A mechanistic dichotomy in scandium ion-promoted hydride transfer of an NADH analogue: Delicate balance between one-step hydride-transfer and electron-transfer pathways

Article abstract of DOI:10.1021/ja064708a

The rate constant (k_H) of hydride transfer from an NADH analogue, 9,10-dihydro-10-methylacridine (AcrH₂), to 1-(p-tolylsulfinyl)-2,5-benzoquinone (TolSQ) increases with increasing Sc ³⁺ concentration ([Sc³⁺]) to reach a constant value, when all TolSQ molecules form the TolSQ-Sc³⁺ complex. When AcrH ₂ is replaced by the dideuterated compound (AcrD₂), however, the rate constant (k_D) increases linearly with an increase in [Sc³⁺] without exhibiting a saturation behavior. In such a case, the primary kinetic deuterium isotope effect (k_H/k_D) decreases with increasing [Sc³⁺]. On the other hand, the rate constant of Sc³⁺-promoted electron transfer from tris(2- phenylpyridine)iridium [Ir(ppy)₃] to TolSQ also increases linearly with increasing [Sc³⁺] at high concentrations of Sc³⁺ due to formation of a 1:2 complex between TolSQ^?- and Sc ³⁺, [TolSQ^?- (Sc³⁺)₂], which was detected by ESR. The significant difference with regard to dependence of the rate constant of hydride transfer on [Sc³⁺] between AcrH₂ and AcrD² in comparison with that of Sc³⁺-promoted electron transfer indicates that the reaction pathway is changed from one-step hydride transfer from AcrH₂ to the TolSQ-Sc³⁺ complex to Sc³⁺-promoted electron transfer from AcrD₂ to the TolSQ-Sc³⁺ complex, followed by proton and electron transfer. Such a change between two reaction pathways, which are employed simultaneously, is also observed by simple changes of temperature and concentration of Sc³⁺.

Full text of DOI:10.1021/ja064708a

Published on Web 10/17/2006
A Mechanistic Dichotomy in Scandium Ion-Promoted Hydride
Transfer of an NADH Analogue: Delicate Balance between
One-Step Hydride-Transfer and Electron-Transfer Pathways
Junpei Yuasa, Shunsuke Yamada, and Shunichi Fukuzumi*
Contribution from the Department of Material and Life Science, DiVision of AdVanced Science
and Biotechnology, Graduate School of Engineering, Osaka UniVersity, SORST, Japan Science
and Technology Agency (JST), Suita, Osaka 565-0871, Japan
Received July 6, 2006; E-mail: fukuzumi@chem.eng.osaka-u.ac.jp
Abstract: The rate constant (kH) of hydride transfer from an NADH analogue, 9,10-dihydro-10-methylacridine
(AcrH2), to 1-(p-tolylsulfinyl)-2,5-benzoquinone (TolSQ) increases with increasing Sc3+ concentration ([Sc3+])
to reach a constant value, when all TolSQ molecules form the TolSQ-Sc3+ complex. When AcrH2 is replaced
by the dideuterated compound (AcrD2), however, the rate constant (kD) increases linearly with an increase
in [Sc3+] without exhibiting a saturation behavior. In such a case, the primary kinetic deuterium isotope
effect (kH/kD) decreases with increasing [Sc3+]. On the other hand, the rate constant of Sc3+-promoted
electron transfer from tris(2-phenylpyridine)iridium [Ir(ppy)3] to TolSQ also increases linearly with increasing
[Sc3+] at high concentrations of Sc3+ due to formation of a 1:2 complex between TolSQ•- and Sc3+, [TolSQ•--
(Sc3+)2], which was detected by ESR. The significant difference with regard to dependence of the rate
constant of hydride transfer on [Sc3+] between AcrH2 and AcrD2 in comparison with that of Sc3+-promoted
electron transfer indicates that the reaction pathway is changed from one-step hydride transfer from AcrH2
to the TolSQ-Sc3+ complex to Sc3+-promoted electron transfer from AcrD2 to the TolSQ-Sc3+ complex,
followed by proton and electron transfer. Such a change between two reaction pathways, which are employed
simultaneously, is also observed by simple changes of temperature and concentration of Sc3+
.
Introduction
has been a long standing ambiguity as to the mechanistic
borderline in the hydride-transfer reactions of NADH and
analogues (Scheme 1).2-6
Dihydronicotinamide adenine dinucleotide (NADH) acts as
an important source of two electrons and a proton (equivalent
to a hydride ion) in biological redox systems.1 There is a
mechanistic dichotomy whether hydride transfer from NADH
and analogues to a hydride acceptor (A) occurs via one-step
hydride transfer (H-) or electron transfer followed by proton-
electron transfer (e- + H+ + e-) as shown in Scheme 1.2-6
The mechanistic borderline between one-step and multistep
reactions has always been of large general interest to chemists.
Do the mechanisms merge at the borderline; i.e., is there a
mechanistic continuity. Or are both pathways employed
simultaneously? Mechanisms of hydride-transfer reactions of
NADH analogues have so far been extensively studied in the
reactions with various inorganic7-12 and organic13-24 sub-
strates including the effect of metal ions.25-31 However, there
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14938
J. AM. CHEM. SOC. 2006, 128, 14938-14948
10.1021/ja064708a CCC: $33.50 © 2006 American Chemical Society

Sc Ion-Promoted Hydride Transfer of NADH Analogue
A R T I C L E S
Scheme 1
The effects of the metal ion on the mechanistic borderline in
the hydride-transfer reactions of NADH and analogues have
particularly attracted interest because of the essential role of
metal ions in the redox reactions of nicotinamide coenzymes
in the native enzymatic system.3-5,25-31 Metal ions (Mn+) acting
as a Lewis acid are known to promote hydride-transfer reactions
of NADH analogues25-31 as well as electron transfer from
electron donors (D) to electron acceptors, such as p-benzo-
quinones (Q), which have been commonly used in the hydride-
transfer and electron-transfer reactions of NADH analogues,
where Mn+ bind to the product radical anion.32-41 Semiquinone
radical anions (Q•-) derived from p-benzoquinones form not
only simple 1:1 complexes (Q•--Mn+) with Mn+ but also more
intricate complexes with Mn+, i.e., 1:2 complexes [Q•--(Mn+)2]
as shown in Scheme 2a.29,32 In such a case, the rate constants
of Mn+-promoted electron-transfer reactions increase with
increasing Mn+ concentration ([Mn+]), exhibiting a second-order
dependence on [Mn+] at high concentrations due to formation
of the 1:2 complexes [Q•--(Mn+)2] (Scheme 2a).29,32 Virtually
the same second-order dependence is observed in Mn+-promoted
hydride-transfer reactions of NADH analogues, such as 1-ben-
zyl-1,4-dihydronicotinamide (BNAH), when the hydride-transfer
reactions proceed via an electron-transfer pathway, which is
promoted by the formation of 1:2 complexes [Q•--(Mn+)2]
(Scheme 2b).29,32 In contrast to the case of an electron-transfer
pathway, a one-step hydride-transfer pathway is not promoted
by Mn+, because Mn+ has generally no interaction with Q.29,32
If a hydride acceptor (A) has a metal ion-binding site, the
complex formation of A with Mn+ (A-Mn+), which results in
enhancement of both electrophilicity and electron-acceptor
ability of A, would provide a delicate balance between the two
reaction pathways.42 However, the mechanistic borderline
between the two reaction pathways in Mn+-promoted hydride-
transfer reactions of NADH analogues has yet to be clarified,
despite the important role of NADH in biological redox systems.
