Metal ionic size directed complexation in manganese(II) coordination chemistry: Efficient candidates showing phenoxazinone synthase mimicking activity

Article abstract of DOI:10.1039/c4ra03427a

The present report describes the syntheses and structural characterizations of two new mononuclear manganese(II) complexes, [Mn(L¹)Cl ₂]·2MeOH (1) and [Mn(L²)Cl₂] (2), in which L¹ and L² are tetradentate ligands. Although the previous studies described that ligand L¹ exclusively binds the metal centers (Fe²⁺, Ni²⁺ and Zn²⁺) in the acyclic isomeric form (Schiff dibasic) of the ligand, in the present investigation it selectively binds Mn²⁺ ion in its cyclic (hexahydropyrimidine) analogue during the complexation reaction as evidenced by X-ray crystallography. The structure of 2 is quite interesting as it shows that one arm of the Schiff dibasic form of the ligand has been hydrolyzed, suggesting that these types of ligands with the Schiff dibasic form are incapable of yielding the stable manganese(II) complexes. The metal ionic size directed hydrolysis of one arm of the ligand has been confirmed by IR spectral studies. Both the complexes are reactive towards the oxidation of o-aminophenol (OAPH), and their relative catalytic efficiencies can be clearly explained by considering the steric contribution from the ligands and the electrochemical responses of the metal center. From the experimental data, a nice correlation, wherein the lower the E_1/2 value the higher the catalytic activity, can be drawn between E_1/2 and V_max of the complexes. The kinetics study exhibited a deuterium kinetic isotope effect in the catalytic oxidative coupling of two moles of OAPH by O₂ as evidenced by the 1.6 times rate retardation in the deuterated solvent, suggesting hydrogen atom transfer in the rate-determining step from the substrate hydroxy group to the metal-bound superoxo species. the Partner Organisations 2014.

Full text of DOI:10.1039/c4ra03427a

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PAPER
Metal ionic size directed complexation in
manganese(II) coordination chemistry: efficient
candidates showing phenoxazinone synthase
mimicking activity†
Cite this: RSC Adv., 2014, 4, 37085
Anangamohan Panja*
The present report describes the syntheses and structural characterizations of two new mononuclear
1
2
1
2
manganese(II) complexes, [Mn(L )Cl
2
]$2MeOH (1) and [Mn(L )Cl
2
] (2), in which L and L are tetradentate
1
2+
ligands. Although the previous studies described that ligand L exclusively binds the metal centers (Fe
,
2+
2+
Ni and Zn ) in the acyclic isomeric form (Schiff dibasic) of the ligand, in the present investigation it
2+
selectively binds Mn ion in its cyclic (hexahydropyrimidine) analogue during the complexation reaction
as evidenced by X-ray crystallography. The structure of 2 is quite interesting as it shows that one arm of
the Schiff dibasic form of the ligand has been hydrolyzed, suggesting that these types of ligands with the
Schiff dibasic form are incapable of yielding the stable manganese(II) complexes. The metal ionic size
directed hydrolysis of one arm of the ligand has been confirmed by IR spectral studies. Both the
complexes are reactive towards the oxidation of o-aminophenol (OAPH), and their relative catalytic
efficiencies can be clearly explained by considering the steric contribution from the ligands and the
electrochemical responses of the metal center. From the experimental data, a nice correlation, wherein
the lower the E1/2 value the higher the catalytic activity, can be drawn between E1/2 and Vmax of the
complexes. The kinetics study exhibited a deuterium kinetic isotope effect in the catalytic oxidative
Received 15th April 2014
Accepted 30th July 2014
2
coupling of two moles of OAPH by O as evidenced by the 1.6 times rate retardation in the deuterated
DOI: 10.1039/c4ra03427a
solvent, suggesting hydrogen atom transfer in the rate-determining step from the substrate hydroxy
group to the metal-bound superoxo species.
www.rsc.org/advances
and two factors, namely, Lewis acidity and the size of the metal
Introduction
6,7
ions, are mainly responsible in such isomerization processes.
8,9
Schiff-base complexes that contain a carbon–nitrogen double Bo ˇc a et al. have concluded that the relative acidity of imine-C
bond have been extensively studied in coordination chemistry, and metal centers ultimately determine the direction in which
mainly due to their ease of synthesis, tremendous structural the isomerization of the ligand will shi. For example, weak
2
+
2+
2+
diversities, and enormous possibilities towards various appli- Lewis acids, such as Fe , Co , and Cu , are incapable (or only
1
–3
cations, including catalysis.
In addition, they can easily partly capable) of opening the heterocyclic ring, whereas
3
+
2+
undergo reversible reactions under certain conditions, such as stronger Lewis acids (e.g., Fe and Zn ) can readily do it in
E–Z isomerization reactions, nucleophilic additions, trans- order to gain the denticity of the ligands. In contrast, Tuchagues
10
amination reactions, tautomerism, and aza Diels–Alder reac- et al. postulated that, for each specic cation, the size of the
tions. Among these, the condensation reactions of aromatic metal ion is the determining factor in shiing the ligand
aldehydes with a,u-di-primarypolyamines that contain both the equilibrium towards the most appropriate tautomeric form. For
2
+
primary and secondary amines are known to afford both Schiff instance, low-spin Fe has a small enough ionic radius (75 pm)
dibases and their isomers with saturated heterocyclic rings to t inside the void provided by the imine isomers, while the
2
+
4,5
(imidazolidine or hexahydropyrimidine).
Isomerization ionic radius of Ni (83 pm) is probably too large to allow the
among these products through formation or opening of the coordination of the imine tautomer, and thus it stabilizes the
heterocyclic ring in the presence of metal ions is quite common cyclic analogue.
We are working on the transition-metal complexes with
pyridine containing ligands in order to develop the functional
Medinipur, Panskura RS, West Bengal 721 152, India. E-mail: ampanja@yahoo.co.in mimics of various oxidase (oxygenase) metalloenzymes.
