Synthesis, structure and catalase-like activity of Cu(N-baa)2(phen) (phen = 1,10-phenanthroline, N-baaH = N-benzoylanthranilic acid)

Article abstract of DOI:10.1016/j.inoche.2006.06.005

The mononuclear copper(II) complex Cu(N-baa)₂(phen) is synthesized by the reaction of Cu(OCH₃)₂ with N-benzoylanthranilic acid in the presence of 1,10-phenanthroline; the structure and catalase-like activity are investigat

Full text of DOI:10.1016/j.inoche.2006.06.005

Inorganic Chemistry Communications 9 (2006) 1037–1039
www.elsevier.com/locate/inoche
Synthesis, structure and catalase-like activity of
Cu(N-baa)2(phen) (phen = 1,10-phenanthroline,
N-baaH = N-benzoylanthranilic acid)
a
b
a,b,
c
c
*
´
´
´
´
, Marius Reglier , Michel Giorgi
Jozsef Kaizer , Tamas Csay , Gabor Speier
a
Research Group for Petrochemistry, Hungarian Academy of Sciences at University of Veszpre´m, 8201 Veszpre´m, Hungary
b
Department of Organic Chemistry, University of Veszpre´m, 8201 Veszpre´m, Hungary
Laboratoire de Cristallochimie et Laboratoire de Bioinorganique, Structurale Universite´ Paul, Ce´zanne Aix-Marseille III F.S.T.
ˆ
Saint-Je´rome, Service 432 Avenue Escadrille Normandie-Niemen, 13397 Marseille cedex 20, France
c
Received 7 March 2006; accepted 11 June 2006
Available online 20 June 2006
Abstract
The mononuclear copper(II) complex Cu(N-baa)2(phen) is synthesized by the reaction of Cu(OCH3)2 with N-benzoylanthranilic acid
in the presence of 1,10-phenanthroline; the structure and catalase-like activity are investigated.
ꢀ 2006 Elsevier B.V. All rights reserved.
Keywords: Copper; Carboxylates; N-Benzoylanthranilic acid; Catalase-like activity
Enzymatic antioxidants regulate superoxide concentra-
tion by dismutation of superoxide to hydrogen peroxide
(SOD), which is then converted to water (peroxidases) or dis-
muted to water and dioxygen (catalases) [1]. These reactions
are important for cell detoxification, and are linked to a vari-
ety of pathological consequences such as aging, diabetes and
cancer [2]. Besides heme type catalases [3], a number of man-
ganese containing catalases have been isolated and charac-
terized [4–7]. The direct utilization of these natural
enzymes as pharmaceutical agents is limited because of low
membrane permeability as a consequence of their high
molecular weight. So considerable efforts were made in order
to obtain non-toxic, low molecular weight biomimetic mol-
ecules, which are able to catalyze the dismutation of super-
oxide anion and/or destroy the forming hydrogen peroxide.
Compared with manganese-containing model systems
[8–11], the reported copper-containing systems are rela-
tively rare [12–15]. Several copper(II) carboxylates of
anti-inflammatory drugs such as salicylates [16], indometh-
acin [17] and lonazolac [18] were studied as SOD mimics,
and some binuclear and tetranuclear copper(II) complexes
with macrocyclic ligands have been reported as functional
models for catalases [13,14]. As a continuity of this topic,
binuclear copper complexes Cu2(bpy)2(phga)4 (1) and
Cu2(ba)4(bpy)2 (2), which functionally mimic the catalase
enzyme, have been thoroughly investigated and it has been
found that the mechanism of their reaction is a direct func-
tion of the nature of their ligands associated with the metal
ion (Scheme 1) [15]. The observed initial rates for these
complexes showed that Cu2(bpy)2(phga)4 is almost three-
fold more reactive than compound Cu2(ba)4(bpy)2, and
the rate dependence on the catalyst suggested that the (ben-
zoato)copper complex is mainly in the monomeric form,
while that of the ketocarboxylato(copper) complex exists
in the dimeric form during the catalytic process.
In this communication, we present the synthesis and
structural characterization of a new neutral (N-benzoylanth-
ranilato)copper(II) complex with a bidentate ligand 1,10-
phenanthroline (phen), Cu(N-baa)2(phen) (3), obtained with
*
Corresponding author. Address: Research Group for Petrochemistry,
´
Hungarian Academy of Sciences at University of Veszprem, 8201
Veszprem, Hungary. Fax: +36 88 62 4469.
