Synthesis, spectroscopic and cyclic voltammetry studies of copper(II) complexes with open chain, cyclic and a new macrocyclic thiosemicarbazones

Article abstract of DOI:10.1016/S0277-5387(99)00383-6

New copper complexes have been prepared from benzilbisthiosemicarbazone (L¹H₆) and from the cyclic 6-methoxi-1,6-diphenyl-4-thio-3,4,5,6-tetrahydro-2,3,5-triazine (L²H₂). The complexes were characterized by mass spectrometry, IR, electronic and electron paramagnetic resonance spectra. Complexes from L¹H₆ (1-5) present 1:1 stoichiometry and show different characteristics with a variable grade of deprotonation in the ligand, depending on the salt used (chloride, nitrate or sulfate) and the presence of acid in the medium. A macrocyclic Schiff base, 3,4,9,10-tetraphenyl-1,2,5,6,8,11-hexaazacyclododeca-7,12-dithione-3,4,9,10-t etraene (L³H₂), containing thiosemicarbazone moieties is readily prepared and characterized for the first time, with fairly good yield, from the mesocycle (L²H₂) in methanol with copper chloride as template. Near quantitative synthesis of the precursor, L²H₂, which is a potential chemotherapeutic agent against cancer, has been achieved by reacting benzil and thiosemicarbazide in the absence of metal salt and using a high dilution technique. Macrocyclic complexes 6 and 7 containing thiosemicarbazone moieties were obtained from L²H₂ and copper nitrate and sulfate. Direct reaction between the copper salt and the macrocyclic thiosemicarbazone (L³H₂) gave similar complexes but with a lower grade of purity. Macrocyclic complexes 6 and 7 present metal-ligand ratios of 1:2 and 1:1 and the ligand is in a deprotonated form. The redox behaviour was explored by cyclic voltammetry. L¹H₆ complexes show Cu(II)/Cu(I) couples and quasireversible waves associated with the Cu(III)/Cu(II) process. The reduction/oxidation potential depends on the structure and conformation of the central atom in the coordination compounds. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0277-5387(99)00383-6

www.elsevier.nl/locate/poly
Polyhedron 19 (2000) 441–451
Synthesis, spectroscopic and cyclic voltammetry studies of copper(II)
complexes with open chain, cyclic and a new macrocyclic
thiosemicarbazones
a
a
a
a,
a
b
´
*
Eva Franco , Elena Lopez-Torres , M Antonia Mendiola , M Teresa Sevilla
a
´
´
´
Departamento de Quımica Inorganica, Universidad Autonoma, Cantoblanco, 28049 Madrid, Spain
Departamento de Quımica Analıtica y Analisis Instrumental, Universidad Autonoma, Cantoblanco, 28049 Madrid, Spain
b
´
´
´
´
Received 28 October 1999; accepted 10 December 1999
Abstract
New copper complexes have been prepared from benzilbisthiosemicarbazone (L1H6) and from the cyclic 6-methoxi-1,6-diphenyl-4-thio-
3,4,5,6-tetrahydro-2,3,5-triazine (L2H2). The complexes were characterized by mass spectrometry, IR, electronic and electron paramagnetic
resonance spectra. Complexes from L1H6 (1–5) present 1:1 stoichiometry and show different characteristics with a variable grade of
deprotonation in the ligand, depending on the salt used (chloride, nitrate or sulfate) and the presence of acid in the medium. A macrocyclic
Schiff base, 3,4,9,10-tetraphenyl-1,2,5,6,8,11-hexaazacyclododeca-7,12-dithione-3,4,9,10-tetraene (L3H2), containing thiosemicarbazone
moieties is readily prepared and characterized for the first time, with fairly good yield, from the mesocycle (L2H2) in methanol with copper
chloride as template. Near quantitative synthesis of the precursor, L2H2, which is a potential chemotherapeutic agent against cancer, has been
achieved by reacting benzil and thiosemicarbazide in the absence of metal salt and using a high dilution technique. Macrocyclic complexes 6
and 7 containing thiosemicarbazone moieties were obtained from L2H2 and copper nitrate and sulfate. Direct reaction between the copper salt
and the macrocyclic thiosemicarbazone (L3H2) gave similar complexes but with a lower grade of purity. Macrocyclic complexes 6 and 7
present metal–ligand ratios of 1:2 and 1:1 and the ligand is in a deprotonated form. The redox behaviour was explored by cyclic voltammetry.
L1H6 complexes show Cu(II)/Cu(I) couples and quasireversible waves associated with the Cu(III)/Cu(II) process. Thereduction/oxidation
potential depends on the structure and conformation of the central atom in the coordination compounds.
rights reserved.
q2000 Elsevier Science Ltd All
Keywords: Thiosemicarbazones; Macrocyclic ligands; Electrochemistry; Copper complexes; Dithio-Schiff base complexes
1. Introduction
these molecules special reactivity. For a particulardicarbonyl
and diamine as precursors, control of the reaction conditions
allows the condensation product formed to be determined:
[1q1], [1q2] and [2q2] condensation products, with
open chain and cyclic structures. Alternatively, the high dilu-
tion technique is a good method to obtain macrocyclic Schiff
bases [14]. The most important factors are the solvent, pH,
temperature and the presence of metal ions. Metal salts have
been used as templating agents to yield macrocyclic Schiff
bases from diamine and dicarbonyl as precursors [15,16],
but transition metals such as copper and nickel, which have
been used in the preparation of aza crowns, are surprisingly
absent [17]. If the metal is present, the size, charge and
favourable geometries of the metal have to be considered.
