A robust Mn catalyst for H2O2 disproportionation in aqueous solution

Article abstract of DOI:10.1002/ejic.201300184

The pyridinophane complex [Mn(Py₂N₂)(H ₂O)₂]²⁺ catalyses the disproportionation of H₂O₂ in aqueous solution over a wide pH range. Kinetic investigations reveal an induction perio

Full text of DOI:10.1002/ejic.201300184

FULL PAPER
DOI:10.1002/ejic.201300184
A Robust Mn Catalyst for H O Disproportionation in
2
2
Aqueous Solution
CLUSTER
ISSUE
[a]
[a]
[b]
Wei-Tsung Lee, Song Xu, Diane A. Dickie, and
Jeremy M. Smith*[
a]
Keywords: Manganese / Reaction mechanisms / Peroxides / Homogeneous catalysis / Macrocycles
The pyridinophane complex [Mn(Py
2
N
2
)(H
2
O)
2
]2+ catalyses
ates has been proposed. Spectroscopic investigations under
turnover conditions are consistent with this proposal and
show that the resting state of the catalyst is a mononuclear
Mn complex. The robustness of the catalyst is evidenced by
its ability to achieve turnover numbers of 58000 in aqueous
the disproportionation of H in aqueous solution over a
2
O
2
wide pH range. Kinetic investigations reveal an induction
period, which is proposed to involve the formation of a hydro-
peroxo intermediate, as well as evidence for catalyst self-in-
II
hibition. A catalytic cycle involving mononuclear intermedi- solution.
catalysis of H O
disproportionation.[5] Whereas most of
2 2
these complexes are structurally related to MnCAT in that
Introduction
Excess levels of reactive oxygen species (ROS) are impli-
cated in a number of pathologies, such as tissue injury, in-
flammatory disorders, cardiovascular diseases, pulmonary
diseases, and neurodegenerative diseases.[ Hydrogen per-
oxide is one type of ROS that is formed by aerobic organ-
they are either prepared as or assemble into Mn dimers
2
under catalytic conditions, a smaller class of MnCAT mim-
ics appears to remain monomeric during catalysis. Most of
these catalysts are only active in organic or mixed aqueous–
organic solvents at a relatively high pH. Despite these
limitations, a number of Mn complexes have been investi-
gated as low-molecular-weight catalytic antioxidants for
1]
isms through the partial reduction of O . In the presence of
2
metal ions, H O can be decomposed in Fenton-like reac-
2
2
tions to provide the highly reactive hydroxyl radical, which
readily oxidizes cellular macromolecules.
[6]
treating overt inflammation associated with excess H O ,
2
2
III[7]
III[8]
most notably, (porphyrin)Mn
plexes.
and (salen)Mn
com-
Cellular antioxidant defences are used to detoxify ROS
by reducing them to water. In the case of H O , catalase
2
2
We report a new catalyst for H O disproportionation,
2 2
enzymes catalyse the disproportionation of H O to O and
II
2
2
2
namely, the (pyridinophane)Mn complex [Mn(Py N )-
2 2
H O:
2
2+
(H O) ] {Figure 1, Py N2 = N,NЈ-dimethyl-2,11-diaza-
2 2 2
[3,3](2,6)pyridinophane}. This catalyst is remarkably ro-
2
2 2 2 2
H O Ǟ O + 2 H O
bust, operating over a wide pH range in aqueous solution.
Mechanistic studies provide evidence for a reaction mecha-
nism that involves a monomeric catalyst. Although the rate
of H O disproportionation is intermediate, the catalyst is
There are two catalase families. The more common
heme-containing catalases contain an iron(III) protopor-
phyrin IX prosthetic group,[ whereas the Mn-containing
catalases (MnCAT) have an active site with two Mn ions
bridged by carboxylato and single-atom ligands (likely
water or hydroxide).[
2]
2
2
long-lived, achieving turnover numbers of 58000.
3,4]
The structure and reactivity of MnCAT has motivated
the synthesis of many functional model complexes for the
[
a] Department of Chemistry and Biochemistry, New Mexico State
University,
O)]2+
.
Figure 1. [Mn(Py
2
N
2
)(H
2
Las Cruces, NM 88003, USA
Fax: +1-575-646-2649
E-mail: jesmith@nmsu.edu
Homepage: http://www.chemistry.nmsu.edu/Faculty/
SMITHJEREMY.htm
Results and Discussion
[b] Department of Chemistry and Chemical Biology, The Univer-
sity of New Mexico,
The reaction of N,NЈ-dimethyl-2,11-diaza[3,3](2,6)pyrid-
inophane with MnBr leads to the formation of the (macro-
Albuquerque, NM 87131, USA
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejic.201300184.
