Metal ion effect on the switch of mechanism from direct oxygen transfer to metal ion-coupled electron transfer in the sulfoxidation of thioanisoles by a non-heme iron(IV)-oxo complex

Article abstract of DOI:10.1021/ja200901n

The mechanism of sulfoxidation of thioaniosoles by a non-heme iron(IV)-oxo complex is switched from direct oxygen transfer to metal ion-coupled electron transfer by the presence of Sc³⁺. The switch in the sulfoxidation mechanism is dependent on the one-electron oxidation potentials of thioanisoles. The rate of sulfoxidation is accelerated as much as 10²-fold by the addition of Sc³⁺.(Figure Presented)

Full text of DOI:10.1021/ja200901n

COMMUNICATION
pubs.acs.org/JACS
Metal Ion Effect on the Switch of Mechanism from Direct Oxygen
Transfer to Metal Ion-Coupled Electron Transfer in the Sulfoxidation of
Thioanisoles by a Non-Heme Iron(IV)ꢀOxo Complex
Jiyun Park,† Yuma Morimoto,‡ Yong-Min Lee,† Wonwoo Nam,*,† and Shunichi Fukuzumi*,†,‡
†Department of Bioinspired Science, Ewha Womans University, Seoul 120-750, Korea
‡Department of Material and Life Science, Graduate School of Engineering, Osaka University, Suita, Osaka 565-0871, Japan
S Supporting Information
b
Scheme 1
ABSTRACT: The mechanism of sulfoxidation of thioanio-
soles by a non-heme iron(IV)ꢀoxo complex is switched
from direct oxygen transfer to metal ion-coupled electron
transfer by the presence of Sc3þ. The switch in the sulfox-
idation mechanism is dependent on the one-electron oxida-
tion potentials of thioanisoles. The rate of sulfoxidation is
accelerated as much as 102-fold by the addition of Sc3þ
.
xygen atom transfer (OAT) from high-valent metalꢀoxo
O
species to organic or inorganic substrates is ubiquitous in
biological and catalytic oxygenation processes.1 Extensive efforts
have been devoted to clarifying the mechanisms of OAT reactions of
iron(IV)ꢀoxo complexes bearing heme and non-heme ligands as
chemical models of cytochromes P450 (CYP 450) and non-heme
iron oxygenases, respectively.2 In sulfoxidation reactions, two
plausible mechanisms for the oxidation of sulfides by high-valent
metalꢀoxo complexes have been proposed:3ꢀ5 direct oxygen
transfer (DOT) and electron transfer followed by oxygen transfer
(ETOT). As shown in Scheme 1, sulfoxide [ArS(O)R] is formed
either by DOT from a metalꢀoxo species [Mnþ(O)] to sulfide
(ArSR) (i.e., DOT mechanism, pathway a) or by electron transfer
from ArSR to Mnþ(O) followed by OAT from M(nꢀ1)þ(O) to the
radical cation (ArSR•þ) (i.e., ETOT mechanism, pathways b and c).
Although the mechanisms of the oxidation of sulfides by high-
valent ironꢀoxo intermediates of CYP 450 and model compounds
have been extensively investigated experimentally and theoretically,4,6
non-heme iron(IV)ꢀoxo species have rarely been explored in the
mechanistic studies of sulfoxidation reactions.7 We report herein the
remarkable effects of a metal ion (i.e., Sc3þ) in accelerating the
reaction rate and changing the mechanism from DOT to ETOT in
the sulfoxidation of thioanisoles by a non-heme iron(IV)ꢀoxo
complex, [(N4Py)FeIV(O)]2þ [N4Py = N,N-bis(2-pyridylmethyl)-
N-bis(2-pyridyl)methylamine].8ꢀ10 The role of the metal ion in the
sulfoxidation reactions is discussed as well.
Figure 1. Changes in the visible spectrum observed in the reaction of
[(N4Py)FeIV(O)]2þ (0.50 mM) with p-methylthioanisole (5.0 mM) in
the (a) absence and (b) presence of Sc3þ (10 mM) in CH3CN at 298 K
(left panels). The right panels show time courses monitored at 695 nm.