Biological activities may be related to the redox properties
of complexes. For some copper(II) compounds a lower
reduction potential seems to be related to an increased anti-
Schiff base macrocyclic ligands based on thiosemicarba-
zones and their complexes have received considerable atten-
tion since, because of their pharmacological properties, they
have numerous applications, for example as antibacterialand
anticancer agents [1–3]. They can yield mono- or polynu-
clear complexes, some of which are biologically relevant[4–
7]; for example, some copper complexes can serve as models
for enzymes such as galactose oxidase and may be used as
effective oxidant and redox catalysts [8,9]. Furthermore,
they allow selective complexation and extraction of metallic
cations and anions of biochemical and environmental impor-
tance [10–13]. The number and relative position of donor
atoms and the cavity size in the macrocyclic compounds give
0277-5387/00/$ - see front matter q2000 Elsevier Science Ltd All rights reserved.
PII S0277-5387(99)00383-6
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E. Franco et al. / Polyhedron 19 (2000) 441–451
fungal activity [1,3]. Some copper complexes exhibit the
abilities of superoxide dismutase (SOD) and chemicalnucle-
ases [18,19]. Moreover, copper is also toxic in elevated con-
centration so many investigations have attempted to develop
sensors to determine its presence with high selectivity.Poten-
tiometric measurements with copper ion-selective electrodes
(ISE) allow the free ion concentration to be determined
directly in water samples. The possible biomimetic activity
and the potential application as sensors for copper complexes
can be evaluated from the electrochemical behaviour and
visible and EPR spectra.
The redox properties include oxidation and reduction of
the central metal ion, various oxidation and reduction reac-
tions of the ligand, and processes which involve both the
central atom and the ligand [20]. The redox potentials of the
Cu(III)/Cu(II) and Cu(II)/Cu(I) couples have been
shown to be markedly affected by the nature of the solvent,
background electrolyte and by the structure of the chelating
ligand and of the complex as a whole. Redox potentials of
Cu(II)–Cu(I) systems depend on the relative thermody-
namic stabilities of the two oxidation states in a given ligand
environment. The factors influencing the metal-locatedredox
properties of the copper systems have been extensively stud-
ied. The influence of various structural features has been
gauged, including ring size, degree and arrangement of unsa-
turation and alkyl substitution [21–23].
and different structure, with a particular metal ion. In addi-
tion, we are trying to determine the best conditions to control
the nature of copper complexes, since the different structures
can improve their potential applications. Therefore, wereport
the reactions of an open chain ligand, benzilbisthiosemicar-
bazone L1H6, a cyclic molecule 6-methoxi-1,6-diphenyl-4-
thio-3,4,5,6-tetrahydro-2,3,5-triazine L2H2 (Fig. 1) with
copper(II) chloride, nitrate and sulfate in variable work con-
ditions. Since a new free macrocycle 3,4,9,10-tetraphenyl-
1,2,5,6,8,11-hexaazacyclododeca-7,12-dithione-3,4,9,10-
tetraene L3H2 (Fig. 1) has been obtained from the reaction
of L2H2 with copper chloride, we have studied its interactions
with copper nitrate and sulfate. We have studied the electro-
chemical behaviour of complexes by cyclic voltammetry,
because their applications as SOD mimetic complexes and as
copper sensors are related to the redox properties.
2. Experimental
2.1. Reagents
Copper salts were commercial products of highest chemi-
cal grade (Fluka). Solvents were purified according to stan-
dard procedures.
In previous work, we obtained different condensation
products from the reaction of benzil and thiosemicarbazide
depending on the reaction conditions: open chain molecule,
benzilbisthiosemicarbazone L1H6, and a cyclic [1q1] mol-
ecule L2H2. Both compounds were obtained in the absence
of metalsalts(nickel, copperoriron), becauseinthepresence
of these salts the product isolated was always a thiosemicar-
bazide complex, even when working with high dilution con-
ditions [24]. However, the reaction between the open chain
molecule and iron chloride in methanol and in the presence
of lithium hydroxide gave an iron complex of a macrocyclic
species, but it is not possible to obtain the free macrocycle
from this complex [25]. We have prepared metal complexes
from L1H6 with several metal salts [24,26]. Redox properties
of cobalt(II) and nickel(II) complexes have been explored
[26]. Some copper derivatives have shown that the changes
in the coordination sphere are connected with the halfwave
potential values for the Cu(II)/Cu(I) redox couple, and
these results and the spectral data on solution agree with the
superoxide dismutase (SOD) mimetic activity [27]. More-
over, carbon paste ion selective electrodes based on thio-
hydrazone and thiosemicarbazone complexes exhibit rapid
response, adequate sensitivity and selectivity for copper ions
[28].
2.2. Synthesis of the organic molecules
Benzilbisthiosemicarbazone, L1H6, was prepared follow-
ing the procedure previously reported [24].
L2H2 was prepared by modifying the published procedure
[25]. A solution of thiosemicarbazide (1.14 g, 12.5 mmol)
in methanol (150 cm3), a solution of hydrochloric acid (25
cm3, 2 M), 1 cm3 of HCl (12 M) and a solution of benzil
(2.63 g, 12.5 mmol) in methanol (100 cm3) were added
alternately dropwise and slowly with strong stirring to 75 cm3
of methanol. After completion of the addition of all reactants,
the mixture was heated for 8 h. Overnight a crystalline solid
wasformed, whichwasfilteredoff, washedanddriedinvacuo
(yield 95%).