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J. AM. CHEM. SOC. VOL. 128, NO. 46, 2006 14939

A R T I C L E S
Scheme 2
Yuasa et al.
from ethanol.46 Synthesis of dideuterated 9,10-dihydro-10-methylacri-
dine (AcrD2) was described previously.47 Tris(2-phenylpyridine)iridium
[Ir(ppy)3] was prepared according to the literature.48 Scandium triflate
[Sc(OTf)3] (99%) was purchased from Pacific Metals Co., Ltd.
(Taiheiyo Kinzoku). 10,10′-Dimethyl-9,9′-biacridine [(AcrH)2] was
prepared by the one-electron reduction of 10-methylacridinium per-
chlorate by hexamethylditin.49a Acetonitrile (MeCN) used as a solvent
was purified and dried according to the standard procedure.50
[2H3]Acetonitrile (CD3CN) was obtained from EURI SO-TOP, CEA,
France. [2H2]Water (D2O) was purchased from Cambridge Isotope
Laboratories. Tetra-n-butylammonium perchlorate (TBAP) was pur-
chased from Fluka Chemical Co., twice recrystallized from absolute
ethanol, and dried in a vacuum at 45 °C prior to use.
In this paper, we demonstrate the delicate balance between
one-step hydride-transfer and electron-transfer pathways in a
scandium ion (Sc3+)-promoted hydride-transfer reaction of an
NADH analogue, 9,10-dihydro-10-methylacridine (AcrH2), is
changed by deuterium substitution of AcrH2 by AcrD2 and also
by simple changes of temperature and Sc3+ concentration.43 We
have introduced a metal ion-binding site into p-benzoquinone
to employ 1-(p-tolylsulfinyl)-2,5-benzoquinone (TolSQ) as a
hydride acceptor. Sc3+, which is one of the strongest Lewis acids
among metal ions,32 can form a complex with TolSQ, and this
is the reason we chose Sc3+ to increase both electron- and
hydride-acceptor abilities of TolSQ.43 The TolSQ-Sc3+ com-
plex is a common reactive intermediate in both Sc3+-promoted
hydride transfer from AcrH2 to TolSQ and Sc3+-promoted
electron transfer from tris(2-phenylpyridine)iridium [Ir(ppy)3]44
to TolSQ. The direct ESR detection of Sc3+ complexes of a
semiquinone radical anion (TolSQ•-), combined with the kinetic
analysis of Sc3+-promoted electron-transfer and hydride-transfer
reactions, provides valuable insight into the mechanistic bor-
derline between one-step hydride-transfer and electron-transfer
Reaction Procedures and Analysis. Typically, AcrH2 (2.8 × 10-2
M) was added to an NMR tube that contained an [2H3]acetonitrile (CD3-
CN) solution (0.6 mL) of TolSQ (1.0 × 10-2 M) in the presence of
Sc3+ (3.0 × 10-2 M) under an atmospheric pressure of argon. Then
the solution was deaerated with argon gas for 5 min, and the NMR
tube was sealed with a rubber septum. The reaction was complete in 1
min under these conditions. The product of the hydride reduction of
TolSQ, 1-(p-tolylsulfinyl)-2,5-benzohydroquinone (TolSQH2), was
identified by comparing the 1H NMR spectra with those in the
literatures.51 The total yield of TolSQH2 was determined to be 99%
pathways as well as the mechanistic changeover in a Sc3+
-
1
from the H NMR spectra in comparison with the internal standard,
promoted hydride-transfer reaction of an NADH analogue for
the first time.
1,4-dioxane (7.1 × 10-2 M). 1H NMR measurements were performed
with a JMN-AL-300 (300 MHz) NMR spectrometer at 298 K.
TolSQH2: 1H NMR (300 MHz, CD3CN) in the presence of Sc3+ (3.0
× 10-2 M):52 δ (ppm) 7.58 (d, J ) 8.3 Hz, 2H), 7.33 (d, J ) 8.3 Hz,
2H), 6.96 (d, J ) 2.9 Hz, 1H), 6.80 (dd, J ) 2.9 Hz, 8.4 Hz, 1H), 6.71
(d, J ) 8.4 Hz, 1H), 2.37 (s, 3H).
Experimental Section
Materials. 1-(p-Tolylsulfinyl)-2,5-benzoquinone (TolSQ) was pre-
pared according to the literature.45 9,10-Dihydro-10-methylacridine
(AcrH2) was synthesized by the reduction of 10-methylacridinium iodide
(AcrH+I-) with NaBH4 in methanol and purified by recrystallization
Spectral Measurements. Formation of Sc3+ complexes of TolSQ
[TolSQ-Sc3+] was examined from the UV-vis spectral change of
(46) Roberts, R. M. G.; Ostovic, D.; Kreevoy, M. M. Faraday Discuss. Chem.
Soc. 1982, 74, 257.
(42) We have previously demonstrated that an electrophilicity of the carbonyl
compound methyl vinyl ketone (MVK) is significantly increased by the
complex formation with a scandium ion (Sc3+), which enhances both the
Diels-Alder reaction of anthracenes with MVK and photoinduced electron
transfer from electron donors to MVK; see: Fukuzumi, S.; Yuasa, J.;
Miyagawa, T.; Suenobu, T. J. Phys. Chem. A 2005, 109, 3174.
(43) The formation constants of other metal ion complexes of TolSQ were not
large enough to be employed in this work.
(44) Cyclometalated Ir(III) complexes such as Ir(ppy)3 have been used as
outstanding phosphorescent materials for a wide variety of applications;
see: (a) Holder, E.; Langeveld, B. M. W.; Schubert, U. S. AdV. Mater.
2005, 17, 1109. (b) Wang, X.-Y.; Prabhu, R. N.; Schmehl, R. H.; Weck,
M. Macromolecules 2006, 39, 3140.
(47) Fukuzumi, S.; Tokuda, Y.; Kitano, T.; Okamoto, T.; Otera, J. J. Am. Chem.
Soc. 1993, 115, 8960.
(48) Dedeian, K.; Djurovich, P. I.; Garces, F. O.; Carlson, G.; Watts, R. J. Inorg.
Chem. 1991, 30, 1685.
(49) (a) Fukuzumi, S.; Kitano, T.; Mochida, K. J. Am. Chem. Soc. 1990, 112,
3246. (b) Fukuzumi, S.; Tokuda, Y. J. Phys. Chem. 1992, 96, 8409.
(50) Armarego, W. L. F.; Perrin, D. D. Purification of Laboratory Chemicals,
4th ed.; Butterworth-Heinemann: Boston, 1996.
(51) (a) Garc´ıa Ruano, J. L.; Alemparte, C. J. Org. Chem. 2004, 69, 1405. (b)
Carren˜o, M. C.; Garc´ıa Ruano, J. L.; Toledo, M. A.; Urbano, A. Tetrahedron
Lett. 1994, 35, 9759. (c) Carren˜o, M. C.; Garc´ıa Ruano, J. L.; Lafuente,
C.; Toledo, M. A. Tetrahedron: Asymmetry 1999, 10, 1119.
(52) Small amount of D2O [in D2O/CD3CN (1:10, v/v)] was added to the CD3-
CN solution of TolSQH2 in order to avoid the coordination of Sc3+ to
TolSQH2.
