Synthesis, crystal structure and antiradical effect of copper(ii) Schiff base complexes containing five-, six- and unusual seven-membered rings

Article abstract of DOI:10.1039/c0dt00901f

The synthesis and solid-state structure of mononuclear copper(ii) complexes [Cu(SAIB)(H₂O)₂] (1), [Cu(SBAIB)(H₂O) ₂]·H₂O (2) and [Cu(SGABA)(H₂O) ₂] (3) are described. Schiff base

Full text of DOI:10.1039/c0dt00901f

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PAPER
Synthesis, crystal structure and antiradical effect of copper(II) Schiff base
complexes containing five-, six- and unusual seven-membered rings†
Zita Puterova´,*a Jindra Valentova´,a Zuzana Bojkova´,b Jozef Kozˇ´ısˇekb and Ferdinand Dev´ınskya
Received 23rd July 2010, Accepted 19th November 2010
DOI: 10.1039/c0dt00901f
The synthesis and solid-state structure of mononuclear copper(II) complexes [Cu(SAIB)(H2O)2] (1),
[Cu(SBAIB)(H2O)2]·H2O (2) and [Cu(SGABA)(H2O)2] (3) are described. Schiff base ligands H2SAIB,
H2SBAIB and H2SGABA chelate the copper(II) ion in an O,N,O tridentate fashion. The
square-pyramidal geometry of the final complexes is completed by two water ligands. The formation of
an unusual seven-membered ring in the set of copper(II) N-salicylidene-aminoacidates is reported.
Compounds 1–3 were evaluated by the antiradical activity assay.
salicylidene-b-amino acids which form a six-membered ring upon
complexation are relatively rare.5b,9 It can be assumed that, among
the known copper(II) complexes with N-salicylideneamino acids,
the coordination properties of compounds containing a seven-
membered chelate ring remained undeveloped up to the present.
Here we present the synthesis of three model N-salicylidene-
aminoacidato copper(II) complexes with different Schiff base
ligands: N-salicylidene-a-amino-isobutyric acid (H2SAIB), N-
salicylidene-b-amino-iso-butyric acid (DL-H2SBAIB) and N-
salicylidene-g-aminobutyric acid (H2SGABA) (Scheme 1). Unlike
the more readily accessible creation of five- and six- membered
chelate rings in the case of complexes 1 and 2, respectively, we show
that methylene chain elongation in the ligand H2SGABA resulted
in a novel structural feature in final copper(II) complex 3–the
seven-membered chelate ring. As a part of preliminary biological
studies, the compounds have been tested for antiradical activity.
Introduction
Significant advances in understanding the structural and chem-
ical properties of copper proteins have been achieved through
the comparison of synthetic models with naturally occurring
molecules.1 In particular, copper(II) complexes with Schiff bases
of N-salicylideneaminoalkanoate type represent an important
class of chelates which may serve as structural and/or functional
models for some copper-containing enzymes such as Cu,Zn-
superoxide dismutase (Cu,Zn-SOD).2 The crystal structure of
Cu,Zn-SOD reveals that this protein has a binuclear Cu/Zn
centre and square-pyramidal geometry around the copper(II)
atom,3 which is proposed as being assumed to be responsible
for the enzyme activity.4 The group of N-salicylideneamino
acid, produced by the condensation reaction of salicylaldehyde
with the corresponding amino acid, acts as a tridentate moiety
coordinating the copper(II) ion through phenolato oxygen, imine
nitrogen, and carboxylate oxygen.5 The common feature of N-
salicylidene-aminoacidato Cu(II) complexes [Cu(L)(H2O)2] (L =
Schiff base ligand) is the square-pyramidal geometry with the
chromophore Cu{O,N,O¢} completed by water ligand in the
basal plane of the pyramid and the fifth water ligand being
weakly bound apically.6 A special focus in the past decades was
directed towards screening their ability to scavenge the superoxide
radical (known as antiradical or SOD-mimic activity).2,6a,7 Most
modelling efforts at mimicking the structure and function of the
native enzyme were carried out with copper(II) N-salicylidene-
aminoacidates containing predominantly a-amino acids as parts
of Schiff base ligands.6–8 Studies on copper(II) complexes with N-
Scheme
1 Schiff base ligands employed for the synthesis of
N-salicylidene-aminoacidato copper(II) complexes. The numbers of the
corresponding complexes [Cu(L)(H2O)2]·xH2O are given in brackets.
