tetrameth-
ylthiourea) ) 8.0 × 109 dm3 mol-1 s-1 has been determined.
We have also determined k3(•OH + thiourea) by competition
with sodium azide (Figure 3, inset). This is possible since the
reverse reaction between N3• and thiourea does not materialize
(see below). Taking k(•OH + N3-) ) 1.2 × 1010 dm3 mol-1
s-1 24
,
k3(•OH + thiourea) ) 1.3 × 1010 dm3 mol-1 s-1 is
obtained from the slope of the plot shown in the Figure 3 inset.
From these two independent measurements, the average value
for k3(•OH + thiourea) is 1.2 × 1010 dm3 mol-1 s-1 (for a
compilation of the rate constants determined in this study, see
Table 1). The thiourea concentrations used in these competition
(27) Robinson, R. A.; Stokes, R. H. Electrolyte Solutions; Butterworth:
London, 1959; 571 pp.

OH-Radical-Induced Oxidation of Thiourea
J. Am. Chem. Soc., Vol. 121, No. 1, 1999 241
Table 1. Compilation of Rate Constants Determined in This Study
no.
reactions
rate constants
3
3′
4
5
-5
9
9′
10
12
13
14
-14
21
21′
22
23
thiourea + •OH f thiourea-OH adduct
1.2 × 1010 dm3 mol-1 s-1
8.0 × 109 dm3 mol-1 s-1
6 × 107 s-1
Me4(thiourea) + •OH f Me4(thiourea)-OH adduct
thiourea-OH adduct f thiourea+• + OH-
thiourea+• + thiourea f (thiourea)2
5.0 × 109 dm3 mol-1 s-1
9.1 × 103 s-1
+•
(thiourea)2+• f thiourea+• + thiourea
2(thiourea)2+• f [(thiourea)2]2+ + 2thiourea
2(Me4(thiourea))2+• f [(Me4(thiourea))2]2+ + 2Me4(thiourea)
9.0 × 108 dm3 mol-1 s-1
1.3 × 109 dm3 mol-1 s-1
5.9 × 107 dm3 mol-1 s-1
2.8 × 109 dm3 mol-1 s-1
6 × 109 dm3 mol-1 s-1
1.2 × 107 dm3 mol-1 s-1
2 × 103 s-1
•
(thiourea)2+• + OH- f (thiourea)2
thiourea+• + OH- f thiyl radical + H2O
thiyl radical + thiourea f neutral dimer radical
(thiourea)2+• + O2 f [(thiourea)2O2 ]+
•
[(thiourea)2O2 ]+ f (thiourea)2+• + O2
•
(thiourea)2+• + O2•- f 2thiourea + O2
4.5 × 109 dm3 mol-1 s-1
3.8 × 109 dm3 mol-1 s-1
4 × 106 dm3 mol-1 s-1
3.0 × 108 dm3 mol-1 s-1
(Me4(thiourea))2+• + O2•- f 2Me4(thiourea) + O2
(thiourea)2+• + N3- f 2thiourea + N3
•
(Me4(thiourea))2+• + PhO- f 2Me4(thiourea) + PhO•
eq 6, where Ao is the absorbance at 400 nm in thiourea solution
of 2 × 10-3 mol dm-3 and A is the absorbance (corrected for
G(•OH) according to ref 23) at a given concentration of thiourea.
Ao/A ) 1 + K5-1[thiourea]-1
(6)
In Figure 4, the term (Ao/A) - 1 is plotted against the
reciprocal of the thiourea concentration. From the reciprocal
value of the slope of this linear plot, K5 ) 5.5 × 105 dm3 mol-1
is obtained for thiourea. The corresponding value of K5 ) 7.6
× 104 dm3 mol-1 for tetramethylthiourea (cf. Figure 4) is lower
than that of thiourea, indicating that, in this case, the equilibrium
reaction 5/-5 is less favorable toward the formation of the
secondary, dimeric radical cation.
Figure 4. Dependence of the term (Ao/A) - 1 at 400 nm (4 for
thiourea) and at 450 nm (b for tetramethylthiourea) on the reciprocal
of substrate concentration in the pulse radiolysis of N2O-saturated
solution of thiourea and tetramethylthiourea solution (6 × 10-6 to 2 ×
10-3 mol dm-3) at pH 6.6.
