Chelate electronic properties control the redox behaviour and superoxide reactivity of seven-coordinate manganese(II) complexes

Article abstract of DOI:10.1039/b906100m

We have synthesized and characterized two Mn(II) seven-coordinate complexes with N5 pentadentate ligands, which contain hydrazone and hydrazide groups respectively. We have shown that insertion of hydrazido (amido) groups into the ligand sphere increases

Full text of DOI:10.1039/b906100m

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Chelate electronic properties control the redox behaviour and superoxide
reactivity of seven-coordinate manganese(II) complexes†
Gao-Feng Liu, Katharina Du¨rr, Ralph Puchta, Frank W. Heinemann, Rudi van Eldik and
Ivana Ivanovic´-Burmazovic´*
Received 18th February 2009, Accepted 29th May 2009
First published as an Advance Article on the web 23rd June 2009
DOI: 10.1039/b906100m
We have synthesized and characterized two Mn(II) seven-
coordinate complexes with N5 pentadentate ligands, which
contain hydrazone and hydrazide groups respectively. We
have shown that insertion of hydrazido (amido) groups
into the ligand sphere increases the negative charge of the
chelate, without changing a donor atom set and coordination
geometry, and radically modulate a redox activity of seven-
coordinate manganese complexes, which is important for the
function of manganese as a superoxide dismutase catalytic
center.
[MnII(H2Daphp)(H2O)2](ClO4)2 (2) (H2Daphp
=
2,6-bis((2-
(pyridin-2-yl)hydrazono)ethyl)pyridine),‡ and studied their
reaction with KO2 electrochemically, spectrophotometrically and
by sub-millisecond mixing UV/vis stopped-flow in DMSO, in a
manner recently reported by us.6
X-Ray structure determinations§ (Tables S1 and S2)† of both
complexes show (Fig. 1 and Fig. 2) a distorted pentagonal-
bipyramidal geometry around MnII with five nitrogen atoms of
the pentadentate chelates in the equatorial positions and two
oxygen atoms of methanol or water as axial donors. Both the bis-
deprotonated Dcphp2- hydrazide, as well as the neutral H2Daphp
hydrazone, coordinate to Mn(II) in a kind of helical mode, with
a dihedral angle between the disadjacent five-membered rings
-
Superoxide (O2 ) reactions with metal centers are of interest since
they occur within enzymatic catalysis (superoxide dismutases,
SOD, and superoxide reductases, SOR)1,2 as well as in undesired
processes that might cause pathophysiological conditions. Their
understanding helps in conceiving whether and how metal com-
plexes can be used as pharmaceuticals for treatment of disease
-
states caused by O2 overproduction and possible negative effects
of superoxide interactions with metal centers under physiological
conditions. Up to now the most active SOD mimetics are seven-
coordinate macrocyclic Mn(II) complexes of pentaaza crowns
which have been considered as clinical candidates for a variety of
inflammatory conditions.3,4 The effects of chelate substituents on
the SOD activity of that class of complexes have been extensively
investigated, and it has been concluded that their prominent
conformational flexibility is the key property that assists the high
SOD activity.5
We have recently shown that an acyclic and rigid
pentadentate chelate system (H2dapsox = 2,6-diacetylpyridine-
bis(semioxamazide)) can also be considered as structural
motif that supports the SOD-activity of iron and manganese
complexes.6 The advantage of such types of complexes is that
their syntheses are much easier and with higher yields than the
syntheses of the corresponding macrocyclic ones. To understand
the effects of electronic properties of acyclic and more rigid
pentadentate chelates on redox and structural features of the
Fig. 1 Thermal ellipsoid representation of [MnII(Dcphp)(CH3OH)2)] in
the crystal structure of 1 (50% probability level).
-
corresponding Mn(II) complexes and their reactivity towards O2 ,
we have now synthesized and characterized the seven-coordinate
complexes [MnII(Dcphp)(CH3OH)2](CH3OH)2 (1) (H2Dcphp =
2
6
N¢ ,N¢ -di(pyridin-2-yl)pyridine-2,6-dicarbohydrazide)
and
Department of Chemistry and Pharmacy, University of Erlangen-Nu¨rnberg,
Egerlandstr. 1, 91058, Erlangen, Germany. E-mail: Ivana.Ivanovic@
chemie.uni-erlangen.de
† Electronic supplementary information (ESI) available: Fig. S1–S4 and
Tables S1–S3. CCDC reference numbers 720837–720839. For ESI and
crystallographic data in CIF or other electronic format see DOI:
10.1039/b906100m
Fig. 2 Thermal ellipsoid representation of [MnII(H2Daphp)(H2O)2]2+ in
the crystal structure of 2 (50% probability level).