(45) (a) Grennberg, H.; Gogoll, A.; Ba¨ckvall, J.-E. J. Org. Chem. 1991, 56,
5808. (b) Carren˜o, M. C.; Garc´ıa Ruano, J. L.; Urbano, A. Tetrahedron
Lett. 1989, 30, 4003.
9
14940 J. AM. CHEM. SOC. VOL. 128, NO. 46, 2006

Sc Ion-Promoted Hydride Transfer of NADH Analogue
A R T I C L E S
TolSQ (1.0 × 10-3 M) at λ ) 343 nm in the presence of various
concentrations of Sc3+ [(0-5.7) × 10-3 M] by using a Hewlett-Packard
8453 diode array spectrophotometer.
Kinetic Measurements. Kinetic measurements were performed by
using a UNISOKU RSP-601 stopped-flow spectrophotometer with an
MOS-type high sensitive photodiode array. Rates of electron transfer
from Ir(ppy)3 (2.5 × 10-5 M) to TolSQ [(0-2.5) × 10-3 M] in the
presence of Sc3+ [(0-5.0) × 10-2 M] were monitored by the rise and
decay of the absorption band at 580 and 380 nm due to [Ir(ppy)3]+ and
Ir(ppy)3, respectively, in deaerated MeCN at 298 K. Rates of hydride
transfer from AcrH2 and AcrD2 (3.0 × 10-5 M) to TolSQ [(0-1.0) ×
10-3 M] in the presence of Sc3+ [(0-5.0) × 10-1 M] were monitored
by an increase in the absorption band due to a 10-methylacridinium
ion (AcrH+: λmax ) 358 nm, ꢀ max ) 1.80 × 104 M-1 cm-1) in deaerated
MeCN at 233-333 K in the dark. All kinetic measurements were carried
out under pseudo-first-order conditions where the concentrations of
TolSQ were maintained at more than 10-fold excess of the concentra-
tions of Ir(ppy)3 and AcrH2 at 298 K. Pseudo-first-order rate constants
were determined by least-squares curve fits using a personal computer.
Cyclic Voltammetry. Cyclic voltammetry measurements were
performed on a ALS 630 A electrochemical analyzer in deaerated
MeCN containing 0.1 M TBAP as a supporting electrolyte at 298 K.
A conventional three-electrode cell was used with a platinum working
electrode (surface area of 0.3 mm2) and a platinum wire as the counter
electrode. The Pt working electrode (BAS) was routinely polished with
a BAS polishing alumina suspension and rinsed with acetone before
use. The measured potentials were recorded with respect to the Ag/
AgNO3 (0.01 M) reference electrode. All potentials (vs Ag/Ag+) were
converted to values vs SCE by adding 0.29 V.53 All electrochemical
measurements were carried out under an atmospheric pressure of argon.
ESR Measurements. TolSQ (1.6 × 10-1 M) was dissolved in
deaerated MeCN and purged with argon for 10 min. Sc(OTf)3 (3.2 ×
10-2 M in 1.0 mL) was dissolved in deaerated MeCN. The TolSQ (200
µL) and Sc3+ (200 µL) solutions were introduced into an ESR cell
(1.8 mm i.d.) containing (AcrH)2 (1.6 × 10-2 M) and mixed by bubbling
with an Ar gas through a syringe with a long needle. The ESR spectra
of the Sc3+ complexes with the semiquinone radical anion of TolSQ
[TolSQ•--(Sc3+)] and [TolSQ•--(Sc3+)2] were recorded on a JEOL
JES-RE1XE spectrometer under irradiation of a high-pressure mercury
lamp (USH-1005D) focusing at the sample cell in the ESR cavity at
298 K. The magnitude of modulation was chosen to optimize the
resolution and signal-to-noise (S/N) ratio of the observed spectra under
nonsaturating microwave power conditions. The g values were cali-
brated using a Mn2+ marker. Computer simulation of the ESR spectra
was carried out by using Calleo ESR version 1.2 (Calleo Scientific
Publisher) on a personal computer.
Figure 1. UV-vis absorption spectra of TolSQ (1.0 × 10-3 M) in the
presence of Sc3+ [(0-5.7) × 10-3 M] in MeCN at 298 K. Inset: Plot of (A
- A0)/(A∞ - A) vs [Sc3+] - R[TolSQ]0, where R ) (A - A0)/(A∞ - A0) at
λ ) 343 nm.
to the complex formation between TolSQ and Sc3+ is expressed
by eq 2, where A0 and A∞ are absorbance due to TolSQ and
absorbance due to the TolSQ-Sc3+ complex at 343 nm, and
[TolSQ]0 denotes the initial concentration of TolSQ. The
formation constant (K) is determined as (2.5 ( 0.1) × 103 M-1
from a linear plot of (A - A0)/(A∞ - A) vs ([Sc3+] - R[TolSQ]0)
[R ) (A - A0)/(A∞ - A0)]; see inset of Figure 1.
(A - A0)/(A∞ - A) ) K{[Sc3+] - R[TolSQ]0}
(2)
Hydride transfer from an NADH analogue, 9,10-dihydro-10-
methylacridine (AcrH2), to TolSQ is expected to be accelerated
by the complex formation of TolSQ with Sc3+. In fact, hydride
transfer from AcrH2 to TolSQ occurs efficiently in the presence
of Sc3+ to yield the 10-methylacridinium ion (AcrH+) and 1-(p-
tolylsulfinyl)-2,5-benzohydroquinone (TolSQH2) in deaerated
MeCN at 298 K (eq 3; for the product analysis, see Experimental
Section), whereas no hydride-transfer reaction has occurred in
the absence of Sc3+. The spectral titration of AcrH2 by TolSQ
Results
Sc3+-Promoted Hydride Transfer from AcrH2 to TolSQ.
1-(p-Tolylsulfinyl)-2,5-benzoquinone (TolSQ) forms a 1:1
complex with the scandium ion (eq 1) as indicated by UV-vis
spectral changes of TolSQ in the presence of various concentra-
tions of Sc(OTf)3 [OTf ) OSO2CF3] in acetonitrile (MeCN) at
298 K as shown in Figure 1.54 Such an absorbance change due
(53) Mann, C. K.; Barnes, K. K. Electrochemical Reactions in Nonaqueous
Systems; Marcel Dekker: New York, 1990.
(54) The complex formation between TolSQ (2.0 × 10-2 M) and Sc3+ was also
confirmed by the 1H and 13C NMR. 1H NMR (300 MHz, CD3CN) in the
absence of Sc3+: δ (ppm) 7.65 (d, J ) 8.1 Hz, 2H), 7.35 (d, J ) 8.1 Hz,
2H), 7.24 (d, J ) 2.4 Hz, 1H), 6.82 (dd, J ) 2.4 Hz, 10.1 Hz, 1H), 6.73
(d, J ) 10.1 Hz, 1H), 2.38 (s, 3H). 1H NMR (300 MHz, CD3CN) in the
presence of Sc3+ (6.0 × 10-2 M): δ (ppm) 7.77 (d, J ) 8.7 Hz, 2H), 7.52
(d, J ) 2.2 Hz, 1H), 7.44 (d, J ) 8.7 Hz, 2H), 6.92 (dd, J ) 2.2 Hz, 10.1
Hz, 1H), 6.82 (d, J ) 10.1 Hz, 1H), 2.42 (s, 3H). 13C NMR (300 MHz,
CD3CN) in the absence of Sc3+: δ (ppm) 186.6, 185.2, 155.8, 144.3, 140.1,
138.7, 137.5, 132.9, 131.2, 127.3, 21.5. 13C NMR (300 MHz, CD3CN) in
the presence of Sc3+ (6.0 × 10-2 M): δ (ppm) 185.5, 184.1, 147.8, 147.6,
139.3, 137.1, 135.0, 132.4, 131.9, 129.4, 21.8.
was examined in order to confirm the stoichiometry in eq 3
(Figure 2). The ratio of the AcrH+ concentration to the initial
concentration of AcrH2 ([AcrH+]/[AcrH2]0) is plotted against
the ratio of the TolSQ concentration to the initial concentration
of AcrH2 ([TolSQ]/[AcrH2]0). All AcrH2 molecules are con-
sumed by the addition of 1 equiv of TolSQ to yield 1 equiv of
9
J. AM. CHEM. SOC. VOL. 128, NO. 46, 2006 14941

A R T I C L E S
Yuasa et al.
