Synthesis, spectral properties, crystal structures and antimicrobial effects of copper(II) pyridinecarboxylate adducts with chelating ligands

Article abstract of DOI:10.1016/S0277-5387(00)00585-4

The reaction of an ethanolic solution of copper(II) pyridinecarboxylates CuX₂·nH₂O (where X is nicotinate (nic) (n = 0) or isonicotinate (isonic) (n = 4)) with ethylenediamine (en) in a molar ratio of 1:2 lead to the isolation of solid tetragonally distorted octahedral complexes of the type [Cu(en)₂(H₂O)₂] X₂·nH₂O (n = 1 for nic; n = 0 for isonic). The analogous reaction of CuX₂·nH₂O with diethylenetriamine (dien) in a molar ratio of 1:1 leads to the formation of square-pyramidal pentacoordinated complexes of the type [CuX(dien)(H₂O)]X. On the other hand, the reaction of equimolar quantities of copper(II) nitrate and dien with nicotinate anions (equimolar quantities of pyridinecarboxylic acid and NaOH) in ethanolic solutions gives a solid monomeric complex [Cu(nic)(NO₃)dien)(H₂0)]· H₂O in which the coordination polyhedron around the Cu(II) atom is a (4 + 1 + 1) distorted tetragonal bipyramid. Based on the molecular structure the electronic and IR spectra are discussed. Moreover, the results of the quantitative determination of antimicrobial activity of the isonic complexes [Cu(isonic)₂(H₂O)₄], [Cu(en)₂(H₂O)₂] (isonic)₂, [Cu(isonic)(dien)(H₂O)](isonic), as well as isonicotinic acid, ethylenediamine and diethylenetriamine alone are discussed.

Full text of DOI:10.1016/S0277-5387(00)00585-4

www.elsevier.nl/locate/poly
Polyhedron 19 (2000) 2689–2695
Synthesis, spectral properties, crystal structures and antimicrobial
effects of copper(II) pyridinecarboxylate adducts with chelating
ligands
a,
a
Martina Palicova´ *, Peter Segl’a a, Dusˇan Miklosˇ a, Miroslava Kopcova´ ,
Milan Meln´ık a, Barbora Dudova´ , Daniela Hudecova´ , Tadeusz Glowiak c
b
b
a Department of Inorganic Chemistry, Slo6ak Technical Uni6ersity, 812 37 Bratisla6a, Slo6ak Republic
b Department of Biochemistry and Microbiology, Slo6ak Technical Uni6ersity, 812 37 Bratisla6a, Slo6ak Republic
c Institute of Chemistry, Uni6ersity of Wroclaw, F. Joliot-Curie 14, 50 383 Wroclaw, Poland
Received 27 July 2000; accepted 8 September 2000
Abstract
The reaction of an ethanolic solution of copper(II) pyridinecarboxylates CuX2·nH2O (where X is nicotinate (nic) (n=0) or
isonicotinate (isonic) (n=4)) with ethylenediamine (en) in a molar ratio of 1:2 lead to the isolation of solid tetragonally distorted
octahedral complexes of the type [Cu(en)2(H2O)2]X2·nH2O (n=1 for nic; n=0 for isonic). The analogous reaction of CuX2·nH2O
with diethylenetriamine (dien) in a molar ratio of 1:1 leads to the formation of square-pyramidal pentacoordinated complexes of
the type [CuX(dien)(H2O)]X. On the other hand, the reaction of equimolar quantities of copper(II) nitrate and dien with
nicotinate anions (equimolar quantities of pyridinecarboxylic acid and NaOH) in ethanolic solutions gives a solid monomeric
complex [Cu(nic)(NO3)dien)(H2O)]·H2O in which the coordination polyhedron around the Cu(II) atom is a (4+1+1) distorted
tetragonal bipyramid. Based on the molecular structure the electronic and IR spectra are discussed. Moreover, the results of the
quantitative determination of antimicrobial activity of the isonic complexes [Cu(isonic)2(H2O)4], [Cu(en)2(H2O)2](isonic)2,
[Cu(isonic)(dien)(H2O)](isonic), as well as isonicotinic acid, ethylenediamine and diethylenetriamine alone are discussed. © 2000
Elsevier Science B.V. All rights reserved.
Keywords: Chelating ligands; Crystal structures; Copper(II) complexes; Pyridinecarboxylate complexes; Antimicrobial activity
1. Introduction
tion of activity of most drugs when their ligating
potential is utilized.