Electronic supplementary information (ESI) available: Fig. S1–S5. CCDC 962739 These studies are helpful in getting an insight of the natural
Postgraduate Department of Chemistry, Panskura Banamali College, Purba
11–15
†
and 997081. For ESI and crystallographic data in CIF or other electronic format see
systems in which metalloenzymes facilitate the spin-forbidden
DOI: 10.1039/c4ra03427a
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interaction between dioxygen and organic matter in the various complexes in KBr pellets were recorded in the range of 400–4000
16–18
ꢀ1
biochemical reactions
and ultimately provide a clue for the cm on a PerkinElmer Infrared spectrum two spectrometer.
development of bioinspired catalysts for the oxidation reactions Electronic absorption spectra were recorded using a Perki-
in the industrial and synthetic processes. Our recent reports nElmer Lamda-35 spectrophotometer with a 1 cm-path-length
revealed that cobalt complexes with pyridine-containing ligands quartz cell. Cyclic voltammetry measurements were performed
are good functional models for the phenoxazinone synthase on an EG&G Princeton Applied Research potentiostat model
14
irrespective of the oxidation state of cobalt. This multicopper 263A with a conventional three electrode system using a Pt
oxidase is found naturally in the bacterium Streptomyces anti- working electrode, Pt auxiliary electrode and Ag/AgCl reference
19,20
bioticus
and catalyzes the oxidative coupling of two mole- electrode. Electrospray ionization mass (ESI-MS positive)
cules of substituted o-aminophenol to the phenoxazinone spectra were recorded on
chromophore in the nal step for the biosynthesis of actino- spectrometer.
a
micromass Q-TOF mass
21
mycin D. The latter is used clinically for the treatment of
Wilm's tumor, gestational choriocarcinoma, and other tumors Synthesis of [Mn(L )Cl ]$2MeOH (1)
1
2
in which phenoxazinone chromophore is recognized to inhibit
0
A mixture of pyridine-2-aldehyde (0.428 g, 4.0 mmol) and 3,3 -
iminobis(propylamine) (0.262 g, 2.0 mmol) in 30 ml of methanol
was reuxed for 30 min. To the resulting yellow solution a
22,23
DNA-dependent RNA synthesis by intercalation to DNA.
In
addition to copper-based models, some functional models of
3
+
2+
2/3+
other metal ions, e.g. Fe , Mn and Co , have also been
reported.
2 2
methanol solution of MnCl $4H O (0.396 g, 2 mmol) was added,
11–15,24–31
Moreover, few structure–property correlations
and the mixture was further allowed to reux for 30 min. The
solution was allowed to cool to room temperature, and on
addition of ether, a pale-yellow powder separated out from the
solution. The precipitate was collected by ltration, washed with
methanol/ether solution, and air dried, and a yield of 0.800 g
that were determined are sufficiently not wide but applicable
only for a set of few compounds; therefore, phenoxazinone
synthase activity of new systems should be explored to get better
insight and more straightforward structure–property
correlations.
(
83%) was obtained. Crops of pale-yellow crystals suitable for X-
ray analysis were obtained from the slow diffusion of ether into a
methanolic solution of the complex. Anal. calcd for C19
MnN expected: C, 48.11%; H, 6.25%; N, 14.02%. Found: C,
7.67%; H, 6.00%; N, 14.08%. IR (KBr, cm ): 3348 br (nN–H and
O–H); 1646 s (nC]N, imine); 1597 s (nC]N, pyridine). A major peak
Our recent reports disclosed that the cobalt ion exclusively
shows selectivity towards the Schiff dibasic form of the ligands
derived from the condensation of pyridine-2-aldehyde with a,u-
di-primarypolyamines, and even this selectivity is found to be
insensitive to the oxidation states of cobalt, while manganese(II)
H
2
27Cl -
5 2
O
ꢀ1
4
n
14,15
ion prefers to bind with their cyclic analogue.
The size of the
1
+
was detected at m/z ¼ 399.07 corresponding to [Mn(L )Cl] .
manganese(II) ion is too large to t inside the cavity provided by
the Schiff dibasic form of the ligands thus preferring the cyclic
analogue, which is consistent with the proposition made by
2
Synthesis of [Mn(L )Cl ] (2)
2
10
A similar synthetic methodology was applied using 2-ace-
tylpyridine (0.488 g, 4.0 mmol), 3,3 -iminobis(propylamine)
0.262 g, 2.0 mmol) and MnCl $4H O (0.396 g, 2 mmol) as
starting materials, and 0.574 g (80%) of a pale-yellow precipitate
was obtained. Crops of dark-yellow crystals suitable for X-ray
analysis were obtained from slow diffusion of ether into a
Tuchagues et al. In order to check whether manganese(II) ion
exclusively selects the cyclic isomer over its Schiff dibasic form,
in the present investigation, the coordination ability of man-
ganese(II) ion has been tested with the ligands derived from the
condensation of a triamine with longer propylenic linkers and
pyridine-2-aldehyde (or 2-acetylpyridine). Syntheses and struc-
tural characterizations of two new manganese(II) complexes,
0
(
2 2
methanol solution of complex 2. Anal. calcd C13
2 4
H22Cl MnN : C,
1
2
43.35%; H, 6.15%; N, 15.55%. Found: C, 43.37%; H, 6.27%; N,
15.38%. IR (KBr, cm ): 3239 br (nN–H); 1645 s (nC]N, imine);
598 s (nC]N, pyridine). A base peak was detected at m/z ¼
[
2 2
Mn(L )Cl ]$2MeOH (1) and [Mn(L )Cl ] (2), have been reported
ꢀ
1
1
2
in which L and L are tetradentate ligands, as depicted in
Scheme 1. The phenoxazinone synthase-like activity and its
detailed kinetic studies to evaluate various kinetic parameters,
including the turnover number for both the complexes, have
also been described.
1
3
2 +
24.09 corresponding to [Mn(L )Cl] .
