Redox-active antifungal cobalt(II) and copper(II) complexes with sterically hindered o-aminophenol derivatives

Article abstract of DOI:10.1016/j.poly.2007.11.028

Co(II) complexes with 4,6-di(tert-butyl)-2-aminophenol (HL^I) and 2-anilino-4,6-di(tert-butyl)phenol (HL^II) have been synthesized and characterized by means of physico-chemical methods. The compounds HL^I and HL^II coordinate in their singly deprotonated forms and behave as bidentate O,N-coordinated ligands; their low-spin Co(II) complexes are characterized by CoN₂O₂ coordination modes and square planar geometry. Both the free ligands and their Co(II) and Cu(II) complexes (we have produced and characterized the latter before) exhibit a pronounced antifungal activity against Aspergillus niger, Fusarium spp., Mucor spp., Penicillium lividum, Botrytis cinerea, Alternaria alternata, Sclerotinia sclerotiorum, Monilia spp., which in a number of cases is comparable with that of Nystatin and Terbinafine or even higher. The reducing properties of the ligands and their metal(II) complexes, as well as their antifungal activities, were found to decrease in the order: Cu(L^I)₂ > Cu(L^II)₂ ≥ Co(L^I)₂ > Co(L^II)₂ > HL^I > HL^II.

Full text of DOI:10.1016/j.poly.2007.11.028

Available online at www.sciencedirect.com
Polyhedron 27 (2008) 985–991
www.elsevier.com/locate/poly
Redox-active antifungal cobalt(II) and copper(II) complexes
with sterically hindered o-aminophenol derivatives
a,
b
b
a
a
*
N.V. Loginova , T.V. Koval’chuk , N.P. Osipovich , G.I. Polozov , V.L. Sorokin ,
A.A. Chernyavskaya a, O.I. Shadyro a
a Faculty of Chemistry, Belarusian State University, Leningradskaya Strasse 14, 220050 Minsk, Belarus
b Research Institute for Physico-Chemical Problems of The Belarusian State University, Leningradskaya Strasse 14, 220050 Minsk, Belarus
Received 28 September 2007; accepted 27 November 2007
Available online 2 January 2008
Abstract
Co(II) complexes with 4,6-di(tert-butyl)-2-aminophenol (HLI) and 2-anilino-4,6-di(tert-butyl)phenol (HLII) have been synthesized
and characterized by means of physico-chemical methods. The compounds HLI and HLII coordinate in their singly deprotonated forms
and behave as bidentate O,N-coordinated ligands; their low-spin Co(II) complexes are characterized by CoN2O2 coordination modes and
square planar geometry. Both the free ligands and their Co(II) and Cu(II) complexes (we have produced and characterized the latter
before) exhibit a pronounced antifungal activity against Aspergillus niger, Fusarium spp., Mucor spp., Penicillium lividum, Botrytis cine-
rea, Alternaria alternata, Sclerotinia sclerotiorum, Monilia spp., which in a number of cases is comparable with that of Nystatin and Ter-
binafine or even higher. The reducing properties of the ligands and their metal(II) complexes, as well as their antifungal activities, were
found to decrease in the order: Cu(LI)2 > Cu(LII)2 P Co(LI)2 > Co(LII)2 > HLI > HLII.
Ó 2007 Elsevier Ltd. All rights reserved.
Keywords: o-Aminophenol derivatives; Co(II) and Cu(II) complexes; Spectroscopic study; Cyclic voltammetry; Antifungal activities
1. Introduction
with o-aminophenol derivatives, comprises a promising
field of study in bioinorganic chemistry. Cell- and ani-
mal-based testing allowed to reveal a set of promising
pharmacological properties for sterically hindered
o-aminophenols, e.g. antioxidant, antihypoxic, anti-
inflammatory and antiviral ones [6–10]. In particular, an
antiherpetic medicine has been developed from 2-anilino-
4,6-di(tert-butyl)phenol and is currently available [11,12].
The non-substituted o-aminophenol is known as Questio-
mycin B antibiotic with specific antifungal (antimycobacte-
rial) activity [13]. However, alkylated o-aminophenol
derivatives, particularly those with tert-butyl groups, are
known to be substantially less toxic [14].