As a part of our work involving the preparation of free
iminomacrocyclic compounds and their metal complexes, we
are interested in obtainingthefree[2q2]condensationprod-
uct from benzil and thiosemicarbazide. The aim of our work
is to compare the reactivity of different macroligands con-
taining the same functional group, but with variable number
Fig. 1. Structures proposed for the organic molecules.
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443
A solution of copper chloride dihydrate (0.23 g, 1.40
mmol) in methanol (50 cm3) was added to a solution of L2H2
(0.41 g, 1.40 mmol) in methanol (50 cm3). The mixture was
stirred for 2 h at room temperature. The cream solid L3H2
formed was filtered off, washed several times with methanol
and dried in vacuo (yield 79%), m.p. 2058C. Anal. Calc. for
C30H22N6S2: C, 67.92; H, 4.15; N, 15.85; S, 12.07. Found:
C, 67.82; H, 4.28; N, 15.75; S, 12.13%. Selected spectro-
scopic data: m/z (FAB) 529.1 (C30H21N6S2, 100%). 13C
NMR (DMSO, 300 MHz): 166.90 (CS), 156.57, 155.97
(CN), 134.89, 134.54, 131.31, 129.79, 129.47, 128.67,
128.57 (Ph).
1.50 mmol) in methanol (20 cm3). The mixture was stirred
for 3 h at room temperature. The brown solid 4 formed was
filtered off, washed with methanol and dried in vacuo (yield
65%).
A solution of copper(II) nitrate trihydrate (0.36 g, 1.50
mmol) in methanol (20 cm3) and 50 cm3 of nitric acid (15
M) was added to L1H6 (0.53 g, 1.50 mmol) in methanol (20
cm3). The mixture was stirred for 2 h at room temperature.
The green oil formed was concentrated in a rotary evaporator
to half the initial volume and then the solvent was evaporated
slowly at room temperature. Finally needle shaped yellow
crystals were separated.
Identical results were obtained adding the acid (2 M)
dropwise.
2.3. Synthesis of the complexes from L1H6 and copper(II)
chloride dihydrate
2.5. Synthesis of complexes from L1H6 and copper(II)
sulfate pentahydrate
To L1H6 (0.20 g, 0.56 mmol) in methanol (25 cm3) was
added a solution of copper(II) chloride dihydrate (0.10 g,
0.56 mmol) in methanol (40 cm3). The mixture was stirred
for 5 h at room temperature, heated under reflux for 5 h or
heated under reflux for 5 h in the presence of LiOH. In all
cases a brown solid 1 was formed, which was filtered off,
washed with methanol and dried in vacuo (yield 40%).
To L1H6 (0.20 g, 0.56 mmol) in methanol (25 cm3) was
added a solution of copper(II) chloride dihydrate (0.05 g,
0.28 mmol) in methanol (20 cm3). The mixture was stirred
for 12 h at room temperature. The reddish solid 2 formed was
filtered off, washed with methanol and dried in vacuo (yield
20%).
A solution of copper(II) chloride dihydrate (0.24 g, 1.40
mmol) and hydrochloric acid (50 cm3, 12 M) in methanol
(50 cm3), was added to L1H6 (0.50 g, 1.40 mmol) in meth-
anol (100 cm3). The mixture was refluxed for 3 h with stir-
ring. The green solid 3 formed was filtered off, washed with
methanol and dried in vacuo (yield 85%).
To a suspension of L1H6 (0.10 g, 0.30 mmol) in methanol
(40 cm3) was added a solution of copper(II) sulfate penta-
hydrate (0.06 g, 0.28 mmol) in methanol (40 cm3). The
mixture was stirred for 6 h at room temperature. The reddish
solid formed was filtered off, washed withmethanolanddried
in vacuo (yield 20%).
To a suspension of L1H6 (0.10 g, 0.30 mmol) in methanol
(40 cm3) were added three drops of sulfuric acid (18 M)
and then a solution of copper(II) sulfate pentahydrate (0.07
g, 0.28 mmol) in methanol (40 cm3). The mixturewasstirred
for 12 h at room temperature. On slow diffusion of ether
through the dark blue oil formed, a crystalline dark blue solid
5 was obtained. The solid was filtered off, washed with ether
and dried in vacuo (yield 51%).
2.6. Synthesis of complexes derived from L2H2
The same solid was obtained if the acid (2 M) was added
dropwise.
A solution of copper(II) nitrate trihydrate (0.15 g, 0.63
mmol) in methanol (20 cm3) was added to a suspension of
L2H2 (0.37 g, 1.26 mmol) in methanol (20 cm3). The mix-
ture was stirred for 12 h at room temperature. The brown
solid 6 formed was filtered off, washed with methanol and
dried in vacuo (yield 27%).
A solution of copper(II) sulfate pentahydrate(0.10g, 0.40
mmol) in methanol (20 cm3) was added to a suspension of
L2H2 (0.24 g, 0.80 mmol) in methanol (20 cm3). The mix-
ture was stirred for 12 h at room temperature. The orange–
brown solid 7 formed was filtered off, washed with methanol
and dried in vacuo (yield 37%).