2
II
cycle)Mn complex Mn(Py N )Br in high yield. The anal-
2
2
2
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FULL PAPER
ogous chloride complex Mn(Py N )Cl has been previously
2
2
2
[
9,10]
reported.
The conductivity Λ of the complex in aque-
ous solution (ΛM = 268 Ω cm mol ) is consistent with
M
–
1
2
–1
the presence of three ions, and therefore the complex is fully
2
+
aquated as [Mn(Py N )(H O) ] at pH = 7 (Figure 1). The
2
2
2
2
2
+
magnetic susceptibility of [Mn(Py N )(H O) ] , deter-
2
2
2
2
mined by the Evans method, is χM = 5.91(3) μ , which is
B
II
consistent with high-spin Mn (S = 5/2). The EPR spec-
trum is also consistent with Mn , resembling the spectra of
II
II
[11,12]
certain non-heme Mn enzymes.
The complex is
slightly air-sensitive, and its aqueous solutions develop a
yellow colour over the course of several days.
Hydrogen peroxide is catalytically disproportionated by
2+
[
Mn(Py N )(H O) ] . Disproportionation is observed in
2 2 2 2
aqueous solution over a wide pH range (pH = 2–8.5). In
contrast, most other Mn catalysts for H O disproportiona-
2
5]
2
tion are only active at high pH values.[ At higher pH val-
ues, no difference to the background H O decomposition
2
2
is observed. Interestingly, the catalyst is remarkably long-
lived, achieving a turnover number of 58000 when the initial
2
+
pH is 4.3. The robustness of [Mn(Py N )(H O) ] is note-
2
2
2
2
worthy, as the complex achieves very high turnover num-
bers and operates over a relatively wide pH range, which
includes very acidic conditions, under which most other cat-
alase mimics are inactive. Given the relative rarity of mono-
nuclear Mn catalysts for H O disproportionation, particu-
2
2
larly in aqueous solution, as well as the robustness of this
particular catalyst, we have undertaken investigations
towards understanding the catalytic mechanism.
Attempts to determine the initial rates of O evolution at
2
Figure 2. (a) Dependence of the initial rate of H
on the concentration of [Mn(Py N )(H O) ]
2 2 2 2
2
O
2
decomposition
catalyst. Initial
] = 3.1 m. (b) Doubly reciprocal plot of the same data.
relatively low H O concentrations (Ͻ1 mm) with a Clark-
2+
2
2
type electrode were plagued by difficulties in reproducib- [H
2
O
2
ility. However, at very high H O concentrations (3.1–6.1 m)
2
2
a reproducible kinetic behaviour was observed. Addition-
ally, because decreased reaction rates were observed in
buffer solutions, all kinetic experiments were conducted in
unbuffered aqueous solutions.
investigated as a catalytic antioxidant.[8,14] It should be
noted that a range of conditions have been used for these
measurements. An H/D kinetic isotope effect (KIE) of 0.8 is
The initial rates of H O decomposition, as determined
2
2
observed for the disproportionation of isotopically enriched
by volumetric measurements of the evolved O , were pro-
[15]
2
hydrogen peroxide in a D O/H O solution.
An Eyring
2
2
portional to [H O ] with no evidence of saturation kinet-
2
2
ics.[ In contrast, the dependence of the initial rate con-
11]
stants on the catalyst concentration reveals saturation kinet- Table 1. Monometallic Mn catalysts for H
2
O
2
disproportionation
that exhibit second-order kinetics.
ics (Figure 2a). A double-reciprocal plot of this data is lin-
ear (Figure 2b), and thus the kinetic behaviour fits the fol- Precatalyst[a]
k [m–1 s–1]
Solvent
EtCN
MeCN
2
H O
H O
2
DMF/H
DMF/H O
H O
2
Ref.
lowing equation:
II
[17]
[18]
[19]
[19]
[20]
[20]
[8]
Mn (bimindH)Cl
2
4.12
1.55
0.478
0.636
0.00417
II
Mn (indH)Cl
2
kK[Mn]
II
[b]
Mn (pbmpa)Cl
k =
obs
1
+ K[Mn]
II
[b]
Mn (mpbmpa)Cl
2
II
Mn {(3-OMe)salen}
2
O
with k = 1.8(5) and K = 0.01(2).