According to the results presented in a series of papers
[15–20], sterically hindered o-aminophenol molecules are
redox non-innocent when O,N-coordinated to some transi-
tion metal ions, and can exist in different protonation and
oxidation forms (the o-aminophenol or o-iminosemiqui-
none) in coordination compounds. Thus, sterically
Modern antifungal therapies include two main classes of
compounds: polyene and azole drugs [1,2]. Despite the fact
that it is Candida spp. and Aspergillus spp. that remain the
main causative pathogens, the number of cases of systemic
fungal infections due to strains of Fusarium spp., Mucor
spp., Scedosporium spp. and others, which are resistant to
the most widely used antifungal agents, is increasing [3].
In order to prevent this serious medical problem, the elab-
oration of new types of antifungal agents or the expansion
of bioactivity of the previously known drugs is a pressing
task [4,5]. The synthesis and characterization of metal com-
plexes with organic bioactive ligands, in particular, of those
*
Corresponding author. Tel.: +375 172 09 55 16; fax: +375 172 26 46
96/55 67.
E-mail addresses: loginonv@yahoo.com, loginonv@gmail.com (N.V.
Loginova).
0277-5387/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.poly.2007.11.028

986
N.V. Loginova et al. / Polyhedron 27 (2008) 985–991
hindered o-aminophenols may be assumed to have great
potential as ligands in synthesis of new bioactive metal
complexes. As for the coordination chemistry of transition
metal complexes formed by O,N-coordinated ligands of
this sort, it is quite possible that synthetic difficulties have
inhibited the study of metal complexes of sterically hin-
dered o-aminophenols, since the attempts to isolate com-
plexes of this type were often unsuccessful and resulted in
the ligand being recovered without coordination [21,22].
This has prompted us to investigate the peculiarities of
complexation of some di-tert-butylated o-aminophenolate
ligands with transition metal ions [23,24]. Selecting Co(II)
and Cu(II) complexes as the main subjects for this study,
we had in mind that the antifungal effect of copper(II)
and cobalt(II) ions had been known, their complexes still
being under study in order to find effective antifungal
agents [25–29]. The effect of some transition metal
complexes on the structure of fungal and mammalian
cell organelles has been studied [25,30–35]. In particular,
when administered to some fungal strains, both metal-free
1,10-phenantroline derivatives and the their metal com-
plexes inhibited respiration, reduced the levels of ergosterol
in the membrane and altered cytochrome content [25,32–
35]. In this connection it may be expected that metal com-
plexes capable of participating in redox processes and of
affecting electron-transport cell systems will be promising
in the search for antifungal agents. Other papers should
be also mentioned, their authors having shown that the
bioactivity of metal complexes may be due to their redox
effect on electron-transport cell systems, and that a correla-
tion between in vitro potency and reduction potential is
possible [36,37]. This encouraged us to investigate redox
properties of the synthesized o-aminophenol derivatives
and their Co(II) and Cu(II) complexes by cyclic voltamme-
try. In so doing we took into account that Co(II) and
Cu(II) ions were able to take part in redox processes, thus
affecting the properties of the ligands of the phenolic or
quinoid types [38]. It was also interesting to find out
whether there is any correlation between the antifungal
activity of the compounds under study and their redox
properties.
Cu(II) and Co(II), which may be less toxic than the oxi-
dized (radical) forms of respective ligands [42,43].
HLI — R=H
OH
HLII — R=Ph
NH
R
2. Experimental
2.1. Materials and methods
Chemicals were purchased from commercial sources and
were used without further purification. The two sterically
hindered o-aminophenols and their Cu(II) complexes were
prepared as described elsewhere [24,44,45]. The prepara-
tion of Co(II) complexes is described later.
Infrared spectra of solids were recorded with a Spectrum
1000 spectrophotometer in the wavelength range 4000–
400 cmꢀ1 at room temperature, using nujol mulls of the
ligands and their complexes, and polyethylene windows.
Thermal analysis was performed with a derivatograph
OD-103 MOM. TG/DTA measurements were run in the
air between 20 and 450 °C (5 °C minꢀ1). Elemental
analyses were carried out according to the standard
methods by Microanalytical Laboratory, Bioorganic
Chemistry Institute, National Academy of Sciences, Bela-
rus. Metal determination was carried out using an atomic
emission spectrometer with an inductively coupled plasma
excitation source (Spectroflame Modula). A sample of the
Co(II) complex was decomposed on treatment with
HNO3 + H2O2 using Milestone mls 1200 mega microwave
digestion system. After the complex had been decomposed,
the content of the metal in the resulting solution was deter-
mined. XRD studies were made with an HZG 4 A diffrac-
tometer. The UV–Vis absorption spectra were measured in
the 220–900 nm range with a Specord M500 spectropho-
tometer, using acetonitrile solutions of the compounds.
