Synthesis, characterization, and catalase activity of a water-soluble diMnIII complex of a sulphonato-substituted schiff base ligand: An efficient catalyst for H2O2 disproportionation

Article abstract of DOI:10.1021/ic2011452

A new diMn^III complex, Na[Mn₂(3-Me-5-SO ₃-salpentO)(μ-MeO)(μ-AcO)(H₂O)]?4H ₂O (1), where salpentOH = 1,5-bis(salicylidenamino) pentan-3-ol, was synthesized and structurally characterized. The complex possesses a bis(μ-alkoxo)(μ-acetato) triply bridged diMn^III core, the structure of which is retained upon dissolution. Complex 1 is highly efficient to disproportionate H₂O₂ in an aqueous solution of pH ≥ 8.5 or in DMF, with only a slight decrease of activity. Electrospray ionization mass spectrometry, EPR, and UV-vis spectroscopy used to monitor the H ₂O₂ disproportionation in buffered basic medium, suggest that the major active form of the catalyst during cycling occurs in the Mn ^III₂ oxidation state and that the starting complex retains the dinuclearity and composition during catalysis, with the acetate that moves from bridging to terminal ligand. UV-vis and Raman spectroscopy of H ₂O₂ + 1 + Bu₄NOH mixtures in DMF suggest that the catalytic cycle involves Mn^III₂/Mn^IV ₂ oxidation levels. At pH 10.6 in an Et₃N/Et ₃NH⁺ buffer, complex 1 catalyzes dismutation of H ₂O₂ with saturation kinetics on the substrate, first order dependence on the catalyst, and k_cat/K_M = 16(1) ×10² s^-1 M^-1. During catalysis, the exogenous base contributes to retain the integrity of the bis(μ-alkoxo) doubly bridged diMn core and favors the formation of the catalyst-peroxide adduct (low value of K_M), rendering 1 a highly efficient catalyst for H₂O₂ disproportionation.

Full text of DOI:10.1021/ic2011452

ARTICLE
pubs.acs.org/IC
Synthesis, Characterization, and Catalase Activity of a Water-Soluble
diMnIII Complex of a Sulphonato-Substituted Schiff Base Ligand: An
Efficient Catalyst for H2O2 Disproportionation
Claudia Palopoli,† Natalia Bruzzo,† Christelle Hureau,‡ Sonia Ladeira,‡,§ Daniel Murgida,^ and
Sandra Signorella*,†
†Departamento de Química Física/IQUIR-CONICET, Facultad de Ciencias Bioquímicas y Farmacꢀeuticas, Universidad Nacional de
Rosario, Suipacha 531, S2002LRK Rosario, Argentina
‡CNRS, LCC (Laboratoire de Chimie de Coordination), 205, route de Narbonne, F-31077 Toulouse, France and Universitꢀe de
Toulouse, UPS, INPT, LCC, F-31077 Toulouse, France
§Institut de Chimie de Toulouse, FR2599, 118 route de Narbonne, F-31062 Toulouse, France
^Departamento de Química Inorgꢀanica, Analítica y Química Física/INQUIMAE-CONICET, Facultad de Ciencias
Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pabellꢀon 2, Buenos Aires C1428EHA, Argentina
S Supporting Information
b
ABSTRACT: A new diMnIII complex, Na[Mn2(3-Me-5-SO3-salpentO)(μ-MeO)(μ-
AcO)(H2O)] 4H2O (1), where salpentOH = 1,5-bis(salicylidenamino) pentan-3-ol,
3
was synthesized and structurally characterized. The complex possesses a bis(μ-
alkoxo)(μ-acetato) triply bridged diMnIII core, the structure of which is retained
upon dissolution. Complex 1 is highly efficient to disproportionate H2O2 in an
aqueous solution of pH g 8.5 or in DMF, with only a slight decrease of activity.
Electrospray ionization mass spectrometry, EPR, and UVꢀvis spectroscopy used to
monitor the H2O2 disproportionation in buffered basic medium, suggest that the
major active form of the catalyst during cycling occurs in the MnIII2 oxidation state and
that the starting complex retains the dinuclearity and composition during catalysis,
with the acetate that moves from bridging to terminal ligand. UVꢀvis and Raman
spectroscopy of H2O2 + 1 + Bu4NOH mixtures in DMF suggest that the catalytic cycle
involves MnIII2/MnIV oxidation levels. At pH 10.6 in an Et3N/Et3NH+ buffer,
2
complex 1 catalyzes dismutation of H2O2 with saturation kinetics on the substrate, first order dependence on the catalyst, and kcat/
KM = 16(1) ꢁ 102 sꢀ1 Mꢀ1. During catalysis, the exogenous base contributes to retain the integrity of the bis(μ-alkoxo) doubly
bridged diMn core and favors the formation of the catalystꢀperoxide adduct (low value of KM), rendering 1 a highly efficient catalyst
for H2O2 disproportionation.
’ INTRODUCTION
control catalysis. A number of dinuclear manganese-based
complexes have been investigated as low-molecular-weight cata-
lytic scavengers of H2O2.6ꢀ19 However, most of the tested
complexes are not soluble in water or lose activity in aqueous
media.15ꢀ19 Therefore, there is a need to design efficient catalytic
antioxidants with improved stability in aqueous media to be useful
as drugs.
Catalases (CATs) protect biological systems against oxidative
damage caused by hydrogen peroxide generated during aero-
bic metabolism through bielectronic reduction of molecular
oxygen.1 In a variety of pathological situations, the production
of peroxide overwhelms the activity of endogenous defense
systems and results in cell damage.2 In this context, the
development of low molecular weight CAT mimics as ther-
apeutic agents have been actively sought for the prevention of
oxidative stress injuries,3 and Mn-based catalytic antioxidants
have shown beneficial effects against oxidative stress in vivo.4
MnCATs are a group of enzymes that catalyze disproportio-
nation of intracellular H2O2 into H2O and O2 by using a
Mn2(μ-O2CR)(μ-O/OH/H2O)2 structural unit as the active
site.5 To mimic this metallosite, it is essential to employ
ligands that reproduce the singularities of the metal environ-
ment in the biosite as well as the electronic properties that
We report here the synthesis, structure, properties, and
catalase-like activity of a new water-soluble MnIII complex:
2
Na[Mn2(3-Me-5-SO3-salpentO)(μ-OAc)(μ-OMe)(H2O)] -
3
4H2O (1), where 3-Me-5-SO3-salpentOH = 1,5-bis(3-methyl-5-
sulphonatosalicylideneamino)pentan-3-ol. Further, we check the
CAT activity in protic and nonprotic solvents and determine the
Received: May 28, 2011
Published: August 22, 2011
r
2011 American Chemical Society
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dx.doi.org/10.1021/ic2011452 Inorg. Chem. 2011, 50, 8973–8983
|

Inorganic Chemistry
ARTICLE
Scheme 1. Synthesis of Na2[3-Me-5-SO3-salpentOH]
effect of an exogenous base on the catalyst stability in aqueous
medium.
pale yellow solid filtered off, washed with ethanol, and dried. Yield: 2.05
g (8.61 mmol, 63%) of sodium 3-methylsalicylaldehyde-5-sulfonate. 1H
NMR (D2O) δ: 10.34 (s, 1H, OdCHꢀ), 8.38 (dd, 1H, C6ꢀH), 8.26
(dd, 1H, C4ꢀH), 2.67 (s, 3H, 3-CH3). 13C NMR (D2O) δ: 199.07
(CHdO), 162.18 (C2), 137.24, 135.98, 130.52, 128.69, 120.51 (Ar),
15.41 (3-CH3). Significant IR bands (KBr, ν cmꢀ1): νCdO 1655, νSO
3
1112/1052.
Synthesis of Sodium Salt of 1,5-bis(3-methyl-5-sulphona-
tosalicylidenamino)pentan-3-ol (Na2[3-Me-5-SO3-salpentOH]
3
3H2O). The ligand was prepared by Schiff-base condensation of sodium
3-methylsalicylaldehyde-5-sulfonate (1.90 g, 7.99 mmol) with 1,5-dia-
minopentan-3-ol21 (3.99 mmol) in ethanol (50 mL), at reflux for 5 h.
Na2[3-Me-5-SO3-salpentOH] 3H2O was isolated as a pure yellow solid
by precipitation from the reaction mixture at room temperature. Yield:
3
’ EXPERIMENTAL SECTION
2.19 g (3.58 mmol, 90%). Anal. Calcd. for C21H24N2Na2O9S2 3H2O: C
Materials. All reagents or AR chemicals were used as purchased.
Solvents were purified by standard methods. The concentration of the
H2O2 stock solution was determined by iodometric titration.
3
41.17, H 4.90; N 4.58%. Found: C 40.63; H 4.87; N 4.51%. 1H NMR
(D2O) δ: 8.73 (s, 2H, NdCHꢀ), 8.14 (d, 2H, C6ꢀH), 7.92 (dd, 2H,
C4ꢀH), 4.16 (m, 4H, ꢀCH2ꢀN), 3.45 (m, 1H, HꢀC(OH)ꢀ), 2.50
(s, 6H, ꢀCH3), 2.29 (m, 4H, (HO)CꢀCH2ꢀ). 13C NMR (D2O) δ:
176.27 (Ar), 167.74 (CHdN), 133.15, 132.63, 127.03, 124.75, 121.93
(Ar), 66.49 (R2CHꢀOH), 48.16 (NꢀCH2ꢀ), 36.04 (ꢀCH2ꢀ
CHOHꢀ), 15.73 (3-CH3). UVꢀvis λmax nm (ε Mꢀ1 cmꢀ1) in H2O:
222 (43000), 241 (25630), 277 (sh), 258 (sh), 333 (3950), 386 (3890).