Synthesis, spectral and thermal properties of various
complexes CuX2·nH2O (where X is pyridine-3-carboxy-
late or nicotinate (nic) and pyridine-4-carboxylate or
isonicotinate (isonic); n=0–4) have been reported [3,4].
Only a few structures of [CuX2(H2O)4] [5] and their
adducts with chelating ligands 1,10-phenanthroline and
2,2%-bipyridine have been reported [6,7]. Different coor-
dination modes of the pyridinecarboxylate (coordinated
not only through the carboxylate group, but also
through the nitrogen atom of the pyridine ring) lead to
formation of mononuclear [5] or polynuclear [6,7] struc-
tures. Recently, we have studied [8] the adducts of
Cu(II) isonicotinate with ethylenediamine (en) and di-
ethylenetriamine (dien), prepared [Cu(en)2(H2O)2]-
(isonic)2 and [Cu(isonic)(dien)(H2O)1.5]·0.5SO4·2.5H2O
and solved their structures by X-ray analysis.
Carboxylatocopper(II) complexes are interesting
from both a chemical and biological point of view.
Different possible coordinations of the carboxyl group
to the central atom lead to the existence of compounds
with distinct crystal structures. Pyridinecarboxylic acid
and its derivatives possessing very interesting pharma-
ceutical properties constitute an important group of
anthelmintics and vitamins. It is known that some
drugs act via chelation [1] or via inhibition of metal-
loenzymes [2], but little is known about the modifica-
* Corresponding author. Tel.: +421-7-593-25611; fax: +421-7-
524-93198.
E-mail address: palicova@chtf.stuba.sk (M. Palicova´).
0277-5387/00/$ - see front matter © 2000 Elsevier Science B.V. All rights reserved.
PII: S0277-5387(00)00585-4

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M. Palico6a´ et al. / Polyhedron 19 (2000) 2689–2695
Table 1
In the present paper, we report as a part of our
Analytical data a for the complexes
investigation of metal ion–drug interactions the com-
plexation of isonic and nic in the presence of en and
dien. The stereochemistry and the mode of ligand coor-
dination in solid copper(II) complexes have been deter-
mined by IR and electronic measurements. The crystal
and molecular structure of one of the products, [Cu-
(nic)(NO3)(dien)(H2O)]·H2O, has also been solved.
Moreover, for some of the isonicotinate complexes
antimicrobial activity has been determined.
Complex
Calculated (%)
(Found) (%)
Cu
C
H
N
[Cu(nic)2
20.7
46.8
2.6
9.1
(20.5)
(46.5) (2.6)
(8.9)
[Cu(en)2(H2O)2](nic)2·H2O
[Cu(nic)(dien)(H2O)]nic
13.2
(13.4)
39.9 6.7
(40.2) (6.3)
43.0 5.6
(42.7) (5.8)
31.1 5.7
(31.4) (5.6)
44.8 4.9
(45.2) (5.0)
17.4
(17.5)
14.2
(13.9)
15.7
(16.0)
2. Experimental
[Cu(nic)(NO3)(dien)(H2O]·H2O 16.4
(16.1)
18.1
(18.1)
2.1. Chemical reagents
[Cu(dien)(isonic)(H2O)]isonic
14.8
(14.6)
16.3
(16.5)
All the chemicals used were of reagent grade and
without further purification. All organic reagents were
purchased from Aldrich; their purity was checked by IR
spectra.
a Microanalysis results obtained with maximum deviations: Cu,
90.3; C, 90.5; H, 90.4; N, 90.3%.
2.2. Analysis and physical measurements
Copper was determined by electrolysis after mineral-
ization of the complexes; carbon, hydrogen, nitrogen
and sulfur were determined by microanalytical methods
(Carlo Erba Instruments EA 1180). Besides the elemen-
tal analysis, the water content in the hydrates was
determined from thermogravimetrical curves. The
yields of products were related to the metal contents in
the reacting mixtures. Analytical data for solid com-
plexes are given in Table 1.
Table 2
Crystal
(nic)(NO3]dien)(H2O]·H2O
data
and
structure
refinement
for
[Cu-
Empirical formula
Formula weight
Crystal size (mm)
Crystal system
Space group
C10H21CuN5O7
386.86
0.15×0.15×0.15
Triclinic
(
P1
2
Z
Electronic spectra (9000–50 000 cm−1) of the pow-
dered samples in nujol mulls were recorded at room
temperature (r.t.) on a Specord 200. IR spectra in the
region of 100–4000 cm−1 were recorded on a Philips
Analytical PU 9800 FTIR spectrometer and on a
Magna 750 spectrometer at r.t. Spectra of solid samples
were obtained in nujol mulls and KBr pellets (1 wt%).