This saturation behaviour suggests that catalyst self-inhi-
bition occurs at higher concentrations, for example, by the [Mn {(C F ) (SO ) }(corrole)]
II
Mn {(3-OMe)salen}(imidazole) 0.00794
2
III
–6
[c]
Mn (salen)Cl
4.97ϫ10
5.6
0.18
III
2–
[d]
[e]
[21]
6
5 3
3 2
2+
2
H O
H
II
[
Mn (Py
2
N
2
)(H
2
O)
2
]
2
O
this work
formation of catalytically inactive dimers.
2
+
At [Mn(Py N )(H O) ] concentrations below the satu- [a] bimindH = 1,3-bis(2Ј-benzimidazolylimino)isoindoline; indH =
2
2
2
2
ration limit, the second-order rate constant for the H O
disproportionation k = 0.176(7) m s is smaller than those
1,3-bis(2Ј-pyridylimino)isoindoline; pbmpa = 3-[bis(2-pyridylmeth-
yl)amino]propanoate; mpbmpa = methyl 3-[bis(2-pyridylmethyl)-
amino]propanoate (see the Supporting Information for structures
of the ligands). [b] Maximum rate observed at pH = 11, phosphate
buffer. [c] pH = 8.1. [d] pH = 9.5. [e] Initial pH = 5.5, [Mn] =
2
2
–
1 –1
of many other reported catalysts that follow second-order
[
13]
kinetics (Table 1), although it is significantly faster than
III
Mn (salen)Cl (EUK-134), a catalase mimic that has been 0.33 mm, unbuffered.
Eur. J. Inorg. Chem. 2013, 3867–3873
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analysis of the temperature-dependent rate constants (T = and methylene blue bleaching involve common intermedi-
‡
2
+
5–44 °C) gives the activation parameters ΔH
=
ates.
We have also tested the possibility of superoxide forma-
–
1
‡
–1 –1
13.5(8) kcalmol and ΔS = +25(2) Jmol K . The large
positive value of ΔS is notable and is similar to the entropy tion during catalysis by using red-CLA.
of activation for dissociative ligand-substitution reac- there is no change in the fluorescence spectrum of the dye
‡
[23,24]
However,
[
16]
tions.
under catalytic conditions, and thus the formation of free
An induction period for the O formation was observed superoxide during catalysis is also unlikely.
2
during the kinetic measurements. This induction period
To obtain spectroscopic information about the nature of
shows no H/D isotope effect and is concomitant with a de- the catalytic intermediates, the EPR spectrum of
2+
crease in the solution pH (Figure 3) as well as with the [Mn(Py N )(H O) ] was measured in the presence of ex-
2
2
2
2
growth of a band at approximately 390 nm in the UV/Vis cess H O2 (Figure 4). Interestingly, the EPR spectrum,
2
[
11]
spectrum.
Whereas this band decays after the induction which is different from that of the starting complex, reveals
period, no further change in the solution pH is observed. a single Mn species with no evidence of significant
These observations suggest that the induction period is as- amounts of Mn or Mn . Moreover, because the inte-
sociated with a deprotonation step. The magnitude of the grated signals of [Mn(Py N )(H O) ] before and after the
II
III
IV
2+
2
2
2
2
pH change (ca. 1.3 pH units) is an order of magnitude addition of H O are the same, the formation of significant
2
2
smaller than the initial concentration of [Mn(Py N )- amounts of EPR-silent species is unlikely. Thus, the spectro-
2
2
2
+
(
H O) ] (0.67 mm), and it is insufficient to account for the scopic data strongly suggest that the catalyst resting state is
complete deprotonation of all the Mn complex molecules a mononuclear Mn species that is not [Mn(Py N )-
2 2
II
2
2
2
+
in solution.
(H O) ] .
2 2
2
Figure 3. Change of pH and induction period for the O formation.
2 2
Initial conditions: [Mn] = 0.67 mm, [H O ] = 3.1 m, aqueous solu-
tion, 298 K.
2
+
2 2 2 2
Figure 4. EPR spectrum of [Mn(Py N )(H O) ] in the presence
2 2 2 2
of excess H O . Initial conditions: [Mn] = 4 μm, [H O ] = 20 mm.
One possible pathway of O formation involves the ho-
2
molysis of the O–O bond in H O , which leads to hydroxyl
A mechanism consistent with the experimental data is
2
2
radical formation. To test this possibility, we investigated presented in Scheme 1. Entry into the catalytic cycle in-
the bleaching of methylene blue in the presence of H O volves the substitution of an aqua ligand by H O and a
2
2
2
2
2
+ [22]
and [Mn(Py N )(H O) ] .