X-ray crystallography
Single crystal X-ray diffraction data for complexes 1 and 2 were
obtained on a Bruker SMART APEX-II CCD diffractometer using
graphite monochromated Mo-Ka radiation. The unit cell was
determined from the setting angles of 36 frames of data. Several
Experimental section
Materials and physical measurements
Chemicals such as pyridine-2-aldehyde, 2-acetylpyridine and scans in 4 and u directions were made to increase the number of
0
3
,3 -iminobis(propylamine) (Aldrich), and manganese(II) chlo- redundant reections and were averaged during the renement
ride tetrahydrate and o-aminophenol (Merck, India) of reagent cycles. Data processing for both the complexes were performed
32
grade were used without further purication. Solvents like using the Bruker Apex2 suite. Reections were then corrected
methanol, CD OD and diethyl ether (Merck, India) of analytical for absorption, inter-frame scaling, and other systematic errors
3
32
grade were used as received.
with SADABS. All the structures were solved by direct methods,
Elemental analysis for C, H and N were carried out using a and all non-hydrogen atoms were rened by the full-matrix least
2
33
PerkinElmer 240 elemental analyzer. The infrared spectra of the squares based on F using the SHELXL-97 program using the
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Scheme 1 Synthetic route to complexes 1 and 2.
34
WINGX package. Hydrogen atoms attached to carbon atoms oxidation of OAPH was investigated spectrophotometrically by
were included in the structure factor calculation in geometrically monitoring the growth of the absorbance as a function of time
3
ꢀ1
ꢀ1 27
idealized positions, while those connected to nitrogen and at 435 nm (3 ¼ 24 ꢁ 10 M cm ), which is a characteristic
oxygen atoms were located in the difference Fourier maps. Using absorbance of 2-aminophenoxazin-3-one in methanol. To
a riding model, the hydrogen atoms were isotropically treated determine the dependence of the rate of the reaction on
with their isotropic displacement parameters depending on the substrate concentration and to evaluate various kinetic
ꢀ4
parent atoms. Relevant crystallographic data along with rene- parameters, 1 ꢁ 10 M solutions of the complexes were treated
ment details for the complexes are given in Table 1.
with at least 10 equivalents of substrate in order to maintain the
pseudo-rst order condition. Similarly, varying amounts of
ꢀ
5
Kinetics of the phenoxazinone synthase activity
catalyst (5–100) ꢁ 10 M were mixed with a xed concentration
ꢀ2
(
1 ꢁ 10 M) of substrate in methanol (2.0 ml) saturated with
In a typical experiment, complexes 1 or 2 were mixed with o-
aminophenol (OAPH) in air-saturated methanol and the
dioxygen in order to examine the dependence of the rate of the
Table 1 Crystal data and structure refinement for complexes 1 and 2
1
2
Empirical formula
Formula weight
Temperature (K)
Wavelength ( A˚ )
Crystal system
Space group
C
20
H
31Cl
2
5
MnN O
2
13 2 4
C H22Cl MnN
360.19
150(2)
0.71073
Monoclinic
C2/c
19.2620(3)
11.7960(1)
17.1290(3)
122.207(5)
3293.09(20)
8
499.34
293(2)
0.71073
Monoclinic
P2 /c
10.4242(2)
9.1757(1)
24.4086(5)
100.971(1)
2292.00(7)
4
1
˚
a (A)
˚
b (A)
˚
C (A)
ꢂ
b ( )
3
˚
Volume (A )
Z
D
ꢀ3
calc. (g cm
)
1.401
0.833
1004
2.80–30.08
1.453
1.122
1496
2.90–32.05
ꢀ
1
m (mm
F(000)
q range ( )
)
ꢂ
Limiting indices
ꢀ14 # h # 14, ꢀ12 # k # 12, ꢀ33 # l # 34
ꢀ28 # h # 28, ꢀ17 # k # 17, ꢀ25 # l # 25
Reections collected
Independent reection/Rint
Observed reections
Data/restraints/parameters
23 831
10 331
6697/0.0592
4739
6697/0/310
1.043
5725/0.0159
5238
5725/0/185
1.071
2
Goodness-of-t on F
Final R indices [I > 2s(I)]
R indices (all data)
Largest diff. peak/hole (e A
R1 ¼ 0.0482, wR2 ¼ 0.1286
R1 ¼ 0.0791, wR2 ¼ 0.1441
0.881/ꢀ0.766
R1 ¼ 0.0279, wR2 ¼ 0.0645
R1 ¼ 0.0279, wR2 ¼ 0.0710
0.514/ꢀ0.528
ꢀ3
˚
)
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reaction on catalyst concentration. The initial rate method was
applied to determine the rate of a reaction, and the average
initial rate over three independent measurements was deter-
mined by linear regression from the slope of absorbance versus
time plot.
Results and discussion
Syntheses and general characterizations
The condensation of a polyamine with pyridine-2-aldehyde in
1
: 2 molar ratio yields a mixture of Schiff dibase and its
heterocyclic analogue, and the ratio of which can be examined
9,10,35
by the NMR spectroscopy.
Recent reports revealed that the
metal-assisted ring opening/closing processes are common for
such ligand systems, and several factors are responsible in this
isomerization process, including the size of the metal ions,
1
Fig. 1 Crystal structure of Mn(L )Cl
2
$2MeOH (1) with the atom labeling
9,10,35
scheme. Ellipsoids are drawn at the 50% probability level and solvent
molecules are omitted for clarity.
Lewis acidity, and the stereochemistry of the metal centers.
We have recently examined the coordination ability of man-
ganese(II) ion with this class of ligands derived from the
condensation of two different triamines with pyridine-2-alde-
hyde, and the results show the selective complexation ability of
1
from the folded dissymmetric ligand L , and two exogenous
chloride ions. In the crystal structure, both the folded dissym-
metric pyridyl nitrogen atoms and two chloride ions are cis
coordinated, and two pyridyl rings are approximately perpen-
dicular to each other (dihedral angle: 86.30 ). The Mn–Npy
2.302(2) and 2.324 A] and Mn–N
very similar but somewhat shorter than the Mn–Namine [2.367(2) A˚ ]
distance, which is along the line of the state of hybridizations of
15
manganese(II) ion with the cyclic form of the ligands. In order
to explore whether the manganese(II) ion exclusively selects the
cyclic isomeric form, in the present work, the ligands derived
from the condensation of two equivalents of pyridine-2-alde-
ꢂ
˚
˚
[
[2.302(2) A) distances are
0
imine
hyde (or 2-acetylpyridine) and one equivalent of 3,3 -imino-
bis(propylamine) with two longer propylenic linkers were
allowed to react with the hydrated salt of manganese(II) chloride
in methanol (Scheme 1). On the basis of the characterizations of
the complexes, including X-ray crystal structures (vide infra),
1
2
they are formulated as [Mn(L )Cl
(
2
]$2MeOH (1) and [Mn(L )Cl
2
]
Table 2 Selected bond lengths (A) and bond angles (ꢂ) for 1 and 2
˚
15
2). Complex 1 is as usual found in our recent report, but
1
complex 2 is quite different as one arm of the Schiff base has
been hydrolyzed during course of the reaction (vide infra).