The fact that, for thiourea, the relationship shown in Figure
4 retains its linear appearance near a concentration of 10-5
M
suggests that the spontaneous deprotonation of the radical cation
1 of thiourea does not significantly contribute to its disappear-
ance. This implies, on the basis of a comparison of the rates of
reactions 5 and 7, that the lower limit of the pKa of 1 should be
in the vicinity of 6. A pKa value of 5 ( 2 has been estimated
on thermochemical grounds.28
Bimolecular Decay of the Dimeric Radical Cation. In the
absence of additives that are reactive toward these intermediates,
the decay of the absorption near 400 nm exhibits second-order
kinetics. The fact that these intermediates carry unit charge of
the same sign is corroborated by the behavior of the bimolecular
decay rate constants, 2k, which show the characteristic depen-
dence on the ionic strength µ (added electrolyte, NaClO4) and
fulfill expression 829 (Figure 5).
log(k/ko) ) 1.02z1z2µ1/2/(1 + µ1/2)
(8)
With the values of k3 and K5 obtained above, we have
simulated the reaction sequence 3-5 for the absorbance build-
up of the dimeric radical cation 2 (cf. Scheme 1, R ) H) at
400 nm (cf. Figure 1 inset). The best fit (solid line in the inset
of Figure 1) was obtained with k3 ) 1.2 × 1010 dm-3 mol-1
s-1, k4 ) 6 × 107 s-1, k5 ) 5.0 × 109 dm-3 mol-1 s-1, and k-5
) 9.1 × 103 s-1, as well as with the assumption that the
absorption coefficient at 400 nm of the monomeric radical cation
1 is about 10% of that of 2. These results support the above
hypothesis that the reaction of the OH radical with the thioureas
leads first to an adduct, albeit a short-lived one (reaction 3).
On the other hand, a simulation which pretends direct formation
of the ion pair, leaving out the OH adduct altogether, shows a
build-up kinetics with a much shorter lag phase that does not
match the experimental data shown in the Figure 1 inset.
Although such a simulation has to date not been carried out
in the case of tetramethylthiourea, a similar mechanism can be
assumed since the build-up behavior of the intermediate at 450
nm resembles that from thiourea.
The slope of the plot in Figure 5 is positive and near unity,
indicating that the numbers of the electric charge z1 and z2
(expression 8) of the reaction partners are unity and of the same
sign, in agreement with a bimolecular decay as proposed in
reaction 9.
Taking G(total radicals) ) 6.4 × 10-7 mol J-1 (this includes
the contribution from the primary H atoms), a bimolecular decay
rate constant of 2k9 ) 9.0 × 108 dm3 mol-1 s-1 (1.3 × 109 dm3
(28) Bordwell, F. G.; Algrim, D. J.; Harrelson, J. A., Jr. J. Am. Chem.
Soc. 1988, 110, 5903-5904.
(29) Lin, S. H.; Li, K. P.; Eyring, H. In Physical Chemistry. An AdVanced
Treatise; Eyring, H., Ed.; Academic Press: New York, 1975; pp 1-58.

242 J. Am. Chem. Soc., Vol. 121, No. 1, 1999
Wang et al.
Figure 7. Conductance change following an electron pulse of ∼4 Gy/
pulse in N2O-saturated solutions of 2 × 10-3 mol dm-3 thiourea (9,
lower curve) and of 10-3 mol dm-3 tetramethylthiourea (O, upper curve)
at pH 10.8.
Figure 5. Ionic strength effect on the rate constant of termination of
the radical cation from thiourea monitored at 400 nm (b, O) and
tetramethylthiourea (450 nm, 4, 2), observed at pH 6.6 (open symbols)
and at pH 3.1 (filled symbols).
Figure 6. Transient absorption spectra obtained in the pulse radiolysis
(6 Gy/pulse) of an N2O-saturated solution of thiourea (2 × 10-3 mol
dm-3) at pH 11.9. Initial spectrum (O), 1 µs after the pulse. Final
spectrum (b), 13 µs after the pulse. Inset: dependence of kobs of
absorption decay at 400 nm on hydroxide concentration.
Figure 8. Conductance change in N2O-saturated solution of thiourea
(2 × 10-3 mol dm-3) at 20 µs after the pulse (b) and at the end of the
OH--induced transformation (4, cf. Figure 7) (4 Gy/pulse).
Scheme 2
mol-1 s-1 for the tetramethyl derivative) is obtained under
conditions (neutral, salt-free) where the ionic strength is very
low (µ < 10-6 mol dm-3).