Under pseudo-first-order subsequent deprotonation, which yields the (aqua)(hydro-
conditions, the initial rate of bleaching kobs was determined peroxido)Mn complex [Mn(Py N )(H O)(O H)] . Be-
by UV/Vis spectroscopy [kobs = 1.05(5)ϫ10 s ]. Control cause H O is a poor ligand, the substitution step is ex-
2
2
2
2
II
2+
2
2
2
2
–
3
–1
[25]
2
2
experiments established that both the catalyst and H O are pected to be rate-determining for the catalyst induction,
2
2
required to bleach methylene blue. However, the rate of which is consistent with the lack of an H/D isotope effect.
bleaching is the same in the presence of excess tBuOH, The equilibrium for this step is likely to favour the reac-
·
–3 –1
which reacts as an OH scavenger [k = 1.01(2)ϫ10 s ]. tants. Therefore, we propose that the slow formation of
obs
+
Thus, O–O bond homolysis is unlikely to be significant in [Mn(Py N )(H O)(O H)] accounts for the observed induc-
the reaction mechanism, and OH does not play an impor- tion period. We note that it is also possible that H O binds
tant role in the methylene blue bleaching. As with H O2 in a bidentate fashion to provide [Mn(Py N )(κ -O H)] .
2
2
2
2
·
2
2
2
+
2
2
2
2
disproportionation, there is also an induction period for the However, for the sake of clarity, only species, in which H O2
2
bleaching of methylene blue. This induction period is also is monodentate, will be discussed.
associated with the growth of a band at 390 nm in the UV/
An aqua-ligand-assisted intramolecular O–O bond hetero-
Vis spectrum, which suggests that H O disproportionation lysis in the hydroperoxido complex (with loss of water) is
2
2
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Scheme 1. Proposed mechanism for the H
inhibition, are not shown.
2
O
2
disproportionation catalysed by [Mn(Py
2
N
2
)(H
2
O)
2
]2+. Side reactions, such as catalyst self-
IV
proposed to provide the (hydroxido)(oxido)Mn interme- likely on the basis of results observed for the similarly sized
+
[29]
diate [Mn(Py N )(O)(OH)] , similar to mechanistic propos- Me EDC ligand, for which only monomeric oxido com-
2
2
2
[
26]
als for non-heme (hydroperoxido)iron complexes.
The plexes have been observed.
alternate possibility of O–O bond homolysis can be dis-
As noted above, we have observed that the decrease in
counted, as there is little evidence for hydroxyl radical for- pH associated with the induction period is insufficient to
mation. Heterolysis of the O–O bond is often observed in account for the deprotonation of all the [Mn(Py N )-
2
2
27]
2+
(
hydroperoxido)manganese complexes.[ The loss-of-coor- (H O) ] molecules in solution. One possible explanation
2 2
+
dinated-water step is also consistent with the large positive is that the hydroxido ligand in [Mn(Py N )(OH)(OH )] is
value of ΔS . We also note that a (hydroxido)(oxido)Mn
complex supported by a related macrocyclic ligand, ate the starting bis(aqua)Mn complex [Mn(Py N )-
2
2
+
2
‡
IV
reprotonated by the previously released H ions to regener-
II
2
2
+
2+
[
Mn(Me EBC)(O)(OH)]
(Me EBC
=
4,11-dimethyl- (H O) ] . The formation of this dormant complex would
2 2
2
2
1
,4,8,11-tetraazabicyclo[6.6.2]hexadecane) has been charac- account for the substoichiometric decrease in the solution
[
28,29]
terized.
pH during the induction period. Alternatively, it is possible
The reaction of [Mn(Py N )(O)(OH)] with a second that not all metal complex molecules enter the catalytic
+
2
2
molecule of H O provides the (hydroperoxido)(oxido)- cycle.
2
2
IV
+ [30]
Mn species [Mn(Py N )(O)(OOH)] .
It is likely that
It is interesting to contrast the reactivity of the pyrid-
2
2
2+
this species is the active oxidant in the methylene blue inophane complex [Mn(Py N )(H O) ]
towards H O2
2
2
2
2
2
2
+
[31]
bleaching by [Mn(Py N )(H O) ] and H O . The low- with that of Mn complexes supported by related ligands.