Magnetic susceptibility was determined with the use of a
Gouy balance at room temperature using Hg[Co(SCN)4]
as a calibrant. ESR spectra of polycrystalline samples were
measured with ERS-220 X-band spectrometer (9,45 GHz)
at room temperature and at 77 K, using 100-kHz field
modulation; g factors were quoted relative to the standard
marker DPPH (g = 2.0036). The molar conductance of
10ꢀ3 mol Lꢀ1 solution of the metal(II) complex in acetoni-
trile was measured at 20 °C using a TESLA BMS91 con-
ductometer (cell constant 1, 0). Electrochemical
measurements were performed under dry nitrogen in a
three-electrode two-compartment electrochemical cell
using a glassy-carbon (GC) working electrode, Pt auxiliary
electrode and AgjAgClj0.1 mol Lꢀ1 (C2H5)4NCl reference
electrode. The supporting electrolyte was 0.1 mol Lꢀ1
(C2H5)4NClO4. The AgjAgClj0.1 mol Lꢀ1 (C2H5)4NCl ref-
Since our earlier work had revealed that Ag(I) and
Cu(II) complexation led to an enhancement of the antimi-
crobial activity of some sterically hindered phenolic deriv-
atives [24,39–41], we were motivated to explore whether
there was a similar trend in the case of other transition
metal(II) complexes of these organic compounds. We
report here the complexation of Co(II) ion with two steri-
cally hindered o-aminophenols, namely, 4,6-di(tert-butyl)-
2-aminophenol (HLI, see the scheme below, R = H) and
2-anilino-4,6-di(tert-butyl)phenol (HLII, R = Ph), in order
to compare their coordinative behaviour in relation to
Co(II) ion with the data obtained previously for their
Cu(II) complexes [24] and to assess the influence of com-
plexation on antifungal activities and redox properties of
o-aminophenols. We have examined the possibility of the
formation of tert-butyl-substituted o-aminophenolates of

N.V. Loginova et al. / Polyhedron 27 (2008) 985–991
987
erence electrode was calibrated with ferriciniumjferrocene
redox couple located at E1/2 = +0.52 V. Acetonitrile was
used as a solvent.
eter of the fungal colonies in the presence of a given con-
centration of the compound tested, and C is the mean
value of the diameter of the fungal colonies in the absence
of the compound, measured under the same conditions.
2.2. Synthesis of the Co (II) complexes with sterically
hindered o-aminophenol derivatives
3. Results and discussion
Based on our previous findings [23], the conditions were
created to purposefully provide the preferential formation
of the Co(II) complexes, with the composition correspond-
ing to the general formula CoL2: a solution of Co(II) salt
was added in small portions to the ligand solution under
continuous stirring, so that the complexation always took
place with the excess ligand present. A solution of
0.050 mmol Co(CH3COO)2 ꢁ 4H2O in 10 mL of water
was added dropwise to a colorless solution of 0.100 mmol
of HLI or HLII dissolved in 10 mL of ethanol (molar ratio
Co(II):HL = 1:2). As these ligands can be readily oxidized
by oxygen, it is to be taken into account when producing
their complexes in order to guard against formation of oxi-
dized ligands (in particular, o-iminosemiquinones, as it was
shown in some papers [15–21]). To this end, argon was
bubbled through the solutions (pH 6 6) during the synthe-
sis. Colored precipitates formed instantaneously. After 1.5–
2 h stirring, they were collected on membrane filters (JG
0.2 lm), washed with ethanol and water, and dried in vacuo
(yield > 70%). It should be specially emphasized that to
separate individual Co(LI)2 complex, the precipitate must
be more thoroughly washed with ethanol (5 ꢂ 50 mL) in
order to eliminate uncoordinated ligand molecules which
otherwise could be able to form adducts with the metal
complex through hydrogen bonding.