Transformation of the Radical Cations (Monomer and
Dimer) in Basic Solution. With basic solutions of tetrameth-
ylthiourea, the UV spectrum and the conductance signal do not
change as the pH is varied (within a range of pH 7-11.2). In
contrast, in basic solutions of thiourea above pH 10, the
absorption at 400 nm decays rapidly by first-order kinetics
within a time where the bimolecular decay of the intermediates
is still relatively minor. At the end of this transformation, a
new species with λmax at 510 nm (ꢀ ) 750 dm3 mol-1 cm-1) is
observed (Figure 6). The rate of the absorption decay at 400
nm is proportional to the OH- concentration (Figure 6, inset).
From the slope of this plot, the bimolecular rate constant 5.9 ×
107 dm3 mol-1 s-1 is obtained.
These optical detection results, and the conductivity ones
described below for thiourea, are summarized in Scheme 2. The
OH--induced 400-nm absorption decay is ascribed to the
reaction of OH- with the secondary, dimeric radical cation 2
to give the neutral species 3 (reaction 10), since under these
conditions (high thiourea concentration) the absorption near 400
nm (due to 2) is already fully developed at the end of the pulse.
Conductance measurements also reveal that, in basic solu-
tions, the radical cation of thiourea shows a pronounced
difference from that of tetramethylthiourea. In Figure 7, the
actual conductance change following an electron pulse in
thiourea solution at pH 10.8 is shown to decrease from a positive
value to a negative value in the course of this transformation.
For comparison, in tetramethylthiourea solution at identical pH
the corresponding change is much smaller and is due to the
bimolecular decay only (Figure 7).
In Figure 8, the initial conductance gain and final conductance
loss in basic solutions of thiourea are shown over a range of
pH values. It appears that, at pH < 10, a neutral species, e.g.,
the dimeric radical 3, is formed as the initial conductance gain
decays to zero within about 10 ms. At pH > 10, the initial
conductance gain decays rapidly and attains a negative value.
At pH 11.4, the net loss in conductance reaches a value of

OH-Radical-Induced Oxidation of Thiourea
J. Am. Chem. Soc., Vol. 121, No. 1, 1999 243
Figure 9. Competition plot of the reactions of the radical cation 1
with OH- and with thiourea. The absorbance A at 400 nm was taken
1 µs after the pulse (∼2 Gy/ pulse) in N2O-saturated solution of thiourea
(2 × 10-4-2 × 10-3 mol dm3) at pH 10.8-12. Ao is the absorbance at
400 nm at neutral pH.
Figure 10. Dependence of kobs of the disappearance, extrapolated to
zero dose, of the thiourea dimeric radical cation, monitored at 400 nm,
on the oxygen concentration in N2O/O2-saturated solution of thiourea
(10-3 mol dm-3) at pH 6.6. Inset: Pulse radiolysis of N2O/O2 (9:1
v/v)-saturated solution of thiourea (4 × 10-4 mol dm-3) and sodium
formate (10-2 mol dm-3) at pH 6.6. Dependence of kobs of absorbance
decay at 400 nm on superoxide concentration.
G(-OH-) ≈ G(OH•); i.e., the neutral species 3 consumes 1
molar equiv of OH-. The explanation for this is that a further
deprotonation, e.g., reaction 11, takes place to give the dimeric
radical anion 4. Obviously, such a deprotonation reaction is not
possible in the case of tetramethylthiourea, where only the
bimolecular decay is observed (Figure 7). The new species with
kobs ) 1.4 × 105 s-1) is only ∼60% of the value at pH 11.9. As
can be judged from Figure 8, at pH 10.3, the dimeric thiyl radical
3 is only partially deprotonated, and the lower absorbance at
510 nm observed under these conditions lends additional support
to our assumption that the neutral species 3 and 5 do not (or
only weakly) absorb at this wavelength and that the species with
λ
max at 510 nm observed at the end of OH--induced transforma-
tion (cf. Figure 6) at pH > 10.5 can thus be attributed to the
dimeric radical anion 4.
λmax at 510 nm can be attributed to the dimeric radical anion 4.