´
E-mail address: speier@almos.vein.hu (G. Speier).
1387-7003/$ - see front matter ꢀ 2006 Elsevier B.V. All rights reserved.
doi:10.1016/j.inoche.2006.06.005

1038
J. Kaizer et al. / Inorganic Chemistry Communications 9 (2006) 1037–1039
Scheme 1.
practically quantitative yield by interaction of Cu(OCH3)2,
N-benzoylanthranilic acid, and 1,10-phenanthroline in ace-
tonitrile under argon atmosphere [19]. The determination
of its structure was carried out by X-ray single crystal study.
In addition, IR and UV–Vis analysis of the title compound
and its catalase-like activity was also examined in order to
get an insight into the mechanism of these curious reactions.
Complex 1 isolated as a blue solid is stable in air and
analyzed satisfactorily for C, H, N. The infrared (IR) spec-
trum of the complex shows bands corresponding to the
coordinated N-benzoylanthranilate at 3446 m(NH), 1675
m(CO), 1589, and 1379 m(CO2) cmÀ1 [20]. The difference
between the asymmetric and symmetric stretching frequen-
cies of the carboxylato group [Dm = mas(CO2) À ms(CO2)] is
210 cmÀ1, rendering these to an asymmetrical carboxylate
bonding mode [21]. The stretching vibrations correspond-
ing to those typical of coordinated 1,10-phenanthroline
occur at 723, 848, and 1510 cmÀ1 [22]. The electronic spec-
trum of complex 3 obtained in DMF solution exhibits a
very broad absorption band at 680 nm due to d–d transi-
tion. The position of this band falls within the range
expected for mononuclear copper(II) complexes that con-
tain a CuN2O2 + O2 chromophore in a distorted tetragonal
geometry [23]. A higher energy band at 316 nm is associ-
ated with charge transfer transition. These spectral features
are comparable with those of the Cu(phen)(valproate)2
complex [22].
Fig. 1. Molecular structure of Cu(N-baa)2(phen) (3) with crystallographic
numbering. Hydrogen atoms are omitted for clarity. Relevant bond
˚
lengths (A) and angles (ꢁ): Cu(1)–O(1) 1.945(3), Cu(1)–O(2) 2.626, Cu(1)–
N(1) 2.023(3), O(1)–C(1) 1.274(4), O(2)–C(1) 1.242(4), O(3)–C(8) 1.226(4),
C(1)–C(2) 1.498(5), N(2)–C(7) 1.394(4), N(2)–C(8) 1.367(4), O(1)–Cu(1)–
O(1) 95.61(16), O(1)–Cu(1)–N(1) 173.21(11), N(1)–Cu(1)–N(1) 82.04(17),
C(1)–O(1)–Cu(1) 106.7(2), C(15)–N(1)–Cu(1) 129.4(3), C(19)–N(1)–Cu(1)
112.3(2), C(8)–N(2)–C(7) 129.3(3).
Table 1
Kinetic data for the Cu(N-baa)2(phen)-catalyzed decomposition of
hydrogen peroxide
Suitable crystals of 3 were obtained from DMF solution
of the complex at 20 ꢁC. The molecular structure of Cu(N-
baa)2(phen) (3) [24] as well as selected bond lengths and
angles is shown in Fig. 1.
Molecule 3 is monomeric in the solid state. The overall
geometry around the four-coordinate copper ion is
described as a distorted tetragonal geometry, which con-
tains trans-CuN2O2 + O2 chromophore.
À5
Expt. no.
10À3[Cu]a (M)
10À1[H2O2]b (M)
10
V
in
(M sÀ1
)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
a
1.12
1.53
1.95
2.25
2.79
3.05
1.54
1.54
1.54
1.54
1.54
1.54
1.54
1.54
1.54
1.64
1.64
1.64
1.64
1.64
1.64
0.31
0.46
0.62
0.96
1.30
1.64
1.98
2.28
2.62
2.23
8.48
12.5
20.0
30.1
36.2
3.78
Catalase activity of complex 3 was performed in DMF
solution and examined at 20 ꢁC with a ratio of 1:20–175
between initial concentration of Cu(N-baa)2(phen) and
H2O2 (Table 1) [27]. On the basis of kinetic experiments, a
Michaelis–Menten type kinetics could be observed for the
catalytic disproportionation of hydrogen peroxide (Fig. 2).