In the IR spectra of complex 2, a medium intense peak at
Mn1–N1
Mn1–N2
2.302(2)
2.302(2)
2.367(2)
71.69(7)
158.37(8)
93.63(8)
91.35(8)
86.30(8)
71.38(8)
Mn1–N5
Mn1–Cl1
Mn1–Cl2
2.324(2)
2.4674(7)
2.4620(7)
89.80(5)
160.94(6)
105.41(6)
90.46(6)
98.19(5)
86.74(6)
94.02(6)
163.64(6)
100.79(3)
ꢀ1
3
239 cm indicates N–H stretching vibration of the ligand; Mn1–N3
however, the N–H stretching band overlaps with the O–H N1–Mn1–N2
Cl1–Mn1–N1
Cl1–Mn1–N2
Cl1–Mn1–N3
Cl1–Mn1–N5
Cl2–Mn1–N1
Cl2–Mn1–N2
Cl2–Mn1–N3
Cl2–Mn1–N5
Cl1–Mn1–Cl2
N1–Mn1–N3
stretching vibration of the lattice methanol molecules in 1, and
ꢀ1
N1–Mn1–N5
N2–Mn1–N3
N2–Mn1–N5
the resultant broad band was observed at 3348 cm . In the IR
spectra of both the complexes, a strong and sharp band due to
ꢀ
1
azomethine n(C]N) appeared at 1646 and 1645 cm , respec- N3–Mn1–N5
tively. In addition, sharp peaks were observed at 1597 and 1598
ꢀ
1
cm
for complexes 1 and 2, respectively, which might be
assigned to the stretching vibration of pyridyl C]N bond.
2
Structural studies
Mn1–N1
2.2536(9)
2.2434(9)
2.2266(9)
72.60(3)
166.36(3)
100.61(3)
94.83(3)
172.83(4)
92.13(4)
Mn1–N4
Mn1–Cl1
Mn1–Cl2
2.2284(9)
2.5781(3)
2.5535(3)
88.07(2)
97.45(3)
88.37(3)
84.40(3)
93.91(2)
84.47(2)
90.02(3)
93.87(3)
177.58(1)
The crystal structure of complex 1 along with the atom Mn1–N2
numbering scheme is depicted in Fig. 1, and selected bond
lengths and angles are given in Table 2. Complex 1 crystallizes
in the monoclinic P2 /c space group with two lattice methanol
molecules, one of which is disordered over a crystallographic N2–Mn1–N3
inversion center. Although ligand L possesses one chiral center N2–Mn1–N4
but the centrosymmetric space group suggests that the
compound crystallizes as a racemate. The geometry of the metal
center is a pseudo-octahedron comprised of two pyridyl, one
amine (hexahydropyrimidine) and one imine nitrogen donors
Mn1–N3
N1–Mn1–N2
N1–Mn1–N3
N1–Mn1–N4
Cl1–Mn1–N1
Cl1–Mn1–N2
Cl1–Mn1–N3
Cl1–Mn1–N4
Cl2–Mn1–N1
Cl2–Mn1–N2
Cl2–Mn1–N3
Cl2–Mn1–N4
Cl1–Mn1–Cl2
1
1
N3–Mn1–N4
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nitrogen atoms. The Mn–Cl bond lengths are found to be Complex 2 crystallizes in the monoclinic C2/c space group in
˚
2
.461(1) and 2.467(1) A, and all the bond lengths are compa- which the complex molecule sits in a general position. The
35–39
rable to the related complexes with a similar environment.
The degree of distortion from the ideal octahedral geometry comprised of the four nitrogen atoms of the L ligand in the
90 /180 ) is reected from both the cisoid and transoid angles equatorial plane and two exogenous chloride anions in the
manganese(II) ion is in a distorted-octahedral environment,
2
ꢂ ꢂ
(
as shown in Table 2. Such distortion from the ideal octahedral apical positions. The Mn–Cl and Mn–N distances are similar to
geometry is presumably due to the shorter bite angles of the what is observed for the manganese(II) complexes of similar
dissymmetric ligands, especially for those forming ve- coordination environments. Several bond angles in 2 (Table 2)
ꢂ
ꢂ
membered chelate rings. Five-membered chelates involving deviate signicantly from the ideal value of 90 or 180 , a
imine-N are conjugated and as expected have a nearly planar characteristic of a regular octahedron. The crystal packing of
conformation, while the remaining one is in the envelope complex 2 is mainly stabilized by moderately strong hydrogen
ꢀ
conformation indicating a saturated non-planar characteristic. bonding interactions between amine-H and coordinated Cl
Moreover, the six-membered hexahydropyrimidine rings are in ions (Table 3), which leads to the construction of a supramo-
a more stable chair conformation as found in the most of the lecular 1D chain propagating along the b axis (Fig. 3). These
10
systems. The secondary amine hydrogen atom of hexahy- supramolecular chains further interact with each other by
˚
dropyrimidine ring undergoes an intramolecular hydrogen means of C–H/p stacking interaction (2.951 A), which forms a
bonding with a coordinated Cl atom, the dimension of which is 2D sheet in the ab plane.
given in Table 3. In addition, the secondary amine nitrogen
atom forms a hydrogen bond with the ordered solvent methanol
molecule in 1. The disordered molecule of methanol solvent,
sitting on an inversion center, also forms hydrogen bonds with
two adjacent ordered molecules of methanol (Table 3). These
hydrogen bonds along with the edge-to-edge p–p stacking
Metal-catalyzed hydrolysis of imine bond
The crystal structure of complex 1 shows that the manganese(II)
ion again selects the cyclic isomer for stability during the
1
5
10
complexation process. Tuchagues et al. reported a number of
2
+
2+
2+
˚
complexes having different metal ions (Fe , Ni and Zn ) with
three different ligand systems. They found that regardless of the
metal ions, the cyclic form of the ligand derived from a triamine
with two shorter ethylenic linkers is stabilized through tetra-
interaction (3.422 A) lead to the formation of a 3D supramo-
lecular network of 1, as shown in Fig. S1.†
The crystal structure of compound 2 is presented in Fig. 2,
and principle bond lengths and angles are listed in Table 2.