In Et3N/Et3NH+ buffer, pH 10.75: 240 (50300), 259 (sh, 14700), 374
(9890). Significant IR bands (KBr, ν cmꢀ1): νOH 3426 (broad), νCdN
Synthesis of the Ligand. Na2[3-Me-5-SO3-salpentOH] was
synthesized through the reaction sequence shown in scheme 1.
Sodium 3-methylsalicylaldehyde-5-sulfonate was prepared through a
synthetic procedure adapted from references.20a,20b A mixture of
3-methyl-2-hydroxybenzaldehyde (4.17 g, 30.66 mmol) and aniline
(375 μL, 44.84 mmol) in ethanol (25 mL) was heated at reflux for
2 h. The solvent was evaporated, and the orange oil was treated with a
chloroform/water mixture. The organic layer was dried over anhydrous
Na2SO4 and the solvent evaporated. Yield: 6.33 g (30 mmol, 98%) of N-
1646, νSO 1111/1041.
3
1
Synthesis of Na[Mn2(3-Me-5-SO3-salpentO)(μ-OAc)(μ-
OMe)(H2O)] 4H2O (1). Mn(OAc)3 2H2O (1.36 g, 5.07 mmol) was
phenyl-3-methyl salicylaldimine. H NMR (DCCl3) δ: 8.63 (s, 1H,
NdCHꢀ), 7.44 (m, 2H, C4ꢀH, C6ꢀH), 7.28 (m, 5H, ph), 6.87 (t, 1H,
C5ꢀH), 2.34 (s, 3H, 3-CH3). 13C NMR (DCCl3) δ: 162.84 (CHdN),
159.48, 148.54, 134.15, 129.99, 129.41 (ꢁ2), 126.81, 126.52, 121.17
(ꢁ2), 118.60, 118.44, (Ar), 15.73 (3-CH3). To N-phenyl-3-methyl-
salicylaldimine (6.33 g, 30 mmol) was added concentrated sulphuric acid
(40 mL, 98 wt %, δ = 1.84 g/mL), and the mixture was stirred at 90 ꢀC
for 2 h. After cooling, the solution was added slowly to iceꢀwater with
vigorous stirring and a yellowish green solid precipitated. The mixture
was reheated until all of the solid dissolved, and then it was allowed to
cool. The yellow N-phenyl-3-methylsalicylaldimine-5-sulfonic acid was
filtered off, washed with iceꢀwater and ethanol, and dried under
3
3
added to a solution of Na2[3-Me-5-SO3-salpentOH] 3H2O (1.53 g,
3
2.5 mmol) in methanol (50 mL). The mixture was stirred for 20 min,
then filtered, and the resulting green solution was left to stir for 24 h. The
green precipitate was collected by filtration, washed with cold methanol,
and dried under vacuum. Yield 1.52 g (1.85 mmol, 74%). Anal. Calcd. for
Mn2C24H29N2O13S2Na 4H2O: C 35.04, H 4.53, Mn 13.36, N 3.41, Na
3
2.79%; found C 34.70, H 4.19, Mn 12.95, N 3.31, Na 2.80%. Significant
IR bands (KBr, ν cmꢀ1): νOH 3440, νCH 2930, νCdN 1613, νAcO 1558/
1432, νSO 1118/1042. UVꢀvis λmax nm (ε Mꢀ1 cmꢀ1) in H2O: 276
3
(29595), 360 (6450), 445 (sh, 2152), 592 (904). In Et3N/Et3NH+
buffer, pH 10.75: 240 (70500), 260 (sh), 375 (19640). Molar con-
ductivity = 74 Ωꢀ1 cm2 molꢀ1. Single crystals of Na[Mn2(3-Me-5-SO3-
1
vacuum. Yield: 3.95 g (13.6 mmol, 45%). H NMR (D4-methanol/
D2O) δ: 9.22 (s, 1H, NdCHꢀ), 8.26 (dd, 1H, C6ꢀH), 8.14 (dd, 1H,
C4ꢀH), 7.79 (m, 5H, Ar), 2.55 (s, 3H, 3-CH3). 13C NMR (D4-
methanol/D2O) δ: 162.05 (C2ꢀOH), 158.73 (CHdN), 137.4,
135.96, 131.73, 131.38 (x2), 130.49, 130.37, 128.55, 124.17 (x2),
120.46 (Ar), 15.54 (3-CH3). N-Phenyl-3-methylsalicylaldimine-5-sul-
fonic acid (3.95 g) in a saturated solution of Na2CO3 (23 mL) was boiled
vigorously for 2 h. After cooling, glacial acetic acid was slowly added to
pH 5 followed by ethanol (980 mL). The mixture was cooled to 0 ꢀC, the
salpentO)(μ-OMe)(μ-OAc)(MeOH)] 3MeOH (1(MeOH)) suitable
3
for X-ray diffraction were obtained by crystallization of 1 from methanol
upon standing in air for about one fortnight.
Physical Measurements. Electronic spectra were recorded on a
JASCO V550 spectrophotometer with cell compartments thermostatted
at 25 ꢀC. IR spectra were recorded on a Perkin-Elmer Spectrum One FT-
IR spectrophotometer. ESI-mass spectra were recorded on an API
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Inorganic Chemistry
ARTICLE
365 MS mass spectrometer. The electrospray solutions were prepared
from solutions of the complex or reaction mixtures and then diluted
100 times with methanol to reach a final ≈10ꢀ5 M concentration at a
flow rate of 5 μL minꢀ1. EPR data were recorded using an Elexsys E 500
Bruker spectrometer, operating at a microwave frequency of approxi-
mately 9.5 GHz. All spectra were recorded using a microwave power of
0.5 mW (under nonsaturating conditions) with a modulation amplitude
of 0.5 mT. Experiments were carried out at 110 K using a liquid nitrogen
cryostat. 1H and 13C NMR spectra were recorded on a Bruker AC 300
NMR spectrometer at ambient probe temperature (ca. 25 ꢀC). Para-
magnetic spectra were recorded using the super WEFT sequence, with
an acquisition time of 23 ms. Conductivity measurements were per-
formed using a Horiba F-54 BW conductivity meter on 1.0 mM
solutions of the complex in water. The electrochemical experiments
were performed with a computer-controlled Princeton Applied Re-
search potentiostat, model VERSASTAT II, with model 270/250
Research Electrochemistry Software. Studies were carried out under
Ar in methanol solutions using 0.1 M Bu4NPF6 as a supporting
electrolyte and ≈10ꢀ3 M of the complex. The working electrode was
a Pt wire or a glassy carbon disk, and the reference electrode was Ag/
AgCl with Pt as the auxiliary electrode. All potentials are referred to the
Ag/AgCl electrode. Using the described conditions, the ferrocene/
ferrocenium redox couple was observed at E1/2 = 417 mV. Resonance
Raman spectra were measured in backscattering geometry by using a
confocal microscope (Olympus BX41) coupled to a single-stage spectro-
graph (Jobin Yvon XY 800) equipped with a liquid-nitrogen-cooled
back-illuminated CCD detector and an 1800 L/mm grating. Elastic
scattering was rejected with an edge filter (Semrock). The 514 nm line of
a cw argon laser (Coherent Innova 70c) was focused into ca. 100 μL
solution film in a rotating quartz cell using a 20ꢁ objective (20.5 mm wd,
0.35 N.A.). Spectra were acquired with laser powers of about 13 mW at
the sample and were processed with homemade software for baseline
correction and peak determination. Spectral positions were aligned
toward standard Hg and Na lamps.