Results and discussion
The general route towards the synthesis of copper(II) N-
salicylidene-aminoacidato complexes includes the reaction of the
corresponding amino acid with salicylaldehyde and copper(II) salt.
In the literature, two possible procedures have been reported: (i)
the one-pot reaction of all three components in ethanol/aqueous
conditions at a temperature of 60 ◦C resulting in the final
complex,10 and (ii) an in situ formation of the ligand at room
temperature, followed by subsequent complexation with copper(II)
aDepartment of Chemical Theory of Drugs, Faculty of Pharmacy, Comenius
University, Kalincˇiakova 8, 832-32, Bratislava, Slovakia. E-mail: puterova@
fpharm.uniba.sk; Fax: +4212-50117357; Tel: +4212-50117323
bDepartment of Physical Chemistry, Faculty of Food and Chemical Tech-
nology, Slovak University of Technology, Radlinske´ho 9, 812-37, Bratislava,
Slovakia
† CCDC reference numbers 784967–784969. For crystallographic data in
CIF or other electronic format see DOI: 10.1039/c0dt00901f
1484 | Dalton Trans., 2011, 40, 1484–1490
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salt,11 both usually performed without the isolation of the
appropriate ligand. By choosing a set of ligands containing a-
amino-isobutyric acid (H2SAIB), b-amino-isobutyric acid (DL-
H2SBAIB) and g-aminobutyric acid (H2SGABA) (Scheme 1), we
have successfully incorporated five-, six- and the unusual seven-
membered ring into the final copper(II) complexes 1–3.
The syntheses of copper(II) N-salicylidene-a-aminoisobutyrato
copper(II) complex [Cu(SAIB)(H2O)2] (1) and N-salicylidene-
b-aminoisobutyrato copper(II) complex monohydrate [Cu(DL-
SBAIB)(H2O)2]·H2O (2) were carried out at 50 ◦C, in ac-
cordance with.11 In the case of compound 3, N-salicylidene-
g-aminobutyrato copper(II) comple◦x [Cu(SGABA)(H2O)2], the
temperature must be kept below 40 C to prevent the possibility
of dehydration of g-aminobutyric acid towards pyrrolidin-2-one.
Table 2 Crystallographic data and structure refinement details
1
2
3
Formula
Formula weight
T/K
Wavelength l/A
Crystal system
Space group
C11H15CuNO5 C11H15CuNO6 C11H13CuNO4
304.78
293 (2)
320.78
293 (2)
286.76
293 (2)
˚
0.71073
Monoclinic
P21/n
0.71073
Monoclinic
P21/c
0.71073
Monoclinic
P21/n
Unit cell dimensions
˚
a/A
17.3438 (12)
6.9318 (3)
21.7275 (14)
93.486 (5)
2607.3 (3)
8
6.1624 (2)
25.7141 (10)
8.8937 (4)
109.076 (4)
1331.91 (9)
4
8.0368 (3)
5.4782 (2)
25.5765 (9)
91.251 (3)
1125.79 (7)
4
˚
b/A
˚
c/A
b (◦)
3
˚
Volume/A
Z
Dc/g cm-3
m/mm-1
F(000)
1.553
1.600
1.692
1.687
1256
1.661
660
1.941
588
Infrared and electronic spectra
Reflections collected
38736
15521
20145
Independent reflections 10433
26634
0.0485
1.070
0.0453
0.0572
0.1239
2279
0.0813
1.060
0.0472
0.0667
0.1215
For the complexes [Cu(SAIB)(H2O)2] (1), [Cu(DL-
SBAIB)(H2O)2]·H2O (2) and [Cu(SGABA)(H2O)2] (3) in the
IR spectra, the absorption band around 3445 cm-1 confirms the
presence of water molecules. The C N stretching frequencies
are observed within the region 1627–1635 cm-1. A band of
asymmetric vibrations of the coordinated carboxylate group
[nas(COO-)] is observed in the region 1540 cm-1 and a band
within the region 1340–1350 cm-1 is assigned to symmetric
vibration of the coordinated carboxylate group [ns(COO-)]. The
difference between [nas(COO-)] and [ns(COO-)] in frequencies
indicates (Dn ~ 200 cm-1) the monodentate coordination of the
carboxylate group. The band around 1200 cm-1 can be assigned
to C–O vibrations of the phenolic group in complexes.5b,9b,11,12
Ligand deprotonation can be seen from the disappearance
of the stretching vibrations in the region 2500–3300 cm-1 for
the carboxylic OH group and in the region 3200–3500 cm-1
for the phenolic OH group, respectively. The electron spectra
1–3 in DMSO (c = 4 ¥ 10-3 mol dm-3) display ligand-to-metal
charge-transfer (CT) transitions at around 350 nm. The d–d
transitions occur in the range 658–682 nm and correspond to the
square-pyramidal arrangement of {CuNO3} chromophore.5b,11,13
The electronic spectral data (DMSO), as well as the characteristic
solid-state IR absorption bands (KBr), are given in Table 1. All
these observations are in agreement with the solid-state structure
determined by X-ray crystallography.