4.54
6.04
7.50
7.95
7.80
7.27
7.97
8.13
For complex 3, values of kcat = 6.62 · 10À2 sÀ1, KM
=
52 mM, and kcat/KM = 1.27 sÀ1 MÀ1 have been obtained.
In 30 ml DMF at 20 ꢁC.
The amount of residual H2O2 was determined by iodometric titration.
b
A straight line was obtained in a plot of the reaction rate ver-

J. Kaizer et al. / Inorganic Chemistry Communications 9 (2006) 1037–1039
1039
[7] G.S. Allgood, J.J. Perry, J. Bacteriol. 168 (1986) 563.
[8] Y. Naruta, K. Maruyama, J. Am. Chem. Soc. 113 (1991) 3595.
[9] A.C. Rosenzweig, C.A. Frederick, S.J. Lippard, P. Nordlund, Nature
366 (1993) 537.
10
8
[10] E.J. Larson, V.L. Pecoraro, J. Am. Chem. Soc. 113 (1991) 7809.
[11] M.U. Triller, W.-Y. Hsieh, V.L. Pecoraro, A. Rompel, B. Krebs,
Inorg. Chem. 41 (2002) 5544.
[12] M.L. Pires dos Santos, A. Faljoni-Ala´rio, A.S. Mangrich, A.M. da
Costa Ferreira, J. Inorg. Biochem. 71 (1998) 71.
[13] J. Gao, A.E. Martell, J.H. Reibenspies, Inorg. Chim. Acta 346 (2003)
32.
40
30
20
10
0
6
4
[14] J. Gao, J.H. Reibenspies, A.E. Martell, S. Yizhen, D. Chen, Inorg.
Chem. Commun. 5 (2002) 1095.
2
0
2
4
6
8
10
10-6[Cu(phen)( -baa)2]2 (M2)
N
´
[15] J. Kaizer, R. Csonka, G. Speier, M. Giorgi, M. Reglier, J. Mol. Catal.
A: Chem. 236 (2005) 12.
0
[16] R.G. Bhirud, T.S. Srivastava, Inorg. Chim. Acta 173 (1990) 121.
[17] U. Weser, K.H. Sellinger, E. Lengfelder, W. Werner, J. Strahle,
Biochim. Biophys. Acta 631 (1980) 232.
0
5
10
15
20
25
30
10-2[H2O2] (M)
[18] U. Deuschle, U. Weser, Inorg. Chim. Acta 91 (1984) 237.
[19] Synthesis of Cu(N-baa)2(phen) (3): Cu(OMe)2 (0.126 g, 1 mmol), N-
benzoylanthranilic acid (0.482 g, 2 mmol) and 1,10-phenanthroline
monohydrate (0.196 g, 1 mmol) were dissolved in 20 cm3 of acetoni-
trile under argon. After 10 h stirring, the product was collected by
filtration, washed with diethyl ether, dried in vacuum and then
Fig. 2. Initial rate of decomposition of hydrogen peroxide as a function of
[H2O2] in DMF at 20 ꢁC. Inset: plots of Vin versus [Cu(N-baa)2(phen)]2.
sus the initial concentration of Cu (N-baa)2(phen) (3) to
establish a rate law of d[O2]/dt= kapp[Cu(N-baa)2(phen)]2
(Fig. 2). This result supports the fact that the active form
of the (carboxylato)copper complex 3 similar to the com-
pound 2 is dimeric during the catalytic process.
A variation of H2O2 concentration revealed saturation
behavior with Kass value of about 20 MÀ1. These two phe-
nomena indicated that under the condition of steady-state
turnover, the binding of hydrogen peroxide to the Cu(II)–
Cu(II) center is much more favored compared to its mono-
meric form.
recrystallized from DMF (0.62 g, 85%). M.p. 165 ꢁC. IR (KBr) cmÀ1
:
3446 m, 3150 vw, 3109 vw, 3062 vw, 1675 s, 1589 vs, 1510 vs, 1449 m,
1436 m, 1424 m, 1421 m, 1379 s, 1304 s, 1257 m, 1106 w, 848 m, 761
m, 723 m, 711 m, 667 m, 591 w, 536 w. UV–Vis (DMF) kmax (loge/
dm3 molÀ1 cmÀ1): 316 (4.17); 680 (1.88). Anal. Calcd For
C40H28N4O6Cu: C, 66.34; H, 3.90; N, 7.74%. Found: C, 67.11; H,
3.98; N, 7.59%.