2
2
2
2
2
2
+
est-energy conformation of [Mn(Py N )(O)(OOH)] is ex- The strapped cyclam ligand Me EBC provides a coordina-
2
2
2
pected to have an intramolecular hydrogen bond between tion environment similar to that of Py N , most notably
2
2
the hydroperoxido and the oxido ligand.[ This conforma- creating cis coordination sites for substrate binding, but it
32]
tion facilitates intramolecular proton transfer, which leads binds through different donor groups. Although H O dis-
2
2
2+
to the reductive elimination of O and the formation of the proportionation by [Mn(Me EBC)(H O) ] was noted, the
2
2
2
2
II
+
(
aqua)(hydroxido)Mn complex [Mn(Py N )(OH)(OH )] . complex was ultimately oxidized by H O to afford purple
An acid/base reaction between this species and H O regen- [Mn (Me EBC)(OH) ] , which is in contrast to our ob-
erates the (aqua)(hydroperoxido) species [Mn(Py N )- servations for [Mn(Py N )(H O) ] . It is likely that this dif-
2 2 2 2 2
IV
2+ [29]
2
2
2
2
2+
2
2
2
2
2
2
2
+
(
H O)(O H)] along with H O.
ference is due to the ability of the Me EBC ligand to better
2
2
2
2
The EPR spectrum recorded under turnover conditions stabilize higher oxidation states, which is reflected by com-
[
33,34]
is also consistent with this proposed mechanism and sug- parative electrochemical data.
gests that the (aqua)(hydroxido) complex [Mn(Py N )-
Although the tetradentate open-chain ligand bipicen
H O)(O H)] is likely to be the resting state of the catalyst. [bispicen N,NЈ-dimethyl-N,NЈ-bis(2-pyridylmethyl)eth-
On the basis of the Eyring analysis, the step leading to the ane-1,2-diamine] contains the same donor groups as Py N ,
2
2
+
(
=
2
2
2
2
II
cleavage of the O–O bond is expected to be the rate-de- the reaction of Mn (bispicen)Cl2 with stoichiometric
termining step in the catalytic cycle. The observed catalyst amounts of H O affords the corresponding dimer
self-inhibition may be due to the reversible formation of a [Mn (bispicen) (μ-O) ] . This is likely a result of the li-
2
2
3+ [35]
2
2
2
dimer having an [Mn(μ-O) Mn] (or related) core. The gand being insufficiently bulky to thwart the formation of
2
irreversible formation of such dimers is expected to be un- the bis(μ-oxido) dimer. Similarly, the formation of [Mn(μ-
Eur. J. Inorg. Chem. 2013, 3867–3873
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II[36]
O) Mn] dimers from the reaction of (cyclam)Mn
and with acetone (100 mL) in a Soxhlet apparatus overnight. The ex-
tract was concentrated to dryness to afford the desired product.
2
II[37]
(cyclen)Mn
complexes is also related to the reduced
Yield: 1.1 g (39%). The spectral properties are identical to those
reported in the literature.
steric bulk of these macrocycles.
Synthesis
Py ): 2,11-Diaza[3,3](2,6)pyridinophane (0.25 g, 1.0 mmol),
7% formaldehyde (4.4 g, 4.0 mL, 54.3 mmol), and formic acid
3.1 g, 2.5 mL, 67.3 mmol) were heated at reflux for 24 h. The reac-
of
N,NЈ-Dimethyl-2,11-diaza[3,3](2,6)pyridinophane
(
3
(
2 2
N
Conclusions
The MnII complex [Mn(Py N )(H O) ] is a precursor tion mixture was basified with 2 n NaOH, extracted with dichloro-
2+
2
2
2
2
methane (2ϫ 50 mL), and the extracts were dried with sodium sulf-
ate. Removal of the volatiles under reduced pressure furnished an
off-white solid, which was purified by recrystallization from n-hex-
ane. Yield: 0.19 g (71%). The spectral properties are identical to
those reported in the literature.[
to a H O disproportionation catalyst. The catalyst is ro-
2
2
bust, being active over a wide pH range and achieving very
high turnover numbers. On the basis of mechanistic and
spectroscopic investigations, we have proposed a catalytic
cycle that involves only monomeric intermediates. The
structural features of the pyridinophane ligand are believed
to be critical to the catalytic reactivity, namely, its ability
to stabilize monomeric species with vacant cis coordination
sites.
39]
Synthesis of Mn(Py
in THF (3 mL) was mixed with Py
2 mL) and stirred at ambient temperature under N
2
N
2
)Br
2
: A slurry of MnBr
(134 mg, 0.5 mmol) in THF
for 3 h. The
2
(107 mg, 0.5 mmol)
2
N
2
(
2
reaction mixture was filtered through a sintered glass filter and
washed with tetrahydrofuran (5 mL) to afford a solid. The product
was purified by slow diffusion of diethyl ether into an acetonitrile
solution of the complex at –30 °C. A yellow solid was obtained.
Experimental Section
Yield: 210 mg (87%). HRMS (ESI): calcd. for C16
H
20BrMnN
4
+
[
M – Br] 402.0252; found 402.0243. μeff = 5.91(3) μ
B
. Λ (H
M
2
O) =
General Remarks: All anaerobic manipulations were performed un-
der nitrogen by using standard Schlenk techniques or in an M.