Unit cell dimensions
,
a (A)
7.303(2)
8.147(2)
13.164(3)
96.00(3)
91.53(3)
94.18(3)
776.4(3)
1.655
,
b (A)
,
c (A)
h (°)
i (°)
k (°)
3
,
V (A )
Dcalc (Mg m−3
F(000)
)
402
2.3. X-ray structure determination
Linear absorption coefficient (v)
1.451
(mm−1
)
Data collection and cell refinement (see Table 2) for
the complex [Cu(nic)(NO3)(dien)(H2O)]·H2O were car-
ried out using a KUMA KM4 diffractometer and soft-
ware [9]. The diffraction intensities were corrected for
Lorentz-polarization effects. The structure was solved
by Patterson methods using XFPS [10] and subsequent
Fourier difference maps. Anisotropic thermal parame-
ters were refined for all non-hydrogen atoms. All hy-
drogen atoms were found from the difference Fourier
maps and their positional parameters refined. Geomet-
rical analysis was performed using SHELXL-93 [11]. The
structure of the complex was drawn by ORTEP [12] (Fig.
1). Basic crystallographic data are summarized in Table
2.
,
Radiation type (A)
Temperature (K)
Mo Ka, u=0.71073
100(1)
3.79–28.71
−75h59, −105k510,
−175l517
5531
q Range for data collection
Index ranges
No. reflections collected
No. independent reflections
Refinement method
3505 [Rint=0.0304]
Full-matrix least-squares on
F2
Data/restraints/parameters
Goodness-of-fit on F2
Final R indices (I\2|(I))
R indices (all data)
3082/0/293
1.093
R=0.0261, Rw=0.0701
R=0.0313, Rw=0.0717
0.458/−0.487
Largest difference peak and hole
−3
,
(e A
)

M. Palico6a´ et al. / Polyhedron 19 (2000) 2689–2695
2691
rate at r.t. In isolating the crystals, it was necessary to
add a few cm3 of acetone to the concentrated reaction
solution. Well-shaped crystals, suitable for X-ray struc-
ture analysis, were collected after a few hours by filtra-
tion, washed with acetone and finally dried in vacuo
(yield 83%).
2.5. Antimicrobial assays
The antimicrobial activity of the isonic complexes
[Cu(isonic)2(H2O)4],
[Cu(en)2(H2O)2](isonic)2,
[Cu-
(isonic)(dien)(H2O)](isonic), as well as isonicotinic acid,
ethylenediamine and diethylenetriamine alone was eval-
uated by a macrodilution method using G+ Staphylo-
coccus aureus CCM 3953, G− Escherichia coli CCM
3988 and the yeasts Candida parapsilosis (purchased
from the Laboratory of Medical Mycology, Postgradu-
ate Medical Institute, Bratislava) in L-shaped tubes.
The cultures of bacteria and yeasts were incubated
under vigorous shaking [13]. The efficiency of prepared
compounds on filamentous fungi Rhizopus oryzae, Al-
ternaria alternata, Fusarium moniliforme (obtained from
the Collection of Microorganisms of Department of
Biochemistry and Microbiology, Slovak University of
Technology), Botrytis cinerea CCM F-16 and Mi-
crosporum gypseum (received from the Laboratory of
Medical Mycology, Postgraduate Medical Institute,
Bratislava) was tested by macrodilution technique
on solidified broth medium during static culturing
[14].
Chromatographically pure compounds were dis-
solved in dimethylsulfoxide, its final concentration
never exceeded 1.0 vol.% in either control or treated
samples. The concentration of tested compounds used
in all experiments ranged from 1.0 to 10.0 mmol l−1 for
filamentous fungi and from 0.125 to 5.0 mmol l−1 for
yeasts and bacteria.
The antimicrobial activity was characterized by the
IC50 values (concentration of a compound which in
comparison to the control inhibits the growth of mi-
croorganisms to 50%) and MIC values (minimal in-
hibitory concentration of a compound which inhibits
microbial growth by 100%). The IC50 and MIC values
were read from toxicity curves.