(OTf = CF3SO3ꢀ), the reaction was remarkably accelerated, and the
time course was monitored using a stopped-flow spectrometer
(Figure 1b).10 The rate obeyed pseudo-first-order kinetics [Figure
S1 in the Supporting Information (SI)], and the pseudo-first-order
rate constant increased linearly with increasing concentration of p-
methylthioanisole (Figure S2). The second-order rate constant (kobs)
was obtained from the slope of the linear correlation between the
Sulfoxidaton of para-substituted thioanisoles by [(N4Py)-
FeIV(O)]2þ has been suggested to occur via an electrophilic reaction
that quantitatively gives the corresponding methyl phenyl sulfoxides
and an FeII complex as products.7 As shown in Figure 1a, the time
course of the reaction of [(N4Py)FeIV(O)]2þ with p-methylthioa-
nisole was readily monitored by the decrease in the absorbance due to
[(N4Py)FeIV(O)]2þ (λmax =695nm).8 InthepresenceofSc(OTf)3
Received: January 29, 2011
Published: March 16, 2011
r
2011 American Chemical Society
5236
dx.doi.org/10.1021/ja200901n J. Am. Chem. Soc. 2011, 133, 5236–5239
|

Journal of the American Chemical Society
COMMUNICATION
Figure 3. Plot of log kobs for oxidation of para-X-substituted thioanisoles
[X = (1) Me, (2) H, (3) Cl, (4) Br, (5) CN, (6) NO2] by [(N4Py)
FeIV(O)]2þ in MeCN at 298 K vs the driving force for electron transfer
[ꢀΔGet = e(Ered ꢀ Eox)] from the thioanisoles to [(N4Py)FeIV(O)]2þ in
the absence of Sc3þ (black b) and the presence of 10 mM Sc3þ (red b).
The blue O show the driving-force dependence of the rate constants (log
ket) for electron transfer to [(N4Py)FeIV(O)]2þ from the one-electron
reductants (7) [FeII(Ph2-Phen)3]2þ, (8) [FeII(bpy)3]2þ, (9) [RuII(Me2-
bpy)3]2þ, (10) [FeII(Cl-phen)3]2þ, and (11) [RuII(bpy)3]2þ) in the
presence of Sc3þ (10 mM) in MeCN at 298 K.
Figure 2. Plots of kobs vs Sc3þ concentration in the oxidation of para-X-
substituted thioanisoles [X = (a) Me, (b) H, (c) Cl, (d) CN] by
[(N4Py)FeIV(O)]2þ in MeCN at 298 K.
pseudo-first-order rate constant and the concentration of p-
methylthioanisole.
The dependence of kobs on [Sc3þ] for the reaction of
[(N4Py)FeIV(O)]2þ with p-methylthioanisole is shown in
Figure 2a. The kobs value increased, exhibiting a first-order
dependence on [Sc3þ] at low concentrations and a second-order
dependence at high concentrations (eq 1):
in the presence of 10 mM Sc3þ.11,15a In the absence of Sc3þ, ꢀΔGet is
largely negative. This indicates that electron transfer from the
thioanisoles to [(N4Py)FeIV(O)]2þ is highly endergonic and there-
fore quite unlikely to occur. In such a case, the DOT pathway
(Scheme 1a) predominates over the ETOT pathway (Scheme 1b,c),
and the kobs values are only slightly dependent on the ꢀΔGet values.
In contrast, the log kobs values obtained in the presence of Sc3þ
increased remarkably with increasing ꢀΔGet. In the case of
p-methylthioanisole, the free-energy change for electron transfer
becomes negative. In such a case, the ETOT pathway (Scheme 1b,c)
becomes dominant over the DOT pathway (Scheme 1a). The
dependence of log kobs on the driving force for electron transfer
(ꢀΔGet) in the presence of Sc3þ (red line in Figure 3) is remarkably
parallel to that of log ket for actual electron transfer from one-electron
reductants to [(N4Py)FeIV(O)]2þ (blue line in Figure 3). The
driving-force dependence of both the rate constants for sulfoxidation
of thioanisoles by [(N4Py)FeIV(O)]2þ and electron transfer from
one-electron reductants to [(N4Py)FeIV(O)]2þ in the presence of
10 mM Sc3þ was well-fitted in light of the Marcus theory of adiabatic
outer-sphere electron transfer (eq 2):
ꢀ
ꢁ
kobs ¼ k0 þ ½Sc3þꢁ k1 þ k2½Sc3þꢁ
ð1Þ
where k0 is the rate constant for the sulfoxidation of a para-substituted
thioanisole derivative by [(N4Py)FeIV(O)]2þ (5.0 ꢂ 10ꢀ4 M) in
the absence of Sc3þ. The k1 and k2 values were determined from the
intercept and slope, respectively, of the linear plot of (kobs ꢀ k0)/-
[Sc3þ] vs [Sc3þ] (Figure S3). The kobs value p-methylthioanisole in
the presence of 10 mM Sc3þ was 8.4 ꢂ 10 Mꢀ1 sꢀ1, which is ∼102-
fold larger than the value determined in the absence of Sc3þ. The
dependence of the first- and second-order rate constants on the
concentration of Sc3þ was reported previously for metal ion-coupled
electron transfer from one-electron reductants to [(N4Py)FeIV-
(O)]2þ, and this was ascribed to binding of one Sc3þ ion and two
Sc3þ ions to [(N4Py)FeIV(O)]2þ, respectively.11ꢀ14
Similar remarkable acceleration effects of Sc3þ were observed in
the reactions of [(N4Py)FeIV(O)]2þ with para-X-substituted thio-
anisoles with X = H, Cl, and Br (Figure 2b,c and Figure S4). When a
strongly electron-withdrawing substituent (X = CN, NO2) was
employed, however, only a small acceleration was observed, as
shown for X = CN in Figure 2d (see Figure S4 for X = NO2).