3.1. Physico-chemical characterization
The stoichiometry of the solid complexes was confirmed
by elemental analyses of the isolated chelates. The data
show satisfactory agreement with the proposed formulae
CoL2. The complexes demonstrated X-ray patterns of their
own, which were significantly different from those of the
respective ligands. However, a full structural analysis could
not be performed, no crystals suitable for single-crystal
X-ray analysis having been obtained, which is not uncom-
mon for compounds with sterically hindered ligands [22]. It
is noteworthy that a similar problem when carrying out
crystallization of metal complexes of aminophenol deriva-
tives is described in [21,47]. Because of the well-known dif-
ficulties in direct X-ray investigations of these complexes,
the geometrical arrangement of the ligating atoms in the
Co(II) complex has been investigated by several spectro-
scopic and magnetochemical methods.
Thermal analysis in air flow with identification of the
final products by X-ray powder diffraction has shown
Co(LI)2 and Co(LII)2 complexes to be anhydrous and
unsolvated. No weight loss was observed until decomposi-
tion which began about 185 °C (for Co(LI)2) or 200 °C (for
Co(LII)2), with exothermic peaks at 190 °C (for Co(LI)2) or
210 °C (for Co(LII)2) without any noticeable weight loss,
and at 360 °C (for both complexes), ultimately leaving
CoO as the residue. The maximal weight loss (83.72%
and 84.1%, respectively, for Co(LI)2 and Co(LII)2) corre-
sponds to the loss of two ligand molecules (Calc. 84.99%
and 85.2%, respectively, for Co(LI)2 and Co(LII)2). The
agreement between the experimental and theoretical weight
losses for the above processes confirms the above-men-
tioned general formula CoL2.
Co(LI)2 complex. Grey-brown. Anal. Calc. for C28H44-
N2O2Co: C, 67.29; H, 8.88; N, 5.61; Co, 11.80. Found:
C, 67.25; H, 8.83; N, 5.58; Co, 11.75%.
Co(LII)2 complex. Blue. Anal. Calc. for C40H52N2O2Co:
C, 73.69; H, 8.04; N, 4.30; Co, 9.05. Found: C, 73.61; H,
7.95; N, 4.23; Co, 8.96%.
2.3. Antifungal activities
The Co(II) complexes are soluble in acetonitrile, ace-
tone, dimethyl formamide, dimethyl sulfoxide, insoluble
in nitromethane and ethanol. The conductivity data for
the complexes Co(LI)2 (Kmol = 11.4 Xꢀ1 cm2 molꢀ1) and
Co(LII)2 (Kmol = 5.8 Xꢀ1 cm2 molꢀ1) indicate their being
essentially non-electrolytes in acetonitrile [48], and suggest
that the bidentate ligands HLI and HLII may be coordi-
nated to Co(II) ion as uninegatively charged ligands.
To specify the coordination modes in the Co(II) com-
plexes, we used IR spectroscopy (Table 1).
The IR spectra of the Co(II) complexes as against those
of the free ligands are distinguished by the following fea-
tures: (i) the bands corresponding to m(OH) vibrations in
the free ligands disappear, suggesting the participation of
the o-OH in complex formation through proton displace-
ment; (ii) the bands at 1230–1140 cmꢀ1 assigned to C–I
stretching vibrations are shifted towards lower wave num-
Antifungal activities of the compounds were tested
against the following fungal species (the collection of the
Department of Microbiology, The Belarusian State Uni-
versity): Aspergillus niger, Fusarium spp., Mucor spp., Pen-
icillium lividum, Botrytis cinerea, Alternaria alternata,
Sclerotinia sclerotiorum, Monilia spp. Compounds were
dissolved in DMSO and diluted in potato dextrose agar
medium to yield working solutions of the test compounds
with the concentration of 100 lg mLꢀ1. The amount of
DMSO in the medium was 1% and did not affect the
growth of the tested microorganisms. Antifungal activities
of the compounds against moulds and common plant
pathogens were checked by the agar plate technique as
described elsewhere [41]. The degree of inhibition of radial
growth (RI) was calculated as follows [46]: RI =
100(C ꢀ T)/C (%), where T is the mean value of the diam-

988
N.V. Loginova et al. / Polyhedron 27 (2008) 985–991
Table 1
IR spectral assignments (cmꢀ1) of the ligands and Co(II) complexes
Compound
HLI
m(OH)
m(C–O)
m(C–N)
m(C@C)
m(N–H)
m(Co–N)
m(Co–O)
3290m
1235s
1292w
1593m
3366m
1204m
1142w
1180s
1091m
1044m
1021m
1202m
1150w
1144s
Co(LI)2
1300m
1556m
3340w
469w
435w
570w
539m
514m
HLII
3585m
1311s
1599s
1495s
1537m
3352m
3334w
Co(LII)2
1302m
469w
424w
571w
545w
513m
1106s
1074w
bers as compared to their positions in the spectra of the
ligands; (iii) the positions of the bands assigned to N–H
m(C@N) stretching vibrations lacking in the IR spectrum
of Co(II) complex, respectively, in the ranges of 1400–
1500 and 1690–1640 cmꢀ1, confirm the phenolate character
of the ligand.