A suspension of L1H6 (0.75 g, 2.10 mmol) in dichloro-
methane (25 cm3) was mixed with a suspension of cop-
per(II) chloride dihydrate (0.36 g, 2.10 mmol) in the same
solvent (20 cm3). The mixture was refluxed for 2 h with
stirring. The green solid formed was filtered under nitrogen
and dried in vacuo. The solid decomposes very quickly in the
presence of air.
The reaction was carried out using toluene and cyclohex-
ane as solvent with the same results described above.
A solution of copper(II) chloride dihydrate (0.10 g, 0.58
mmol) in methanol (50 cm3) was added to a suspension of
L1H6 (0.20 g, 0.58 mmol) and benzil (0.12 g, 0.58 mmol)
in methanol (60 cm3). The mixture was refluxed for 4 h with
stirring. The brown solid formed was filtered off, washed
with methanol and dried in vacuo (yield 45%).
2.7. Synthesis of complexes from L3H2
A solution of copper(II) chloride dihydrate (0.02 g, 0.23
mmol) in dried methanol (10 cm3)wasaddedtoasuspension
of L3H2 (0.11 g, 0.23 mmol) in dried methanol (10 cm3).
The mixture was heated under reflux with stirring for 2 h.
The red solid 8 formed was filtered off, washedwithmethanol
and dried in vacuo (yield 27%).
2.4. Synthesis of complexes from L1H6 and copper(II)
nitrate trihydrate
A solution of copper(II) nitrate trihydrate (0.36 g, 1.50
mmol) in methanol (20 cm3) was added to L1H6 (0.53 g,
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A solution of copper(II) nitrate trihydrate (0.02 g, 0.90
absorption bands observed in the IR spectrum are consistent
with the functional groups present in the molecule.
mmol) in methanol (20 cm3) was added to a suspension of
L3H2 (0.05 g, 0.90 mmol) in methanol (20 cm3). The mix-
ture was heated under reflux with stirring for 2 h. The clear
brown solid 9 formed was filtered off, washed with methanol
and dried in vacuo (yield 47%).
The reaction of compound L2H2 with copper chloride,
under the described conditions, is the first direct procedure to
isolate a free macrocycle L3H2 containing thiosemicarbazone
moieties. The copper chloride acts as a selective template in
the reaction from the mesocycle. This effect is original
because the template usually acts from diamine and dicar-
bonyl as precursors, but with benzil and thiosemicarbazide
the condensation reaction does not work [24].
2.8. Physical measurements
Microanalyses were carried out using a Perkin-Elmer2400
II CHNS/O elemental analyser. Copper was analysed on a
Hitachi Z-8200 atomic absorption spectrophotometer.
The direct reaction, using the high dilution technique,
improves the yield of the cyclic ligand L2H2, which could be
useful in the future since this molecule is a potential antican-
cer agent and it is being currently tested against the full panel
of 60 human tumours (NSC no. 711635-Y) by the National
Cancer Institute (USA).
The complexes characterized are stable to air andmoisture.
The analytical data of complexes are consistent with the stoi-
chiometries proposed which are summarized in Table 1.
IR spectra in the 4000–400 cmy1 range were recorded as
KBr pellets on a Bomen-100 spectrophotometer and in the
range 550–200 cmy1 on a Bruker IFS 66V spectrophoto-
meter. UV–Vis spectra in solution were registered on an Ati-
Unicam UV2 spectrophotometer and the solid reflectance
spectra on a Pye-Unicam SP-8-100 spectrophotometer. Con-
ductivity data were measured using freshly prepared DMF
solutions (ca. 10y3 M) at 258C with a Metrohm Herisau
1
model E-518 instrument. H and 13C NMR spectra were
3.1. L1H6 complexes
recorded on a Bruker AMX-300 spectrophotometer using
dimethylsulfoxide-d6 as solvent and TMS as internal refer-
ence. EPR spectra in the solid state were run on a Bruker ER
200D X-band spectrophotometer.
Fast atom bombardment mass spectra were recorded on a
VG Auto Spec instrument using Cs as the fast atom and m-
nitrobenzylalcohol (mNBA) as the matrix.
Electrochemical measurements were performed with a
BAS CV 27 voltammograph and a BAS A-4 XY register
using a glassy carbon (f 5 mm) working electrode, a plati-
num wire as auxiliary, and a double junction, with porous
ceramic wick, Ag/AgCl reference electrode, standardizedfor
the redox couple ferricinium/ferrocene (E1/2sq0.400 V,
DEps60 mV). Cyclic voltammetry studies of ligands and
complexes were carried out on 0.01 M solutions in dimeth-
ylsulfoxide (L1H6 complexes) and dichloromethane (L2H2
derivatives) containing 0.1 M [NBu4][PF6] as supporting
electrolyte. The range of potential studied was between q1
andy1.5 V. All solutions were purged with nitrogen steam
for 5 min before measurement and the working electrode was
polished before each experiment with diamond paste. The
procedure was performed at room temperature and a nitrogen
atmosphere was maintained over the solution during the
measurements.
Complexes from L1H6 present different formulae and var-
iable grades of deprotonation depending on the halide and/
or the working conditions, in particular the presence of
protons.
From the copper chloride reactions, three type of com-
plexes with the same stoichiometry are obtained. In methanol
as solvent, complexes 1, 2 and 3 are isolated; the last com-
pound appears only in the presence of hydrochloric acid.