6292 | Dalton Trans., 2009, 6292–6295
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[N5–N6–C13–N7–Mn1] and [N2–N3–C7–N4–Mn1] of 22.7◦ in
1, and a corresponding dihedral angle in 2 of 24.8◦. Com-
pared to the structure of the free H2Dcphp ligand (Fig. S1
and Table S3),† the geometry of the hydrazide groups in 1
changes substantially upon coordination. The average Chydrazide–N
˚
bond distance decreases from 1.34 to 1.31 A and the average
˚
Chydrazide–O distance increases from 1.23 to 1.29 A. The average
˚
Mn1–Nhydrazide bond length (2.267 A) is significantly shorter than
˚
the average Mn1–Npyridine bond length (2.386 A) (Table S2).† These
structural features result from the chelate’s negative charge and its
coordination in a hybrid form of the deprotonated hydrazide–
-
=
=
HN–N–C O and a-oxiazine–HN–N C–O resonance struc-
tures. The asymmetry in the two Mn–Nterminal pyridine bonds in the
˚
crystal structure of 1 is prominent (Mn1–N4 = 2.467(2) A vs.
5
˚
Mn1–N7 = 2.360(2) A), which is not typical for high-spin d
electronic configurations. The intra- and especially intermolecular
hydrogen bonds (N6–H ◊ ◊ ◊ O) within the crystal packing are
responsible for this asymmetry, similar to that observed in the
structure of [MnII(H2dapsox)(CH3OH)(H2O)]2+.6 The lack of the
carbonyl groups in H2Daphp makes it less acidic, resulting in its
coordination in the neutral hydrazone form, which is reflected
in a longer average Mn1–Nimine bond length and general higher
symmetry in the Mn–N bond distances in the structure of 2
compared to those in 1.
The cyclic voltammogram of 1 in DMSO purged with nitrogen
exhibits a quasi-reversible MnIII/MnII couple at 0.372 V and
irreversible reduction process at -0.325 V vs. Ag/AgCl (Fig. 3),
which is confirmed to be ligand centered by measuring the cyclic
voltammogram of free H2Dcphp under the same conditions. How-
ever, under the same experimental conditions 2 is electrochemically
silent in the scan range from -1 to 1.2 V. These results demonstrate
the effect of the deprotonated amide (hydrazide) groups and a
consequent increase of the ligand negative charge on the redox
behaviour of the manganese center. A strong s-donor ability of
the negatively charged hydrazido nitrogen in the coordination
sphere of manganese significantly decreases the MnIII/MnII redox
potential by stabilizing the MnIII form of the complex, which was
Fig. 3 Cyclic voltammograms of: a) 1 purged with nitrogen (inset:
spectro-electrochemical oxidation of 1 at 0.5 V vs. Ag/AgCl); b) 1 purged
with nitrogen (A), oxygen (B), and pure DMSO purged with oxygen
(C). Conditions: [1] = 0.5 ¥ 10-3 M, [Bu4NPF6] = 0.1 M, T = 298 K,
scan rate = 0.5 V s-1.
from 1 to -1.5 V (Fig. 3b), and when the scan proceeds toward
more negative potentials, superoxide is generated by reduction of
oxygen. When the scan is returned toward positive potentials, no
characterized by spectro-electrochemical measurements (lmax
=
360–390 nm, inset in Fig. 3a). Alternating bulk electrolyses at
0.5 V (inset of Fig. 3a) and 0 V vs. Ag/AgCl (Fig. S2)† show
that 1 can be oxidized and reduced in a quantitatively reversible
manner. In iron chemistry it is known that one amido nitrogen
as a donor atom within TPA (tris-(2-pyridylmethyl)amine) type
chelates stabilizes the Fe3+ oxidation state in the six-coordinate
geometry by about 1 V.7 However, in the seven-coordinate
geometry, two deprotonated amide groups of the macrocyclic
ligand stabilize the Fe3+ oxidation state only by about 0.3 V.8 In the
-
anodic peak assigned to the oxidation of O2 is found, suggesting
that 1 present in solution (experiments were performed with [1] =
1 mM and 0.1 mM) decomposes superoxide. The same experiment
was performed in the presence of free ligand and the disappearance
-
of the anodic peak assigned to the oxidation of O2 was not
observed. Consequently, decomposition of O2- in the presence of 1
is related to the metal-centered redox process. Complex 2 does not
affect the superoxide reoxidation in the same type of experiments.