1
coordination, while the acyclic Schiff dibasic isomer of L
(derived from a triamine with two longer propylenic linkers) is
stabilized through penta-coordination in order to gain extra
stability by increasing the donor sites. Based on the observa-
tions, they concluded that size of the metal ions is a deter-
mining factor over Lewis acidity for the stability of the different
isomeric forms of the ligands in the complexation process.
Unlike their observation, the longer propylenic linkers of the
ꢂ
a
Table 3 Geometry of important hydrogen bonds ( A˚ , ) for 1 and 2
D–H/A
D–H
H/A
D/A
<D–H/A
1
O2–H1A/N4
O2–H2A/O1
N4–H4/Cl1
N3–H3A/Cl1a
N4–H4B/Cl2b
0.82
0.93
1.00
0.89
0.90
2.03
1.98
2.36
2.58
2.47
2.836(5)
2.842(13)
3.285(4)
3.318(1)
3.357(1)
168
152
154
140
167
2
a
Symmetry code: a ¼ 1/2 ꢀ x, ꢀ1/2 ꢀ y and ꢀz; b ¼ 1/2 ꢀ x, 1/2 ꢀ y
and ꢀz.
Fig. 3 Molecular packing showing hydrogen bonding and C–H/p
(2) with the atom labeling interactions in complex 2; hydrogen atoms not participating in
2
Fig. 2 Molecular structure of Mn(L )Cl
2
scheme. Ellipsoids are presented at the 50% probability level.
hydrogen bonding are omitted for clarity.
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1
present triamine (in L ) are unable to stabilize the Schiff dibasic observation supports the hydrolysis of one arm of the ligand
form of the ligand in the manganese(II) coordination during the complexation process. The present results signi-
2
+
2+
compound. The ionic radius of Mn is even larger than Fe , cantly conclude that the size of the manganese(II) ion is too
2
+
2+
1
Ni and Zn ; thus, the Schiff dibasic form of ligand L is large to allow the coordination of the Schiff dibasic form of the
2
+
unable to accommodate the Mn ion. This result further ligands, especially those derived from triamines and pyridine-2-
strengthens the proposition made by Tuchagues and coworkers aldehyde (or 2-acetylpyridine).
that the size of the metal ions plays a critical role in selective
coordination of the ligands in the complexes with either cyclic
or acyclic isomer. In order to further conrm whether the
manganese(II) ion has any tendency to stabilize the Schiff
Cyclic voltammetry
dibasic form, a similar experiment was carried out with the The transition metal-based enzymes catalyze the redox
ligand derived from the condensation of the same triamine with processes in the biochemical reactions in which the redox
2-acetylpyridine, which is expected to produce only the Schiff potential of the metal centers plays an important role. There-
dibasic ligand because methyl substitution on the azomethine- fore, the electrochemical behaviors of their models are of
C not only reduces the electrophilic character of the imine-C but profound importance as they could give us clues for their
also increases the steric hindrance to the approaching nucleo- catalytic ability. The electrochemical behavior of the complexes
phile. However, the structural study of complex 2 indicates that was investigated in acetonitrile solution containing 0.1 M tet-
one arm of the Schiff base has been hydrolyzed. In our recent raethylammonium perchlorate (TEAP) as a supporting electro-
0
report, we have shown that the in situ condensation of 3,3 - lyte. Cyclic voltammograms of complexes 1 and 2 are depicted
iminobis(propylamine) and 2-acetylpyridine, followed by the in Fig. 5 and S2,† respectively, and the electrochemical data for
addition of cobalt(II) salt, yielded a dinuclear cobalt(III) complex both the complexes are summarized in Table 4. Scanning in the
in which the Schiff dibasic ligand was coordinated to the metal anodic direction revealed a reduction wave at 0.93 and 0.76 V for
14
centers. IR spectral studies of solution were carried out to 1 and 2, respectively, which is due to the oxidation of man-
check whether the complex 2 arises from the hydrolysis of one ganese(II) to manganese(III). On reversal of the scan direction,
arm of the Schiff dibasic ligand instead of the half condensation the resultant manganese(III) complex was reduced to man-
reaction of triamine and 2-acetylpyridine (1 : 1 condensation). ganese(II) at 0.75 and 0.61 V for 1 and 2, respectively. These
The in situ prepared ligand derived from the condensation of nearly quasi-reversible electrode responses for the Mn(II)/Mn(III)
0
3
,3 -iminobis(propylamine) and 2-acetylpyridine in 1 : 2 molar oxidation process are in line with the closely related man-
15,39,40
ratio did not show any stretching of the keto group (Fig. 4). The ganese(II) complexes of similar ligand environment.
The
absence of the stretching band for the keto group and the E1/2 value of 0.84 V for complex 1 is signicantly higher than 2
appearance of the stretching band of the azomethine group (at (0.68 V), which might be due to the different electronic envi-
ꢀ
1
1
645 cm ) conrm the double condensation. Interestingly, on ronments in these complexes. The higher s donor ability of
2
addition of manganese(II) chloride, a new band appeared at both the primary and secondary amine groups in L pushes
ꢀ
1
1
697 cm , which is due to the free 2-acetylpyridine, and this
Fig. 5 Cyclic voltammogram of a 5 mM acetonitrile solution of 1 with a
conventional three electrode system using a Pt working electrode, Pt
Fig. 4 IR spectra of the in situ prepared condensation of 3,3 -imino- auxiliary electrode and Ag/AgCl reference electrode in the presence of
0
bis(propylamine) and 2-acetylpyridine in 1 : 2 molar ratio (top) and on tetraethylammonium perchlorate (TEAP) as the supporting electrolyte
ꢀ1
addition of manganese(II) chloride (bottom).
at ambient temperature; scan rate: 100 mV s .