The reason that the acceleration effect of Sc3þ is quite different
depending on the substituent X can be explained by plots of log kobs
versus the driving force for electron transfer from the thioanisole to
[(N4Py)FeIV(O)]2þ (ꢀΔGet) in the absence and presence of
Sc3þ, as shown in Figure 3. The ΔGet values were obtained from the
difference between the one-electron oxidation potentials of the
thioanisoles (Eox vs SCE)4a and the one-electron reduction poten-
tials of [(N4Py)FeIV(O)]2þ (Ered vs SCE) in the absence and
presence of Sc3þ.11,15 It should be noted that the Eox values of the
thioanisoles did not change in the presence of Sc3þ, whereas the Ered
value of [(N4Py)FeIV(O)]2þ was significantly shifted in the positive
direction from 0.51 V vs SCE in the absence of Sc3þ to 1.19 V vs SCE
"
#
2
λ ð1 þ ΔGet=λÞ
ket ¼ Z exp ꢀ
ð2Þ
4
kBT
where Z is the collision frequency (taken as 1 ꢂ 1011 Mꢀ1 sꢀ1), λ is
the reorganization energy for electron transfer, kB is the Boltzmann
constant, and T is the absolute temperature.15,16 The best-fit λ value
for electron transfer in sulfoxidation of thioanisoles was determined
to be 2.02 eV, which agrees reasonably well with the λ value for
electron transfer from one-electron reductants (2.27 eV).17 Such an
agreement with the Marcus equation indicates that the sulfoxidation
of thioanisoles by [(N4Py)FeIV(O)]2þ in the presence of Sc3þ
proceeds via Sc3þ ion-coupled electron transfer from thioanisoles to
[(N4Py)FeIV(O)]2þ, which is the rate-determining step, followed
5237
dx.doi.org/10.1021/ja200901n |J. Am. Chem. Soc. 2011, 133, 5236–5239

Journal of the American Chemical Society
COMMUNICATION
’ ACKNOWLEDGMENT
The research at EWU was supported by KRF/MEST of Korea
through CRI (to W.N.) and GRL (2010-00353) and WCU
(R31-2008-000-10010-0) (to S.F. and W.N.). The work at OU
was supported by a Grant-in-Aid (20108010) and a Global COE
Program, “the Global Education and Research Center for Bio-
Environmental Chemistry”, from the Ministry of Education,
Culture, Sports, Science, and Technology, Japan (to S.F.)
’ REFERENCES
(1) (a) Biological Inorganic Chemistry: Structure and Reactivity;
Bertini, I., Gray, H. B., Stiefel, E. I., Valentine, J. S., Eds.; University
Science Books: Sausalito, CA, 2007. (b) Ortiz de Montellano, P. R.
Cytochrome P450: Structure, Mechanism, and Biochemistry, 3rd ed.;
Kluwer Academic/Plenum Publishers: New York, 2005. (c) Biomimetic
Oxidations Catalyzed by Transition Metal Complexes; Meunier, B., Ed.;
Imperial College Press: London, 2000.
Figure 4. Difference UVꢀvis spectral changes in the reaction of
[(N4Py)FeIV(O)]2þ (1.0 ꢂ 10ꢀ4 M) with p-methoxythioanisole (4.0
ꢂ 10ꢀ3 M) in the presence of Sc3þ (4.0 ꢂ 10ꢀ3 M) in MeCN at 298 K.
The inset shows the time courses monitored at 580 nm for p-metho-
xythioanisole radical cation and 695 nm for [(N4Py)FeIV(O)]2þ
.
(2) (a) Nam, W. Acc. Chem. Res. 2007, 40, 465 and review articles in
the special issue. (b) Meunier, B.; de Visser, S. P.; Shaik, S. Chem. Rev.