Table 1. Summary of Crystal Data for 1(MeOH)
empirical formula
C27H39Mn2N2NaO15S2 CH4 O
3
M
860.65
temperature (K)
180
wavelength (Å)
0.71073
crystal system, space group
triclinic, P1
a (Å)
b (Å)
11.3916(8)
12.3230(7)
c (Å)
15.8306(10)
100.284(5)
R (deg)
β (deg)
γ (deg)
V (Å3)
Z
108.520(6)
106.187(6)
1934.7(3)
2
F
(calcd.) (Mg/m3)
1.477
μMο (mmꢀ1
)
0.840
F(000)
892
crystal size (mm)
θ range (deg)
index ranges
0.14 ꢁ 0.12 ꢁ 0.02
3.44 to 25.35
ꢀ13 e h e 13, ꢀ14 e k e 14,
ꢀ19e k e 19
29280/7057 [R(int) = 0.0875]
99.7%
full-matrix least-squares on F2
7057/25/477
0.834
reflections collected/unique
completeness to θ = 25.35
refinement method
data/restraints/parameters
goodness-of-fit on F2
final R indices [I > 2σ(I)]
R indices (all data)
largest diff. peak and hole e (Å ꢀ3
R1 = 0.0463, wR2 = 0.0885
R1 = 0.1003, wR2 = 0.0959
0.582 and ꢀ0.515
)
Volumetric Measurements. The stoichiometry of the reaction
was measured by volumetric determination of the evolved O2 from
reaction mixtures in DMF, methanol, water, aqueous base, or buffer. A
round-bottom flask with a stopcock equipped gas delivery side tube
connected to a gas-measuring buret (precision of 0.1 mL) was used. A
closed vessel containing a solution of catalyst was stirred at constant
temperature on a water bath. Reactions in basic media were performed
for non-hydrogen atoms. Semiempirical absorption correction was
applied with the aid of the program DIFABS.26 The molecular plots
were drawn using the CAMERON program,27 with 50% probability
displacement ellipsoids. Crystal data collection and refinement para-
meters are summarized in Table 1. In the crystal lattice, methanol
molecules appear to be highly disordered, and it was difficult to model
their positions and distribution reliably. Therefore, the SQUEEZE
function of PLATON28 was used to eliminate the contribution of the
electron density in the solvent region from the intensity data, and the
solvent free model was employed for the final refinement.
using aqueous NaOH or Et3N/Et3NH ClO4 buffer. Previously thermo-
3
statted H2O2 ([H2O2]:[catalyst] ratio 150:1 or 175:1) was injected
through a silicon stopper, and the evolved dioxygen was volumetrically
measured. Blanc experiments performed in an Et3N/Et3NH+ buffer (pH
10.5 to 11.1) without the catalyst showed that after 40 min only 5% of
the initial H2O2 had disproportionated, while when the catalyst was
present, all H2O2 decomposed in 1 min.
’ RESULTS AND DISCUSSION
Solid State Characterization of Complex 1. The N2O3
pentadentate symmetric ligand, 3-Me-5-SO3-salpentOH, which
provides an alkoxo oxygen for the endogenous bridging of two
metal ions and two arms with N/O chelating donor sets, was
Kinetic Measurements. Oxygen evolution studies were carried
out polarographically using a Clark-type oxygen electrode with an YSI
oxygen-monitoring system (Model 5300, Yellow Springs Instruments
Co., Inc.). The initial rate method was used to determine the rate
constants (see ref 22 for further details). Each rate constant reported
here represents the mean value of multiple determinations that fall
within (5%. Experiments were carried out at 25 ꢀC.
reacted with 2 equiv of Mn(OAc)3 2H2O in methanol to prepare
3
a water-soluble diMn complex. In this reaction, acetate basicity
facilitates deprotonation of the alcohol and phenol groups for
coordination to the metal, to afford Na[Mn2(3-Me-5-SO3-
X-ray Structure Determination. Crystallographic data for com-
salpentO)(μ-OAc)(μ-OMe)(H2O)] 4H2O (1). Although the
pound Na[Mn2(3-Me-5-SO3-salpentO)(μ-OMe)(μ-OAc)(MeOH)] -
3
3
disodium salt of the ligand was used, the analytical results show
that the complex retains only one sodium ion per complex
molecule in the solid state. The IR spectrum of complex 1
(Figure 1) exhibits strong imine and phenolate absorptions at
1613 and 1545 cmꢀ1 that are shifted by ≈30 cmꢀ1 from those
in the free ligand due to the coordination of the metal to these
groups. The two strong bands at 1118 and 1042 cmꢀ1 are
3MeOH were collected at 180(2) K on an Oxford-Diffraction GEMINI
Diffractometer using a graphite-monochromated Mo-KR radiation (λ =
0.71073 Å) and equipped with an Oxford Cryosystems Cryostream
cooler device. Unit cell determination, data collection, and reduction
were carried out using the CrysAlis package.23 The structure was solved
by direct methods with SIR 9224 and refined by full-matrix least-squares
on Fo2 with SHELXL-97,25 using anisotropic displacement parameters
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Inorganic Chemistry
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attributable to the antisymmetric and symmetric stretching
coordination position of Mn(2) is occupied by one oxygen atom
from an exogenous methanol molecule and that of Mn(1) by one
oxygen atom of the sulphonato group of an adjacent complex
molecule. The MnꢀN/O bond lengths listed in Table 2 are
typical of the MnIII oxidation state.31ꢀ34 The coordination
polyhedra of the Mn centers may be described as elongated
octahedra, with the axial MnꢀO bond distances (av. 2.238(3) Å)
distinctly longer than the equatorial MnꢀN/O ones (av.
1.925(3) Å), a clear signature of the JahnꢀTeller distorted
coordination sphere of MnIII ions. The deviation from an ideal
octahedral geometry is also revealed by the range of angles
observed around each metal center (from 78.58(12)ꢀ to
ꢀ
modes of the ꢀSO3 groups, and absorption peaks at 1558
and 1432 cmꢀ1 identify the antisymmetric and symmetric
stretching vibrations of the syn,syn-1,3-bridging acetate.29 Com-
parison of the FT-IR spectrum of 1 with those of other diMnIII
complexes of the X-salpentOH family30 evidence the fingerprint
pattern of the Schiff-base ligand and μ1,3-carboxylato coordi-
nated to the Mn ions.
Crystal Structure of Na[Mn2(3-Me-5-SO3-salpentO)(μ-
OAc)(μ-OMe)(MeOH)] 3MeOH (1(MeOH)). Single crystals of
3
Na[Mn2(3-Me-5-SO3-salpentO)(μ-OAc)(μ-OMe)(MeOH)] -
3
3MeOH (1(MeOH)) suitable for X-ray diffraction studies were
obtained by slow evaporation of a methanol solution of 1. The
asymmetric unit of 1(MeOH) contains one diMn complex
anion, one sodium cation, and solvate methanol molecules.
The molecular structure of complex 1(MeOH) is illustrated in
Figure 2. In each complex anion, 3-Me-5-SO3-salpentO5ꢀ acts as
a pentadentate ligand through the N2O3 donor set. The two Mn
atoms are six-coordinated and triply bridged by the central alkoxo
of 3-Me-5-SO3-salpentO5ꢀ and exogenous syn,syn-acetato and
methoxo ligands. The phenolato-O, imino-N, and alkoxo-O
atoms of the ligand and the methoxo-O donor atom form a
meridional geometry around each Mn. One of the axial positions
of each Mn atom is occupied by an acetato-O atom, and the sixth
Table 2. Selected Bond Lengths and Angles for Na[Mn2-
(3-Me-5-SO3-salpentO)(μ-OMe)(μ-OAc)-
(MeOH)] 3MeOH (1(MeOH))
3
bond lengths (Å)
Mn(1)ꢀO(1)
Mn(1)ꢀO(2)
Mn(1)ꢀO(4)
Mn(1)ꢀO(5)
Mn(1)ꢀO(7)
Mn(1)ꢀN(2)
1.842(3)
1.910(3)
1.933(3)
2.238(3)
2.262(3)
2.005(4)
Mn(2)ꢀO(2)
Mn(2)ꢀO(3)
Mn(2)ꢀO(4)
Mn(2)ꢀO(6)
Mn(2)ꢀO(12)
Mn(2)ꢀN(1)
1.925(3)
1.849(3)
1.933(3)
2.220(3)
2.232(4)
1.999(4)
angles (deg)
O(1)ꢀMn(1)ꢀO(2) 170.48(13) O(3)ꢀMn(2)ꢀO(2) 171.79(12)
O(1)ꢀMn(1)ꢀO(4) 91.84(12) O(3)ꢀMn(2)ꢀO(4) 93.24(13)
O(2)ꢀMn(1)ꢀO(4) 78.94(12) O(2)ꢀMn(2)ꢀO(4) 78.58(12)
O(1)ꢀMn(1)ꢀN(2) 92.67(13) O(3)ꢀMn(2)ꢀN(1) 91.68(14)
O(2)ꢀMn(1)ꢀN(2) 96.55(13) O(2)ꢀMn(2)ꢀN(1) 96.52(14)
O(4)ꢀMn(1)ꢀN(2) 175.48(13) O(4)ꢀMn(2)ꢀN(1) 174.47(15)
O(1)ꢀMn(1)ꢀO(5) 90.06(13) O(3)ꢀMn(2)ꢀO(6) 90.17(13)
O(2)ꢀMn(1)ꢀO(5) 88.26(13) O(2)ꢀMn(2)ꢀO(6) 89.19(13)
O(4)ꢀMn(1)ꢀO(5) 94.01(13) O(4)ꢀMn(2)ꢀO(6) 90.96(12)
N(2)ꢀMn(1)ꢀO(5) 85.78(14) N(1)ꢀMn(2)ꢀO(6) 91.53(15)
O(1)ꢀMn(1)ꢀO(7) 92.67(12) O(3)ꢀMn(2)ꢀO(12) 89.74(14)
O(2)ꢀMn(1)ꢀO(7) 90.27(12) O(2)ꢀMn(2)ꢀO(12) 91.44(14)
O(4)ꢀMn(1)ꢀO(7) 93.45(13) O(4)ꢀMn(2)ꢀO(12) 92.86(13)
N(2)ꢀMn(1)ꢀO(7) 86.55(14) N(1)ꢀMn(2)ꢀO(12) 84.66(15)
O(5)ꢀMn(1)ꢀO(7) 171.97(12) O(6)ꢀMn(2)ꢀO(12) 176.18(12)
Mn(1)ꢀO(2)ꢀMn(2) 99.76(13) Mn(1)ꢀO(4)ꢀMn(2) 98.68(13)
Figure 1. FT-IR spectra of complex 1 (black) and Na2[3-Me-5-SO3-
salpentOH] (gray).