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a
Table 4 Electrochemical data for 1 and 2 in acetonitrile
the catalytic process, a control experiment was performed in
which OAPH was treated only with ligand L , and the time-
1
c
p
a
p
Complex
E
(V)
E
(V)
DE
p
(V)
E1/2 (V)
course data of the resulted solution was recorded at 435 nm,
which did not show any signicant growth of absorbance
(Fig. S3†). On addition of the methanolic solution of complex 1
to the same solution, progressive increase in the peak intensity
was noticed. These observations clearly conclude that the phe-
1
2
0.75
0.61
0.93
0.76
0.18
0.15
0.84
0.68
a
Pt working and Ag/AgCl reference electrodes; supporting electrolyte is
tetraethylammonium perchlorate; scan rate 100 mV s ; E
anodic and cathodic peak potentials, respectively; E1/2 ¼ 0.5(E
ꢀ1
a
p
c
and E
p
p
are
p
a
c
ꢀ E
); noxazinone synthase activity arises solely from the man-
a
p
c
DE
p
¼ E
ꢀ E
p
.
ganese(II) complexes.
In order to understand the degree of catalytic efficiency,
ꢂ
kinetic studies of both the complexes were performed at 25 C.
For this purpose, 1 ꢁ 10 M solutions of the complexes were
more electron density towards the metal center, favoring the
oxidation of the manganese(II) center in 2.
ꢀ4
treated with at least a 10-fold concentrated substrate solution as
that of the complex to maintain the pseudo-rst-order condi-
tion. For a particular complex–substrate mixture, time scan at
the maximum band for 2-aminophenoxazine-3-one was carried
out for a period of 30 min, and the initial rate was determined
by linear regression from the slope of the absorbance versus
time plot. The initial rate of the reactions versus the concen-
tration of the substrate plot shows rate saturation kinetics
Phenoxazinone synthase-like activity
The reaction between o-aminophenol and dioxygen in the
presence of a catalytic amount of complexes 1 or 2 was per-
formed in dioxygen-saturated methanol because of the good
solubility of the complexes, the substrate, and the nal product
in this solvent. In order to avoid the autoxidation of the
substrate by air, the catalytic activity was examined in the
absence of an added base. Before going to the detailed kinetic
investigation, it is necessary to check the ability of the
complexes to behave as catalysts for the oxidation of o-amino-
(Fig. 7). This observation indicates that formation of 2-amino-
phenoxazine-3-one proceeds through a relatively stable inter-
mediate, a complex–substrate adduct, followed by the redox
decomposition of the intermediate at the rate determining step.
The initial rates versus the concentration of substrate data were
then analyzed on the basis of the Michaelis–Menten approach
of enzymatic kinetics to obtain the Lineweaver–Burk (double
ꢀ
4
phenol. For this purpose, 1.0 ꢁ 10
M solutions of the
complexes (1 or 2) were treated with a 0.01 M solution of OAPH,
and the growth of the absorption band of the phenoxazinone
chromophore at 435 nm as a function of time was observed,
which indicates the catalytic oxidation of o-aminophenol to the
reciprocal) plot as well as values of the parameters Vmax, K , and
M
K
cat. The observed and simulated initial rates versus the
substrate concentration plots for 1 and 2 are depicted in Fig. 7,
while the Lineweaver–Burk plots are displayed in Fig. 8. Anal-
corresponding 2-aminophenoxazin-3-one.
A representative
time-resolved spectral prole for a period of 2 h aer the
addition of OAPH for complex 1 is shown in Fig. 6. In order to
establish the importance of the metal-complex conclusively in
yses of the experimental data yielded the Michaelis binding
–2
constant (K
M
) value of (1.11 ꢃ 0.08) ꢁ 10 M for 1 and (8.53 ꢃ
ꢀ3
ꢀ7 ꢀ1
1
.05) ꢁ 10 M for 2, and the V values of (6.54 ꢃ 0.42) ꢁ 10
M
max
Fig. 6 UV-vis spectral profile showing the growth of phenoxazinone
chromophore at 435 nm after the addition of o-aminophenol (0.01 M) Fig. 7 Initial rate verses substrate concentration plot for the oxidation
ꢀ
4
ꢂ
to a solution of 1 (1 ꢁ 10 M) in methanol at 25 C. The spectra were of o-aminophenol catalyzed by 1 and 2 in methanol. Symbols and solid
recorded for a period of 2 h.
lines represent the experimental and simulated profiles, respectively.
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order dependence of reaction on the complex concentration
(Fig. S4†).
Comparative phenoxazinone synthase activity and probable
mechanism
The reaction kinetics shows that both the complexes are very
reactive towards the oxidation of o-aminophenol, and the rate
saturation kinetics study clearly indicates that the reaction
proceeds through the stable complex–substrate intermediate
formation. In order to justify the involvement of molecular
dioxygen in the catalytic cycle, the UV-vis spectra of a mixture of
ꢀ
4
1
ꢁ 10 M solution of complex 2 with 100 fold excess of OAPH
were recorded in a nitrogen atmosphere, and no spectral growth
at 435 nm was observed until one hour of mixing. This obser-
vation unambiguously proves that molecular dioxygen oxidizes
OAPH to the corresponding 2-aminophenoxazine-3-one in the
catalytic cycle in the presence of manganese(II) complex as a
catalyst. Based on the above results, a plausible mechanism is
Fig. 8 Lineweaver–Burk plots for the oxidation of o-aminophenol attempted, involving stepwise pathways, keeping in mind that it
catalyzed by 1 and 2 in methanol. Symbols and solid lines represent the is impossible to prove any single mechanism. A tentative cata-
experimental and simulated profiles, respectively.