Parallel to the reaction of OH- with the dimeric radical cation
2 (reaction 10), there is also the reaction of OH- with the
monomeric radical cation 1 to give the neutral thiyl radical 5
(reaction 12), which will compete with dimer formation (reaction
5). Indirect evidence for reaction 12 is in the fact that the initial
absorbance of 2 at 400 nm decreases with increasing OH-
concentration. By measuring the absorbance A at 400 nm (at 1
µs after the pulse to minimize loss due to reaction 10) in basic
solutions of thiourea, we obtained the competition plot shown
in Figure 9. Its slope gives the ratio k12/k5 ) 0.55. Taking the
Reactions of the Dimeric Radical Cations with O2. In the
presence of O2, the rate of decay of the absorption at 400 nm
in thiourea solution at neutral pH is slightly faster than that in
the absence of oxygen. The rate constant of the reaction of O2
with the dimeric radical cation is obtained by extrapolating the
observed first-order decay rate constants to zero radical con-
centration. This is repeated at various O2 concentrations. The
intercepts so obtained are plotted versus the O2 concentration
(Figure 10). From the slope of the latter plot, a bimolecular
rate constant of k14 ) 1.2 × 107 dm3 mol-1 s-1 is obtained.
value of k5 ) 5.0 × 109 dm3 mol-1 s-1 obtained above, k12
)
It is assumed that the reaction with O2 involves the formation
2.8 × 109 dm3 mol-1 s-1 is calculated. This value is much higher
of a peroxyl radical (reaction 14). The intercept (2 × 103 s-1
,
than that of the equivalent reaction of the dimer 2 (i.e., k10
)
Figure 10) could signify the existence of a reverse reaction
(-14) and might be interpreted as k-14 (a reversibility of peroxyl
radical formation, even at room temperature, has been observed
in other cases, cf. refs 30-33). The behavior in the tetrameth-
ylthiourea case is similar (not shown).
5.9 × 107 dm3 mol-1 s-1, see above) and corresponds more
closely to what is expected for such reactions.
To elucidate the fate of the neutral thiyl radical 5, condi-
tions were chosen such that, at sufficiently low thiourea
concentration, >99% of the radical cations 1 react with OH-
to give 5, and <1% of 1 react with thiourea to give 2. Thus, in
a 2 × 10-5 mol dm-3 thiourea solution at pH 11.9, only the
build-up of absorption at 510 nm (kobs ) 1.3 × 105 s-1), but no
absorption at 400 nm is observed. Nevertheless, the resulting
absorption at 510 nm is identical to the corresponding absorption
obtained in 4 × 10-3 mol dm-3 thiourea solution (also at pH
11.9), where half of 1 will react to give 4 through the reactions
5, 10, and 11. These results indicate that the thiyl radical 5
subsequently reacts to give 4, via an addition to thiourea to give
the neutral dimeric thiyl radical 3 (reaction 13), followed by
the deprotonation reaction 11 to give 4. The value of kobs ) 1.3
× 105 s-1 for the build-up at 510 nm may be attributed to the
pseudo-first-order rate constant of reaction 13, as the deproto-
nation reaction 12 is not rate-determining at this high pH. This
gives k13 ≈ 6 × 109 dm3 mol-1 s-1, similar in order of
magnitude to k5.
Radical cations usually do not show reactivity toward O2 on
the time scale of pulse radiolysis; in the present case, there is
reactivity (k14), but it is moderate compared to that of other
radicals, where rate constants above 109 dm3 mol-1 s-1 are the
norm for the formation of peroxyl radicals (cf. ref 34).
(30) Tamba, M.; Simone, G.; Quintiliani, M. Int. J. Radiat. Biol. 1986,
50, 595-600.
(31) Zhang, X.; Zhang, N.; Schuchmann, H.-P.; von Sonntag, C. J. Phys.
Chem. 1994, 98, 6541-6547.
(32) Pan, X.-M.; von Sonntag, C. Z. Naturforsch. 1990, 45b, 1337-
1340.
(33) Fang, X.; Pan, X.; Rahmann, A.; Schuchmann, H.-P.; von Sonntag,
C. Chem. Eur. J. 1995, 1, 423-429.
(34) von Sonntag, C.; Schuchmann, H.-P. In Peroxyl Radicals; Alfassi,
Z. B., Ed.; Wiley: Chichester, 1997; pp 173-234.
Furthermore, in a 2 × 10-5 mol dm-3 thiourea solution at
pH 10.3, the build-up of absorbance at 510 nm observed at the
end of the OH--induced transformation (30 µs after the pulse,

244 J. Am. Chem. Soc., Vol. 121, No. 1, 1999
Wang et al.
Puzzlingly, in the presence of oxygen, thiourea may decom-
pose with very high G values under certain conditions. G(ele-
mental sulfur) values of up to about 10-3 mol J-1 have been
observed in oxygenated solutions under conditions of very low
dose rate (10-4 Gy s-1) and relatively high thiourea concentra-
tion (1 M).8 The mechanism of this chain reaction is unknown.