The reaction of 1 with a large excess of KO2 in DMSO containing
a controlled amount of water (0.06%) was followed by time
resolved UV/vis spectroscopy, and the rapid decomposition of
case of manganese complexes it is known that the tetraamido and
9,10
=
diamidodialkoxido ligands stabilize high-valent Mn O species.
However the effect of the amide group on the redox behaviour of
seven-coordinate manganese complexes has not been reported. It
has been qualitatively demonstrated that the bound carboxamido
nitrogen to the six-coordinate Mn center makes the complex more
sensitive to oxidation in comparison to the analogous Schiff base
complex.11 Our results show that in the seven-coordinate geometry,
coordination of two hydrazido nitrogens instead of two imine
nitrogens stabilizes the MnIII oxidation state by at least 0.8 V.
Cyclic voltammetric measurements6 were also performed in
oxygen saturated DMSO ([O2] = 2.1 mM) in the scan range
-
O2 was quantified by following the corresponding absorbance
decrease at 270 nm (best fitted as a first-order process) in a series
of a sub-millisecond mixing stopped-flow measurements, in which
the catalytic concentration of the studied complexes was varied.6
A good linear correlation between the corresponding kobs value
and the complex concentration was observed, and from the slope
of the plot the catalytic rate constant (kcat) was determined
to be (6.1
0.7) ¥ 106 M-1 s-1 (Fig. 4). The products of
superoxide disproportionation, O2 and H2O2, were qualitatively
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intermediate are not crucial for the SOD activity of the complex,
in agreement with our recent findings.6,19 In the case of 2, the
solvent dissociation energies for its MnII and MnIII species are
+1.7 and +7.9 kcal mol-1, respectively (Fig. S4).† The latter value
indicates that formation of the six-coordinate MnIII form of 2 is
significantly less favorable than in the case of 1. This structural
feature together with the electronic properties of H2daphp might
contribute to the low stability of the MnIII oxidation state of 2 and
consequently its high E1/2. Interestingly, in the case of macrocyclic
Mn(II) SOD mimetics, ligand structural features do not affect
their redox potential, but have an influence on their SOD activity.5
In conclusion, we have shown how insertion of amido groups
into the ligand sphere, without changing the donor atom set and
coordination geometry, can radically modulate the redox activity
of seven-coordinate manganese complexes, which is important for
the function of Mn as catalytic center.20 It still remains to be
seen to what extent the ligand structural and electronic features
can control the SOD activity of these complexes by affecting
the mechanism (associative vs. dissociative) of their substitution
processes. Studies along these lines are in progress.
Fig. 4 Plot of kobs for the decay at 270 nm versus [1]. Conditions: [O2-] =
2 mM, 25 ◦C in DMSO. Inset: UV/vis spectra recorded for the reaction of
5 ¥ 10-5 M of 1 with 1 mM KO2 in DMSO at room temperature. A: spectrum
recorded before mixing; B: final spectrum obtained after decomposition
of KO2.
detected.6 Upon superoxide decomposition the complex remains
in solution in the MnIII form (lmax = 360–390 nm, inset in Fig. 3),
similar to what was observed in the case of the SOD active
[MnII(H2dapsox)(CH3OH)(H2O)]2+ complex.6 As expected from
the electrochemical behaviour of 2, its mixing with an excess of
KO2 in DMSO does not cause rapid decay of the absorbance
characteristic for superoxide.12
Acknowledgements
The authors gratefully acknowledge financial support from the
Deutsche Forschungsgemeinschaft within SFB 583 “Redox-active
Metal Complexes”.