2004, 104, 3947. (c) Abu-Omar, M. M.; Loaiza, A.; Hontzeas, N. Chem.
Rev. 2005, 105, 2227. (d) Espenson, J. H. Coord. Chem. Rev. 2005,
249, 329. (e) Denisov, I. G.; Makris, T. M.; Sligar, S. G.; Schlichting, I.
Chem. Rev. 2005, 105, 2253. (f) Borovik, A. S. Acc. Chem. Res. 2005,
38, 54. (g) Bakac, A. Coord. Chem. Rev. 2006, 250, 2046. (h) Krebs, C.;
Fujimori, D. G.; Walsh, C. T.; Bollinger, J. M., Jr. Acc. Chem. Res. 2007,
40, 484. (i) Nam, W. Acc. Chem. Res. 2007, 40, 522. (j) Comba, P.; Kerscher,
M.; Schiek, W. Prog. Inorg. Chem. 2007, 55, 613.
(3) (a) Arias, J.; Newlands, C. R.; Abu-Omar, M. M. Inorg. Chem.
2001, 40, 2185. (b) Fertinger, C.; Hessenauer-Ilicheva, N.; Franke, A.;
van Eldik, R. Chem.—Eur. J. 2009, 15, 13435. (c) Arunkumar, C.; Lee,
Y.-M.; Lee, J. Y.; Fukuzumi, S.; Nam, W. Chem.—Eur. J. 2009, 15, 11482.
(d) Kumar, A.; Goldberg, I.; Botoshansky, M.; Buchman, Y.; Gross, Z. J.
Am. Chem. Soc. 2010, 132, 15233. (e) Benet-Buchholz, J.; Comba, P.;
Llobet, A.; Roeser, S.; Vadivelu, P.; Wiesner, S. Dalton Trans. 2010,
39, 3315.
(4) (a) Goto, Y.; Matsui, T.; Ozaki, S.; Watanabe, Y.; Fukuzumi, S. J.
Am. Chem. Soc. 1999, 121, 9497. (b) Baciocchi, E.; Gerini, M. F.;
Lanzalunga, O.; Lapi, A.; Lo Piparo, M. G. Org. Biomol. Chem. 2003,
1, 422.
(5) Khenkin, A. M.; Leitus, G.; Neumann, R. J. Am. Chem. Soc. 2010,
132, 11446.
(6) (a) Shaik, S.; Wang, Y.; Chen, H.; Song, J.; Meir, R. Faraday
Discuss. 2010, 145, 49. (b) Porro, C. S.; Sutcliffe, M. J.; de Visser, S. P. J.
Phys. Chem. A 2009, 113, 11635. (c) Kumar, D.; de Visser, S. P.; Sharma,
P. K.; Hirao, H.; Shaik, S. Biochemistry 2005, 44, 8148. (d) Sharma, P. K.;
de Visser, S. P.; Shaik, S. J. Am. Chem. Soc. 2003, 125, 8698.
(7) Park, M. J.; Lee, J.; Suh, Y.; Kim, J.; Nam, W. J. Am. Chem. Soc.
2006, 128, 2630.
by rapid OAT from [(N4Py)FeIII(O)]þ to the radical cation
(ArSR•þ), as described in Scheme 1b,c.
When the ΔGet value becomes more negative than 0.4 eV, the
ket value becomes smaller than the kobs value for DOT. Thus, the
borderline between the DOT pathway (Scheme 1a) and the
ETOT pathway (Scheme 1b,c) may be determined by the Eox
value of the para-X-substituted thioanisole, ∼1.6 V vs SCE, that
corresponds to p-cyanothioanisole.
The occurrence of electron transfer is clearly shown in the case
of p-methoxythioanisole in the presence of Sc3þ (4 mM), where
the driving force for electron transfer is positive (ꢀΔGet = 0.01 eV).
As shown in Figure 4, the transient absorption band at 580 nm
due to p-methoxythioanisole radical cation appears, accompanied
by a decrease in the absorption band at 695 nm due to [(N4Py)
FeIV(O)]2þ (for the reference spectrum of p-methoxyanisole
radical cation, see Figure S5).18 This result clearly demonstrates
that the ETOT pathway becomes dominant over the DOT pathway
when the sulfoxidation by the iron(IV)ꢀoxo complex is carried out
in the presence of a metal ion (Scheme 1).