a
Rint
GOF
0.604
b
R1
R1
0.0272
0.0481
0.0500
c
d
wR2
a TWIN (HKLF5) b R [F2 > 2s(F2)] c R (F2) d wR (F2).
◦
˚
Table 3 Selected bond lengths (A) and angles ( )
1
2
3
˚
Bond lengths (A)
O1–Cu1
1.9032(13)
1.9028(14)
1.9507(13)
1.9519(14)
—
1.903(2)
—
1.940(2)
—
—
1.985(2)
—
2.281(2)
—
1.948(3)
—
1.904(3)
—
1.975(2)
—
1.961(3)
—
—
2.365(3)
—
1.960(3)
—
O21–Cu21
O2–Cu1
O22–Cu21
O3–Cu1
O4–Cu1
O24–Cu21
O5–Cu1
O25–Cu21
N1–Cu1
N21–Cu21
1.9661(13)
1.9608(14)
2.3735(15)
2.3097(16)
1.9368(16)
1.9300(16)
Bond angles (◦)
O1–Cu1–N1
O21–Cu21–N21
O1–Cu1–O2
O21–Cu21–O22
N1–Cu1–O2
N21–Cu21–O22
N1–Cu1–O3
N1–Cu1–O4
N21–Cu21–O24
N1–Cu1–O5
N21–Cu21–O25
94.72(6)
95.31(7)
174.80(6)
169.08(6)
82.79(6)
83.29(7)
—
163.17(7)
163.69(7)
104.88(6)
100.34(7)
93.24(10)
—
170.59(9)
—
94.59(10)
—
—
91.49(15)
—
168.92(13)
—
93.54(13)
—
173.88(16)
—
Structure of complexes
168.48(13)
—
89.72(17)
—
The crystallographic data of complexes 1–3 are described in detail
in this section. A suitable single crystal of 1 was obtained from
water/methanol solution (1 : 1), of 2 from water/ethanol solution
96.65(13)
—
(1 : 1) and of 3 from water/i-propylalcohol solution (1 : 1). Selected
crystallographic data and refinement details are shown in Table
2. Selected bond lengths and bond angles are given in Table 3.
Characteristic values for hydrogen bonds are compared in Table 4.
Table 1 Selected IR and electronic absorption data for 1–3
Absorption bands
Infrared bands
c
l/nm a; log eb
n/cm-1
Complex CT
d–d
n(C N)
n(COO-
)
as
[Cu(SAIB)(H2O)2], 1
1
2
3
353; 2.39
352; 2.48
352; 2.60
658; 1.65
667; 1.28
682; 1.48
1636
1627
1635
1541
1540
1540
Compound [Cu(SAIB)(H2O)2] (1) crystallises in the monoclinic
space group P21/n. The crystal studied was non-merohedrally
twinned with a ratio of twin components 0.52(1) : 0.48(1),
the fractional contribution of the minor twin component being
a DMSO solution (c = 4 ¥ 10-3 mol dm-3). b e [m2 mol-1]. c KBr pellets.