Figure 2. Absorption spectral changes observed upon addition of TolSQ
[(0-1.5) × 10-4 M] to a deaerated MeCN solution of AcrH2 (1.0 × 10-4
M) in the presence of Sc3+ (1.0 × 10-2 M) at 298 K. Inset: Plot of the
ratio of the AcrH+ concentration to the initial concentration of AcrH2 (1.0
× 10-4 M), [AcrH+]/[AcrH2]0, vs the ratio of the TolSQ concentration to
the initial concentration of AcrH2, [TolSQ]/[AcrH2]0.
AcrH+ (λmax ) 358 nm, ꢀmax ) 1.80 × 104 M-1 cm-1) as shown
in the inset of Figure 2.55,56
Rates of hydride transfer from AcrH2 to TolSQ in the
presence of Sc3+ were determined by monitoring an increase
in the absorption band due to AcrH+ in deaerated MeCN. The
rates obeyed pseudo-first-order kinetics in the presence of a large
excess of TolSQ and Sc3+ relative to the concentration of AcrH2
(see the first-order plots in Supporting Information S1). The
observed pseudo-first-order rate constants (kobs) increase pro-
portionally with TolSQ concentration (see Supporting Informa-
tion S2). Thus, the rate exhibits a second-order kinetics showing
a first-order dependence on each reactant concentration.
The dependence of the observed second-order rate constant
(kH) on [Sc3+] was examined for hydride transfer from AcrH2
to TolSQ at various concentrations of Sc3+ as shown in Figure
3a (red closed circles). The kH value increases with increasing
Sc3+ concentration to reach a constant value (kH ) 1.4 × 103
M-1 s-1). The rates of hydride transfer exhibit a large primary
kinetic deuterium isotope effect (kH/kD ) 5.3 ( 0.1) at low
concentrations ([Sc3+] < 1.0 × 10-2 M) when AcrH2 is replaced
by the dideuterated compound (AcrD2). In contrast to the case
of AcrH2, the observed second-order rate constant (kD) increases
linearly with an increase in [Sc3+] without exhibiting a saturation
behavior at high concentrations ([Sc3+] > 1.0 × 10-2 M) as
shown in Figure 3a (blue closed circles). The primary kinetic
deuterium isotope effect (kH/kD) therefore decreases with
increasing [Sc3+] at high concentrations ([Sc3+] > 1.0 × 10-2
M).57 The dependence of the observed second-order rate
constants (kH and kD) on [Sc3+] are changed drastically when
the temperature is lowered to 233 K, where both kH and kD
values increase linearly with increasing [Sc3+], exhibiting a
Figure 3. Dependence of kH (red closed circle) and kD (blue closed circle)
on [Sc3+] for hydride transfer from AcrH2 (3.0 × 10-5 M) and AcrD2 (3.0
× 10-5 M) to TolSQ in the presence of Sc3+ in deaerated MeCN at (a) 298
K and (b) 233 K.
primary kinetic deuterium isotope effect (kH/kD ) 2.6 ( 0.2)
irrespective of Sc3+ concentration as shown in Figure 3b (red
and blue closed circles, respectively).
The remarkable change with regard to the dependence of the
rate constant of hydride transfer on [Sc3+] by deuterium
substitution of AcrH2 by AcrD2, and also by simple change of
temperature indicates a mechanistic changeover in the hydride-
transfer reaction. In such a case, a temperature dependence of
rates of the hydride-transfer reactions would provide valuable
insight into the mechanistic changeover in the hydride-transfer
reaction: one-step hydride transfer and electron transfer fol-
lowed by proton-electron transfer. Thus, we examined the
temperature dependence of rates of hydride-transfer reactions
of AcrH2 and AcrD2 in the presence of high and low concentra-
tions of Sc3+ (2.5 × 10-1 M and 1.0 × 10-2 M, respectively).58
A plot of ln kH vs T-1 for the hydride-transfer reaction of
AcrH2 in the presence of a high concentration of Sc3+ (2.5 ×
10-1 M) is shown in Figure 4a (red open circles), where there
are two segments in the temperature range 233-298 K and
298-333 K with clearly different slopes. In contrast, a single
(55) There is no isosbestic point in the spectral titration of AcrH2 by TolSQ
after the 1:1 ratio of TolSQ to AcrH2, since the absorption band due to an
excess of TolSQ-Sc3+ is overlapped with the isosbestic points (269 and
310 nm).
(56) The source of a proton in eq 3 is a small amount of water (6.5 mM)
contained in MeCN.
(57) The kD values at higher concentrations of Sc3+ ([Sc3+] > 0.5 M) could not
be determined because Sc(OTf)3 was not soluble in MeCN at higher
concentrations.
(58) Almost all TolSQ molecules form the TolSQ-Sc3+ complex under these
conditions.
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14942 J. AM. CHEM. SOC. VOL. 128, NO. 46, 2006

Sc Ion-Promoted Hydride Transfer of NADH Analogue
A R T I C L E S
Figure 5. Absorption spectral changes observed in electron transfer from
Ir(ppy)3 (5.0 × 10-5 M) to TolSQ (5.0 × 10-5 M) in the presence of Sc3+
(3.0 × 10-4 M) in deaerated MeCN at 298 K. Inset: Time course of
absorption changes at λ ) 380 nm (O) and 580 nm (b).
iridium [Ir(ppy)3],48 which is used as an electron donor, no
electron transfer from Ir(ppy)3 (E°ox vs SCE ) 0.71 V) to TolSQ
(E°red vs SCE ) -0.26 V) occurs in the absence of Sc3+
,
because the free energy change of electron transfer is largely
positive (∆Get ) 0.97 eV). The E°ox value of Ir(ppy)3 and the
E°red value of TolSQ were determined by cyclic voltammetry
measurements (see Supporting Information S3).