In summary, we have demonstrated that Sc3þ ion promotes
sulfoxidation of thioanisoles significantly via Sc3þ ion-coupled
electron transfer and that the borderline between a direct oxygen
atom transfer pathway (Scheme 1a) and an electron-transfer
pathway (Scheme 1b,c) is determined by the Eox value of
thioanisole that is ∼1.6 V vs SCE. Thus, the present study
provides a new and rational way to enhance the reactivity of high-
valent metalꢀoxo species by binding of redox-inactive metal ions
such as Sc3þ. The generality of this idea is under investigation.
(8) Kaizer, J.; Klinker, E. J.; Oh, N. Y.; Rohde, J.-U.; Song, W. J.;
Stubna, A.; Kim, J.; M€unck, E.; Nam, W.; Que, L., Jr. J. Am. Chem. Soc.
2004, 126, 472.
(9) An acceleration effect of metal ions (including Sc3þ) on OAT
from high-valent manganeseꢀoxo complexes to triphenylphosphine or
olefins has been reported, although the acceleration mechanism has yet
to be clarified. See: Miller, C. G.; Gordon-Wylie, S. W.; Horwitz, C. P.;
Strazisar, S. A.; Peraino, D. K.; Clark, G. R.; Weintraub, S. T.; Collins,
T. J. J. Am. Chem. Soc. 1998, 120, 11540.
’ ASSOCIATED CONTENT
S
Supporting Information. Experimental details, second-
b
order rate constants (Table S1), pseudo-first-order kinetics
(Figure S1), second-order kinetics (Figures S2), the linear plot
of (kobs ꢀ k0)/[Sc3þ] vs [Sc3þ] (Figure S3), the dependence of
kobs on [Sc3þ] for other substrates (Figure S4), and UVꢀvis
spectra for p-MeO-PhSMe•þ (Figure S5). This material is
available free of charge via the Internet at http://pubs.acs.org.
(10) The products and product yields formed in the presence of
Sc3þ were the same as those reported in the reactions carried out in the
absence of Sc3þ (see ref 7 and the Experimental Section in the SI).
(11) Morimoto, M.; Kotani, H.; Park, J.; Lee, Y.-M.; Nam, W.;
Fukuzumi, S. J. Am. Chem. Soc. 2011, 133, 403.
(12) An X-ray crystal structure of a Sc3þ-bound iron(IV)ꢀoxo
complex has been reported. See: (a) Fukuzumi, S.; Morimoto, Y.;
Kotani, H.; Naumov, P.; Lee, Y.-M.; Nam, W. Nat. Chem. 2010,
2, 756. (b) Karlin, K. D. Nat. Chem. 2010, 2, 711.
’ AUTHOR INFORMATION
Corresponding Author
wwnam@ewha.ac.kr; fukuzumi@chem.eng.osaka-u.ac.jp
5238
dx.doi.org/10.1021/ja200901n |J. Am. Chem. Soc. 2011, 133, 5236–5239

Journal of the American Chemical Society
COMMUNICATION
(13) For metal ion-coupled electron transfer, see: (a) Fukuzumi, S.
Prog. Inorg. Chem. 2009, 56, 49. (b) Fukuzumi, S. Bull. Chem. Soc. Jpn.
1997, 70, 1. (c) Fukuzumi, S.; Ohkubo, K. Coord. Chem. Rev. 2010,
254, 372.
(14) Sc3þ ion is known to be most the effective for metal
ion-coupled electron transfer. See: Fukuzumi, S.; Ohkubo, K. Chem.—Eur.
J. 2000, 6, 4532.
(15) (a) Lee, Y.-M.; Kotani, H.; Suenobu, T.; Nam, W.; Fukuzumi, S.
J. Am. Chem. Soc. 2008, 130, 434. (b) Fukuzumi, S.; Kotani, H.; Suenobu,
T.; Hong, S.; Lee, Y.-M.; Nam, W. Chem.—Eur. J. 2010, 16, 354.
(16) (a) Marcus, R. A. Annu. Rev. Phys. Chem. 1964, 15, 155. (b)
Marcus, R. A. Angew. Chem., Int. Ed. Engl. 1993, 32, 1111.
(17) The slightly smaller λ value for thioanisoles than that for metal
complexes may be ascribed to the delocalization of the charge in the π-
radical cations. See: Eberson, L. Electron-Transfer Reactions in Organic
Chemistry: Reactivity and Structure; Springer: Berlin, 1987; Vol. 25.
(18) Yokoi, H.; Hatta, A.; Ishiguro, K.; Sawaki, Y. J. Am. Chem. Soc.
1998, 120, 12728.
5239
dx.doi.org/10.1021/ja200901n |J. Am. Chem. Soc. 2011, 133, 5236–5239