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◦
˚
Table 4 Overview of hydrogen bond lengths (A) and angles ( )
1, [Cu(SAIB)(H2O)2]
D–H ◊ ◊ ◊ A
d(D–H)
d(H ◊ ◊ ◊ A)
d(D ◊ ◊ ◊ A)
<(DHA)
O4–H4a ◊ ◊ ◊ O21a
O4–H4b ◊ ◊ ◊ O22b
O5–H5a ◊ ◊ ◊ O3c
0.944(4)
0.955(4)
0.827(5)
0.826(5)
0.834(5)
0.830(5)
0.838(5)
0.835(5)
1.836(10)
1.764(4)
2.135(5)
2.080(6)
1.879(6)
1.872(6)
1.914(6)
2.060(7)
2.7241(19)
2.6864(19)
2.805(2)
155.7(18)
161.3(11)
138.1(6)
155.7(10)
175(2)
162.1(14)
174.7(8)
171.0(14)
O5–H5a ◊ ◊ ◊ O3d
2.853(2)
O24–H24a ◊ ◊ ◊ O2b
O24–H24b ◊ ◊ ◊ O1a
O25–H25a ◊ ◊ ◊ O23d
O25–H25b ◊ ◊ ◊ O5a
2.7109(19)
2.6741(19)
2.750(2)
2.888(2)
2, [Cu(DL-SBAIB)(H2O)2]·H2O
D–H ◊ ◊ ◊ A
d(D–H)
d(H ◊ ◊ ◊ A)
d(D ◊ ◊ ◊ A)
<(DHA)
O4–H4a ◊ ◊ ◊ O6e
O4–H4b ◊ ◊ ◊ O6
O5–H5a ◊ ◊ ◊ O2f
O5–H5b ◊ ◊ ◊ O3g
O6–H6a ◊ ◊ ◊ O1h
O6–H6b ◊ ◊ ◊ O3i
0.840(5)
0.840(5)
0.839(5)
0.839(5)
0.840(5)
0.838(5)
2.06(4)
2.04(4)
2.31(5)
2.17(5)
2.03(4)
2.19(4)
2.787(3)
2.759(3)
2.938(4)
2.828(4)
2.807(3)
2.841(3)
167(4)
165(5)
178(7)
158(6)
171(4)
160(5)
3, [Cu(SGABA)(H2O)2]
D–H ◊ ◊ ◊ A
d(D–H)
d(H ◊ ◊ ◊ A)
d(D ◊ ◊ ◊ A)
<(DHA)
O5–Hwa ◊ ◊ ◊ O3j
O5–Hwb ◊ ◊ ◊ O1k
0.840(5)
0.838(6)
2.18(6)
2.39(6)
3.001(4)
2.989(4)
171(5)
171(8)
Symmetry transformations used to generate equivalent atoms. For 1:a -x
+ 1, -y + 1, -z; b -x + 1, -y + 2, -z; c -x + 2, -y + 2, -z; d x, y - 1, z. For
2:e -x, -y, -z + 1; f -x + 1, -y, -z + 2; g x + 1, y, z; h -x + 1, -y, -z + 1; i x,
y, z - 1. For 3:j -x + 5/2, y - 1/2, -z + 1/2; k x, y - 1, z.
Fig. 1 (a) View of the compound 1 with the atom numbering scheme.
Displacement ellipsoids for non-hydrogen atoms are drawn at 30%
probability level. (b) Crystal packing for 1 with hydrogen bonds. Symmetry
code used: (i) -x + 1, -y + 1, -z; (ii) -x + 1, -y + 2, -z; (iii) -x + 2, -y +
2, -z; (iv) x, y - 1, z.