Fig. 1. ORTEP plot of [Cu(nic)(NO3)(dien)(H2O)]·H2O also indicating
the hydrogen bonds interconnecting neighbouring molecules (thermal
ellipsoids are shown at the 50% probability level).
2.4. Preparation of the complexes
[Cu(nic)2] was prepared similarly as described by
Kleinstein [4]. Aqueous solution (10 cm3) of the nico-
tinic acid and an equimolar quantity of sodium hydrox-
ide (10 mmol) were added to 30 cm3 of an aqueous
solution of copper(II) sulfate (5 mmol), and the reac-
tion mixture was refluxed for 15 min. The blue precipi-
tate was filtered off in a nearly quantitative yield (95%).
The violet complex [Cu(en)2(H2O)2](nic)2·H2O was
formed in an ethanolic solution (30 cm3) of [Cu(nic)2]
(1.25 mmol) by adding ethylenediamine (in the molar
ratio of 1:2). Similarly, the blue complexes [Cu(-
nic)(dien)(H2O)](nic)
and
[Cu(isonic)(dien)(H2O)]-
(isonic) were formed in an ethanolic solution (30 cm3)
of 1.25 mmol [Cu(nic)2] or [Cu(isonic)2(H2O)4] [8] by
adding diethylenetriamine (in the molar ratio of 1:1),
respectively. All resulting solutions were left to slowly
evaporate at r.t. In isolating the above complexes, it
was necessary to add acetone to the concentrated solu-
tion. Precipitates of the complexes were filtered off,
washed with ethanol and finally dried in vacuo (yields
of the complexes [Cu(en)2(H2O)2](nic)2·H2O, [Cu(-
MIC experiments on subculture dishes were used
to assess the minimal microbicidal concentration
(MMC). Subcultures were prepared separately in Petri
dishes containing competent agar medium and incu-
bated at 30°C for 48 h (bacteria, yeasts) and at 25°C
for 96 h (filamentous fungi). The MMC value was
taken as the lowest concentration which showed no
visible growth of microbial colonies in the subculture
dishes.
nic)(dien)(H2O)](nic)
(isonic) were 66, 72 and 75%, respectively).
and
[Cu(isonic)(dien)(H2O)]-
The blue crystals of [Cu(nic)(NO3)(dien)(H2O)]·H2O
were obtained dissolving copper(II) nitrate (1.25 mmol)
and dien (1.25 mmol) in 20 cm3 of ethanol. The solu-
tion was heated for 1 h at 70°C, then 20 cm3 of an
aqueous solution of the nicotinic acid and an equimolar
quantity of sodium hydroxide (1.25 mmol) were slowly
added. The resulting solution was left to slowly evapo-

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M. Palico6a´ et al. / Polyhedron 19 (2000) 2689–2695
,
3. Results and discussion
A] with the uncoordinated water molecule (O7), (b) via
the two carboxyl oxygen atoms O1, O2 with the water
molecules (O6a, O6c), and (c) via the nitrate oxygen
3.1. Crystal structure description of complex
[Cu(nic)(NO3)(dien)(H2O)]·H2O
,
atom O4 creating a hydrogen bond [2.817(2) A] with
the uncoordinated water molecule (O7a).
In the structure of [Cu(nic)(NO3)(dien)(H2O)]·H2O
(Fig. 1) the coordination polyhedron around the Cu(II)
atom is a (4+1+1) distorted tetragonal bipyramid,
where three of the equatorial positions are occupied by
three nitrogen atoms of the diethylenetriamine ligand,
the Cu–N distances ranging from 2.017(2) to 2.035(2)
3.2. Spectroscopic data
All the typical features of IR spectra are clearly
compatible with the structural characteristics of the
complexes under study.
,
The most characteristic bands in the IR spectra cor-
respond to carboxyl group stretching vibrations in the
expected regions [15]. The carboxylate stretching fre-
quencies was(COO−) and ws(COO−) for each of the
complexes under study are given in Table 4. The differ-
ence between the antisymmetric stretch and symmetric
stretch, which gives information on the carboxylate
bonding mode for the complexes, could not be deter-
mined accurately due to an overlap of was(COO−) with
the stretching vibration of CꢀN of the pyridine ring.
Moreover, the positions of the absorption bands are
strongly affected by hydrogen bonding interactions of
the carboxyl group of nic or isonic with other ligands as
confirmed by the crystal structures of some of the
complexes. However, considerable splitting of bands
assigned to was(COO−) and ws(COO) for anhydrous
[Cu(nic)2] confirms that the nicotinic acid anion as a
ligand is most probably coordinated via a bridging
carboxyl group.