Figure 2. Asymmetric unit of 1(MeOH) with atom numbering.
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Figure 5. Electronic spectra of 1.3 ꢁ 10ꢀ5 M 1 in H2O (black) and
buffer of pH 10.75 (gray); l = 1 cm.
NaꢀO-sulphonato bonds (see Figure S1 in the Supporting
Information), and in turn, each Na+ is attached to a near Na+
through methanol bridges, thus reinforcing an overall 3-D
structure.
Figure 3. Packing diagram of 1(MeOH) viewed along the crystal-
lographic b axis.
Solution Studies. ESI-Mass Spectrometry (ESI-MS). ESI-mass
spectra of complex 1 confirmed its chemical composition as well
as retention of nuclearity in solution. The positive mode mass
spectrum of 1 in methanol (Figure 4a) is dominated by the peak
at m/z = 755.3 (100%) and originates from the monocation
Na2[MnIII2L(OAc)(OMe)]+. The positive mode ESI-mass spec-
trum of 1 in water (Figure 4b) exhibits, besides the parent peak at
m/z = 755.3 (100%), three other major peaks at m/z = 733.3
(84%, HNa[MnIII2L(OAc)(OMe)]+) where one Na+ is replaced
by H+, m/z = 673.5 (88%, Na[MnIII2L(OMe)]+) corresponding
to the loss of acetate, and m/z = 659.0 (41%, Na[MnIII2L-
(OH)]+) where the methoxo bridging ligand is substituted by a
hydroxo originated from the solvent in the latter species. Addi-
tional peaks at m/z 764.3 (11%), 705.3 (60%), and 643.2 (69%),
corresponding to the Na3[MnII,III2L(OAc)(OH)]+ mixed va-
lence and Na3[MnII L(OH)]+ and NaH[MnII L]+ cations also
2
2
appear in the ESI-mass spectra of the complex. These species are
most likely to be generated within the spectrometer. Upon the
addition of NaOH to an aqueous solution of 1, Na2[MnIII2L-
(OAc)(OMe)]+ (m/z 755.3) is observed together with other
monocations generated during the electrospray experiments,
with the main corresponding to H[MnIV2L(OMe)(OH)2]+
(m/z 685.5), H3[MnII,III2L(OH)2]+ (m/z 656.3), and Na3-
[MnIIIL]+ (m/z = 633.0). In the Et3N/Et3NH+ buffer, even
when the ESI-mass spectra are dominated by the peak of the
buffer (m/z = 303.5, [(Et3NH)2(ClO4)]+, 100%), monocations
H2[MnIII2L(OAc)(OMe)]+ (m/z = 711.2) and NaH[Mn2L-
(OAc)(OMe)]+ (m/z = 733.3) could be well identified as main
species.
Electronic Spectroscopy. The electronic spectrum of 1 in H2O
(Figure 5, black) shows an intense absorption at 276 nm which
can be attributed to intraligand πꢀπ* transitions. Absorptions in
the 350ꢀ500 nm range correspond to ligand-centered transi-
tions overlapping with LfM charge-transfer transitions from pπ
orbitals of the phenoxo oxygen to the partially filled dπ orbitals of
the MnIII ion, as also observed for other diMnIII complexes with
phenoxo ligands.39ꢀ42 Absorption at 592 nm (ε = 904
Mꢀ1 cmꢀ1) can be assigned to a d-d transition in agreement
with reported values for related diMnIII complexes.35,39ꢀ41
Figure 4. ESI-mass spectra of (a) 1 in methanol and (b) 1 in H2O; (c) a
reaction mixture of 1 + 5 equiv NaOH + 100 equiv H2O2, in H2O; (d) 1
+ 150 equiv H2O2, in Et3N/Et3NH+ buffer, after reaction.
96.55(13)ꢀ). The Mn Mn separation (2.933(1) Å) and the
3 3 3
MnꢀOꢀMn angles (98.68(13)ꢀ99.76(13)ꢀ) defining the core
of the asymmetric unit are typical of triply bridged bis(μ-
alkoxo)(μ-carboxylato) diMnIII complexes of polydentate li-
gands derived from 1,5-diaminopentan-3-ol30,35 and smaller than
those of MnIII complexes of polydentate ligands derived from
2
1,3-diaminopropan-2-ol (≈ 3.2 Å), which possess a JahnꢀTeller
elongation axis oriented along the bridging core.32,34,36ꢀ38
Figure 3 displays the packing structure parallel ac plane of
compound 1(MeOH). In the crystal structure, each dinuclear
entity is connected to an adjacent diMn anion through coordina-
tion of Mn(1) and O(7) of the sulphonato group of the basic
dinuclear unit to the respective O(7) and Mn(1) of a neigh-
bor complex anion. Additionally, the Na cations link each di-
manganese unit to its symmetrically related congener through
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Figure 6. 1H NMR spectra of 1 (20 mM), before (black) and after the
addition of 1.25 (orange) and 5.0 equiv (purple) of NaOH, in D4-
methanol.
UVꢀvis spectra of basic solutions of complex 1, in either a
NaOH, Et3N, or Et3N/Et3NH+ buffer, show an intense absorp-
tion at 375 nm due to intraligand transitions of the sulphonato
ligand superimposed to phenolate to MnIII CT transitions
(Figure 5, gray). The intensity of this absorption is around twice
that of the free ligand, and the results are useful to monitor the
integrity of the catalyst during H2O2 disproportionation. In these
basic solutions, no discernible bands corresponding to d-d
transitions have been resolved in the lower energy visible region.
1H NMR Spectroscopy. 1H NMR spectra of mono- and
dinuclear MnIII-salycilidenamino complexes display a set of
upfield resonances corresponding to protons of the phenolato
ring that has proven to be particularly valuable in the character-
ization of the species in solution.43a The paramagnetic 1H NMR
spectrum of 1 in D4-methanol contains a characteristic acetate
peak and distinctive ligand resonances that reveal a pattern
typical of a highly symmetrical environment for the Schiff base
ligand (Figure 6) and confirms that this complex retains its
dinuclear structure in solution. The spectrum shows two broad
upfield resonances at ꢀ23.54 and ꢀ7.75 ppm, assigned to the H4
and H6 protons of the two magnetically equivalent terminal
phenolate rings, in accordance with previous studies.43 The
intense resonance that appears at 13.51 ppm corresponds to
the methyl substituent in the aromatic ring. This peak shows the
broadened features of a paramagnetic signal, and the assignment
is further confirmed by comparison with the corresponding
spectrum of [Mn2(μ-OAc)(μ-OMe)(3-Me-salpentO)].30b The
broad resonance at 38 ppm can be assigned to the methyl group
of the bridging acetate of 1 on the basis of comparison with the
spectra of other MnIII2(μ-OAc) complexes previously studied.43b,c
The effect of the addition of base on the 1H NMR spectrum of
1 in D4-methanol was examined. Spectra taken after the addition
of increasing amounts of NaOH (from 1 to 5 equiv) showed that
the proton resonances from the Schiff base ligand remain
unchanged, but the intensity of the bridging acetate protons
decreased and the peak disappeared when 5 equiv of base were
added (Figure 6). The same decrease of the resonance of the
bridging acetato protons was observed upon the addition of 5
equiv of Et3N. The unchanging paramagnetic shift of the ligand
protons indicates that the magnetic coupling between Mn ions is
the same as in starting 1. Besides, ESI-MS results described above
showed that in a basic medium the complex retains acetate.
Therefore, the disappearance of the broad resonance corre-
sponding to the acetate protons together with the unchanged
chemical shift of the aromatic protons can be interpreted in terms
Figure 7. Cyclic voltammogram of (a) 1 in methanol: scan rate =
100 mV/s, working electrode = Pt wire; (b) 1 in methanol, before
(black) and after the addition of Et3N (gray): scan rate = 300 mV/s,
working electrode = glassy carbon. Conc. = 1 mM. Supporting electro-
lyte = Bu4NPF6. Reference electrode = AgCl/Ag.
of the conversion of bridging acetate into a monodentate
terminal ligand, chemical shift of monodentate acetate being
within the diamagnetic region of the spectrum, which might
accommodate the coordination of an additional terminal base
ligand.44a 1H NMR spectra obtained in a basic medium also
exclude the formation of an oxo-bridged MnIII2, which should
provide a better exchange pathway between Mn ions affording a
spectrum with paramagnetic shifts different from those of the
starting compound.43a,44
Electrochemical Studies. The electrochemical properties of
complex 1 were investigated by cyclic voltammetry in methanol
solutions containing 0.1 M Bu4NPF6, using a Ag/AgCl reference
electrode. The complex exhibits one quasi-reversible wave at E1/2
95 mV (ΔEp = 200 mV, Figure 7a) that can be attributed to the
MnIII2/MnIIIMnII redox couple, as confirmed by linear and
square-wave voltammetry (w1/2 = 120 mV) experiments. An addi-
tional nonreversible reduction peak was observed at ꢀ570 mV
in the cathodic scan (Figure 7b, black), attributable to the
MnIIIMnII/MnII couple, as suggested for previously reported
2
complexes with a similar ligand environment.30,32 Upon addition
of Et3N to the MeOH solution of 1, no changes were observed in
the cyclic voltammogram, a result that excludes the conversion of
the starting complex into the μ-oxo-Mn2 complex, the signature
of which is significantly different,41,45 and is consistent with the
1H NMR results. An irreversible peak at Ep ≈ 850 mV was also
observed in the oxidative scan, but it was already present in the
voltammogram of the Et3N/MeOH mixture.