˚
0.3856(3) A. Crystal structure is formed by single molecules
bonded via strong hydrogen bonds (Table 4). The coordination
polyhedron is a tetragonal pyramid with O1, O2, O4 and N1
donor atoms in the equatorial plane and O5 in the apical position,
the Schiff base ligand confirmed the existence of the complex as a
dimer with two [Cu(L)] coordination units.9 The crystal structure
of complex 2, with b-amino-isobutyric acid which is the analogue
of b-alanine, is formed by single molecules which via medium
strong hydrogen bonds first form (Table 4) dimers, and later a
one-dimensional chain in a direction. Atoms C9 and C10 of the
six-membered ring are disordered in the ratio 1 : 1. There are four
molecules in the unit cell (Fig. 2b). The coordination polyhedron is
a tetragonal pyramid with O1, O2, O4 and N1 donor atoms in the
equatorial plane and O5 in the apical position, t = 0.035214 (Fig.
2a). Distances in the equatorial plane are in the range 1.903(2)–
1
t = 0.1939 14 (O21, O22, O24, N21 and O25 for the second one,
2
t = 0.0898,14 Fig. 1a).
There are eight molecules in the unit cell, two of which are
independent (Fig. 1b). Distances in the equatorial plane are in
˚
the range of 1.9032–1.9661 A, in the apical position O5–Cu1
˚
˚
2.3735(15) A and O25–Cu21 2.3097(16) A (Table 3). The copper
atom is shifted from the plane defined by four equatorial donor
˚
atoms towards an apical oxygen atom O5 by 0.173(1) A and to
˚
O25 0.214(1) A. The crystal structure of [Cu(SAIB)(H2O)2] (1) was
˚
˚
1.985(2) A, in the apical position Cu1-O5 2.281(5) A (Table 3). The
originally described by Fujimaki et al. in 1971 with an R-factor
of 10%15 Here we report redetermination of the structure with an
R-factor of 2.72% using up-to-date instrumentation, showing that
the compound can exist as a twinned molecule.
copper atom is shifted from the plane defined by four equatorial
˚
donor atoms towards the apical oxygen atom O5 by 0.134(2) A.
[Cu(SGABA)(H2O)], 3
[Cu(DL-SBAIB)(H2O)2]·H2O, 2
Aliphatic chain elongation by the additional methylene group in
the structure of g-aminobutyric acid changes the manner of the
coordination in the final complex [Cu(SGABA)(H2O)] (3). Utilis-
ing the ligand N-salicylidene-g-aminobutyric acid (H2SGABA,
Scheme 1), an unusual seven-membered metallocycle ring is
formed upon cooordination with copper(II) ion (Fig. 3a). Al-
though a significant amount of research interest is focused on
N-salicylidene-aminoacidato copper(II) complexes, there is not,
as yet, any report on the structure of a complex containing more
Compound 2 crystallises in the monoclinic space group P21/c.
The coordination polyhedron in [Cu(DL-SBAIB)(H2O)2]·H2O (2)
is very similar to that found in 1, except that the DL-SBAIB
dianion forms a six-membered ring and there is an additional water
molecule in the crystal structure which forms further hydrogen
bonds. The ring expansion is due to an additional methylene group
in the DL-SBAIB ligand. Previous observation of the molecular
structure of copper(II) complexes containing b-alanine as part of
1486 | Dalton Trans., 2011, 40, 1484–1490
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Fig. 2 (a) Solid state structure of 2 with atom labels and displacement
ellipsoids for non-hydrogen atoms at 30% probability level. (b) Crystal
packing for 2 with hydrogen atoms. Symmetry code used: (i) -x, -y, -z +
1; (ii) -x + 1, -y, -z + 2, -z; (iii) x + 1, y, z; (iv) -x + 1, -y, -z + 1; (v) x,
y, z - 1.
Fig. 3 (a) Structure of the complex 3 with the atom numbering scheme.
The non-hydrogen atoms are shown as 10% thermal ellipsoids. Symmetry
code used: (i) 3/2 - x, -1/2 + y, 1/2 - z. (b) Crystal packing for 3 with
hydrogen bonds. For clarity, only one part is shown. Symmetry code used:
(i) x, y - 1, z; (ii) -x + 5/2, y - 1/2, -z + 1/2.
than a six-membered chelate ring in this category of compounds.