Upon addition of Sc(OTf)3 (3.0 × 10-4 M) to a deaerated
MeCN solution of Ir(ppy)3 (5.0 × 10-5 M) and TolSQ (5.0 ×
10-5 M), however, electron transfer from Ir(ppy)3 (λmax ) 380
Figure 4. (a) Plots of ln kH vs T-1 for hydride transfer from AcrH2 (3.0 ×
10-5 M) to TolSQ in the presence of Sc(OTf)3 (1.0 × 10-2 M: red closed
square, 2.5 × 10-1 M: red open circle) in deaerated MeCN. (b) Plots of ln
nm) to TolSQ occurs efficiently to yield [Ir(ppy)3]+ (λmax
)
k
D vs T-1 for hydride transfer from AcrD2 (3.0 × 10-5 M) to TolSQ in the
580 nm) as shown in Figure 5 (eq 4). The one-electron reduction
presence of Sc(OTf)3 (1.0 × 10-2 M: blue closed square, 2.5 × 10-1 M:
blue open circle) in deaerated MeCN.
linear correlation is observed between ln kH and T-1 for the
hydride-transfer reaction of AcrH2 in the presence of a low
concentration of Sc3+ (1.0 × 10-2 M: red closed squares in
Figure 4a). In consequence, the kH value in the presence of a
high concentration of Sc3+ (2.5 × 10-1 M: red open circles)
increases with increasing temperature to merge into the kH values
in the presence of a low concentration of Sc3+ (1.0 × 10-2 M:
red closed squares). Thus, even though the kH value in the
presence of a high concentration of Sc3+ (2.5 × 10-1 M: kH )
3.1 × 102 M-1 s-1) is 23 times larger than the kH value in the
presence of a low concentration of Sc3+ (1.0 × 10-2 M: kH )
1.4 × 101 M-1 s-1) at 233 K, the kH values in the presence of
high and low concentrations of Sc3+ (2.5 × 10-1 M: red open
circles and 1.0 × 10-2 M: closed squares, respectively) become
virtually the same in the temperature range 298-333 K (see
the first-order plots at 333 and 233 K in Supporting Information
S1). In contrast with the case of kH in Figure 4a, single linear
correlations are observed between ln kD and T-1 for the hydride-
transfer reactions of AcrD2 in the presence of both low and
high concentrations of Sc3+ (1.0 × 10-2 M and 2.5 × 10-1 M)
as shown in Figure 4b (blue closed squares and open circles,
respectively). Such differences in the temperature dependence
of kH and kD depending on concentrations of Sc3+ result from
the changeover of the reaction pathways as discussed later.
Scandium Ion-Promoted Electron Transfer from Ir(ppy)3
to TolSQ. When AcrH2 is replaced by tris(2-phenylpyridine)-
potential of TolSQ (Ered) in the presence of Sc3+ is shifted to
the positive direction due to the complex formation of TolSQ•-
with Sc3+ according to the Nernst equation (eq 5),59 where E°red
is the one-electron reduction potential of TolSQ in the absence
of Sc3+, and K1 and K2 are the formation constant of TolSQ•--
Sc3+ and TolSQ•--(Sc3+)2, respectively.
Ered ) E°red + (2.3RT/F)
log{(1 + K1[Sc3+])(1 + K2[Sc3+])/(1 + K[Sc3+])} (5)
For example, the reduction potential of TolSQ is shifted to 0.70
V in the presence of 1.0 M Sc3+ (see Supporting Information
S4).60
The rates obeyed pseudo-first-order kinetics in the presence
of a large excess TolSQ and Sc3+ relative to the concentration
of Ir(ppy)3 (see the first-order plot in Supporting Information
S5). The observed pseudo-first-order rate constant (kobs
)
(59) Bard, A. J.; Faulkner, L. R. Electrochemical Methods, Fundamentals and
Applications; John Wile & Sons: New York, 1980.
(60) In contrast to the one-electron reduction of TolSQ, the one-electron oxidation
potential of Ir(ppy)3 was hardly affected by the presence of Sc3+
.
9
J. AM. CHEM. SOC. VOL. 128, NO. 46, 2006 14943

A R T I C L E S
Yuasa et al.
superhyperfine splitting due to an additional Sc3+ ion is observed
(Figure 7e).62 This indicates that the TolSQ•--Sc3+ complex
is converted to a 1:2 complex with Sc3+ [TolSQ•--(Sc3+)2] at
a high concentration of Sc3+ (4.6 × 10-1 M) as shown in
Scheme 3.
The g values of the TolSQ•--(Sc3+)2 complex (2.0045) is
smaller than that of the TolSQ•--Sc3+ complex (2.0048) and
free TolSQ•- (2.0057). The smaller g value of the TolSQ•--
(Sc3+
)
complex than that of the TolSQ•--Sc3+ complex
2
(2.0048) and free TolSQ•- (2.0057) indicates that the spin
density on oxygen nuclei in TolSQ•- is significantly decreased
by the binding with two Sc3+ ions.
Discussion
We wish to discuss how the mechanistic changeover, i.e.,
one-step hydride transfer (H-) vs electron transfer followed by
proton-electron transfer (e- + H+ + e-) in the Sc3+-promoted
hydride-transfer reactions of AcrH2 and AcrD2 with TolSQ,
Figure 6. Dependence of ket on [Sc3+] for electron transfer from Ir(ppy)3
(2.5 × 10-5 M) to TolSQ in the presence of Sc3+ in deaerated MeCN at
298 K.
results in the change in the dependence of kH and kD on [Sc3+
]
with temperature (Figure 3 and Figure 4) by comparing the Sc3+
-
promoted hydride-transfer reaction with the Sc3+-promoted
electron transfer from Ir(ppy)3 to TolSQ (Figure 6).
increases proportionally with increasing TolSQ concentration
(see Supporting Information S6). The second-order rate constant
of electron transfer (ket) exhibits a saturated dependence on
[Sc3+] at low concentrations of Sc3+ ([Sc3+] < 1.0 × 10-2 M)
Reactive Intermediate in Sc3+-Promoted Hydride Transfer
from AcrH2 to TolSQ. The saturated dependence of kH of a
hydride transfer from AcrH2 to TolSQ (red closed circles in
Figure 3a) on [Sc3+] is ascribed to the 1:1 complex formation
between TolSQ and Sc3+ (TolSQ-Sc3+). Formation of the
TolSQ-Sc3+ complex is confirmed by UV-vis spectral changes
of TolSQ in the presence of various concentrations of Sc3+
(Figure 1). When hydride transfer from AcrH2 to TolSQ
proceeds via the TolSQ-Sc3+ complex as shown in Scheme
as shown in Figure 6. The saturated dependence of ket on [Sc3+
]
is changed to a first-order dependence on [Sc3+] at high
concentrations ([Sc3+] > 1.0 × 10-2 M) as in the case of
the hydride-transfer reaction of AcrD2 (blue closed circles in
Figure 3a).
ESR Detection of the Sc3+ Complex of TolSQ•-. A Sc3+
complex of the semiquinone radical anion of TolSQ (TolSQ•-)
should be a key intermediate in Sc3+-promoted electron transfer
from Ir(ppy)3 to TolSQ as well as Sc3+-promoted hydride
transfer from AcrH2 to TolSQ. The TolSQ•- and the Sc3+
complex were detected by ESR as follows.
TolSQ•- was produced by photoinduced electron transfer
from the 10,10′-dimethyl-9,9′-biacridine [(AcrH)2] to TolSQ in
deaerated MeCN at 298 K (Scheme 3). The (AcrH)2 is known
to act as an electron donor in contrast with the case of the
monomer, AcrH2, which is a hydride donor.49 The ESR spectrum
of TolSQ•- is shown in Figure 7a together with the computer
simulation spectrum with the hyperfine coupling constants [hfc:
a(H) ) 2.00 G, a(H) ) 2.20 G, and a(H) ) 3.35 G] in Figure
7b.