A (Table 3) and the N–Cu–N angles for dien being
nearly the same [N2–Cu–N3 84.95(6)° and N3–Cu–
N4 85.14(6)°, respectively], while in the fourth equato-
rial position the nic anion is coordinated through the
nitrogen atom of the pyridine ring with the Cu–N1
,
distance of 2.025(2) A. One axial position is occupied
by the oxygen atom O3 of the NO3− anion at a
,
distance of 2.457(2) A, the other axial position being
occupied by the oxygen atom O6 of a water molecule at
a considerably longer distance of 2.716(2) A.
A system of hydrogen bonds is interconnecting each
of the molecules with other molecules (a) via the coor-
dinated water molecule (O6) which creates two hydro-
gen bonds [2.708(2) and 2.731(2) A, respectively] with
two carboxyl oxygen atoms O1a, O2a of two different
neighbouring molecules and a hydrogen bond [2.851(2)
,
,
Table 3
,
Bond lengths (A) and angles (°) for [Cu(nic)(NO3)(dien)(H2O)]·H2O
The N-coordination of the nicotinate or isonicotinate
in complexes [Cu(nic)2], [Cu(isonic)2(H2O)4], [Cu-
(nic)(NO3)(dien)(H2O)]·H2O and [Cu(isonic)(dien)-
(H2O)1.5]·0.5SO4·2.5H2O is in agreement with the posi-
tions of absorption bands in the region from 650 to 667
cm−1 and in the region from 423 to 447 cm−1, respec-
tively, which are due to in-plane ring deformation and
out-of-plane deformation of the coordinated pyridine
ring [15]. However, the positions of bands above 450
cm−1 can not be assigned accurately, because they are
obscured with the Cu–O stretching frequencies [16]
(Table 4). On the other hand, in the IR spectra of both
complexes [Cu(en)2(H2O)2](nic)2·H2O and [Cu(en)2-
(H2O)2](isonic)2, which contain en, medium bands are
observed at 620 and 615 cm−1 as well as at 398 and 395
cm−1, respectively, which are assigned to in-plane ring
deformation and out-of-plane deformation of a non-co-
ordinated pyridine ring [15].
In the spectra of complexes [Cu(nic)(dien)(H2O)](nic)
and [Cu(isonic)(dien)(H2O)](nic) the positions of bands
assigned to in-plane ring deformation and out-of-plane
deformation are characteristic for a coordinated as well
as for a non-coordinated pyridine ring [15].
In the IR spectrum of complex [Cu(nic)(NO3)-
(dien)(H2O)]·H2O, strong bands were observed at 1313
and 1007 cm−1 which were assigned to ws(NO2) and
Cu–N3
Cu–N4
Cu–N1
Cu–N2
Cu–O3
Cu–O6
O1–C7
O2–C7
O3–N5
O4–N5
O5–N5
N1–C2
2.0169(14)
2.0179(15)
2.0249(14)
2.0346(16)
2.4572(16)
2.7161(16)
1.259(2)
1.2646(19)
1.2664(19)
1.2641(19)
1.2441(19)
1.350(2)
N1–C6
N2–C8
N3–C9
N3–C10
N4–C11
C2–C3
C3–C4
C3–C7
C4–C5
C5–C6
C8–C9
C10–C11
1.358(2)
1.495(2)
1.478(2)
1.481(2)
1.493(2)
1.399(2)
1.394(2)
1.519(2)
1.399(2)
1.387(2)
1.523(2)
1.523(2)
N3–Cu–N4
N3–Cu–N1
N4–Cu–NI
N3–Cu–N2
N4–Cu–N2
N1–Cu–N2
C2–N1–C6
C2–NI–Cu
C6–NI–Cu
C8–N2–Cu
O5–N5–O4
O5–N5–O3
O4–N5–O3
C9–N3–C10
C9–N3–Cu
C10–N3–Cu
C11–N4–Cu
85.14(6)
178.60(5)
93.69(6)
84.95(6)
164.27(6)
96.35(6)
118.31(14)
119.70(11)
121.95(11)
107.59(11)
119.81(14)
120.72(14)
119.47(14)
117.29(13)
108.50(10)
107.51(10)
109.25(11)
N1–C2–C3
C4–C3–C2
C4–C3–C7
C2–C3–C7
C3–C4–C5
C6–C5–C4
N1–C6–C5
O1–C7–O2
O1–C7–C3
O2–C7–C3
N2–C8–C9
N3–C9–C8
N3–C10–C11
N4–C11–C10
H61–O6–H62