In the light of the physico-chemical data and elemental
analysis results the mode of bonding in the Co(II) complex
can be represented schematically as shown below:
(3352 and 3366 cmꢀ1) and C–N (1292 and 1311 cmꢀ1
)
stretching vibrations are changed, the presence of the weak
bands 3340 and 3334 cmꢀ1 in the spectra of the complexes
indicating the participation of NH group in coordination
without deprotonation; and (iv) bands of moderate inten-
sity appear at 571–424 cmꢀ1, which can be assigned to
m(Co–N) and m(Co–O). The above-listed facts suggest that
NH-groups and deprotonated hydroxyls take part in form-
ing the CoN2O2 coordination cores in the Co(II) complexes
[49].
OH
.
Co(CH3COO)2
4H2O EtOH, H2O
2
stirring,1.5 h, argon
The electronic absorption spectra of the free ligands in
acetonitrile show characteristic intraligand transition
bands at 225 and 280 nm [21,50]. The spectra of the Co(II)
complexes in acetonitrile solution exhibit absorption bands
in the high-energy region, which can be assigned to intral-
igand transitions: 230–240 nm (loge = 4.3–4.4) and 280–
282 nm (loge = 4.1–4.2). The bands located in the 305–
430 nm region can be attributed to the ligand-to-cobalt(II)
charge transfer transitions N(r) ? CoII and Opheno-
late ? CoII: respectively, 305 nm (loge = 4.1) and 395
(loge = 3.9), 430 nm (loge = 3.7) [50,51]. The new absorp-
tion bands that appeared upwards of 500 nm can be
imputed to the d–d transitions of the Co(LI)2 and Co(LII)2
complexes: respectively, 520 nm (loge = 3.65) and 640 nm
(loge = 3.69), characteristic of the low-spin, square planar
Co(II) complexes [47,50–58]. This is also corroborated by
the effective magnetic moment values: leff = 2.38 BM for
the Co(LI)2 complex and leff = 2.58 BM Co(LII)2 complex,
expected for the low-spin square planar geometry around
Co(II) ions [47,51–56].
NH
R
R
NH
O
Co
O
NH
R
This coordination core agrees with the data obtained by
physico-chemical methods for the Cu(II) complex investi-
gated previously [24], where the copper site has the square
planar stereochemistry. It should be particularly empha-
sized that any departure from the specified conditions of
the synthesis makes the possibility of separating the indi-
vidual complex problematic, the free ligands in their oxi-
dized forms being generally obtained in abundance along
with it.
The ESR spectra of Co(II) complexes were obtained in
the solid (polycrystalline) state at 77 K and room tempera-
ture in order to confirm the geometry of the coordination
3.2. Cyclic voltammetry
cores. These spectra are typical axial ones with g = 1.96
k
k
and g\ = 2.01 (for the Co(LI)2 complex) and g = 1.98
Redox properties of the compounds were examined by
cyclic voltammetry. Cyclic voltammogram of the ligand
HLI at positive potential shows two anodic peaks at 0.58,
1.72 V, and only one cathodic peak at 0.495 V on the
reverse scan (Fig. 1a, solid line). For the ligand HLII a dou-
and g\ = 2.07 (for the Co(LII)2 complex), characteristic
of low-spin, square-planar Co(II) complexes [47,51,54,
55,59–61]. No signal of stabilized radicals present in the
ESR spectrum at 77 K, as well as the m(C@O) and

N.V. Loginova et al. / Polyhedron 27 (2008) 985–991
989
The difficulty of interpreting the electrochemical data
for metal complexes of sterically hindered o-aminophe-
nol derivatives is caused by the fact that, as noted
above, in coordination compounds ligands of this kind
can exist in different protonation and redox forms (o-
aminophenol or o-iminosemiquinone). It should be
emphasized that the electrochemical properties of the
ligands and metal complexes have been studied mainly
to compare their reducing power rather than to monitor
spectral and structural changes accompanying an
electron transfer. The assignment of the redox processes
was facilitated by comparison with the literature
[16,21,62].