lytic cycle for the formation of the phenoxazinone chromophore
is shown in Scheme 2. At the rst step, OAPH forms an adduct
12,13
with the manganese(II) complex,
which yields an OAP radical
ꢀ
7
and (7.59 ꢃ 0.64) ꢁ 10 for 1 and 2, respectively. The turnover
number (kcat) value is obtained by dividing the Vmax by the concen-
by the reaction with molecular dioxygen in the rate determining
step. The OAP radical may generate o-benzoquinone mono-
amine (BQMI) in many ways, including oxidation by the man-
ganese(III) center. Finally, 2-aminophenoxazine-3-one is
produced via several oxidative dehydrogenation processes,
ꢀ1
tration of the complex used and is found to be 23.54 and 27.32 h
for 1 and 2, respectively. Moreover, for a particular substrate
concentration, when complex concentration was varied, a linear
relationship for the initial rates was obtained, which shows a rst-
2
involving OAPH, O , and BQMI, as shown in Scheme 2. In order
Scheme 2 Plausible mechanistic pathway showing the formation of 2-aminophenoxazine-3-one in which complex 1 is chosen as model
complex.
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2
+
to increase the acceptability of the most probable mechanism, radius of the Mn ion enforces the stabilization of the cyclic
the mass spectral investigation of 1 : 50 mixture of complex 1 analogue during complexation. IR spectral results demonstrate
and OAPH were recorded aer 10 minutes of mixing in meth- that the size of manganese(II) ion is too large to allow the
anol (Fig. S5†). The spectrum comprised of all the peaks that coordination of the Schiff dibasic form of the ligands, especially
were only found for the complex, and these peaks at m/z ¼ those derived from triamines and pyridine-2-aldehyde (or 2-
3
10.16, 363.09 and 399.07 are due to the mono-cationic species acetylpyridine). The crystal packing of complex 2 is interesting
1
+
II
1
+
II
1
+
of (L + H) , [Mn (L ) ꢀ H] and [Mn (L )Cl] as indicated by the as it forms 1D supramolecular chain through the hydrogen
isotopic distribution pattern together with the line-to-line bonding interaction. Both the complexes are moderately active
separation of 1.0. In addition, one minor peak at m/z ¼ 472.15 is towards the oxidation of o-aminophenol, and their relative
quite interesting because the peak position and the line-to-line catalytic efficiency mainly arises from the steric contribution
separation of unity clearly indicates that this peak arises due to from the ligands, and the electrochemical responses of the
II
1
+
1
: 1 complex–substrate aggregate [Mn (L )(OAP)] , which is metal center. From the experimental data, a nice correlation,
consistent with the earlier discussed rate saturation kinetics. wherein the lower the E1/2 value the higher the catalytic activity,
However, the mass spectrum does not suggest any species can be established between E1/2 and Vmax of the complexes. The
related to the dioxygen bound metal-complex. In our recent deuterium kinetic isotope effect in the catalytic oxidative
report, we have observed that the acyclic dibasic form of ligand coupling of two moles of OAPH by O
2
as shown by the 1.6 times
1
L yielded a peroxo-bridged dinuclear cobalt(III) complex and rate retardation in the deuterated solvent unambiguously
14
that compound exhibited phenoxazinone synthase activity.
suggests hydrogen atom transfer in the rate-determining step
Therefore, I speculated that in the present case, dioxygen-bound from the substrate hydroxy group to the metal-bound superoxo
metal center could play an important role in the catalytic species.
process. To determine whether manganese(III)-superoxo is the
active species in abstracting the O–H proton of OAPH in the rate
determining step, comparative kinetic studies were performed
Acknowledgements
under a given set of conditions in both methanol and deuter- A. P. is grateful to the University Grants Commission, India, for
ated methanol. It can be assumed that in CH OD the phenolic- the nancial support of this research (Sanction no. PSW-173/11-
3
OH of OAPH undergoes a nearly complete exchange for OD. 12). Jadavpur University and Indian Association for the Culti-
Consequently, if the rate-determining step involves the vation of Science, India, are also gratefully acknowledged for the
breaking of the –O–H (–O–D) bond, a kinetic isotope effect (KIE) instrumentation facilities.
should be observed upon changing the solvent from CH
3
OH to
CH OD. In fact, 1.6 times rate retardation in the deuterated
3
References
solvent suggests that the hydrogen atom transfer in the rate-
determining step from the substrate hydroxy group to the
metal-bound superoxo species is operative in the catalytic
1 E. Tsuchida and K. Oyaizu, Coord. Chem. Rev., 2003, 237,
213–228.
2 L. Canali and D. C. Sherrington, Chem. Soc. Rev., 1999, 28,
85–93.
28
oxidative coupling of two moles of OAPH by O2. However, the
turnover numbers suggest that complex 2 is more reactive than
1
towards the phenoxazinone synthase activity. It has been well
3 J. Tisato, F. Refosco and F. Bandoli, Coord. Chem. Rev., 1994,
135, 325–397.
4 R. J. Ferm and J. L. Riebsomer, Chem. Rev., 1954, 54, 593–613.
5 R. J. Ferm, J. L. Riebsomer, E. L. Martin and G. H. Daub,
J. Org. Chem., 1953, 18, 643–648.
6 M. Bo ˇc a, D. Valigura and W. Linert, Tetrahedron, 2000, 56,
441–446.
7 S. Deoghoria, S. Sain, M. Soler, W. T. Wong, G. Christou,
S. K. Bera and S. K. Chandra, Polyhedron, 2003, 22, 257–262.
8 M. Bo ˇc a, P. Baran, R. Boca, G. Kickelbick, F. Renz and
W. Linert, Inorg. Chem. Commun., 1999, 2, 188–190.
explored that the catalytic activity of a complex depends on
several factors such as the geometry of the complex, the redox
potential of the central metal ion, and the steric factor. The
present results can nicely be interpreted by considering the
electrochemical potential along with the coordination envi-
ronments around the metal center. Ligand L in 2 is less bulky
than L in 1 and thus favors interaction of the substrate to the
metal center. In addition, the lower electrochemical response of
complex 2 facilitates the interaction of the metal center with
molecular dioxygen in the catalytic cycle.