The addition of a small amount of Sc(OTf)3 (1.6 × 10-2 M)
to the (AcrH)2-TolSQ system results in a drastic change in
the hyperfine pattern of TolSQ•- due to the complexation with
Sc3+ (Scheme 3) as shown in Figure 7c. The ESR spectrum is
well reproduced by the computer simulation spectrum with the
hfc values of a(2H) ) 1.85, 0.69 G and superhyperfine splitting
due to one Sc3+ ion [a(Sc3+) ) 1.69 G] (Figure 7d). The
complete agreement of the observed ESR spectrum (Figure 7c)
with the computer simulation spectrum (Figure 7d) indicates
4,63 the dependence of kH on [Sc3+] is expressed by eq 6, which
is rewritten by a linear relation between kH and [Sc3+ -1
]
-1
(eq 7).
kH ) k°HK[Sc3+]/(1 + K[Sc3+])
(6)
(7)
kH-1 ) {k°HK[Sc3+]}-1 + k°H
-1
-1
From the slope and intercepts of the linear plot of kH vs
[Sc3+ -1
(see Supporting Information S7) are obtained the k°H
]
and K values of 1.4 × 103 M-1 s-1 and (2.3 ( 0.1) × 103 M-1
,
respectively. The K values derived from the Sc3+-promoted
hydride-transfer reaction of AcrH2 [(2.3 ( 0.1) × 103 M-1
]
agrees with that determined from UV-vis spectral changes of
TolSQ in the presence of various concentrations of Sc3+
[K ) (2.5 ( 0.1) × 103 M-1] at 298 K. Such agreement
indicates that the TolSQ-Sc3+ complex is indeed a reactive
intermediate in the Sc3+-promoted hydride transfer from AcrH2
to TolSQ as shown in Scheme 4. In contrast with the case of
AcrH2, the kD value of AcrD2 increases linearly with increasing
Sc3+ concentration without exhibiting any saturation behavior
at 298 K, although most TolSQ molecules form the Sc3+
that TolSQ•- forms a 1:1 complex with Sc3+ (TolSQ•--Sc3+
)
(62) A small amount of water was added to a deaerated MeCN solution of the
(AcrH)2-TolSQ system to obtain the high-resolution hyperfine structures
of the TolSQ•--Sc3+ and TolSQ•--(Sc3+)2 complexes, when self-exchange
electron transfer with neutral TolSQ, which results in an increase in the
line width, is slowed; see: ref 36b.
in the presence of low concentrations of Sc3+ (1.6 × 10-2
M).61,62 Upon addition of a large amount of Sc(OTf)3 (4.6 ×
10-1 M) to the (AcrH)2-TolSQ-Sc3+ system, a drastic change
in the hyperfine pattern of TolSQ•--Sc3+ due to further
(63) TolSQH- and TolSQH2 may interact with Sc3+, because even TolSQ (the
oxidized form) that is less electron rich than TolSQH- and TolSQH2 can
form a complex with Sc3+ (Scheme 4) via a metal-ion binding site (carbonyl
oxygen or sulfinyl oxygen). However, the complex formation of TolSQH-
and TolSQH2 with Sc3+ has yet to be confirmed.
(61) Examples of the 1:1 complex formation between semiquinone radical anions
with metal ions; see: ref 36b.
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14944 J. AM. CHEM. SOC. VOL. 128, NO. 46, 2006

Sc Ion-Promoted Hydride Transfer of NADH Analogue
A R T I C L E S
Scheme 3
complex in the high concentration range in Figure 3a (blue
closed circles). At a lower temperature (233 K), both the kH
and kD values increase linearly with increasing [Sc3+] without
exhibiting any saturation behavior (Figure 3b), although the
formation constant of the TolSQ-Sc3+ complex becomes much
larger at 233 K [K ) (9.7 ( 0.1) × 103 M-1; see Supporting
Information S8]. Such a linear dependence of kH and kD on
[Sc3+] cannot be explained by one-step hydride transfer from
AcrH2 and AcrD2 to the TolSQ-Sc3+ complex in Scheme 4.
In the case of Sc3+-promoted electron transfer, however, the
rate of electron transfer increases linearly with increasing [Sc3+
as discussed below.
]
Mechanism of Sc3+-Promoted Electron Transfer from
Ir(ppy)3 to TolSQ. The saturated dependence of ket of
Sc3+-promoted electron transfer from Ir(ppy)3 to TolSQ on
[Sc3+] at low concentrations of Sc3+ ([Sc3+] < 1.0 × 10-2 M)
in Figure 6 indicates that the electron-transfer proceeds
via the TolSQ-Sc3+ complex to produce the TolSQ•--Sc3+
complex.64 The TolSQ•--Sc3+ complex was detected by
ESR (Figure 7c). The first-order dependence of ket on [Sc3+] at
high concentrations ([Sc3+] > 1.0 × 10-2 M) in Figure 6
indicates that an additional Sc3+ ion is involved in the electron
transfer to produce a 1:2 complex of TolSQ•- with Sc3+
[TolSQ•--(Sc3+)2] as shown in Scheme 5. The produced
TolSQ•--(Sc3+)2 complex was also directly detected by ESR
(Figure 7e).
According to Scheme 5, the dependence of ket on [Sc3+] is
expressed by eq 8, which is rewritten by a linear correlation
between ket(1 + K[Sc3+])/(K[Sc3+]) and [Sc3+] (eq 9),
ket ) (k1 + k2[Sc3+])K[Sc3+]/(1 + K[Sc3+])
ket(1 + K[Sc3+])/(K[Sc3+]) ) k1 + k2[Sc3+]
(8)
(9)
where k1 and k2 are the rate constant of electron transfer to
produce TolSQ•--Sc3+ and TolSQ•--(Sc3+)2, respectively.
From the intercept and slope, the k1 and k2 values are determined
as (1.2 ( 0.1) × 103 M-1 s-1 and (4.5 ( 0.4) × 104 M-2 s-1
,
respectively (Supporting Information S9). The dependence of
ket on [Sc3+] can be fitted by eq 8 using the k1 and k2 values as
Figure 7. (a) ESR spectrum of TolSQ•- produced by photoinduced electron
transfer from (AcrH)2 (1.6 × 10-2 M) to TolSQ (1.0 × 10-3 M) in deaerated
MeCN at 298 K and (b) the computer simulation spectrum. (c) ESR
spectrum of TolSQ•--Sc3+ produced by photoinduced electron transfer from
(AcrH)2 (1.6 × 10-2 M) to TolSQ (8.0 × 10-2 M) in the presence of Sc3+
(1.6 × 10-2 M) and H2O (2.2 M) in deaerated MeCN at 298 K and (d) the
shown in Figure 6 (solid line). Such dependence of ket on [Sc3+
]
is diagnostic of Sc3+-promoted electron-transfer reduction of
TolSQ to produce not only the 1:1 complex (TolSQ•--Sc3+
)
but also the 1:2 complex [TolSQ•--(Sc3+)2]. The k2/k1 ratio is
38 ( 6 M-1 that corresponds to the formation constant of
computer simulation spectrum. (e) ESR spectrum of TolSQ•--(Sc3+
)
2
produced by photoinduced electron transfer from (AcrH)2 (1.6 × 10-2 M)
to TolSQ (4.6 × 10-2 M) in the presence of Sc3+ (4.6 × 10-1 M) and H2O
(4.4 M) in deaerated MeCN at 298 K and (f) the computer simulation
spectrum.
(64) The K value could not be determined actually by the dependence of ket on
[Sc3+], because the ket value increases linearly with increasing Sc3+
concentration at high concentrations of Sc3+
.