Working in a molar ratio 1:2, the complex 2 is obtained. This
product had been obtained previously in ethanol under reflux
[24]. The reaction in the presence of benzil yields complex
1.
The reactions with nitrate give only the complex 4 because
by working in the presence of nitric acid only a ligand break-
down product is obtained. However, with sulfate two differ-
ent complexes are obtained, 5 and 2, depending on whether
or not protons are present in the medium.
The analytical data of complexes are in agreement with the
ligand acting as a monoanion in complexes 1 and 4, a dianion
in complex 2 and a neutral molecule in complexes 3 and 5.
The mass spectra of complexes show a peak at 418 amu
corresponding to [C16H15N6S2Cu]qq1 and in addition for
complex 4 the spectrum exhibits the peak corresponding to
the molecular mass.
The conductivity data in DMF indicate that the complexes
are non-electrolyte compounds, but complex 5 is a 1:1 elec-
trolyte [29]. Therefore chloride and nitrate are bonded to the
copper ion, while the sulfate ion is outside the metal coordi-
nation sphere.
3. Results and discussion
The reaction of L2H2 with copper chloride in methanol at
room temperature yields a cream solid. The analytical data
show the modification of the reactant. The mass spectrum
shows a peak at 529 amu corresponding to the macrocyclic
species [C30H21N6S2]q. The H NMR spectrum in DMSO
3.1.1. IR spectra
1
confirms the absence of methanol inserted or as a crystalli-
zation molecule. The 13C NMR spectrum shows signals cor-
responding to one thio group, seven phenyl carbons and two
imine carbons, confirming the proposed structure. The
The most significant IR bands, useful for determining the
ligand mode of coordination, are listed in Table 2. The most
important bands of the ligand were assigned according to
published data [24].
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E. Franco et al. / Polyhedron 19 (2000) 441–451
445
The absence of any bands in the 2600–2800 cmy1 region
of the IR spectra of L1H6 and its complexes suggests the
absence of any thiol tautomer in the solid state [30].
The spectrum of complex 2 shows three bands in the 3500–
3000 cmy1 region, which indicate the total deprotonation of
the ligand. Spectra of complexes 3 and 5 exhibit a larger
number of bands in the amine stretching region, which con-
firms that the neutral form of the ligand is bonded in these
complexes. Spectra of complexes 1 and 4 show an interme-
diate situation, more bands than complex 2 and less than
complex 3, which agrees with a partial loss of the acidic
hydrogens present in L1H6. These conclusions are according
to the analytical data of complexes and the mass spectrum of
complex 4.
The IR spectra of the complexes, except complex 5, show
the band assigned to the azomethine nitrogen shifted to lower
wavenumber [31]. Coordination of these nitrogens is con-
firmed with the presence of new bands assignable to n(Cu–
NC) in the spectra of complexes (Table 2) [32].
In the spectra of complexes 3 and 5, in which the ligand
acts in its neutral form, the band assigned to d(NH2) remains
in the same position as in the free ligand, so the primary
amines are not bonded to the copper ion. In addition, coor-
dination via the sulfur atoms is indicated by a decrease in the
frequency of the thioamide band. The presence of a new band
assignable to n(CuS) confirms that the sulfur atoms are
involved in the coordination.
The spectrum of complex 4 shows bands corresponding to
the nitrate anion coordinated to the copper. Except for these
bands, this spectrum is very similar to the spectra of 1 and 2
in the 1700–700 cmy1 region so the ligand coordination
modes must be the same. The three spectra show a band at
1634 cmy1, which could be related to the d(NH2) shifted
because of bonding to copper or the new CN group since the
ligand is deprotonated. The new bands appearing below 500
cmy1 confirm that the primary amines arebondedtothemetal
ion. Therefore L1H6 acts as a tetradentate ligand through four
nitrogen atoms.
From the IR spectra data, one can deduce that the coordi-
native behaviour of L1H6 depends on whether it is deproton-
ated or acts in its neutral form. In complexes 1, 2, and 4,
which contain the ligand in deprotonated form, it is bonded
to the copper through four nitrogen atoms (provided by the
imine and the primary amine groups). However, in com-
plexes 3 and 5, in which L1H6 acts as a neutral molecule, the
sulfur atoms participate in the coordination. The copper coor-
dination sphere is completed by the anions present in com-
plexes 1, 3 and 4.
3.1.2. Electronic and EPR spectra
The significant electronic absorption bands in the spectra
of complexes recorded in solution and in solid state are pre-
sented in Table 3.
The reflectance spectra of complexes 3, 4 and 5 present
bands in the same region, so the copper will have the same
environment, with a distorted octahedral geometry around
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Table 2
Relevant IR spectral data and assignament of L1H6 complexes (cmy1
)
n(NH)qn(NH2)
n(C_N)qd(NH2) Thioamide I
Thioamide IV n(Cu–N)/n(Cu–S) n(Cu–X)
L1H6
3420 a, 3330 a, 3250, 3090 1610, 1585
1465 a
1445, 1527
1467, 1427
1535, 1446 a
1551, 1532, 1447 848
1560
837
CuC16H15N6S2Cl (1)
CuC16H14N6S2 (2)
CuC16H16N6S2Cl2 (3)
CuC16H15N6S2NO3 (4)
3443, 3240 a, 3084 a
3343, 3271, 3102
3333, 3240 a, 3084
1626, 1611, 1575
848
836
768
447, 427
449, 428
427, 297
447, 428
292
329
1626, 1600, 1569
1609, 1575
284
335, 350
3438 a, 3406 a, 3269, 3082 1634, 1608, 1575
CuC16H16N6S2SO4P2CH3OH (5) 3308 a, 3140, 3100 a
1653, 1632
784
a Several bands.