2
1
9
M. Bo ˇc a, P. Baran, R. Boca, M. Fuess, G. Kickelbick,
W. Linert, F. Renz and I. Svoboda, Inorg. Chem., 2000, 39,
Conclusions
3205–3212.
Two novel mononuclear manganese(II) complexes have been 10 N. Br ´e fuel, C. Lepetit, S. Shova, F. Dahan and
synthesized and structurally characterized by X-ray diffraction J.-P. Tuchagues, Inorg. Chem., 2005, 44, 8916–8928.
2
+
studies. Structural characterization reveals that the Mn ion 11 A. Panja and P. Guionneau, Dalton Trans., 2013, 5068–5075.
prefers the cyclic (hexahydropyrimidine) form of the ligand in 1; 12 A. Panja, M. Shyamal, A. Saha and T. K. Mandal, Dalton
however, in 2, one arm has been hydrolyzed during the
Trans., 2014, 5443–5452.
complexation reaction. It has already been reported that ligand 13 A. Panja, Polyhedron, 2014, 80, 81–89.
1
2+
2+
2+
L exclusively binds the metal centers (Fe , Ni and Zn ) in 14 A. Panja, Dalton Trans., 2014, 7760–7770.
the acyclic isomeric form of the ligand, but the higher ionic 15 A. Panja, Polyhedron, 2014, 79, 258–268.
This journal is © The Royal Society of Chemistry 2014
RSC Adv., 2014, 4, 37085–37094 | 37093

View Article Online
RSC Advances
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1
6 E. I. Solomon, T. C. Brunold, M. I. Davis, J. N. Kemsley, 30 J. Kaizer, G. Bar ´a th, R. Csonka, G. Speier, L. Korecz,
S. K. Lee, N. Lehnert, F. Neese, A. J. Skulan, Y. S. Yang and
J. Zhou, Chem. Rev., 2000, 100, 235–349.
A. Rockenbauer and L. P ´a rk ´a nyi, J. Inorg. Biochem., 2008,
102, 773–780.
1
1
1
2
2
7 E. I. Solomon, R. Sarangi, J. S. Woertink, A. J. Augustine, 31 C. Mukherjee, T. Weyherm u¨ ller, E. Bothe and P. Chaudhuri,
J. Yoon and S. Ghosh, Acc. Chem. Res., 2007, 40, 581–591. C. R. Chim., 2007, 10, 313–325.
8 E. G. Kovaleva and J. D. Lipscomb, Nat. Chem. Biol., 2008, 4, 32 G. M. Sheldrick, SAINT, Version 6.02, SADABS, Version 2.03,
86–193. Bruker AXS Inc., Madison, Wisconsin, 2002.
9 C. E. Barry, P. G. Nayar and T. P. Begley, Biochemistry, 1989, 33 G. M. Sheldrick, SHELXL97, Program for Crystal Structure
1
2
8, 6323–6333.
Renement, University of G ¨o ttingen, G ¨o ttingen, Germany,
1997.
0 A. W. Smith, A. Camara-Artigas, M. Wang, J. P. Allen and
W. A. Francisco, Biochemistry, 2006, 45, 4378–4387.
34 L. J. Farrugia, J. Appl. Crystallogr., 1999, 32, 837–838.
1 C. E. Barry, P. G. Nayar and T. P. Begley, J. Am. Chem. Soc., 35 Y.-M. Lee, E.-S. Kim, H.-J. Kim, H. J. Choi, Y.-I. Kim,
1
988, 110, 3333–3342.
S. K. Kang and S.-N. Choi, Dalton Trans., 2009, 126–133.
36 S. E. Ghachtouli, A. Mohamadou and J.-P. Barbier, Inorg.
Chim. Acta, 2005, 358, 3873–3880.
2
2
2
2 E. Frei, Cancer Chemother. Rep., Part 1, 1974, 58, 49–54.
3 U. Hollstein, Chem. Rev., 1974, 74, 625–652.
4 L. I. Sim ´a ndi, T. M. Sim ´a ndi, Z. May and G. Bensenyei, 37 S. I. M. Paris, U. A. Laskay, S. Liang, O. Pavlyuk,
¨
Coord. Chem. Rev., 2003, 245, 85–93.
5 M. Hassanein, M. Abdo, S. Gerges and S. El-Khalafy, J. Mol.
Catal. A: Chem., 2008, 287, 53–56.
S. Tschirschwitz, P. L ¨o nnecke, M. C. McMills,
G. P. Jackson, J. L. Petersen, E. Hey-Hawkins and
M. P. Jensen, Inorg. Chim. Acta, 2010, 363, 3390–3398.
2
2
2
2
2
6 R. Bakshi, R. Kumar and P. Mathur, Catal. Commun., 2012, 38 C. Hureau, S. Groni, R. Guillot, G. Blondin, C. Duboc and
7, 140–145.
E. Anxolab ´e h `e re-Mallart, Inorg. Chem., 2008, 47, 9238–9247.
7 C. Mukherjee, T. Weyhermuller, E. Bothe, E. Rentschler and 39 S. Groni, C. Hureau, R. Guillot, G. Blondin, G. Blainand and
1
P. Chaudhuri, Inorg. Chem., 2007, 46, 9895–9905.
8 T. M. Sim ´a ndi, L. I. Sim ´a ndi, M. Gy o} r, A. Rockenbauer and
E. Anxolab ´e h `e re-Mallart, Inorg. Chem., 2008, 47, 11783–
11797.
40 C. Hureau, G. Blondin, M.-F. Charlot, C. Philouze,
M. Nierlich, M. C ´e sario and E. Anxolab ´e h `e re-Mallart, Inorg.
Chem., 2005, 44, 3669–3683.
´
¨ ¨
A. Gomory, Dalton Trans., 2004, 1056–1060.
9 T. Horv ´a th, J. Kaizer and G. Speier, J. Mol. Catal. A: Chem.,
2004, 215, 9–15.
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