In fact, relatively few metallocycle rings contain more than six
atoms. Our search in the literature disclosed approximately thirty
copper(II) complexes coordinated via a seven-membered ring, but
only two in which g-aminobutyric acid is inbuilt as a part of
copper(II) complex.16,17 Compound 3 crystallises in the monoclinic
space group P21/n. The crystal structure is formed by dimers in
which carboxyl oxygen O3 is bidentally bonded to one copper(II)
ion in the equatorial plane and axially to the adjacent molecule
(Fig. 3a).
Non-hydrogen atoms C1–C6 and C21–C26 are disordered with
occupation factor 0.495 and 0.505. as well as atoms C8–C10 and
C28–C30 withoccupationfactor 0.508and 0.492. Hydrogenbonds
form a 2D network in the ab plane (Table 4). There are four
molecules in the unit cell (Fig. 3b). The coordination polyhedron
is tetragonal pyramid with O1, O2, O4 and N1 donor atoms in
the equatorial plane and O5 in the apical position, t = 0.074.14
Distances in the equatorial plane are in the range: 1.904(3)–
be described as square pyramid with an insignificant deformation
degree as indicated by the angular structural parameter t14 (for 1:
1
2
t = 0.1939 and t = 0.0898; for 2: t = 0.0352; for 3: t = 0.074).
Preliminary investigations on the antiradical activity
Reactive Oxygen Species (ROS) are physiological by-products of
normal aerobic metabolism18 that can inflict direct injuries on cells
through oxidative stress.19 The most common ROS also includes
∑
superoxide radical anions (- O2) produced by the mitochondrial
electron transport chain20 and by other enzymatic systems such
as NADPH oxidase21 and xanthine oxidase.22 The radical has
been implicated in a broad range of disease states including
inflammatory diseases, diabetes and many others.23 Human su-
peroxide dismutase (Cu,Zn-SOD, EC 1.15.1.1) is from the family
of enzymes that very efficiently catalyze the dismutation of the
superoxide radical anion.24 Typically, proteins make poor drugs
and Cu,Zn-SOD is no exception. Technical reasons (molecular
weight of the enzyme, high price of the treatment) have limited
the use of Cu,Zn-SOD as a drug.7b,25 These problems may be
overcome by the design of Cu,Zn-SOD mimetics. Several N-
salicylidene-aminoacidato copper(II) complexes are of interest as
simple structural and functional models for a Cu,Zn-superoxide
dismutase. Previous experimental findings suggest that the above
mentioned complexes exhibit anti-inflammatory, antipyretic, ra-
dioprotective activities, and have effect on the alloxan induced
diabetes, which were investigated by in vivo experiments.2,6,26 Their
biological action was proposed to arise from their antiradical
˚
˚
1.975(2) A, in the apical position Cu1–O5 2.365(3) A (Table 3). The
copper atom is shifted from the plane defined by four equatorial
˚
donor atoms towards an apical oxygen atom O5 by 0.134 A.
A helpful starting point for comparison of the crystal structures
under study is the strongest bond Cu–O1 which is equal to the
˚
value of 1.903 A in all compounds (Table 3). On the other hand,
the interatomic distance Cu–N1 reflects most evidently the stress
in the five-, six- and seven-membered metallocycle ring. With the
increasing number of atoms, the interatomic distances increase
˚
˚
˚
˚
(1.9368(16) A and 1.930(16) A in 1, 1.948(3) A in 2, 1.960 A(3) in
3, Table 3). The coordination geometry of Cu(II) ion in all cases can
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activity (SOD-mimic activity) measured in vitro.27 Since complexes
1–3 belong to a class of copper(II) N-salicylidene-aminoacidates
and exhibit the square-pyramidal arrangement that make them
particularly suitable for investigations concerning their structure–
activity relationship.
complexes, but constitute a straightforward correlation between
the solid-state structure and catalytic activity of complexes.