Table 3
Electronic spectra (nm) and EPR data for L1H6 complexes
Complex
Diffuse reflectance
Solid
Solution
DMF
EPR
DMSO
MeOH
DMFqHX
g≤
gH
g0
1
2
3
4
5
372, 466, 666(sh) a
420, 490, 540(sh)
424, 590–690
600–520
500, 550(sh)
500, 550(sh)
500, 550(sh)
500, 550(sh)
500, 550(sh)
500, 550(sh)
500, 550(sh)
500, 550(sh)
500, 504
483
484
484
500, 544(sh)
2.17
2.14
2.18
2.15
2.07
2.05
2.07
2.06
2.10
2.08
2.11
2.09
2.07
694, 767
694, 767
580
500, 550(sh)
483
a sh shoulder.
the metal ion [33]. Therefore, the nitrate ion acts as a biden-
tate ligand in complex 4. The spectrum of complex 2 agrees
with a quasiplanar disposition for the copper ion. The spec-
trum of complex 1 is different from the others, the number
and positions of the absorption bands suggest a pentacoor-
dinated geometry.
Structures for each coordination number are illustrated in
Fig. 2, where we have plotted the output of the calculation
carried out using the Hyperchem program (semiempirical
method, ZINDO/1).
The solution spectra of all complexes in DMSO, DMF and
methanol present the same absorption bands (solutions are
red), so the solvent molecules partially replace the anion in
the coordination sphere of copper, giving a quasiplanar envi-
ronment in all complexes. The spectrum of complex 2 does
not change in solution because the disposition in the solid
state was already quasiplanar.
For complexes 3 and 5 the spectra in DMF were registered
after the addition of hydrochloric acid (2 M). An important
change was observed: the solution colour changes to green
and the position of the band indicates a significant modifi-
cation in the copper coordination sphere giving a pseudo-
octahedral geometry for the copper ion as in the complexes
in the solid state (Fig. 3) [33].
We studied the variation of UV–Vis spectra of 10y3
M
Fig. 2. Possible structures for L1H6 complexes: (a) complex 1, (b) complex
2, (c) complex 3.
copper(II) chloride dihydrate solution in DMSO after suc-
cessive additionsof 10y3 M L1H6 solutioninthesamesolvent
with the total volume constant and in the presence of
[NBu4][PF6] to maintain the ionic force. The visible spectra
were recorded and the absorbance variations representedver-
sus the molar fraction of ligand added/Cu (Fig. 4).
From the first addition, a new band appears at 448 nm in
the visible spectrum whose absorbance increases lineally
until a 2 molar fraction; after that the value is constant.
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E. Franco et al. / Polyhedron 19 (2000) 441–451
447
Fig. 5. Solid state EPR spectrum of complex 1.
value, which agrees with the L1H6 being tetradentate dianion
and pseudo-planar, while the higher value is presented for
complex 3 in which the ligand is neutral and the copper is
hexacoordinated [8,30,34].
Fig. 3. UV–Vis spectra of complex 3 [CuL1H6Cl2]: (a) DMF solution; (b)
DMFqHCl (2 M).
The spectra were registered after 2 days, and the position
of the band is shifted to 500 nm (identical position to that in
the isolated complexes in DMSO solutions). The absorbance
increases until a 1.5 molar fraction and then is constant (Fig.
4). Therefore, in DMSO a 1:1 molar ratio complex is formed
but in this solvent an excess of the ligand is necessary.
The EPR parameters observed for complexes in the solid
state (300 K) are presented in Table 3. In Fig. 5 the spectrum
of complex 1 is shown.
3.2. Complexes derived from L2H2
Reactions of the mesocyclic ligand L2H2 with copper(II)
nitrate and sulfate hydrate give stable solids in air and mois-
ture. The colour, melting point and analytical data are
included in Table 1. The formulae of complexes depend on
the metal salt used.
The EPR spectra, which do not show hyperfine coupling,
confirm the copper oxidation state and the mononuclear
nature for the complexes. Complexes 1, 2, 3 and 4 givetypical
axial spectra, but complex 5 has a slightly axial isotropic
spectrum. Values of g≤ and gH are in the range for this kind
of complexes. In all of the complexes, g≤)gH)2 values are
Reaction with nitrate gives complex 6, whose analytical
data and mass spectra indicate that the complex contains the
deprotonated macrocyclic ligand L3H. The mass spectrum
shows a peak at 529 amu corresponding to the macrocycle
molecular mass [C30H21N6S2]q and a peak corresponding
to the fragment [CuC30H21N6S2CH3OH]q. From the reac-
tion with sulfate the complex 7 was obtained. Its analytical
2
2
consistent with a dx yy state. Complex 2 presents a lower g≤
Fig. 4. Absorbance evolution of the L1H6 copper complex, in DMSO solution, versus ligand/Cu molar fraction; (e) direct measurements; (q) after 24 h.