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J. AM. CHEM. SOC. VOL. 128, NO. 46, 2006 14945

A R T I C L E S
Scheme 4
Yuasa et al.
Scheme 5
TolSQ•--(Sc3+)2 (K2) from TolSQ•--Sc3+. The log K1 value
for the TolSQ•--Sc3+ complex is determined as 18.1 from the
positive shift of the Ered value (0.96 V) in the presence of 1.0
M Sc3+ using eq 5 with the K value (2.5 × 103 M-1) for the
TolSQ-Sc3+ complex and K2 value (38 ( 6 M-1) for the
TolSQ•--(Sc3+)2 complex.65 The Ered value in the presence of
3.0 × 10-4 M Sc3+ is estimated as 0.59 V using eq 5 with K,
K1, and K2 values. In such a case, electron transfer from Ir-
(ppy)3 (Eox ) 0.71 V) to TolSQ (Ered ) 0.59 V) is expected to
be slightly uphill. However, the follow-up disproportionation
of the TolSQ•--Sc3+ complex makes the one-electron oxidation
of Ir(ppy)3 undergo to completion (Figure 5). The ket values in
Figure 6 have been determined under the pseudo-first-order
conditions such that concentrations of TolSQ and Sc3+ are in
large excess compared to that of Ir(ppy)3, when the electron-
transfer equilibrium may lie toward the products.
One-Step Hydride Transfer vs Electron Transfer Followed
by Proton-Electron Transfer. The hydride transfer from
AcrH2 to the TolSQ-Sc3+ complex at 298 K may occur via
one-step hydride transfer as indicated by the saturated depen-
dence of kH on [Sc3+] (red closed circles in Figure 3a). In
contrast, the kD value of AcrD2 increases linearly with increasing
[Sc3+] at high concentrations ([Sc3+] > 1.0 × 10-2 M) without
exhibiting any saturation behavior (blue closed circles in Figure
3a). Such dependence of kD on [Sc3+] in Figure 3a is virtually
the same as that observed in the Sc3+-promoted electron-transfer
reduction of TolSQ (Figure 6). Thus, the hydride-transfer
mechanism may be changed from one-step hydride transfer from
AcrH2 to the TolSQ-Sc3+ complex to Sc3+-promoted electron
transfer from AcrD2 to the TolSQ-Sc3+ complex as shown in
Scheme 6a.
The dependence of the rate constant of Sc3+-promoted
electron transfer (ket) from AcrD2 to the TolSQ-Sc3+ complex
can be estimated from the dependence of ket of Sc3+-promoted
electron transfer from Ir(ppy)3 to the TolSQ-Sc3+ complex in
Figure 6 by taking into account the difference in the Eox values
between AcrD2 (0.81 V)21 and Ir(ppy)3 (0.71 V). If the difference
in the free energy change of electron transfer is directly reflected
in the ket value, the ket value of AcrD2 would be smaller than
that of Ir(ppy)3 by exp(0.10F/RT) in which F is the Faraday
constant, R is the gas constant, and T ) 298 K. The exp(0.10F/
RT) value is obtained as 48. Figure 8 shows the estimated
dependence of ket of Sc3+-promoted electron transfer from AcrD2
to the TolSQ-Sc3+ complex (dashed line), which is simply
obtained by dividing the ket value of Sc3+-promoted electron
transfer from Ir(ppy)3 to the TolSQ-Sc3+ complex by 48. The
slope of the observed linear correlation between kD and [Sc3+],
(9.5 ( 0.1) × 102 M-2 s-1, agrees well with that expected from
the electron-transfer reaction, (9.3 ( 0.1) × 102 M-2 s-1. Such
agreement strongly indicates that the hydride transfer from
(65) It should be noted, however, uncertainty of the determination of Ered value
in the presence of Sc3+ ((0.05 V) due to the instability of the Sc3+
complexes of TolSQ•- results in a relatively large error ((0.8) in terms of
log K1 value.
AcrD2 to the TolSQ-Sc3+ complex proceeds via the Sc3+
-
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14946 J. AM. CHEM. SOC. VOL. 128, NO. 46, 2006

Sc Ion-Promoted Hydride Transfer of NADH Analogue
A R T I C L E S
Scheme 6. Hydride-Transfer Mechanism at 298 K
Table 1. Activation Energies (Ea) of Hydride Transfer from AcrH2
and AcrD2 to TolSQ in the Presence of Sc3+ (1.0 × 10-2 M and
2.5 × 10-1 M) in Deaerated MeCN
promoted electron-transfer pathway (Scheme 6b) rather than the
one-step hydride-transfer pathway (Scheme 6a).
The free energy change of electron transfer from AcrD2 to
TolSQ is highly positive judging from the Eox value of AcrD2
(Eox vs SCE ) 0.81 V)21 and the Ered value of TolSQ (Ered vs
SCE ) -0.26 V), and electron transfer from AcrD2 to TolSQ
1
Eaa (kcal mol-
)
NADH analogue
1.0
×
10-2 Mb
2.5 ×
10-1 Mb
AcrH2
AcrD2
9.9 ( 0.2
9.4 ( 0.2
4.3 ( 0.3c (9.8 ( 0.2)d
4.6 ( 0.3
is thermodynamically unlikely to occur. In the presence of Sc3+
,
a Determined by the Arrhenius plots of the rate constants of the hydride-
however, the Ered value is significantly shifted according to eq
5 (vide supra). Although the free energy change of electron
transfer is still slightly positive, electron transfer is followed
transfer reactions. b Concentration of Sc3+ c Determined from the linear
.
plot of ln kH vs T-1 in the temperature range 233-283 K. d Determined
from the linear plot of ln kH vs T-1 in the temperature range 298-333 K.
by proton transfer from AcrD2 to the Sc3+ complexes of
•+
•+
TolSQ•-. If proton transfer from AcrD2 to TolSQ•- is much
because of the low oxidation potential of AcrD• (Eox ) -0.43
V)23 to yield AcrD+ and TolSQD- (Scheme 6b). Thus, the
overall hydride-transfer reaction may also be highly exergonic.
The mechanistic changeover from the one-step hydride-
transfer to the electron-transfer pathway by the deuterium
substitution of AcrH2 by AcrD2 (Figure 3a) may result from a
significant primary kinetic deuterium isotope effect in the direct
one-step hydride transfer from AcrD2 to the TolSQ-Sc3+
complex, when the rate constant of direct one-step hydride
transfer from AcrD2 becomes much smaller than that of the
Sc3+-promoted electron transfer from AcrD2 to the TolSQ-
Sc3+ complex.