H71–O7–H72
122.74(15)
118.52(15)
121.89(14)
119.58(14)
118.91(14)
119.26(15)
122.26(15)
126.20(15)
117.02(14)
116.78(14)
107.82(13)
106.97(13)
107.16(13)
109.64(14)
106(2)
107(3)

M. Palico6a´ et al. / Polyhedron 19 (2000) 2689–2695
2693
Table 4
Spectral data a for the copper(II) complexes
Complex
IR spectra (cm−1
)
Electronic spectra (kK)
Carboxylic group
Pyridine ring
l(py)
Band I
Band II
was(COO−
)
ws(COO−
)
k(py)
[Cu(nic)2
1653s
1630s
1426m 1371s
1386s
650m
447m c
432sh
13.5br
11.8sh
[Cu(en)2(H2O)2](nic)2·H2O
[Cu(nic)(dien)(H2O)]nic
[Cu(nic)(NO3)(dien)(H2O)]·H2O
[Cu (isonic)(dien)H2O)]isonic
[Cu(isonic)2(H2O)4] b
1590s c
1620sb
1387s,br
620m
398m 18.4br
31.2sb
1618sbr
1388s,br
1377sbr
1375s,br
1381s,br
654m 625m 458m c 391m 16.9br
440sh
12.7sh
1622s
1611s
653m
449m
17.6br
1613sbr
673m 624w 456m c 392m 16.6br
27.5sh
28.4sh
445sh
12.5sh
1649s
1418s
667s
436s
15.3br
1597s,br c
1590s c
1375s,br
1375s
615m
395m 18.5br
17.3br
b
[Cu(en)2(H2O)2](isonic)2
[Cu(isonic)(dien)(H2O)1.5]·0.5SO4·2.5H2O b 1603s,br c
667m
423m
27.5sh
a s, strong; m, medium; w, weak; sh, shoulder; br, broad.
b The values are taken from a paper by Seg’la et al. [8].
c Mixed bands or some of the observed bands also belong to another vibrational mode.
w(NO), typical for the unidentate coordination mode of
nitrato groups [15] (see the crystal structure).
copper(II) atom, and oxygen atoms of the water
molecules, lying in the axial positions, complete an
elongated octahedral coordination sphere. The
analogous reaction of CuX2·nH2O with dien in a molar
ratio of 1:1 leads to formation of pentacoordinated
complexes of the type [CuX(dien)(H2O)]X (X=nic or
isonic), which contain coordinated and non-coordi-
nated pyridinecarboxylate anions. In these complexes
the copper(II) atom is coordinated in a square-pyrami-
dal arrangement by three N atoms of dien and one N
atom of the pyridine ring of nic or isonic in equatorial
positions, and by one water molecule in an axial posi-
tion. The analogous structure of the pentacoordinated
complex cation has been found by X-ray structure
analysis [18] for [Cu(isonic)(dien)(H2O)]PF6. On the
other hand, the reaction of equimolar quantities of
copper(II) sulfate or nitrate and dien with pyridinecar-
boxylate anions (equimolar quantities of pyridinecar-
boxylic acid and NaOH) in ethanolic solutions gives
solid monomeric complexes [Cu(isonic)(dien)(H2O)1.5]·
0.5SO4·2.5H2O [8] and [Cu(nic)(NO3)(dien)(H2O)]·H2O,
respectively. The crystal structure of the sulfate com-
The electronic spectra (Table 4) of both complexes
[Cu(nic)(dien)(H2O)](nic) and [Cu(isonic)(dien)(H2O)]-
(nic) exhibit a broad asymmetrical band with a maxi-
mum at 16 900 and 16 600 cm−1 (band I) and shoul-
ders on its low energy side which are typical for
five-coordinated copper(II) complexes with almost a
square-pyramidal structure [17]. The solid-state elec-
tronic spectra of all other copper(II) complexes under
study (Table 4) exhibit a symmetrical broad ligand field
band with a maximum in the range of 18 500 to 13 500
cm−1. For some of the complexes, there is also a
charge transfer band at about 30 000 cm−1 (band II).