CAT Activity Studies. Sensitivity of the Catalase Activity of 1
to the Reaction Medium. The ability of complex 1 to catalyze
H2O2 disproportionation was tested in DMF, methanol, and
water. Addition of H2O2 to a solution of the catalyst causes an
immediate vigorous evolution of dioxygen coupled to color
changes: from green to orange in DMF and from green to pale
yellow in methanol and water. The relative CAT activity of 1 in
these solvents was determined by the volumetric measurement of
evolved O2. As shown in Figure 8, complex 1 dismutates 150
equiv of H2O2 within 11 min in DMF, whereas it requires more
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Figure 8. Time-dependence of O2 evolution upon reaction of 1 with
150 equiv of H2O2 in different solvents. [1] = 1 ꢁ 10ꢀ3 M; T = 25 ꢀC.
than 1 h to dismutate the same H2O2 amount in methanol. In
water, H2O2 disproportionation is still slower, and the catalyst
inactivates after the disproportionation of 70 equiv of H2O2.
Successive additions of 150 equiv of H2O2 to the catalyst solution
showed that complex 1 is able to disproportionate more than
1500 equiv of H2O2 in DMF without significant decomposition,
but in methanol, it inactivates after 200 turnovers. It is likely that
the bridging ligands of the complex serve as internal bases
facilitating deprotonation of the peroxide coupled to the redox
reaction. Therefore, in the protic solvents, protonation of these
bridges may result in the inactivation of the catalyst and metal
dissociation during the reaction.
Figure 9. Time-dependence of O2 evolution after succesive additions of
63 μL of 10.05 M H2O2 (175 equiv) to an (a) aqueous solution of 1
(1.2 ꢁ 10ꢀ3 M) + 5 equiv NaOH; and (b) 1 in a buffer at pH 10.75. (c)
EPR spectra taken at the end of H2O2 disproportionation in NaOH and
a buffer; ν = 9.5 GHz, T = 100 K, and microwave power = 0.5 mW. (d)
Electronic spectra registered after successive additions of H2O2 to the
solution of 1 (1.1 x10ꢀ5 M) in a buffer at pH 10.75 and T = 298 K.
Given the particular interest of evaluating the CAT activity in
aqueous solution, and with the intention to avoid inactivation of
the catalyst in the protic solvent, H2O2 disproportionation by
complex 1 was measured in aqueous NaOH (pH 12.4). Succes-
sive additions of excess H2O2 to the catalyst in aqueous NaOH
solution yielded the stoichiometric amount of O2, but the initial
rate of H2O2 dismutation gradually decreased after each new
addition (Figure 9a). UVꢀvis spectra taken at different reaction
times showed an intensity decrease of the absorption at 375 nm,
indicating a partial loss of catalyst after successive additions of
H2O2. This was confirmed by ESI-mass spectra taken at the
end of the reaction of 1 with excess H2O2 in aqueous NaOH,
that showed an intensity decrease of the peak corresponding
to Na2[MnIII2(OAc)(OMe)L]+ (m/z 755.3) and an increase
of peaks corresponding to Na3[MnIIIL]+ (m/z 633.0) and
H2[L(MeOH)]+ (m/z 546.1) relative to that of the dinuclear
complex (Figure 4c). EPR monitoring of reaction mixtures in
aqueous NaOH provided complementary information on the
inactive form of the catalyst. EPR spectra of a 1:5:150 1:NaOH:
H2O2 reaction mixture showed, in the region of g ≈ 2, a 6-line
were obtained with an aqueous Et3N/Et3NH+ buffer. More than
2500 turnovers were measured for complex 1 in the aqueous
Et3N/Et3NH+ buffer of pH 10.75, with only a slight decrease of
activity (Figure 9b) and without significant decomposition, as
shown by the spectrophotometric monitoring of the buffered
reaction (Figure 9d). The observation of peaks corresponding to
H2[MnIII2L(OAc)(OMe)]+ and HNa[MnIII2L(OAc)(OMe)]+
at m/z = 711.2 and 733.3, respectively, in the ESI-mass spectra
registered during and at the end of the reaction in the Et3N/
Et3NH+ buffer (Figure 4d) provide a clear indication that the
MnIII complex persists during the catalytic cycle. The EPR
2
spectra of complex 1 recorded in buffered solutions at various
time-intervals following the addition of 150 equiv of H2O2 were
essentially EPR silent, except for a very small six-line signal at g ≈
2 with hyperfine splitting of ≈90 G (Figure 9c). Therefore, the
signal (hyperfine splitting of ≈90 G) characteristic of an Mn2+
aq
ion (Figure 9c). This EPR signal grew-in and persisted at the end
of the reaction, indicating accumulation of an inactive MnII
species is responsible for the loss of catalytic activity. Therefore,
as NaOH was consumed, the pH of the reaction mixture
decreased (from 12.4 to 8.2 after 12 additions of 150 equiv of
H2O2), and protonation of the catalyst began to compete with
CAT activity, lowering the efficiency to disproportionate H2O2.
This problem was solved by performing the reaction in a buffered
basic solution. Different buffers were tested in order to find the
optimal pH for the highest catalytic efficiency. It was found that
the pH must be controlled to values g8.5 for the catalyst to retain
its efficiency after successive additions of H2O2. Excellent results
Mn2+ species is only a minor one when the reaction is
aq
performed in a buffered solution (the intensity of the EPR signal
of a 150:1 H2O2/catalyst mixture in an Et3N/Et3NH+ buffer was
less than 10% of that for the same reaction performed in aqueous
NaOH). The absence of the EPR signal during the reaction
course, except for the minor inactive MnII species, suggests that
the MnIII2 form of the catalyst is the dominant species in solution
since no EPR signal is expected for the catalyst in this
oxidation state.
Raman and UVꢀvis Studies of the CAT-Reaction in DMF. In
order to obtain additional information on the diMn species
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Figure 11. Effect of the H2O2 concentration on the initial rate of H2O2
disproportionation at 25 ꢀC in an aqueous Et3N buffer pH 10.6.
LMCT coupled to the νMndO vibration.48 The fact that after
successive additions of H2O2 the activity of 1 remains essentially
constant and the recovery of the catalyst at the end of the reaction
support that the MndO species observed in RR and electronic
spectra still bears the ligand.
Figure 10. (a) RR spectra of a DMF solution of 1 (black) and a mixture
of 1 + 150 equiv H2O2 + 5 equiv Bu4NOH at 6 (orange), 9 (purple), and
16 min (pink) after mixing. 514 nm excitation; [1] = 0.6 mM. (b) Time-
evolution of the multiplet at 528 nm in the electronic spectra of a DMF
reaction mixture under conditions of the RR experiments. The inset: Abs
vs time curve at 528 nm.
In order to verify if the strong enhanced Raman peak was also
observed during the reaction of other diMnIII complexes of the
X-salpentOH family in DMF solution of Bu4NOH, two other
complexes, [Mn2(5-NO2-salpentO)(μ-OMe)(μ-OAc)]Br and
[Mn2(naphpentO)(μ-OMe)(μ-OAc)]ClO4, were studied by
RR spectroscopy. H2O2 disproportionation catalyzed by these
two complexes in Bu4NOH/DMF also exhibit the multiplet
centered at 528 nm in the visible spectra. The enhanced Raman
peak is also observed at 834 cmꢀ1 during the reaction of the two
complexes with H2O2 (see Figure S2 in the Supporting In-
formation), indicating that its frequency is independent of the
substituent in the aromatic ring of the ligand. Therefore, UVꢀvis
and RR spectroscopy agree that MnIV-oxo species are involved in
the catalytic disproportionation of H2O2 by complexes of the
X-salpentOH series in DMF, although the exact role of this
solvent in delaying the reduction of the oxidized form of the
catalyst to the diMnIII species is not yet clear.
involved in the H2O2 disproportionation in basic medium, a
mixture of 1 + 150 equiv H2O2 + 5 equiv Bu4NOH in DMF was
monitored by resonance Raman (RR) spectroscopy. DMF was
used because neither water nor MeOH showed enhanced lines in
the RR spectra. The RR spectra were obtained with 514 nm
excitation and recorded at different times during the reaction
(Figure 10a). Addition of H2O2 to the basic DMF solution of 1
changed the color of the solution from orange to pink during O2
evolution and led to the appearance of a strongly enhanced
Raman peak at 834 cmꢀ1. This peak grew up during the progress
of the reaction and disappeared when the reaction was over. The
signal reappeared with a second addition of 150 equiv of H2O2 to
the DMF basic solution of the catalyst. The observed frequency
at 834 cmꢀ1 is consistent with the double-bond character
between the Mn ion and an oxygen atom and is in the range
expected for the MnIVdO stretching vibration in organic
solvents.46 In the present case, the MnIVdO frequency is higher
than that of MnIV-oxo porphyrin complexes, in accordance with
previous observation that the Mn-oxo complexes bearing non-
porphyrinic ligands exhibit a MnꢀO stretching band at higher
frequency,47 a fact that was attributed to the porphyrin π
delocalization that weakens oxo f dπ donation.