faster than the initial electron transfer from AcrH2 to TolSQ,
the rate-determining step would be the electron transfer when
there should be no kinetic isotope effect. In the presence of
Sc3+, however, the basicity of TolSQ•- is reduced significantly
by the complex formation with Sc3+ [TolSQ•--Sc3+ and
•+
TolSQ•--(Sc3+)2]. In such a case, proton transfer from AcrD2
to the TolSQ•--Sc3+ and TolSQ•--(Sc3+)2 complexes may be
slow enough to be involved in the rate-determining step. Thus,
the observation of a kinetic isotope effect (kH/kD ) 2.5 ( 0.3)
indicates that the proton-transfer step is at least partially involved
in the rate-determining step when the electron-transfer step is
coupled with the proton-transfer step. The subsequent electron
transfer from AcrD• to TolSQD• may be highly exergonic
Mechanistic Changeover by Simple Changes of Temper-
ature and Sc3+ Concentration. An Arrhenius plot for the Sc3+
-
promoted hydride transfer from AcrH2 to the TolSQ-Sc3+
complex in the presence of a high concentration of Sc3+ (2.5 ×
10-1 M) in Figure 4a (red open circles) showed two distinct
regions (233-298 K and 298-333 K) with different slopes,
indicating the occurrence of the mechanistic changeover. The
break in the Arrhenius plot corresponds to a temperature (298
K) to be related to the borderline between the one-step hydride-
transfer and electron-transfer pathways. The activation energies
(Ea) derived from the slopes of Arrhenius plots for the Sc3+
-
promoted hydride transfer from AcrH2 and AcrD2 to the
TolSQ-Sc3+ complex in the presence of a low concentration
of Sc3+ (1.0 × 10-2 M) and a high concentration of Sc3+ (2.5
× 10-1 M) are summarized in Table 1. There are two types of
Ea values: one is 9.6 ( 0.5 kcal mol-1 for the Sc3+-promoted
hydride transfer from AcrH2 and AcrD2 to the TolSQ-Sc3+
complex in the presence of a low concentration of Sc3+ (1.0 ×
10-2 M), and the other is 4.5 ( 0.5 kcal mol-1 for the Sc3+
-
Figure 8. Dependence of kD (b) on [Sc3+] for hydride transfer from AcrD2
(3.0 × 10-5 M) to TolSQ in the presence of Sc3+ in deaerated MeCN at
298 K. The dashed line shows the second-order rate constants of electron
transfer from AcrD2 to TolSQ in the presence of Sc3+ expected from the
dependence of the second-order rate constant (ket) on [Sc3+] for electron
promoted hydride transfer from AcrH2 and AcrD2 to the
TolSQ-Sc3+ complex in the presence of a high concentration
of Sc3+ (2.5 × 10-1 M). The higher Ea value (9.6 ( 0.5 kcal
mol-1) corresponds to that of the one-step hydride-transfer
transfer from Ir(ppy)3 to TolSQ in the presence of Sc3+
.
pathway, and the smaller Ea value (4.5 ( 0.5 kcal mol-1
)
9
J. AM. CHEM. SOC. VOL. 128, NO. 46, 2006 14947

A R T I C L E S
Yuasa et al.
corresponds to that of the electron-transfer pathway. In the case
of the Sc3+-promoted hydride transfer from AcrH2 to the
TolSQ-Sc3+ complex in the presence of a high concentration
of Sc3+ (2.5 × 10-1 M), the changeover of the pathways occurs
at 298 K from the electron transfer (233-298 K) with Ea )
4.5 ( 0.5 kcal mol-1 to the one-step hydride transfer (298-
333 K) with Ea ) 9.6 ( 0.5 kcal mol-1. The changeover of the
reaction pathways results from the Ea and A (pre-exponential
factor) values of the one-step hydride-transfer pathway being
larger than those of the electron-transfer pathway. The smaller
Ea value of the electron-transfer pathway is ascribed to the strong
binding of Sc3+ ions in the 1:2 complex of TolSQ•- with Sc3+
[TolSQ•--(Sc3+)2], which results in stabilization of the transi-
tion state as well as the electron-transfer product.
(TolSQ) occurs efficiently in the presence of Sc3+, whereas no
hydride-transfer reaction occurs in the absence of Sc3+. The
hydride-transfer reaction of AcrH2 occurs via direct one-step
hydride transfer from AcrH2 to the TolSQ-Sc3+ complex
formed between TolSQ and Sc3+ at 298 K. In such a case, the
kH value increases exhibiting a saturated behavior with respect
to Sc3+ concentration ([Sc3+]), when almost all TolSQ molecules
form the TolSQ-Sc3+ complex. The one-step hydride-transfer
mechanism is changed to electron transfer followed by proton
and electron transfer by deuterium substitution of AcrH2 by
AcrD2. The kD value increases linearly with an increase in
[Sc3+]. Similarly, the rate constant of electron transfer (ket) from
the electron donor tris(2-phenylpyridine)iridium [Ir(ppy)3] to
TolSQ increases linearly with increasing [Sc3+]. Such a first-
order dependence of kH and ket on [Sc3+] is ascribed to formation
of a 1:2 complex between TolSQ•- and Sc3+ [TolSQ•--
(Sc3+)2], which was detected by ESR. The one-step hydride-
transfer pathway is also changed to the electron-transfer pathway
with decreasing temperature due to the larger Ea and A values
of the one-step hydride-transfer pathway than those of the
electron-transfer pathway. A break is observed in the Arrhenius
plot for the Sc3+-promoted hydride-transfer reaction of AcrH2,
corresponding to the borderline between the one-step hydride-
transfer and electron-transfer pathways.
The smaller A value of the electron-transfer pathway may
also result from the formation of TolSQ•--(Sc3+)2 where a
higher degree of organization of Sc3+ ions is required as
compared with that the 1:1 TolSQ-Sc3+ complex involved in
the one-step hydride-transfer pathway.
With regard to the kinetic deuterium isotope effect (kH/kD),
the kH/kD value of the one-step hydride-transfer pathway is
nearly temperature independent (kH/kD ) 4.5 ( 0.5), because
the Ea values of AcrH2 and AcrD2 are virtually the same (Table
1). Such a temperature independent kinetic deuterium isotope
effect suggests that the transition state of the one-step hydride-
transfer pathway is nonlinear when the amplitudes of H vibration
are considerably less restricted in a bent transition state as
discussed by Kwart.66 In contrast with the large kH/kD value for
the one-step hydride-transfer pathway, the kH/kD value of the
electron-transfer pathway, followed by proton transfer (kH/kD
) 2.5 ( 0.3), is significantly smaller, but the observation of
the kinetic deuterium isotope effect in the electron-transfer
Acknowledgment. This work was partially supported by
Grants-in-Aid (No. 16205020) from the Ministry of Education,
Culture, Sports, Science and Technology, Japan.
Supporting Information Available: First-order plots for
hydride transfer from AcrH2 to TolSQ in the presence of Sc3+
(S1), dependence of kobs on [TolSQ] (S2), cyclic voltammograms
of TolSQ and Ir(ppy)3 (S3), cyclic voltammogram of TolSQ in
the presence of Sc3+ (S4), first-order plot for Sc3+-promoted
electron transfer from Ir(ppy)3 to TolSQ (S5), dependence of
•+
pathway indicates that the proton transfer from AcrH2 to
TolSQ•--(Sc3+)2 following the Sc3+-promoted electron transfer
is also involved in the rate-determining step (vide supra).
kobs on [TolSQ] (S6), plot of kH-1 vs [Sc3+ -1
(S7), absorption
]
spectra of TolSQ in the presence of various concentrations of
Sc3+ (S8), plot of ket(1 + K[Sc3+])/(K[Sc3+]) vs [Sc3+] (S9).
This material is available free of charge via the Internet at
http://pubs.acs.org.
Summary and Conclusions
Hydride transfer from an NADH analogue, 9,10-dihydro-10-
methylacridine (AcrH2) to 1-(p-tolylsulfinyl)-2,5-benzoquinone
(66) Kwart, H. Acc. Chem. Res. 1982, 15, 401.
JA064708A
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14948 J. AM. CHEM. SOC. VOL. 128, NO. 46, 2006