Braun Labmaster glovebox. Glassware was dried at 150 °C over-
night. Diethyl ether, tetrahydrofuran, DMF, and acetonitrile were
purified with a Glass Contour solvent purification system. Deion-
ized water was used for all kinetic and volumetric measurements.
The compounds 2,6-bis(chloromethyl)pyridine, tosylamide mono-
–
1
2
–1
268 Ω cm mol .
Synthesis of [Mn(Py N )(NCMe) ](PF ) : A solution of TlPF
2
2
2
6 2
6
(210 mg, 0.6 mmol) in acetonitrile (2 mL) was added to a stirred
solution of Mn(Py N )Br (145 mg, 0.3 mmol) in acetonitrile
2
2
2
(3 mL) under N . The reaction mixture was stirred at ambient tem-
2
perature for 3 h. After filtration through Celite, the removal of vol-
sodium salt (TsNHNa), and 2,11-diaza[3,3](2,6)pyridinophane
atiles furnished a white solid. Crystals suitable for X-ray diffraction
analysis were grown by slow diffusion of diethyl ether into an
acetonitrile solution of the complex at –30 °C. Yield: 0.16 g (77%).
were prepared according to literature procedures.[
38,39]
The concen-
2 2
tration of H O was determined by a redox titration with potas-
sium permanganate. All other reagents were purchased from com-
mercial vendors and used as received. H NMR spectroscopic data
were recorded with a Varian Unity 400 spectrometer (400 MHz) at
Kinetics Measurements: Oxygen evolution studies were carried out
volumetrically under pseudo-first-order conditions. The reactions
were performed in a sealed Erlenmeyer flask (25 mL) immersed in
a water bath thermally equilibrated at 25 °C and equipped with a
stirring bar and a gas-delivery side tube connected to an inverted
1
2
2 °C. The stock solution of red-CLA (250 μm) was prepared by
dissolving red-CLA (1 mg) in a H O/MeOH mixture (1:1, v/v;
.2 mL). Photoluminescence spectra were recorded with a CARY
2
4
burette filled with water. The flask was charged with Mn(Py
Br (in 1 mL H O, 1–5 μmol) and water (0–1 mL). H (1–2 mL,
.2–18.4 mmol) was added with a syringe, and the reaction mixture
was stirred vigorously at a constant stirring rate (300 rpm). The
stopwatch was started right after the addition of H . The initial-
2 2
N )-
Eclipse fluorescence spectrophotometer. Solution magnetic suscep-
tibilities were determined by using the Evans method.[ UV/Vis
spectra were recorded with a CARY 100 Bio UV/Vis spectropho-
2
2
2 2
O
40]
9
2
tometer. The conductivity of the complex in H O at 25 °C was
2
O
2
measured with a Radiometer CDM 83. All pH measurements were
acquired with an Orion Star A111 pH meter by using a glass elec-
trode (Orion 9157BNMD). High-resolution mass spectrometry was
conducted through positive electrospray ionization with a Bruker
rate method was used to determine the rate constants. Each rate
constant reported represents the average value of duplicate or trip-
licate determinations. Variable-temperature kinetic experiments
were carried out over the temperature range 25–44 °C.
12 Tesla APEX-Qe FTICR-MS with an Apollo II ion source at the
2 2 2
mass spectrometry facility at Old Dominion University, Norfolk, Reaction of Mn Complexes with H O and Quantification of O
VA. X-band (ca. 9–9.5 GHz) EPR spectra were recorded with a
modified Varian E-9 spectrometer by using DPPH (2,2-diphenyl-1-
picrylhydrazyl) as an external standard.
Evolution: The reactions were performed in a sealed Erlenmeyer
flask (50 mL) immersed in a water bath at 25 °C and equipped with
a stirring bar and a gas-delivery side tube connected to an inverted
graduated cylinder filled with water. The flask was charged with
Synthesis of N,NЈ-Ditosyl-2,11-diaza[3,3](2,6)pyridinophane: This
Mn(Py
(10 mL, 9.7 mmol) was added with a syringe, and the reac-
tion mixture was stirred vigorously. The stopwatch was started
right after the addition of H . The amount of evolved dioxygen
was determined volumetrically, and the yield of O was calculated
2 2 2 2
N )Br (in 0.5 mL H O, 1.5 μmol) and water (0.5 mL).
compound was prepared according to published procedures with
2 2
H O
[
39]
slight modifications. A solution of 2,6-bis(chloromethyl)pyridine
1.8 g,10.2 mmol) in N,N-dimethylformamide (20 mL) was added
(
2
O
2
dropwise to a stirred slurry of TsNHNa (2.0 g, 10.4 mmol) in N,N-
dimethylformamide (200 mL) at 80 °C over a period of 1 h. Solid
TsNHNa (2.0 g, 10.4 mmol) was added all at once, and the reaction
mixture was stirred at 80 °C for 4 h. The volatiles were removed
under reduced pressure to obtain a sticky solid, which was washed
with water (50 mL) followed by methanol (20 mL) and ethanol
2
by using the ideal gas law and by accounting for the reduced atmo-
spheric pressure in Las Cruces. A turnover number of 58000 was
calculated.