On voltammograms of Cu(II) complexes in the range
from ꢀ0.1 to +2.1 V anodic peaks are observed: at 0.27,
0.61, 0.89, 1.27 V for Cu(LI)2 (Fig. 1b, dotted line) and
0.4, 0.7, 0.96 V for Cu(LII)2 (Fig. 1b, dashed-dotted line).
Cathodic peaks are registered on the reverse scan: at
0.14, 0.51, 1.07 V for Cu(LI)2 and 0.25, 0.65, 1.12 V for
Cu(LII)2. Two peaks, at 0.14 and 0.25 V, for Cu(II) com-
plexes are observed in voltammograms on polarization to
about 0.6–1.0 V; upon more anodic polarization on the
reverse scan they are obscured by the peaks at 0.51 and
0.65 V. On anodic polarization two peaks are observed at
0.65 and 1.19 V for Co(LI)2 complex, and three peaks are
observed at 0.71, 0.94 and 1.63 V for Co(LII)2, with catho-
dic ones on the reverse scan at 0.54, 0.21 V for Co(LI)2 and
0.62 V for Co(LII)2) (Fig. 1b, dashed and solid lines). No
prominent cathodic processes are observed on cathodic
polarization from the open circuit potential down to
ꢀ1.8 V.
The cyclic voltammograms of Cu(LI)2 and Cu(LII)2
complexes are more or less similar in their shape, voltam-
mogram of Cu(LII)2 being shifted by 0.15–0.20 V into
cathodic region because of the influence of phenyl substi-
tute in aminogroup (Fig. 1b). A similar regularity can be
observed also for voltammograms of Co(LI)2 and Co(LII)2
complexes. A comparison between cyclic voltammograms
of Cu(LI)2 and Co(LI)2 complexes shows that common
peaks are present at ꢃ0.65 V, and a comparison between
voltammograms of Cu(LII)2 and Co(LII)2 complexes shows
that there are common peaks at 0.9 V, corresponding to
oxidation of the ligands LI and LII, as well as cathodic
peaks at ꢃ0.5 V (for the complexes of the ligand LI) and
at ꢃ0.65 V (for those of the ligand LII), relating, respec-
tively, to the reduction of the products of LI and LII oxida-
tion on the reverse scan.
On the basis of the above findings obtained by cyclic vol-
tammetry, and taking into account the data of [62], it may be
suggested that Cu(II) and Co(II) ions take part in a sequence
of electron transfers; otherwise, whatever the metal (II) ion
nature, the redox potentials of the complexes would have
differed only slightly in a series of ligands. A comparison
between the redox properties of the ligands and those of
their metal(II) complexes shows that their reducing ability
decreases in the following order: Cu(LI)2 > Cu(LII)2 P
Co(LI)2 > Co(LII)2 > HLI > HLII (Fig. 1).
Fig. 1. Cyclic voltammograms (50 mV/s) of the ligands (1.36 mmol Lꢀ1
)
HLI (solid line), HLII (dashed line) (a) and metal complexes
(0.68 mmol Lꢀ1) Cu(LI)2 (dotted line), Cu(LII)2 (dashed-dotted line),
Co(LI)2 (dashed line), Co(LII)2 (solid line) (b) in 0.1 mol Lꢀ1
(C2H5)4NClO4 acetonitrile solution on glassy-carbon electrode. (The
potentials were measured against AgjAgClj0.1 mol dot Lꢀ1 (C2H5)4NCl
reference electrode.)
ble anodic peak is observed at 0.85–0.98 V (is not two over-
lapping peaks), and a cathodic peak (0.70 V) on the reverse
scan (Fig. 1a, dashed line). On cathodic polarization (down
to ꢀ1.8 V) for HLI and HLII no peaks are observed. Con-
trolled potential electrolysis carried out for HLII at 1.2 V
consumed two electron per molecule. The UV–Vis spectra
of the oxidized HLII solution show two broad absorption
bands at 400 and 500 nm. These findings agree with the
results of electrochemical investigation of HLII compound
[16,21], according to which HLII undergoes 2 e-oxidative
transformation to give iminobenzoquinone. Controlled
potential coulometry for HLI shows two 1 e-oxidative pro-
cesses corresponding to anodic peaks at 0.58 and 1.72 V.