This type of d–d spectrum is typical for tetragonally
distorted octahedral copper(II) complexes [17].
3.3. Structure of solid complexes
The reaction of ethanolic solution of copper(II)
pyridinecarboxylates CuX2·nH2O (where X is nic or
isonic, n=0 and 4, respectively) with en in a molar
ratio of 1:2 lead to isolation of solid complexes of the
type [Cu(en)2(H2O)2]X2·nH2O (n=1 and 0) which con-
tain uncoordinated pyridinecarboxylate anions. More-
over, the crystal structure of [Cu(en)2(H2O)2](isonic)2,
which comprises [Cu(en)2(H2O)2]2, cations and isoni-
cotinate anions, has been determined [8]. The four N
atoms of en form the coordination plane around the
plex contains two cations
—
a pentacoordinated
hexacoordinated
[Cu(isonic)(dien)(H2O)]+, and
a
[Cu(isonic)(dien)(H2O)2]+ sulfate anions and water
molecules. In the crystal structure of the nitrate com-
plex the coordination polyhedron around the Cu(II)
atom is a (4+1+1) distorted tetragonal bipyramid
(see Section 3.1).

2694
M. Palico6a´ et al. / Polyhedron 19 (2000) 2689–2695
All the above complexes with chelating ligands (en
activity against G+ S. aureus (IC50=1.9 mmol.1−1).
Isonicotinic acid (isonicH) at a concentration of 5
mmol l−1 has not influenced the S. aureus growth,
inhibition of the bacteria growth by compound
[Cu(isonic)2(H2O)4] at the same concentration was ap-
proximately 90%. Although ethylenediamine (en) alone
has partially inhibited the S. aureus growth, (IC50=2.6
mmol l−1), this influence has not manifested itself with
[Cu(en)2(H2O)2](isonic)2. The effect of the compounds
on G− E. coli was considerably lower. IsonicH at a
concentration of 5 mmol.1−1 did not influence the E.
coli growth, inhibition of the growth by complexes
and dien) are monomeric, and the complexes with en
contain only non-coordinated pyridinecarboxylate an-
ions, while the complexes with dien contain both non-
coordinated and N-coordinated anions. In the case of
the sulfate or nitrate complexes only N-coordinated
anions in the equatorial plane are present. On the other
hand, another type of nic coordination has been re-
vealed by a previous structure determination of the
polymeric
complex
[Cu(nic)(1,10-phenanthro-
line)(aqua)2]NO3·2H2O [6] in which the nicotinate an-
ions bridge the adjacent Cu(II) atoms through both the
pyridine N atom and the carboxyl O atom to form
zigzag polymeric chains along the b axis. Similarly, in
the complex [Cu(nic)(2,2%-bipyridine)(aqua)]NO3·2H2O
[7], the nicotinate anions bridge the adjacent Cu(II)
atoms through both the pyridine N atom and the
carboxyl group to form infinite chains. The carboxyl
group of the nicotinate anion coordinates to the Cu(II)
atom as a chelate.
[Cu(isonic)2(H2O)4],
[Cu(en)2(H2O)2](isonic)2,
and
[Cu(isonic)(dien)(H2O)](isonic) at the same concentra-
tion was approximately 50% (lC50=5 mmol l−1).
The highest effect against the yeasts C. parapsilosis
was observed for the compounds [Cu(isonic)2(H2O)4]
and [Cu(isonic)(dien)(H2O)](isonic) (IC50=2.1 and 3.3
mmol l−1). While isonicotinic acid alone at a concen-
tration of 5 mmol l−1 has not inhibited the yeasts
growth, growth inhibition by the compounds
[Cu(isonic)2(H2O)4] and [Cu(en)2(H2O)2](isonic)2 at the
same concentration was 70–80%. Similarly as in the
case of S. aureus the partial inhibitory activity of en
against C. parapsilosis (IC50=3.7 mmol l−1) was not
observed in the activity of its Cu-adduct
([Cu(en)2(H2O)2](isonic)2, IC50\5 mmol l−1).