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448
E. Franco et al. / Polyhedron 19 (2000) 441–451
Table 4
Relevant IR spectral data and assignment of L2H2 complexes (cmy1
)
n(N–H)
n(C_N)
Thioamide I
Thioamide IV
n(Cu–N)/n(Cu–S)
L2H2
3184, 3131
3057
3053
1608
1599, 1581
1601, 1583, 1575, 1550
1600, 1582, 1575, 1550
1550
1480
1485
1488
846
866
865
878, 866
L3H2C30H22N6S2
Cu(C30H21N6S2)2CH3OH (6)
CuC30H20N6S2 (7)
439
436
3053
data suggest a 1:1 deprotonated ligand:copper ratio. Themass
spectrum confirms the macrocyclation of the ligand. In addi-
tion, in both reactions L3H2 is isolated from the reaction
liquor. Therefore, the macrocyclic ligand is formed in all
reactions where the copper ion acts as template. The charac-
teristics of the final product depend on the salt used. A free
macrocycle is obtained in the reaction with copper chloride,
while complexes were isolated from the reaction with nitrate
and sulfate.
of the Cu(II)/Cu(I) process is related to the potential SOD
mimetic activity. Both ranges of potentials were studiedinde-
pendently. The electrochemical response in the total range
studied (Figs. 6–8) showed a pattern that can be considered
as the sum of the individual responses.
The cyclic voltammogram of L1H6 in DMSO shows irre-
versible reduction waves in the more negative region (Fig.
9(b)) [26,35].
The voltammetric response of all L1H6 complexes exhibits
oxidation and reduction metal centred processes, as for com-
plexes previously published [27]. Cyclic voltammograms
between q1 and 0.0 V show a redox couple associated with
the Cu(III)/Cu(II) process (Table 5). In addition, in the
range 0.0 to y1.5 V, peaks which can be assigned to Cu(II)/
Cu(I) and Cu(I)/Cu(0) processes appear [1].
Cyclic scanning of complex 1 (Fig. 6(a)) between q1
and 0 V shows in the cathodic scan a peak at q0.625 V. In
the forward scan a poorly defined wave at q0.410 V can be
observed and an anodic peak at q0.680 V associated with
3.2.1. IR spectra
The IR spectrum of complex 6 shows only a band assign-
able to n(NH), the thioamide I slightly shifted to higher
frequencies and four bands in the region of stretching vibra-
tion of the imine group (Table 4). These modifications sug-
gest that the L3H2 ligands are partially deprotonated and two
equivalent imine groups of each ligand are bonded to the
copper ion.
The spectrum of complex 7 exhibits the presence of water
and the deprotonation of the ligand. The bands are slightly
shifted with respect to the L3H2, indicating that the ligand is
bonded to the copper ion through four nitrogen atoms.
3.2.2. Electronic spectra
The electronic spectra of complexes in the solid state are
very similar. Both of them show a band at a position which
agrees with a pentacoordination for the copper, so the solvent
molecules are bonded to the copper ion.
3.3. Complexes derived from L3H2
Direct reactions of the macrocyclic ligand with copper
chloride and nitrate give complexes 8 and 9, respectively.
The analytical and spectroscopic data indicate that they are
adulterated with the ligand, although it was necessarytowork
under stronger conditions than with the mesocyclic ligand
L2H2, probably owing to its inherent rigidity.
3.4. Cyclic voltammetry
The study of the electrochemical behaviour of the com-
plexes was carried out in the range from q1 to y1.5 V. In
the positive range, q1 to 0 V, the oxidation processes
Cu(III)/Cu(II) can be observed. Cyclic scanning between
0 and y1.5 V permits study of the copper reduction centred
processes and the ligand reductions; the potential reduction
Fig. 6. Cyclic voltammograms for complexes: (a) complex 1, [CuL1H5Cl];
(b) complex 3, [CuL1H6Cl2]; ns100 mV sy1
.
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E. Franco et al. / Polyhedron 19 (2000) 441–451
449
the cathodic peak at q0.625 V. The DEp values fall in the
range 50–70 mV, when the scan rate is varied between 100–
800 mV sy1, with peak current ratio constant (0.8). Also the
ratio between the cathodic peak current and the square root
of the scan rate (Ipc/n1/2) is practically constant. All of these
data are diagnostic of a quasireversible one-electron transfer
controlled by diffusion following the equation
[Cu(III)L]qeym[Cu(II)L]
Cyclic scans of 1 in the range 0 to y1.5 V reveal peaks at
y0.470 and y0.930 V in the cathodic scan and in the for-
ward scan a peak at y0.390 V associated with the more
negative cathodic peak. These peaks can be assigned to suc-
cessive Cu(II) reduction processes.
The voltammogram of complex 3 (Fig. 6(b)) is very
similar to that of complex 1. The cyclic voltammogram of 3
shows, between q1.5 and 0 V, a cathodic peak at q0.680 V
and an anodic peak at q0.740 V associated with the cathodic
peak. The DEp and the current peak ratio of this couple of
peaks are as expected for a quasireversible Cu(III)/Cu(II)
process.
In the cathodic scan, in the range 0 to y1.5 V, peaks at
y0.400 V and y1.030 V are observed. In the anodic scan
there is a peak at y0.380 V, associated with the more nega-
tive cathodic peak. The first wave is attributed to Cu(II)/
Cu(I) reduction and the other peaks correspond to the
Cu(II)/Cu(0) reduction processes.
Cyclic voltammograms of complexes 4 and 5 (Fig.