It is conceivable that this chain process is mediated by sulfur
peroxyl radicals. This kind of radical may be quite reactive (cf.
refs 35-37). In the present case, such radicals may be generated
via reaction 15. It is tempting to speculate that reactions 16-
20 come into play as well.
Figure 11. Reaction of the thiourea (b) and tetramethylthiourea (O)
radical cation with azide, monitored by the disappearance of the
absorption at 400 nm (thiourea, 10-3 mol dm-3) and at 450 nm
(tetramethylthiourea, 10-3 mol dm-3) in N2O-saturated solution at pH
9-10, ∼3 Gy/pulse.
corresponding value of k21 for tetramethylthiourea is 3.8 × 109
dm3 mol-1 s-1
.
Reaction with Azide. The oxidation of thiourea derivatives
•-
with the oxidizing radicals Cl2•-, Br2•-, and SO4 has been
reported, while their oxidation by N3• was not observed, except
in the case of the thiourea-related compound thiosemicarba-
zide,15,16 even though one would have expected N3• (reduction
potential, 1.33 V)40 to be strong enough to oxidize thiourea;
estimates of values for the reduction potentials of some thioureas
are reported and fall in the vicinity of 1.1 V.28 We have exposed
thiourea and tetramethylthiourea to the azide radical and also
have not observed any effect. This raises the question of the
existence of the reverse reaction, i.e., reaction 22.
The formamidinium sulfinyl radical cation may be expected
to be an even stronger oxidant than the primary radical cation
1 (reaction 17). Cyanamide is a major product in the O2-assisted
oxidative degradation of thiourea.9,38 There is evidence that
hydrogen hydroxysulfide (HSOH) is labile with respect to
decomposition (reaction 20) into water and sulfur.39
This is, indeed, observed. From a plot of kobs of the absorption
decay near 400 nm versus the azide concentration (Figure 11),
one determines k22 ) 4 × 106 dm3 mol-1 s-1 for thiourea and
106 dm3 mol-1 s-1 for tetramethylthiourea. This indicates that
the thiourea radical cations are fairly strong oxidants. The
intercept in Figure 11 is due to the contribution of termination
reactions to the decay. The existence of a reverse reaction would
also add to the intercept in Figure 11. However, any sizable
contribution by a reverse reaction (-22) can be ruled out since
the 400-nm absorption decays to zero (not shown); a reversibility
would be reflected in the existence of a nonzero “plateau”.
The absence of reactivity of the azide radical (reduction
potential 1.33 V)40 toward thiourea compared to the presence
Reaction with the Superoxide Radical. Superoxide radicals
[G(O2•-) ) 5.6 × 10-7 mol J-1] and the dimeric radical cation
of thiourea 2 [reactions 3-5, G(2) ) 7.2 × 10-8 mol J-1] were
generated side by side in N2O/O2 (9:1 v/v)-saturated solution
of sodium formate (10-2 mol dm-3) and thiourea (4 × 10-4
mol dm-3) at pH 6.6. The removal of the dimeric radical cation
of thiourea 2 by O2•- (reaction 21) was monitored by the decay
of its absorption at 400 nm at various O2•- concentrations (dose
rate dependent) (Figure 10, inset). From the slope of the linear
of reactivity15,16 shown by Br2 (1.66 V), OH (1.9 V), and
•-
•
•-
Cl2 (2.3 V) (cf. ref 40) suggests that the reduction potential
plot in the Figure 10 inset, a bimolecular rate constant of k21
)
4.5 × 109 dm3 mol-1 s-1 is obtained. As 2 is present at one-
eighth of the concentration of O2•-, the contribution of the
bimolecular decay of 2 to the slope in the Figure 10 inset is
of the thiourea dimer radical cation is bracketed by 1.33 and
1.66 V. However, in another context, the azide radical has been
shown to be unreactive toward dimethyl sulfide with respect to
radical adduct formation, even though a species (iodine atom)
with a very similar reduction potential does form an adduct;41
quite often, oxidation reactions proceed via the heterolysis of
intermediate adducts and not via direct electron transfer. In fact,
the sequence of reactions 3 and 4 presents another example of
this case.
•-
negligible. The intercept at zero O2 concentration observed
in the Figure 10 inset reflects the reaction of 2 with O2. The
(35) Schuchmann, H.-P.; von Sonntag, C. In Peroxyl Radicals; Alfassi,
Z. B., Ed.; Wiley: Chichester, 1997; pp 439-455.
(36) Asmus, K.-D. In ActiVe Oxygens, Lipid Peroxides, and Antioxidants;
Yagi, K., Ed.; Japan Sci. Soc. Press: Tokyo/CRC Press: Boca Raton, FL,
1993; pp 57-58.