Kinetic Isotope Experiment: The experiment was performed in a
(20 mL). The remaining white residue was continuously extracted
sealed Erlenmeyer flask (10 mL) immersed in a water bath at 25 °C
Eur. J. Inorg. Chem. 2013, 3867–3873
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© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

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FULL PAPER
and equipped with a stirring bar and a gas-delivery side tube con-
nected to an inverted buret filled with water. The flask was charged
with 9.2 m H (1 mL, 9.2 mmol) and D O (1.9 mL, 103 mmol).
After aging for 1 h, (20 mm, 2.0 μmol) in D
0.1 mL, 5 mmol) was added with a syringe, and the reaction mix-
ture was stirred vigorously at a constant stirring rate (300 rpm).
The stopwatch was started immediately after the addition, and the
dioxygen amount was quantified volumetrically.
Acknowledgments
2
O
2
2
Financial support from Department of Energy – Basic Energy Sci-
ences (DOE-BES) (DE-FG02-08ER15996) and American Chemi-
cal Society – Petroleum Research Foundation (ACS-PRF) (50971-
ND3) is gratefully acknowledged. J. M. S. is a Dreyfus Teacher-
Scholar. We thank Joshua Telser (Roosevelt University) for re-
cording the EPR spectra and Michael D. Johnson (NMSU) for
invaluable scientific assistance.
[
41]
Mn(Py
2
N
2
)Br
2
2
O
(
Methylene Blue Bleaching: A 1 cm cuvette was charged with meth-
ylene blue (in 1 mL H
An aqueous solution of Mn(Py
2
O, 0.05 μmol) and H
2
O
2
(1 mL, 92 mmol).
O, 1 μm) was
2
N
2
)Br (in 1 mL H
2
2
[
1] a) V. Costa, P. Moradas-Ferreira, Mol. Aspects Med. 2001, 22,
added, and the reaction mixture was stirred vigorously for 2 s. The
decay of the characteristic absorbance of methylene blue at 665 nm
was monitored by UV/Vis spectroscopy.
217–246; b) D. S. Warner, H. Sheng, I. Batini c´ -Haberle, J. Exp.
Biol. 2004, 207, 3221–3231; c) M. Valko, D. Leibfritz, J. Mon-
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Biol. 2007, 39, 44–84; d) L. M. Sayre, G. Perry, M. A. Smith,
Chem. Res. Toxicol. 2008, 21, 172–188.
Superoxide Detection: A 1 cm cuvette was charged with Mn-
(Py
2
N
2
)Br
2
(in 1.44 mL H
2
O, 1.44 μmol) and H
2
O
2
(1.44 mL, [2] M. J. Mate, G. Murshudov, J. Bravo, W. Melik-Adamyan, P. C.
Loewen, I Fita, Ignacio in Handbook of Metalloproteins, vol. 1
132 μmol). A stock solution of red-CLA (0.12 mL, 0.03 μmol) was
(
Ed.: A. Messerschmidt), John Wiley & Sons, Chichester, 2001,
added, and the reaction mixture was stirred vigorously for 2 s. The
emission at 610 nm was measured with a fluorescence spectropho-
tometer. There was no difference between the fluorescence spectra
recorded under catalytic conditions and similar control experi-
pp. 486–502.
[3] A. J. Wu, J. E. Penner-Hahn, V. L. Pecoraro, Chem. Rev. 2004,
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4] a) S. V. Antonyuk, V. R. Melik-Adamyan, A. N. Popov, V. S.
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Harrison, P. J. Artymiuk, J. W. Whittaker, Structure 2001, 9,
725–738.
2 2 2 2 2
ments for solutions of Mn(Py N )Br , H O , and only red-CLA.
X-ray Crystallography: For the X-ray crystallographic analysis, a
colourless block-like specimen of C20 12MnN (approximate
H
26
F
6 2
P
dimensions 0.26 mmϫ0.29 mmϫ0.42 mm) was cut from a larger
crystal, coated with Paratone oil, and mounted on a CryoLoop
that had been previously attached to a metal pin by using epoxy.