The presented results reveal that 1 catalyzes the fast dispropor-
tionation of superoxide under the applied experimental conditions,
whereas 2 does not show any SOD activity. This can be explained
by the high redox potential of 2, which does not fall between the
Notes and references
‡ Preparation of H2Dcphp: to a solution of 2-hydrazinopyridine (403 mg,
3.70 mmol) in 10 mL of absolute dichloromethane under nitrogen,
degassed triethylamine (0.410 mL, 2.96 mmol) was added. After that
a solution of 2,6-pyridinedicarbonyl dichloride (302 mg, 1.48 mmol) in
30 mL of dichloromethane was added. After 2 h of stirring, the solvent
was evaporated and the residue was washed several times with a saturated
solution of NaHCO3 and with water to give H2Dcphp (321 mg, 62%)
as a white solid. dH(300 MHz, DMSO-d6, 25 ◦C) 11.2 (s, 2H, CONH-
NH); 8.60 (s, 2H, CONH-NH); 8.24 (m, 3H, Pyridyl-H(CON)2); 8.07 (d, 2H,
Pyridyl(6)HNH); 7.54 (m, 2H, Pyridyl(4)HNH); 6.72 (m, 2H, Pyridyl(5)HNH);
6.68 (d, 2H, Pyridyl(3)HNH); dC(100 MHz, DMSO-d6, 25 ◦C) 162.7,
159.6, 148.2, 147.6, 139.7, 137.5, 124.8, 114.7, 106.7; Anal. calcd. for
C17H15N7O2·H2O: C, 55.58; H, 4.66; N, 26.69%. Found: C, 56.04; H, 4.52;
N, 26. 94%.
-
redox potentials for the reduction and oxidation of O2 under the
applied experimental conditions. However, for the Mn complexes
with redox potentials within that window a correlation between
their E1/2 and SOD activities (see Table 1 for the seven-coordinate
Mn complexes) is more complex. It seems that for the complexes
with lower E1/2, reduction of the MnIII form is the rate-limiting step
in the catalysis, whereas for the SOD mimetics with higher E1/2, the
catalytic cycle is a MnII oxidation limited process. Data reported
in the literature for the SOD active MnIII porphyrins13 and Mn
complexes based on N-centered ligands14 also follow such a trend.
To probe whether the ability of 1 and 2 to form six-coordinate
complexes intheir MnII and MnIII oxidation states upon release of a
coordinated solvent molecule, has an influence on their reactivity
Synthesis of complex 1: to a stirred suspension of H2Dcphp (0.367 g, ca.
1 mmol) in absolute methanol (50 mL), a methanol solution (10 mL) of
MnCl2·2H2O (0.852 g, 1 mmol) was added. After 1 h of stirring, NaOCH3
(0.108 g, 2 mmol) was carefully added to the solution under nitrogen
atmosphere. After two hours of refluxing, the red solution was filtered
and concentrated to ca. 30 mL and 0.5 g of NaClO4 was added. The
solution was kept in a refrigerator overnight. Shiny deep-yellow crystals
of 1 (0.14 g, 26%) were collected and washed with small amounts of
acetone. nmax(KBr)/cm-1 3329 s(NH), 3066 s(H2O), 2363 m, 1701 s, 1613 s,
-
towards O2 in a manner that was reported for the macrocyclic
Mn(II) SOD mimetics,15,16 we performed DFT calculations.17 The
energies required for solvent dissociation18 were calculated to be
+2.9 and -1.1 kcal mol-1 for the MnII and MnIII forms of 1,
respectively (Fig. S3).† These small energy differences between
seven- and six-coordinate geometries of both oxidation states,
suggest that solvent dissociation and formation of a six-coordinate
=
1516 m(amide C O), 1341 s (amide), 1191 m (CH), 999 m, 692 m; Anal.
calcd. for C21H29N7O6Mn: C, 47.55; H, 5.51; N, 18.48%. Found: C, 47.04;
H, 5.12; N, 18.49%.
Synthesis of complex 2: 2,6-diacetylpyridine (1.63 g, 10 mmol) and
2-hydrazinopyridine (2.18 g, 20 mmol) were added to 50 mL of methanol
and the mixture was stirred at 55 ◦C for 1 h. A solution of Mn(ClO4)2·4H2O
(3.26 g, 10 mmol) in 20 mL methanol was added dropwise to the resulting
white suspension. The solution color changed to yellow, while some of
the white powder was still undissolved. The addition of 30 mL of CH3CN
resulted in a clear yellow solution. After 3 h of refluxing the hot reaction
mixture was filtered and the dark yellow residue discarded. The deep
orange solution was then allowed to cool to room temperature and kept
in a refrigerator, rendering deep orange crystals of 2 (3.67 g, 57.8%)..