(37) Scho¨neich, C. Antioxid. Health Dis. 1995, 2, 21-47.
(38) Schenck, G. O.; Wirth, H. Naturwissenschaften 1953, 40, 141.
(39) Heinze, E. J. Prakt. Chem., N. F. 1919, 99, 109-179.
(40) Wardman, P. J. Phys. Chem. Ref. Data 1989, 18, 1637-1755.
(41) Merenyi, G.; Lind, J.; Engman, L. J. Phys. Chem. 1996, 100, 8875-
8881.

OH-Radical-Induced Oxidation of Thiourea
J. Am. Chem. Soc., Vol. 121, No. 1, 1999 245
Oxidation of Phenolate Ion by the (Dimeric) Tetrameth-
ylthiourea Radical Cation. In an N2O-saturated solution of
tetramethylthiourea (10-2 mol dm-3) containing phenol (2.2 ×
10-4-10-3 mol dm-3) at pH 11, the absorption spectrum of
the dimeric radical cation (cf. reactions 3-5) with λmax at 450
nm observed 1 µs after the pulse disappears rapidly. At the end
of this process, a new species with λmax at 385 and 402 nm,
characteristic of the phenoxyl radical,42,43 is observed. The kobs
of the absorption decay at 450 nm is proportional to the phenol
concentration. From the slope of this linear plot (data not
shown), the bimolecular rate constant of the oxidation of
phenolate to phenoxyl radical by the radical cation of tetra-
methylthiourea (reaction 23) k23 ) 3.0 × 108 dm3 mol-1 s-1 is
obtained.
base if the pH of the solution is above neutral. Similar
observations, the production of elemental sulfur in particular,
have been reported in the base-catalyzed decomposition of
certain substituted formamide disulfides and related com-
pounds.44 This decomposition proceeds after deprotonation14
where possible. The decomposition of the homologous com-
pound derived from tetramethylthiourea must take a different
course, presumably via hydroxide addition at higher pH.
General Importance of the Thiourea Radical Cation in
Thiourea Oxidation. The radiolytic oxidation of thioureas to
the corresponding formamidinium disulfides represents a special
case within a whole class of oxidation reactions leading to the
same dimer (cf. ref 22 and references therein), among them
anodic oxidation,20 oxidation via nitrosation,45 where the
intermediate S-nitroso cation may be expected to lose nitric
oxide by homolysis,46 and action by oxidants such as chlorine
dioxide47 or methylene blue.48 In radiolysis, the intermediacy,
over a large pH range, of the dimeric thiourea radical cation
has now been unequivocally established. It can be fairly assumed
that this species plays a dominant role in many of these other
processes as well.
Final Products. There is circumstantial evidence10 that
essentially the only primary product of thiourea radiolysis in
aqueous solution is the formamidinium disulfide. The formation
of elemental sulfur and other products such as guanidylthiourea,
guanidine, cyanamide, and dicyandiamide that have been
observed in thiourea radiolytic systems in the past9,10 can in
most cases be explained through the rearrangement and subse-
quent hydrolytic14 or oxidative degradation of the primarily
formed formamidinium disulfide.
Acknowledgment. This work is dedicated to Dr. K. U.
Ingold on the occasion of his 70th birthday. It has been
supported by the European Commission, Project No. F14P-
CP95-0011.
JA983275B
(44) Fromm, E. Liebigs Ann. Chem. 1906, 348, 144-160.
(45) Williams, D. L. H. J. Chem. Soc., Perkin Trans. 2 1977, 128-132.
(46) Schulz, U.; McCalla, D. R. Can. J. Chem. 1969, 47, 2021-2027.
(47) Rabai, G.; Wang, R. T.; Kustin, K. Int. J. Chem. Kinet. 1993, 25,
53-62.
(48) Bhagava, R.; Mishra, K. K. Phosphorus, Sulfur, Silicon 1991, 63,
71-79.
The formamidinium disulfide dication is stable under acidic
conditions14,22 but begins to undergo hydrolysis to the unstable
(42) Land, E. J.; Porter, G.; Strachan, E. Trans. Faraday Soc. 1961, 57,
1885-1893.
(43) Bansal, K. M.; Fessenden, R. W. Radiat. Res. 1976, 67, 1-8.