´
[20] J. Kaizer, T. Csay, M. Czaun, G. Speier, M. Reglier, M. Giorgi,
Inorg. Chem. Commun. 8 (2005) 813.
[21] G.B. Deacon, R.J. Phillips, Coord. Chem. Rev. 33 (1980) 227.
[22] A.L. Abuhijleh, J. Inorg. Biochem. 68 (1997) 167.
[23] E. Labisbal, J.A.G. Vazquez, J. Romero, S. Picos, A. Sousa, A.
Castineiras, C.M. Mossmer, Polyhedron 14 (1995) 663.
[24] Crystal data for 3: C40H28CuN4O6, 724.22 g molÀ1, monoclinic, C2/c,
Acknowledgements
˚
˚
˚
a = 29.0089(9) A, b = 10.2201(4) A, c = 11.6087(3) A, b = 109.175(3)
(ꢁ), Z = 8, V = 3250.73(18) A , l(Mo-Ka) = 0.730 mmÀ1, dcalcd
=
3
˚
Financial supports of the Hungarian National Research
Fund (OTKA T-043414) and Budakonzum Ltd. are grate-
fully acknowledged.
1.480 g cmÀ3, T = 293(2) K, F(000) = 1492. The intensity data were
collected with a Nonius Kappa CCD single-crystal diffractometer
using Mo-Ka radiation (k = 0.71073). Reflections collected = 11540,
reflections total = 2973, reflections unique = 2582. The structure was
refined to R = 0.0489 (0.0600) and wR2 = 0.1456 for the reflections
Appendix A. Supplementary data
with I > 2r(I) (all data) and max. resd. density = 0.370 eAÀ3. The
˚
computer program used was SHELXL97 [25]. The structure was
solved by direct and difmap methods (SIR92) [26]. CCDC Reference
Number: 600586.
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.inoche.
2006.06.005.
[25] G.M. Sheldrick, SHELXL97 Program for the refinement of crystal
structures, University of Go¨ttingen, Germany, 1997.
References
[26] A. Altamore, G. Cascarano, C. Giacovazzo, A. Guagliardi, M.C.
Burla, G. Polidori, M.J. Camalli, J. Appl. Cryst. 27 (1994) 435.
[27] Study of catalase-like activity: All reactions were carried out at 20 ꢁC
in a 50 cm3 reactor containing a stirring bar under air. In a typical
experiment, DMF (30 cm3) was added to the complex (0.05 mmol)
and the flask was closed with a rubber septum. Hydrogen peroxide
(5 mmol) was injected through the septum with a syringe. The
reactor was connected to a graduated burette filled with water and
dioxygen evolution was measured volumetrically at time intervals of
0.5 min. Observed initial rates were expressed as mol dmÀ3 sÀ1 by
taking the volume of the solution (30 cm3) into account and
calculated from the maximum slope of curve describing the evolution
of O2 versus time.
[1] I. Fridovich, Ann. Rev. Biochem. 64 (1995) 97.
[2] O. Hayaish, E. Niki, M. Kondo, Y. Yoshikawa (Eds.), Medical,
Biochemical and Chemical Aspects of Free Radicals, Elsevier,
Amsterdam, 1990.
[3] A. Messerschmidt, R. Huber, T. Poulus, K. Wieghardt (Eds.), Hand-
book of Metalloproteins, John Wiley & Sons Ltd., New York, 2001.
[4] Y. Kono, I. Fridovich, J. Biol. Chem. 258 (1983) 6015.
[5] W.F. Beyer Jr., I. Fridovich, Biochemistry 24 (1985) 6460.
[6] V.V. Barynin, P.D. Hempstead, A.A. Vagin, S.V. Antonyuk, W.R.
Melik-Adamyan, V.S. Lamzin, P.M. Harrison, P.J. Artymyuk, J.
Inorg. Biochem. 67 (1997) 196.