Even when there is no direct evidence to discern if the catalyst
shuttles between MnIII2/MnII or MnIII2/MnIV oxidations
2
2
states during catalysis in an aqueous basic medium, spectroscopic
observation of the oxo-MnIV species in basic DMF suggests that
catalytic disproportionation of H2O2 by 1 involves MnIII2/MnIV
2
oxidation levels. In a basic aqueous solution, oxo-MnIV reduction
should occur in a fast step of the catalytic cycle (fast oxidative
half-reaction). Thus, the MnIII species should be the catalytic
2
form that participates in the slow reductive half-reaction
(turnover-limiting step) and the major form of the catalyst
during catalysis, such as that observed.
The spectrophotometric monitoring of the reaction under the
same conditions used in the RR experiments showed that, as the
reaction progressed, a multiplet appeared centered at 528 nm
with the line separation of ca. 20 nm (Figure 10b), reached a
maximum, and then decreased (Abs528 vs time profile is shown in
the inset of Figure 10b). After a new addition of 150 equiv of
H2O2 to the catalyst, the multiplet reappeared during O2
evolution and disappeared when the O2 evolution had ceased.
This multiplet, which parallels the kinetic profile of the peak at
834 cmꢀ1 in the RR spectra, can be assigned to an oxo-to-manganese
Kinetics. The initial rate of H2O2 disproportionation by
complex 1 was measured as a function of the complex and
substrate concentrations, in the Et3N/Et3NH+ buffer of pH 10.6,
at 25 ꢀC. At constant [H2O2]0, the initial rate of H2O2
disproportionation varies linearly with the [catalyst], meaning
that the reaction is first-order on the catalyst. The first order
dependence of the reaction rate on the catalyst and the lack of
time-lag at the onset of the reaction suggest that the starting
complex is responsible for the rapid disproportionation of H2O2.
At constant [catalyst], the initial rate of H2O2 dismutation
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Table 3. kcat and KM Values for 1 and Other Dimanaganese CAT Models
catalysta,b
kcat (sꢀ1
)
KM (mM)
kcat/KM (sꢀ1 Mꢀ1
)
solvent, T (ꢀC)
ref
1
1
10.5(2)
250
6.6(4)
250
16(1) ꢁ 102
1000
H2O (pH 10.6), 25
Cl2CH2/CH3CN, 25
CH3CN, 25
MeOH:H2O (89:11), 25
DMF, 25
this work
44b,44d
49
2
[MnIV2(salpn)(μ-O)]2
3
[Mn(X-salpnO)]2
4.2ꢀ21.9
2.1
10ꢀ102
3
305ꢀ990
700
4
[Mn2(μ-OAc)(μ-OH2) (benzimpnO)]2+ + 5 equiv OHꢀ
[Mn2(μ-OMe)(μ-OAc)(X-salpentO)S2]+
[Mn2(μ-OMe)(μ-OAc)(X-salpentO)S2]+
[Mn2(μ-OMe)(OAc)(X-hppentO)]+
[Mn2(μ-OAc)2(X-hppnO)]+
50
5
0.75ꢀ7.9
0.48ꢀ6.2
1.31ꢀ2.8
3.4ꢀ23
2.48
16ꢀ66
13ꢀ201
88ꢀ170
150ꢀ600
83c
25ꢀ102
8ꢀ70
15ꢀ100
22ꢀ38
30
22,30
22,30
35
6
MeOH, 25
7
DMF, 10
8
DMF, 25
9
9
Mn2(μ-OAc)2(bphpmp)]+
NR, 25
40
2+
10
[Mn(bpia)(μ-OAc)]2
[Mn2(mesalim)2(MeOH)]2+ + 5 equiv OHꢀ
0.237
45
5.2
DMF, 25
51,52
52,53
11
0.038
21
1.8
EtOH, 25
a Ligands: H2salpn = 1,3-bis(salicylideneiminato)propane, salpnOH = 1,3-bis(salicylideneamino)propan-2-ol, benzimpn = N,N,N0,N0-tetrakis(2-
methylenebenzimidazolyl)-1,3-diaminopropan-2-ol, hppentOH = 1,5-bis[(2-hydroxybenzyl)(2-pyridylmethyl)amino]pentan-3-ol, hppnOH = 1,3-
bis[(2-hydroxybenzyl)(2-pyridylmethyl)amino]propan-2-ol, bphpmp = 2-[bis(2-pyridylmethyl)aminomethyl]-6-{[(2-hydroxybenzyl)(2-pyridylmethyl))-
amino]methyl}-4-methylphenol, bpia = bis(picolyl)(N-methylimidazol-2-yl)amine, mesalim = methyl salicylimidate, X = aromatic substituent, and S =
solvent or labile anion. b For ligand formulas, see Scheme S1 in the Supporting Information. c mmol. NR = not reported.
exhibits saturation kinetics with [H2O2]0 (Figure 11), and the
’ CONCLUSIONS
experimental data could be fitted to the MichaelisꢀMenten
10.5 ( 0.2 sꢀ1 and the Michaelis constant KM = 6.6 (
0.4 mM were determined. On the basis of the kcat/KM criterion,
3-Me-5-SO3-salpentOH affords complex 1, a water-soluble
diMn complex highly efficient to disproportionate H2O2 in an
aqueous solution of pH g 8.5. This complex possesses a triply
bridged bis(μ-alkoxo)(μ1,3-carboxylato) diMnIII core that mi-
mics the geometrical motif and coordination environment of the
equation, from which the catalytic turnover number kcat
=
complex 1, with kcat/KM = 16(1) ꢁ 102 sꢀ1
M
ꢀ1, is the most
MnIII form of Mn catalases.5 Spectroscopic monitoring of
efficient catalyst for H2O2 disproportionation reported to date.
By examining Table 3, it can be seen that, independently of the
solvent, complexes with Mn2(μ-OR)i(μ-OAc)j3+(or 4+) or Mn2-
(μ-OAc)2(μ-OPh)2+ cores disproportionate H2O2 with a kcat in
the range of 2ꢀ23 sꢀ1 (entries 1, 3ꢀ9, Table 2),9,22,30,35,40,49,50
but these values are significantly higher than those found for
2
catalyzed H2O2 disproportionation in an aqueous buffer solution
reveals that the major active form of the catalyst occurs in the
MnIII oxidation state during cycling and that the starting
2
complex retains the dinuclearity and composition during cata-
lysis, with acetate bound as a terminal ligand.
complexes possessing Mn2(μ-OAc)22+ or Mn2(μ-OPh)2
2+(or 4+)
The fact that 1 dismutates H2O2 at a constant rate upon
successive additions of H2O2 to the buffered solution of the
complex confirms that the starting complex is the true catalyst.
Kinetic results show that complex 1 catalyzes the dismutation of
H2O2 with saturation kinetics on the substrate, first order
dependence on the catalyst, and kcat/KM = 16(1) ꢁ 102 sꢀ1
cores (0.02ꢀ0.2 sꢀ1 51ꢀ53
)
(entries 10 ꢀ 11). [MnIV(salpn)
(μ-O)]2 (entry 2, Table 3) disproportionates H2O2 with a rate
higher than any of the other studied compounds, probably
because the two endogenous μ-oxo-ligands are better internal
bases to assist deprotonation of H2O2 coupled to its two-electron
oxidation;44b,d however, this complex has a very poor affinity for
the substrate (high KM value), a fact probably resulting from the
lack of labile positions to react with the substrate, which forces
initial peroxide binding to occur through ligand exchange. The
improved efficiency of 1 relative to other alkoxo- or phenoxo-
bridged complexes results from its high affinity for the substrate
(low value of KM). At pH 10.6, H2O2 coexists with HO2ꢀ; thus,
M
ꢀ1, at pH 10.6. On the basis of the kcat/KM criterion, complex 1
is the most efficient model known to date, and this is the
consequence of its high affinity for the substrate. The KM value
of 6.6 mM determined for complex 1 is lower than the KM of 15,
83, and 350 mM of MnCAT from T. album,55 T. thermophilus,56
and L. plantarum,57 respectively. Thus, the catalytic efficiency
(kcat/KM) of 1 is only 60 times lower than MnCAT from
L. plantarum and 2 ꢁ 103 times lower than that of T. thermo-
philus, the most efficient MnCAT.57,58
ꢀ
the higher affinity of HO2 vs H2O2 for binding 1 may also
contribute to the observed KM value. In fact, the KM value found
for 1 is lower than those of any other complex of the salpentOH
family evaluated in DMF and methanol,22,30 evidencing that it is
the basic aqueous medium that favors peroxide binding to these
catalysts. This is consistent with the enhancement of the affinity
found for [Mn2(μ-OAc)(μ-OH2)(benzimpnO)]2+ upon addi-
tion of 5 equiv OHꢀ in 89:11 MeOH:H2O mixtures, which varies
from KM = 35 mM in methanol to KM = 3 mM in the basic
medium.50 In line with this, the KM value of 1 in the aqueous base
is much lower than KM = 189 mM found for [Mn2(μ-OAc)
(μ-OMe)(3-Me-salpentO)]+ in methanol (RMeOH = 0.9354).30b
These results evidence the significant effect of protons on
lowering the H2O2 affinity of these complexes and the efficiency
of the buffer to offset this effect.