Conclusions
Before going into a detailed biological study, it was necessary
to obtain an estimate of the efficiency of the complexes to
We report the preparation of copper(II) complexes of Schiff
base ligands, N-salicylidene-amino acids, of general structure
[Cu(L)(H2O)2]·xH2O {L = SAIB, x = 0 (1); L = SBAIB, x = 1
(2); L = SGABA, x = 0 (3)}. The compounds are both structural
and functional models for Cu,Zn-superoxide dismutase. Our main
interest concerned the structural characterisation of complexes
utilising solid-state structure X-ray analysis. The principal ob-
servation emerging from the previous studies was the crystal
structure of complex 3 containing a seven-membered metallocycle
ring. In addition, as shown by the preliminary measurements
on the antiradical activity, the increase in the size of the side
chelate ring has a valid influence on the SOD-mimicking effect
of complexes. Further experimental work is required for better
understanding of the relationship between the structure of N-
salicylidene-aminoacidato copper(II) complexes and superoxide
anion radical scavenging action. Work to that end is in progress.
∑
scavenge the superoxide anion radical (- O2). Fort this purpose,
the screening of the antiradical activity of complexes 1–3 was
evaluated in vitro. The chemical method is based on the com-
peting reaction of the tested compounds and tetrazolium dye–
INT [2-(4-nitrophenyl)-3-(4-iodophenyl)-5-phenyl-3H-tetrazol-2-
ium chloride], with a saturated potassium superoxide solution in
DMSO (as a source of superoxide anion radicals). The reaction
product consists of a blue formazane product in accordance with
Scheme 2. The decrease in concentration of formazane is propor-
tional to the antiradical activity of the tested compounds.2a,7,9b,26
Antiradical activity was calculated as the percentage of inhibition
(% INH) of INT-formazane formation (expressed as the mean
SD of three parallel determinations, shown in Chart 1). Cystamine,
which exhibits the ability to trap the free radicals, was used as a
standard.7,26
Experimental
All reagents werecommercially availableand wereused as received.
Reagents used for the physical measurements were of spectroscopic
grade. All syntheses were carried out at temperatures not exceeding
50 ◦C in air.
Scheme 2 Reduction of INT to a blue INT-formazane.
Ligands
The Schiff-condensation of salicylaldehyde with a corresponding
amino acid at a ratio 1 : 1 in water/alcohol solution for 3 h at room
temperature resulted in corresponding tridentate ligands H2SAIB,
H2SBAIB, H2SGABA (Scheme 1).
[Cu(SAIB) (H2O)2] (1)
To a water/methanol solution (1 : 1, 60 mL) of H2SAIB (10 mmol),
an aqueous solution of copper acetate dihydrate (10 mmol in
60 mL) was added and stirred for 1 h at 50 ◦C accompanied
by a colour change to dark green. The resultant reaction mixture
was filtered off and the filtrate was left to crystallise spontaneously
for several days at room temperature. Dark green needle-shaped
crystals of 1 of good quality were formed, and these were separated
by filtration and washed with cold methanol. Yield 1.82 g (63.6%).
Anal. calcd. for C11H15CuNO5 (304.78): C 43.35, H 4.96, N 4.60,
Cu 20.85. Found C 45.69, H 4.52, N 4.88, Cu 20.19%. IR(KBr)
n = 3446 (OH, coord. water), 3290, 2984, 1636 (C N), 1541
(COO-as.), 1340 (COO-sym), 1206, 755, 549, 442 cm-1. UV/Vis
(DMSO, c = 4 ¥ 10-3 mol dm-3) lmax = 658 (loge = 1.65), 353
(loge = 2.39), 264 nm.
Chart 1 Antiradical activity of the N-salicylidene-aminoacidato cop-
per(II) complexes under study: 1–3.
The % INH value is shown graphically for clarity (Chart
1). The antiradical activity follows the order: 3 > 2 > 1 >
cystamine, and is found to increase with increasing ring-size of the
ligand backbone caused by the superimposed methylene moiety.