On the basis of the data on oxidation of o-aminophenols
[15–19,21] it may be suggested that HLI is successively oxi-
dized to iminosemiquinone and iminobenzoquinone.

990
N.V. Loginova et al. / Polyhedron 27 (2008) 985–991
Table 2
Antifungal activities of the compounds tested as evaluated by radial inhibition of mycelial growth (RI, %)
Compound
RI (%)
Alternaria
alternata
Sclerotinia
sclerotiorum
Monilia
spp.
Aspergillus
niger
Fusarium
spp.
Mucor
spp.
Penicillium
lividum
Botrytis
cinerea
HLI
60
100
90
50
90
90
0
100
100
100
90
100
100
0
0
50
50
50
70
100
55
30
70
50
0
55
65
60
40
55
50
0
70
100
90
60
90
80
0
50
100
80
30
70
60
0
40
80
55
30
55
50
0
60
100
90
50
100
90
0
Cu(LI)2
Co(LI)2
HLII
Cu(LII)2
Co(LII)2
Cu(CH3COO)2
Co(CH3COO)2
Nistatin
Terbinafine
Questiomycin B
0
0
0
0
0
0
0
40
50
40
40
50
50
70
100
30
90
80
40
50
50
50
90
60
40
60
60
30
3.3. Antifungal activities
compounds tested, we may suggest that one of the likely
reasons for their different activities is related to the nature
of the substitute in the ring and to a substitute being pres-
ent at the nitrogen atom of the amino group. Moreover,
the antifungal activities of the complexes exhibit some
metal-ion-dependency. By and large the inhibitory effects
of the compounds examined decrease in the order:
Cu(LI)2 > Cu(LII)2 P Co(LI)2 > Co(LII)2 > HLI > HLII
(Table 1), and their reducing ability declines in the same
order, as it was shown above. These data are in accordance
with the results of the studies [32–35], where the influence
of redox properties of the metal complexes on their anti-
fungal effect was found, and it was shown that this effect
appears to be mediated through the disruption of mito-
chondrial function and uncoupling respiration. These facts
may be of interest in designing new antifungal drugs, since
this effect is different to the mode of action of the conven-
tional azole and polyene drugs.
The test microorganisms (the collection of the Depart-
ment of Microbiology, the Belarusian State University)
are listed in Table 1. Inhibition values of the free ligands
and their Co(II) and Cu(II) complexes are listed in Table
1. Commonly used antifungal drugs Nystatin, Terbinafine
and Questiomycin B were tested as positive controls. The
effect of the starting metal(II) acetates is also reported. It
should be emphasized that the antifungal tests of these
ligands and their Co(II) and Cu(II) complexes were first
performed here.
It was found that the inhibitory effects of HLI and HLII
ligands and their metal(II) complexes differed with the
species of fungi. All of them demonstrate the highest inhib-
itory properties against S. sclerotiorum. A like high activity
against Fusarium spp., A. alternata and B. cinerea is char-
acteristic of Co(II) and Cu(II) complexes (Table 1). And
it was only Cu(LI)2 that showed the highest antifungal
activity against Mucor spp. and Monilia spp. Both the free
ligands and Co(II) and Cu(II) complexes exhibit pro-
nounced antifungal activities against some strains, which
in a number of cases were comparable with those of Nysta-
tin and Terbinafine or even higher (Table 2).
Acknowledgement
We are grateful to Dr. R. Zheldakova (The Belarusian
State University) for the antifungal testing.
Antifungal screening in vitro indicated that in the cases
mentioned above a synergistic effect is present, the anti-
fungal activities of the metal(II) complexes being higher
than those of both the ligand and the starting metal salts.
This provides reason to believe that antifungal activities
of the metal(II) complexes synthesized do not correlate
with the toxicity of the metal(II) ions against the fungi
tested. It is noteworthy that the two sterically hindered
derivatives of o-aminophenol synthesized and their meta-
l(II) complexes were more active than Questiomycin B anti-
biotic tested. In this connection, when estimating the effect
of modification of the molecule of o-aminophenol by intro-
ducing substitutes (two tert-butyl ones into the ring and a
phenyl one into aminogroup) and complexation with
Cu(II) and Co(II) ions on the antifungal activities of the
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