The CAT activity and the substrate affinity of 1 are highly
sensitive to pH. In unbuffered solutions of protic solvents, the
complex gradually loses activity with the formation of an inactive
MnII species. At neutral pH, complex 1 is more than two-times
less efficient than at pH 10.6. The pH dependence of the activity
and KM shown by complex 1 parallels the behavior of Y42F LPC,
a mutant of L. plantarum catalase, where Tyr42 has been replaced
by phenylalanine.58 This mutant has less than 5% of the wild type
MnCAT activity at neutral pH and a much higher KM for H2O2
(≈ 1.4 M) at neutral pH than at pH 10 (KM 220 mM). In the wild
type enzyme, Tyr42 is involved in a web of hydrogen bonds that
contributes to stabilize the diMn core with a pair of solvent
bridges. As a consequence, although presenting the highest
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ARTICLE
activity between pH 8 and 10, MnCATs are active over a wide pH
range of 5 to 12.59 Replacement of Tyr42 residue disrupts the
hydrogen-bonded web, the double solvent bridged diMn core is
not further stabilized, and efficient CAT activity and substrate
affinity are only achieved at high pH. In the case of 1, protonation
of the bridging ligands modifies the redox and coordination
properties of the diMn core, causing the gradual loss of activity as
the pH decreases. The exogenous base contributes to retain the
integrity of the double bridged diMn core and favors the
formation of the catalyst-peroxide adduct, rendering 1 a highly
efficient catalyst for H2O2 disproportionation.
(12) Dubois, L.; Pꢀecaut, J.; Charlot, M. F.; Baffert, C.; Collomb,
M. N.; Deronzier, A.; Latour, J. M. Chem.—Eur. J. 2008, 14, 3013–3025.
(13) Jiang, X.; Liu, H.; Zheng, B.; Zhang, J. Dalton Trans. 2009,
8714–8723.
(14) Berggren, G.; Huang, P.; Eriksson, L.; Styring, S.; Anderlund,
M. F.; Thapper, A. Dalton Trans. 2010, 11035–11044.
(15) Shin, B. K.; Kim, M.; Han, J. Polyhedron 2010, 29, 2560–2568.
(16) Lessa, J. A.; Horn, A., Jr.; Bull, E. S.; Rocha, M. R.; Benassi, M.;
Catharino, R. R.; Eberlin, M. N.; Casellato, A.; Noble, C. J.; Hanson,
G. R.; Schenk, G.; Silva, G. C.; Antunes, O. A. C.; Fernandes, C. Inorg.
Chem. 2009, 48, 4569–4579.
(17) Doctrow, S. R.; Huffman, K.; Marcus, C. B.; Tocco, G.; Malfroy,
E.; Adinolfi, C. A.; Kruk, H.; Baker, K.; Lazarowych, N.; Mascarenhas, J.;
Malfroy, B. J. Med. Chem. 2002, 45, 4549–4558.
’ ASSOCIATED CONTENT
(18) Nishida, Y.; Akamatsu, T.; Tsuchiya, K.; Sakamoto, M. Poly-
hedron 1994, 13, 2251–2254.
(19) Kani, I.; Darak, C.; Sahin, O.; B€uy€ukg€ung€or, O. Polyhedron
2008, 27, 1238–1247.
(20) (a) Berry, K. J.; Moya, F.; Murray, K. S.; v. d. Bergen, A. M. B.;
West, B. O. J. Chem. Soc., Dalton Trans. 1982, 109–116. (b) Botsivali, M.;
Evans, D. F.; Missen, P. H.; Upton, M. W. J. Chem. Soc., Dalton Trans.
1985, 1147–1149.
S
Supporting Information. X-ray crystallographic file in
b
CIF format for the structure determination of complex 1-
(MeOH), a stereoview of compound 1(MeOH) showing inter-
molecular Na-bonding, RR spectra of reaction mixtures, and
scheme of ligands mentioned in the text. This material is available
free of charge via the Internet at http://pubs.acs.org.
(21) Murase, I.; Hatano, M.; Tanaka, M.; Ueno, S.; Okawa, H.; Kida,
S. Bull. Chem. Soc. Jpn. 1982, 55, 2404–2408.
’ AUTHOR INFORMATION
(22) Palopoli, C.; Chansou, B.; Tuchagues, J. P.; Signorella, S. Inorg.
Chem. 2000, 39, 1458–1462.
(23) CrysAlis Pro, version 1.171.33.66; Oxford Diffraction Ltd.:
Oxford, U.K., 2010.
Corresponding Author
*E-mail: signorella@iquir-conicet.gov.ar.
(24) Altomare, A.; Cascarano, G.; Giacovazzo, C.; Guagliardi, A. J.
Appl. Crystallogr. 1993, 26, 343–350.
’ ACKNOWLEDGMENT
(25) Sheldrick, G. M. SHELXL-97, Program for Crystal Structure
Refinement; University of G€ottingen: G€ottingen, Germany, 1997.
(26) Walker, N.; Stuart, D. Acta Crystallogr., Sect. A 1983, 39, 158.
(27) Watkin, D. J.; Prout, C. K.; Pearce, L. J. CAMERON, Chemical
Crystallography Laboratory, Oxford, UK, 1996.
(28) Spek, A. L. Acta Crystallogr., Sect. A 1990, 46, C34.
(29) (a) Deacon, G. B.; Phillips, R. J. Coord. Chem. Rev. 1980,
33, 227–250.(b) Nakamoto, K. Infrared and Raman Spectra of Inorganic
and Coordination Compounds, 5th ed.; Wiley-Interscience: New York,
1997; Part B, p 60.
(30) (a) Biava, H.; Palopoli, C.; Shova, S.; De Gaudio, M.; Daier, V.;
Gonzꢀalez-Sierra, M.; Tuchagues, J. P.; Signorella, S. J. Inorg. Biochem.
2006, 100, 1660–1671. (b) Moreno, D.; Palopoli, C.; Daier, V.; Shova,
S.; Vendier, L.; Gonzꢀalez Sierra, M.; Tuchagues, J. P.; Signorella, S.
Dalton Trans. 2006, 5156–5166. (c) Daier, V.; Biava, H.; Palopoli, C.;
Shova, S.; Tuchagues, J. P.; Signorella, S. J. Inorg. Biochem. 2004,
98, 1806–1817. (d) Palopoli, C.; Gonzꢀalez-Sierra, M.; Robles, G.;
Dahan, F.; Tuchagues, J. P.; Signorella, S. J. Chem. Soc., Dalton Trans.
2002, 3813–3819.
(31) Gelasco, A.; Pecoraro, V. L. J. Am. Chem. Soc. 1993, 115,
7928–7929.
(32) Gelasco, A.; Kirk, M. L.; Kampf, J. W.; Pecoraro, V. L. Inorg.
Chem. 1997, 36, 1829–1837.
(33) Bertoncello, K.; Fallon, G. D.; Murray, K. S.; Tiekink, E. R. T.
Inorg. Chem. 1991, 30, 3562–3568.
(34) Mikuriya, M.; Yamato, Y.; Tokii, T. Bull. Chem. Soc. Jpn. 1992,
65, 1466–1468.
(35) Biava, H.; Palopoli, C.; Duhayon, C.; Tuchagues, J.-P.; Signorella,
S. Inorg. Chem. 2009, 48, 3205–3214.
(36) Zhang, Z.; Brouca-Cabarrecq, C.; Hemmert, C.; Dahan, F.;
Tuchagues, J.-P. J. Chem. Soc., Dalton Trans. 1995, 1453–1460.
(37) Zhang, J. J.; Luo, Q. H.; Duan, C. Y.; Wang, Z. L.; Mei, Y. H.
J. Inorg. Biochem. 2001, 86, 573–579.
(38) Miyasaka, H.; Clꢀerac, R.; Wernsdorfer, W.; Lecren, L.; Bonhomme,
C.; Sugiura, K. I.; Yamashita, M. Angew. Chem., Int. Ed. 2004, 43, 2801–2805.
(39) Dubois, L.; Xiang, D. F.; Tan, X. S.; Pꢀecaut, J.; Jones, P.;
Baudron, S.; Le Pape, L.; Latour, J. M.; Baffert, C.; Chardon-Noblat, S.;
Collomb, M. N.; Deronzier, A. Inorg. Chem. 2003, 42, 750–760.
We thank the National University of Rosario, CONICET, and
the National Agency for Sciences Promotion for financial sup-
port and M. De Gaudio for volumetric measurements.
’ REFERENCES
(1) (a) Bravo, J.; Mate, M. J.; Schneider, T.; Switala, J.; Wilson, K.;
Loewen, P. C.; Fita, L. Proteins Struct., Funct., Bioinf. 1999, 34, 155–166.
(b) Riggs-Gelasco, P. J.; Mei, R.; Penner-Hahn, J. E. In Mechanistic
Bioinorganic Chemistry; Thorp, H. H., Pecoraro, V. L., Eds.; American
Chemical Society: Washington, DC, 1995; Ch 8.