Table 1 E1/2 and SOD activities of the seven-coordinate Mn complexes
Complex
1
MnII(H2dapsox)a MnII(pyaneN5)a
E
k
1/2/V vs. Ag/AgCl 0.37
0.66
0.80
cat/M-1 s-1 (6.1 0.7) ¥ 106 (1.2 0.3) ¥ 107 (5.3 0.8) ¥ 106
n
max(KBr)/cm-1 3290 s(NH), 3198 s(H2O), 3112 s, 2362 m, 1701 w, 1687 s,
1551 m, 1341 m(amide), 1279 m, 1243 m(CH) 1085 w, 819 m, 775 m,
a Obtained under the same experimental conditions as in the present work.6
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630 m(py); Anal. calcd. for C19H23Cl2N7O10Mn: C, 35.92, H, 3.65, N,
15.43%. Found: C, 35.47, H, 3.64, N 15.71%.
8 I. V. Korendovych, R. J. Staples, W. M. Reiff and E. V. Rybak-Akimova,
Inorg. Chem., 2004, 43, 3930.
9 F. M. MacDonnell, N. L. P. Fackler, C. Stern and T. V. O’Halloran,
J. Am. Chem. Soc., 1994, 116, 7431.
10 D.-L. Popescu, A. Chanda, M. Stadler, F. T. de Oliveira, A. D. Ryabov,
E. Mu¨nck, E. L. Bominaar and T. J. Collins, Coord. Chem. Rev., 2008,
252, 2050.
11 K. Ghosh, A. A. Eroy-Reveles, B. Avila, T. R. Holman, M. M. Olmstead
and P. K. Mascharak, Inorg. Chem., 2004, 43, 2988.
12 A very slow absorbance decay at 270 nm was observed due to the
spontaneous dismutation of O2 in DMSO containing 0.06% water. See:
D. T. Sawyer and J. S. Valentine, Acc. Chem. Res., 1982, 14, 393.
13 I. Batinic´-Haberle, I. Spasojevic´, R. D. Stevens, B. Bondurant, A.
Okado-Matsumoto, I. Fridovich, I. Vujaskovic´ and M. W. Dewhirst,
Dalton Trans., 2006, 617.
§ Crystal data for 1: C21H29N7O6Mn, FW = 530.45, monoclinic, space
˚
˚
˚
group C2/c, a = 25.251(2) A, b = 7.6250(5) A, c = 27.574(2) A, b =
◦
3
-3
˚
113.044(5) , V = 4885.4(6) A , Z = 8, T = 100(2) K, Dc = 1.442 g cm ;
55979 reflections collected (Rint = 0.0550), 5386 unique reflections, R1 =
0.0396 [I > 2s(I)], wR2 = 0.0882 (all data), GOF = 1.129. CCDC 720837.
For 2: C19H23Cl2N7O10Mn, FW = 635.28, monoclinic, space group◦C2/c,
˚
˚
˚
a = 10.9947(6) A, b = 31.380(4) A, c = 7.9492(6) A, b = 108.613(5) , V =
3
-3
˚
2599.1(4) A , Z = 4, T = 100(2) K, Dc = 1.623 g cm ; 31490 reflections
collected (Rint = 0.0653), 3105 unique reflections, R1 = 0.0331 [I > 2s(I)],
wR2 = 0.0754 (all data), GOF = 1.052. CCDC 720838. For H2Dcphp:
CCDC 720839.
1 I. Fridovich, Ann. N. Y. Acad. Sci., 1999, 893, 13.
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14 S. Durot, C. Policar, F. Cisnetti, F. Lambert, J.-P. Renault, G. Pelosi, G.
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17 (B3LYP(CPCM)/LANL2DZp//B3LYP/LANL2DZp
LANL2MB)), see ESI†.
+ ZPE(HF/
18 For the simplicity, as usual for this type of calculations water was
considered as a coordinated solvent.
7 J. M. Rowland, M. Olmstead and P. K. Mascharak, Inorg. Chem, 2001,
40, 2810. In this reference the complexes with and without the amide
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a significant difference in their redox potentials.
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©