3.4. Antimicrobial acti6ities
Results of the quantitative determination of anti
microbial activity, characterized by the IC50 and MIC
values of the isonic complexes [Cu(isonic)2(H2O)4],
[Cu(en)2(H2O)2](isonic)2,[Cu(isonic)(dien)(H2O)](isonic),
as well as isonicotinic acid, ethylenediamine and di-
ethylenetriamine alone are presented in Table 5. From
among the tested compounds, the compound
[Cu(isonic)2(H2O)4] has shown the highest antibacterial
The growth of filamentous fungi, phytopathogenic
fungi B. cinerea, F. moniliforme and a dermatophytic
fungus M. gypseum was practically not influenced by
Table 5
Antimicrobial activity of copper(II) isonicotinates, isonicotinic acid (isonicH), ethylenediamine (en) and diethylenetriamine (dien) characterized by
a
IC50 and MIC (mmol l−1
)
Microrganism
Compound
[Cu(isonic)2(H2O)4] [Cu(en)2(H2O)2]-
(isonic)2
[Cu
isonicH
en
dien
(isonic)(dien)H2O)]isonic
IC50
\5
\5
\5
MIC
\5
\5
\5
IC50
1.9
MIC
\5
\5
\5
IC50
\5
5
MIC
\5
\5
\5
IC50
\5
5
MIC
\5
\5
\5
IC50 MIC
IC50
\5
\5
\5
MIC
\5
Staphylococcus
aureus
Escherichia coli
2.6
3.2
5s
5s
5
\5
\5
Candida
paropsilosis
2.1
\5
3.3
3.7 \5
5c \10 \10
Rhizopus oryzae \10
\10
\10
3.7
\10
\10
\10
6.8
5
\10
\10
2.2
5
7.2
\10
\10
\10
Alternaria
alternata
\10
\10
\10 \10
Botrytis cinerea \10
\10
\10
\10
\10
\10
\10
\10
\10
\10
\10
\10
\10
\10
\10
\10 \10
\10 \10
4.1
\10
\10
\10
Fusarium
moniliforme
\10
Microsporum
gypseum
8
\10
\10
\10
\10
\10
\10
\10
\10 \10
3.1
\10
a c, microbicidal effect; s, microbistatical effect.

M. Palico6a´ et al. / Polyhedron 19 (2000) 2689–2695
2695
the tested copper compounds at a concentration of 10
Acknowledgements
mmol 1−1 (IC50\10 mmol l−1). The growth of R.
oryzae was most significantly inhibited by the com-
pounds [Cu(isonic)(dien)H2O](isonic) and [Cu(isonic)2-
(H2O)4], IC50=2.2 and 3.7 mmol l−1, respectively. The
inhibition activity decreases in the order [Cu(isonic)-
(dien)H2O](isonic) \ [Cu(isonic)2(H2O)4] \ [Cu(en)2-
(H2O)2](isonic)2\dien\isonic=en. The copper(II)
adducts — compounds [Cu(en)2(H2O)2](isonic)2 and
[Cu(isonic)(dien)H2O](isonic) — have partially inhib-
ited the growth of A. alternata (approximately at the
same level, IC50=5 mmol 1−1) and also strongly inhib-
ited sporulation.
This work was financially supported by grants 1/
6106/20 and 1/7342/20 from the Slovak Grant Agency
for Science.
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Supplementary materials including all atomic coordi-
nates (Table S1), anisotropic displacement parameters
for non-hydrogen atoms (Table S2) and all interatomic
distances and bond angles (Table S3) for the compound
[Cu(nic)(NO3)(dien)(H2O)]·H2O have been deposited
with the Cambridge Crystallographic Data Centre,
CCDC no. 147398. Copies of this information may be
obtained free of charge from The Director, CCDC, 12
Union Road, Cambridge, CB2 1EZ, UK (fax: +44-
1223-336033; e-mail: deposit@ccdc.cam.ac.uk or
www.http://www.ccdc.cam.ac.uk). Observed and calcu-
lated structure factors are available on request from the
authors.
Supplementary material (available from the authors)
concerning the antimicrobial activities include figures
S1–S6 containing graphs on: growth inhibition of S.
aureus by [Cu(isonic)2(H2O)4] (Fig. S1); growth inhibi-
tion of C. parapsilosis by [Cu(isonic)2(H2O)4] (Fig. S2);
colony growth inhibition of R. oryzae by [Cu(isonic)2-
(H2O)4] (Fig. S3); colony growth inhibition of R. oryzae
by [Cu(isonic)(dien)(H2O)]isonic (Fig. S4); colony
growth inhibition of A. alternata by [Cu(en)2(H2O)2]-
(isonic)2 (Fig. S5); effect of [Cu(en)2(H2O)2](isonic)2 on
the sporulation of A. alternata (Fig. S6).
.