(2) Sayre, L. M.; Perry, G.; Smith, M. A. Chem. Res. Toxicol. 2008,
21, 172–188.
(3) (a) Day, B. J. Biochem. Pharmacol. 2009, 77, 285–296. (b) Hanawa,
T.; Asayama, S.; Watanabe, T.; Owada, S.; Kawakamai, H. J. Controlled
Release 2009, 135, 60–64.
(4) (a) Brazier, M. W.; Doctrow, S. R.; Masters, C. L.; Collins, S. J.
Free Radical Biol. Med. 2008, 45, 184–192. (b) Day, B. J. Drug Discovery
Today 2004, 9, 557–566. (c) McDonald, M. C.; di Villa Bianca, R. E.;
Wayman, N. S.; Pinto, A.; Sharpe, M. A.; Cuzzocrea, S.; Chatterjee, P. K.;
Thiemermann, C. Eur. J. Pharmacol. 2003, 466, 181–189.
(5) (a) Antonyuk, S. V.; Melik-Adamyan, V. R.; Popov, A. N.;
Lamzin, V. S.; Hempstead, P. D.; Harrison, P. M.; Artymiuk, P. J.;
Barynin, V. V. Crystallogr. Rep. 2000, 45, 105–116. (b) Barynin, V. V.;
Whittaker, M. M.; Antonyuk, S. V.; Lamzin, V. S.; Harrison, P. M.;
Artymiuk, P. J.; Whittaker, J. W. Structure 2001, 9, 725–738.
(6) Wu, A. J.; Penner-Hahn, J. E.; Pecoraro, V. L. Chem. Rev. 2004,
104, 903–938.
(7) Dubois, L.; Xiang, D. F.; Tan, X. S.; Latour, J. M. Eur. J. Inorg.
Chem. 2005, 1565–1571.
(8) De Boer, J. W.; Browne, W. R.; Feringa, B. L.; Hage, R. C. R.
Chim. 2007, 10, 341–354.
(9) Signorella, S.; Tuchagues, J. P.; Moreno, D.; Palopoli, C. In
Inorganic Biochemistry Research Progress; Hughes, J. G., Robinson, A. J.,
Eds.; Nova Science Publishers Inc.: New York, 2008; pp 243ꢀ279.
(10) Berben, L. A.; Peters, J. C. Inorg. Chem. 2008, 47, 11669–11679.
(11) Kaizer, J.; Csonka, R.; Speier, G. React. Kinet. Catal. Lett. 2008,
94, 157–163.
8982
dx.doi.org/10.1021/ic2011452 |Inorg. Chem. 2011, 50, 8973–8983

Inorganic Chemistry
ARTICLE
(40) Karsten, P.; Neves, A.; Bortoluzzi, A. J.; Str€ahle, J.; Maichle-
M€ossmer, C. Inorg. Chem. Commun. 2002, 5, 434–438.
(41) Sabater, L.; Hureau, C.; Blain, G.; Guillot, R.; Thuꢀery, P.;
Riviꢁere, E.; Aukauloo, A. Eur. J. Inorg. Chem. 2006, 4324–4337.
(42) Hureau, C.; Sabater, L.; Gonnet, F.; Blain, G.; Sainton, J.;
Anxolabꢀehꢁere-Mallart, E. Inorg. Chim. Acta 2006, 359, 339–345.
(43) (a) Bonadies, J.; Maroney, M. J.; Pecoraro, V. L. Inorg. Chem.
1989, 28, 2044–2051. (b) Caudle, M. T.; Riggs-Gelasco, P.; Gelasco,
A. K.; Penner-Hahn, J. E.; Pecoraro, V. L. Inorg. Chem. 1996,
35, 3577–3584. (c) Bermejo, M. R.; Gonzꢀalez, A. M.; Fondo, M.;
García-Deibe, A.; Maneiro, M.; Sanmartín, J.; Hoyos, O. L.; Watkinson,
M. New J. Chem. 2000, 24, 235–241. (d) Bermejo, M. R.; Gonzꢀalez-
Noya, A. M.; Abad, V.; Fernꢀandez, M. I.; Maneiro, M.; Pedrido, R.;
Vꢀasquez, M. Eur. J. Inorg. Chem. 2004, 3696–3705.
(44) (a) Boelrijk, A. E. M.; Khangulov, S. V.; Dismukes, G. C. Inorg.
Chem. 2000, 39, 3009–3019. (b) Larson, E. J.; Pecoraro, V. L. J. Am.
Chem. Soc. 1991, 113, 7809–7810. (c) Bonadies, J. A.; Kirk, M. L.; Lah,
M. S.; Kessissoglou, D. P.; Hatfield, W. E.; Pecoraro, V. L. Inorg. Chem.
1989, 28, 2037–2044. (d) Larson, E. J.; Pecoraro, V. L. J. Am. Chem. Soc.
1991, 113, 3810–3818.
(45) (a) Hureau, C.; Sabater, L.; Anxolabꢀehꢁere-Mallart, E.; Nierlich,
M.; Charlot, M.-F.; Gonnet, F.; Riviꢁere, E.; Blondin, G. Chem.—Eur. J.
2004, 10, 1998–2010. (b) Baldwin, M. J.; Pecoraro, V. L. J. Am. Chem.
Soc. 1996, 118, 11325–11326.
(46) (a) Schardt, B. C.; Hollander, F. J.; Hill, C. L. J. Am. Chem. Soc.
1982, 104, 3964–3972. (b) Czernuszewicz, R. S.; Su, Y. O.; Stern, M. K.;
Macor, K. A.; Kim, D.; Groves, J. T.; Spiro, T.G. J. Am. Chem. Soc. 1988,
110, 4158–4165. (c) Groves, J. T.; Stern, M. K. J. Am. Chem. Soc. 1988,
110, 8628–8638.
(47) Song, W. J.; Seo, M. S.; George, S. D.; Ohta, T.; Song, R.; Kang,
M. J.; Tosha, T.; Kitagawa, T.; Solomon, E. I.; Nam, W. J. Am. Chem. Soc.
2007, 129, 1268–1277.
(48) (a) Sakiyama, H.; Tamaki, H.; Kodera, M.; Matsumoto, N.;
Okawa, H. J. Chem. Soc., Dalton Trans. 1993, 591–595. (b) Sakiyama, H.;
Okawa, H.; Isobe, R. J. Chem. Soc., Chem. Commun. 1993, 882–884.
(c) Higuchi, C.; Sakiyama, H.; Okawa, H.; Fenton, D. E. J. Chem. Soc.,
Dalton Trans. 1995, 4015–4020. (d) Itoh, M.; Motoda, K.; Shindo, K.;
Kamiusuki, T.; Sakiyama, H.; Matsumoto, N.; Okawa, H. J. Chem. Soc.,
Dalton Trans. 1995, 3635–3641. (e) Aono, T.; Wada, H.; Yonemura, M.;
Ohba, M.; Okawa, H.; Fenton, D. E. J. Chem. Soc., Dalton Trans. 1997,
1527–1531.
(49) Gelasco, A.; Bensiek, S.; Pecoraro, V. L. Inorg. Chem. 1998, 37,
3301–3309.
(50) Boelrijk, A. E. M.; Dismukes, G. C. Inorg. Chem. 2000, 39,
3020–3028.
(51) Triller, M. U.; Hsieh, W. Y.; Pecoraro, V. L.; Rompel, A.; Krebs,
B. Inorg. Chem. 2002, 41, 5544–5554.
(52) Signorella, S.; Rompel, A.; Buldt-Karentzopoulos, K.; Krebs, B.;
Pecoraro, V. L.; Tuchagues, J.-P. Inorg. Chem. 2007, 46, 10864–10868.
(53) Godbole, M. D.; Kloskowski, M.; Hage, R.; Rompel, A.; Mills,
A. M.; Spek, A. L.; Bouwman, E. Eur. J. Inorg. Chem. 2005, 305–313.
(54) Shorter, J. Correlation Analysis of Organic Reactivity; Research
Studies Press: New York, 1983; pp 146ꢀ153.
(55) Penner-Hahn, J. E.; Pecoraro, V. L. In Manganese Redox
Enzymes; Pecoraro, V. L., Ed.; VCH: New York, 1992; pp 29, 197.
(56) Shank, M.; Barynin, V.; Dismukes, G. C. Biochemistry 1994, 33,
15433–15436.
(57) Penner-Hahn, J. E. In Manganese Redox Enzymes; Pecoraro,
V. L., Ed.; VCH: New York, 1992; pp 29ꢀ45.
(58) Whittaker, M. M.; Barynin, V. V.; Igarashi, T.; Whittaker, J. W.
Eur. J. Biochem. 2003, 270, 1102–1116.
(59) (a) Amo, T.; Atomi, H.; Imanaka, T. J. Bacteriol. 2002,
184, 3305–3312. (b) Allgood, G. S.; Perry, J. J. J. Bacteriol. 1986,
168, 563–567. (c) Kagawa, M.; Murakoshi, N.;Nishikawa, Y.; Matsumoto,
G.; Kurata, Y.; Mizobata, T.; Kawata, Y.; Nagai, J. Arch. Biochem. Biophys.
1999, 362, 346–355.
8983
dx.doi.org/10.1021/ic2011452 |Inorg. Chem. 2011, 50, 8973–8983