It is assumed that the square-pyramidal geometry of the copper
complex is ideal for possible SOD-mimic activity.2,6–8,9b For the
correct correlation between the structure and catalytic activity of
complexes, their solid-state structure needs to be retained in the
solution. The UV-Vis spectra of compounds 1–3 measured in the
DMSO proved that complexes keep their structure in solution. A
significant contribution to superoxide radical scavenging activity
is attributed to the size of the metallocycle ring, e.g. five-, six-
or seven-membered ring. These results have not been optimised
for a broader range of N-salicylidene-aminoacidato copper(II)
[Cu(SBAIB) (H2O)2]·H2O (2)
To a water/ethanol solution (1 : 1, 60 mL) of H2SBAIB (10 mmol),
an aqueous solution of copper acetate dihydrate (10 mmol in
60 mL) was added and stirred for 1 h at 50 ◦C accompanied with
a colour change to dark green. The resultant reaction mixture was
filtered off and the filtrate was left to crystallise spontaneously for
1488 | Dalton Trans., 2011, 40, 1484–1490
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several days at room temperature. Dark green needle crystals of 2
of good quality were formed, and these were separated by filtration
and washed with cold ethanol. Yield 1.90 g (66.4%). Anal. calcd.
for C11H15CuNO6 (320.78): C 41.19, H 4.71, N 4.37, Cu 19.81.
Found C 40.90, H 4.50, N 4.76, Cu 20.11%. IR(KBr) n = 3444
(OH, coord. water), 3042, 2959, 1627 (C N), 1540 (COO-as.),
1350 (COO-sym), 1205, 769, 606, 470, 410 cm-1. UV/Vis (DMSO,
c = 4 ¥ 10-3 mol dm-3) lmax = 667 (loge = 1.28), 352 (loge = 2.48) nm.
of the complexes. The powdered sample (0.1 g) was dissolved in
10 mL of distilled water in a 250 mL glass beaker. Afterwards,
3 mL of conc. H2SO4 and distilled water up to 100 mL was added
before electrolysis. A Pt-electrode was employed as a cathode for
copper removal for 15–30 min (coating on the cathode indicate the
progress of the electrolysis) at 2 V and 2–3 A. The copper content
was calculated from the mass difference on the electrode before
and after electrolysis.32
Measurements of antiradical activity
[Cu(SGABA) (H2O)2] (3)
The antiradical activity of the copper(II) complexes was deter-
mined following the method used by Valentova´ et al.7,26 The
reaction solution consisted of 0.5 mL of 4 ¥ 10-3 mol dm-3 INT in
borate buffer (pH = 7.1) and 150 mL of a 4 ¥ 10-3 mol dm-3 solution
of the tested compound in 10% DMSO. The addition of 150 mL
of a saturated potassium superoxide solution in DMSO to the
reaction system started the radical reaction. The blue-formazane
product was analysed spectroscopically (absorbance at 560 nm)
on a BioTekSynergy HT instrument.
To a water/i-propylalcohol solution (1 : 1, 60 mL) of H2SGABA
(10 mmol), an aqueous solution of copper acetate dihydrate
(10 mmol in 60 mL) was added and stirred for 1 h at room
temperature accompanied with a colour change to dark green.
The resultant reaction mixture was filtered off and the filtrate
was left to crystallise spontaneously for several days at room
temperature. Dark green needle-shaped crystals of 3 of good
quality were formed, and these were separated by filtration and
washed with cold i-propylalcohol. Yield 1.85 g (64.5%). Anal.
calcd. for C11H13CuNO4 (286.76): C 46.07, H 4.57, N 4.88, Cu
22.16. Found C 46.37, H 4.45, N 4.70, Cu 22.54%. IR(KBr)
n = 3442 (OH, coord. water), 3030, 2917, 1635 (C N), 1540
(COO-as.), 1352 (COO-sym), 1210, 752, 557, 459, 415 cm-1. UV/Vis
(DMSO, c = 4 ¥ 10-3 mol dm-3) lmax = 682 (loge = 1.48), 352 (loge =
2.60), 282 nm.
Acknowledgements
Grant agencies are acknowledged for their financial sup-
port: VEGA Grant Agency of Slovak Ministry of Education
1/0266/10, 1/0229/10, 1/0817/10; Research and Development
Agency (Slovakia) APVV-0093-07. ZP thanks the Grant project
of the Pharmaceutical Faculty FaF UK-16/2010. We thank
the Structural Funds, Interreg IIIA, for financial support in
purchasing the diffractometer.
Structure determination
The X-ray structural determinations of the compounds 1–3
were carried out on a Gemini R CCD difractometer (Oxford
Diffraction XcaliburTM). The diffraction data were collected at
293 K by the standard method (graphite monochromatized Mo-
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