6(a,b)) are very similar. The electrochemical response of
complex 4 in the cathodic scan shows a peak at q0.600 V
and in the reverse scanananodicpeakatq0.675Vassociated
with the cathodic peak. The variation of the redox parameters
of the redox couple is indicated in Table 6, so it is associated
with a quasireversible Cu(III)/Cu(II) process. The voltam-
mogram between 0 and y1.5 V shows peaks at y0.520 V
and y0.960 V, which can be attributed to the reductions
Cu(II)/Cu(I) and Cu(I)/Cu(0), respectively. The electro-
chemical parameters for complex 5 are included in Table 6.
The cyclic voltammogram ofcomplex2(Fig. 7(c))shows
a different electrochemical response and it is close to that
published previously [27]. The most importantcharacteristic
is the quasireversible waves associated with the Cu(II)/
Cu(I) process (Table 6).
Fig. 7. Cyclic voltammograms for (a) complex 4, [CuL1H5NO3], (b) com-
plex 5, [CuL1H6CH3OH]SO4, (c) complex 2, [CuL1H4], ns100 mV sy1
.
For all complexes, redox processes associated with oxi-
dation to Cu(III) are observed, probably because the L1H6 is
Table 5
Oxidation potential values (V) of L1H6 complexes
Compound
E1/2 a Cu(III)/Cu(II)
C16H15N6S2CuCl (1)
C16H14N6S2Cu (2)
C16H16N6S2CuCl2 (3)
C16H15N6S2CuNO3 (4)
CuC16H16N6S2SO4P2CH3OH (5)
0.652
0.645
0.710
0.635
0.640
Fig. 8. Cyclic voltammogram of complex 3, [CuL1H6Cl2], in DMSO after
the addition of HCl (2 M), ns100 mV sy1
.
a E1/2s(EpaqEpc)/2, ns100 mV sy1
.
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450
E. Franco et al. / Polyhedron 19 (2000) 441–451
Fig. 9. Evolution of the cyclic voltammogram of CuCl2P2H2O in DMSO (a); with successive additions of L1H6 (b); after 0.4 ml (c); after 1.4 ml (d); after
2.4 ml (e).
Table 6
Summary of electrochemical data for complexes a
Complex
q1.5 to 0 V
0 to y1.5 V
b
Epc
Epa
DEp
Ipc/Ipa
Epc
Epa
Epc
1
2
3
4
5
0.625
0.620
0.680
0.600
0.610
0.680
0.670
0.740
0.675
0.670
0.055
0.050
0.060
0.075
0.060
0.800
0.860
1.000
0.980
0.820
y0.470
y0.600
y0.400
y0.520
y0.510
y0.390
y0.500
y0.380
y0.930
y1.030
y0.960
y0.990
a Redox potential (V) at 298 K, scan rate 100 mV sy1. Cyclic voltammograms registered in the range from q1 to y1.5 V.
b Scan rate in the range 100–800 mV sy1
.
an open chain ligand and in its complexes the oxidation of
copper is favoured since this ligand can adopt a different
conformation to fit the small copper(III). The change from
the Cu(II) to the Cu(III) state (d8 low spin) involves a
drastic reduction of the metal ion radius. In addition, this
process does not involve changes in the geometries of the
copper(II) complexes in DMSO solution. The oxidation val-
ues in Table 5 agree with that, because more positive values
and more difficulty in stabilizing the copper(III) oxidation
state are observed for complexes 1 and 3 [36,37].
On the other hand, the values of the reduction potential fall
in the range y0.400 to y0.520 V, indicating difficulty in
reducing the copper(II) ion in these complexes. This fact can
be interpreted in terms of less favourable fitting of the
Cu(II)/Cu(I) ion, because this reduction is related to the
level of tetrahedral distortion in the complexes and in our
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E. Franco et al. / Polyhedron 19 (2000) 441–451
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case in solution they seem to be almost planar. In accordance
with these reduction potentials and the electronic spectra of
L1H6 complexes, they do not seem to be suitable SOD
mimetics.
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The electrochemical response of complexes 1 and 3 with
successive additions of hydrochloric acid (2 M) was also
studied. The voltammogram changes immediately with the
first addition, the more positive potential peaks are modified
and a new peak couple arises. These changes increase with
the successive additions of acid or with time until 1 cm3 is
added. The voltammogram (Fig. 8) now shows two peaks at
q0.280 and y1.00 V in the cathodic scan and an anodic
peak at q0.360 V associated with q0.280 V, indicating a
significant change in the complex structure under these con-
ditions. These results agree with thosefromthevisiblespectra
in the same solvent described in the previous section.
Reaction of copper(II) chloride with L1H6 in DMSO was
studied by cyclic voltammetry. Cyclic voltammograms of
CuCl2P2H2O solutions in DMSO, in which L1H6 was added
gradually until a 1:3 molar ratio was reached, were recorded
(Fig. 9(a,b)). Changes in the colour and in the electrochem-
ical response were shown from the first addition. The changes
increase when the ligand proportions increase (Fig. 9(c,d)),
but the cyclic voltammogram does not reproduce the cyclic
voltammogram of isolated complex until a 1:2.5 molar ratio.
These results indicate that the complexation reaction is slow.
The donor character of the solvent may be the reason for that,
owing to the difficult substitution by the ligand as was shown
for the visible spectra of complexes.
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We thank Professor J. Borras (Universitat de Valencia)
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