The X-ray intensity data were measured with an APEX II CCD
[
[
[
5] S. Signorella, C. Hureau, Coord. Chem. Rev. 2012, 256, 1229–
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7] a) B. J. Day, I. Fridovich, J. D. Crapo, Arch. Biochem. Biophys.
sealed tube (λ = 0.71073 Å). The frames were integrated with the
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yielded a total of 42198 reflections to a maximum θ angle of 28.28°
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[
[
[
(0.75 Å resolution), of which 7289 were independent (average re-
9] B. Albela, R. Carina, C. Policar, S. Poussereau, J. Cano, J. Gu-
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dundancy 5.789, completeness = 99.7%, Rint = 3.27%, Rsig
=
2
2.30%), and 5972 (81.93%) were larger than 2σ(F ). The final cell
constants of a = 9.3168(9) Å, b = 16.8827(16) Å, c = 20.5176(18) Å,
10] The complex has also been structurally characterized as the
3
β = 114.245(5)°, and V = 2942.6(5) Å are based on the refinement
acetonitrile solvate after anion metathesis with TlPF
6
in
of the XYZ centroids of reflections above 20σ(I). The calculated
minimum and maximum transmission coefficients (based on the
crystal size) are 0.7703 and 0.8481, respectively. The structure was
solved and refined by using the Bruker SHELXTL Software Pack-
MeCN, see Supporting Information.
[
[
11] See Supporting Information for further details.
12] W. A. Gunderson, A. I. Zatsman, J. P. Emerson, E. R. Far-
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age and by using the space group P2
1
/c, with Z = 4 for the formula
[
13] More comprehensive information on the kinetic parameters of
mono- and dinuclear manganese catalase mimics can be found
in ref.[
unit C20 12MnN . Non-hydrogen atoms were refined aniso-
H
26
F
6 2
P
tropically. Hydrogen atoms were placed in geometrically calculated
positions with Uiso = 1.2Uequiv of the parent atom (Uiso = 1.5Uequiv
for methyl groups). The final anisotropic full-matrix least-squares
5]
2
+
[
[
14] Negligible oxygen evolution in the presence of Mn(H
observed under the same conditions.
15] Given that we do not have full deuteration of the solvent or
as well as the multiple proton-dependent steps in the
proposed mechanism, it is very difficult to interpret this value.
2
O)
6
is
2
refinement on F with 374 variables converged at R1 = 3.98% for
the observed data and at wR2 = 11.54% for all data. The goodness-
2 2
H O
of-fit was 1.046. The largest peak in the final difference electron
–
–3
density synthesis was 0.665 e Å , and the largest hole was
[16] R. G. Wilkins, Kinetics and Mechanism of Reactions of Transi-
tion Metal Complexes, 2nd ed., VCH, Weinheim, 1991.
[17] J. Kaizer, B. Kripli, G. Speier, L. Párkányi, Polyhedron 2009,
28, 933–936.
[
[
[
–
–3
–
–3
–
0.516 e Å with an RMS deviation of 0.068 e Å . On the basis
–
3
of the final model, the calculated density was 1.570 gcm , and
F(000) was 1404 e . CCDC-923209 contains the supplementary
–
18] J. Kaizer, T. Csay, P. K o˝ vári, G. Speier, L. Párkányi, J. Mol.
crystallographic data for this paper. These data can be obtained
free of charge from The Cambridge Crystallographic Data Centre
via www.ccdc.cam.ac.uk/data_request/cif.
Catal. A 2008, 280, 203–209.
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Transition Met. Chem. 2011, 36, 811–817.
Supporting Information (see footnote on the first page of this arti-
cle): Structures of the ligands in Table 1, EPR spectrum of
[21] A. Mahammed, Z. Gross, Chem. Commun. 2010, 46, 7040–
2+
[Mn(Py
2
N
2
)(H
2
O)
2
]
, additional kinetic plots.
7042.
Eur. J. Inorg. Chem. 2013, 3867–3873
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FULL PAPER
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1/2
[
III
IV
II
(
Mn /Mn ). For [(Py
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4 6
2
2 2
NMe )MnCl ]: E1/2 = 0.496 V (Mn /
III
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[41] The rate of hydrogen exchange between H
2
O and H
2 2
O is
7
–1 –1
1.6ϫ10 m
s
under acidic conditions: M. Anbar, A. Loew-
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Received: February 5, 2013
Published Online: May 31, 2013
Eur. J. Inorg. Chem. 2013, 3867–3873
3873
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim