Metal(II) Ion Complexes with 5-(Pyrazin-2-yl)-2,4-dihydro-3H-1,2,4-triazole-3-thione; Synthesis, Structural Characterization, Acid-base, and Complexing Properties in Solution

Article abstract of DOI:10.1002/zaac.201700102

The study reports the synthesis of complexes Co(HL)Cl₂ (1), Ni(HL)Cl₂ (2), Cu(HL)Cl₂ (3), and Zn(HL)₃Cl₂ (4) with the title ligand, 5-(pyrazin-2-yl)-1,2,4-triazole-5-thione (HL), and their characterization by elemental analyses, ESI-MS (m/z), FT-IR and UV/Vis spectroscopy, as well as EPR in the case of the Cu^II complex. The comparative analysis of IR spectra of the metal ion complexes with HL and HL alone indicated that the metal ions in 1, 2, and 3 are chelated by two nitrogen atoms, N(4) of pyrazine and N(5) of triazole in the thiol tautomeric form, whereas the Zn^II ion in 4 is coordinated by the non-protonated N(2) nitrogen atom of triazole in the thione form. pH potentiometry and UV/Vis spectroscopy were used to examine Co^II, Ni^II, and Zn^II complexes in 10/90 (v/v) DMSO/water solution, whereas the Cu^II complex was examined in 40/60 (v/v) DMSO/water solution. Monodeprotonation of the thione triazole in solution enables the formation of the L:M = 1:1 species with Co^II, Ni^II and Zn^II, the 2:1 species with Co^II and Zn^II, and the 3:1 species with Zn^II. A distorted tetrahedral arrangement of the Cu^II complex was suggested on the basis of EPR and Vis/NIR spectra.

Full text of DOI:10.1002/zaac.201700102

Journal of Inorganic and General Chemistry
DOI: 10.1002/zaac.201700102
ARTICLE
Zeitschrift für anorganische und allgemeine Chemie
Metal(II) Ion Complexes with 5-(Pyrazin-2-yl)-2,4-dihydro-3H-
1
,2,4-triazole-3-thione; Synthesis, Structural Characterization,
Acid-base, and Complexing Properties in Solution
[b]
Aleksander Kufelnicki,*[a] Jolanta Jaciubek-Rosi n´ ska,[a] Marta Sobiesiak, Agata Paneth,[c,d] Julia Jezierska,[e]
and Elzbieta Budzisz[f]
Abstract. The study reports the synthesis of complexes Co(HL)Cl
1), Ni(HL)Cl (2), Cu(HL)Cl (3), and Zn(HL) Cl (4) with the title
ligand, 5-(pyrazin-2-yl)-1,2,4-triazole-5-thione (HL), and their charac-
terization by elemental analyses, ESI-MS (m/z), FT-IR and UV/Vis whereas the Cu complex was examined in 40/60 (v/v) DMSO/water
2
by the non-protonated N(2) nitrogen atom of triazole in the thione
(
2
2
3
2
form. pH potentiometry and UV/Vis spectroscopy were used to exam-
II
II
II
ine Co , Ni , and Zn complexes in 10/90 (v/v) DMSO/water solution,
II
II
spectroscopy, as well as EPR in the case of the Cu complex. The
comparative analysis of IR spectra of the metal ion complexes with
solution. Monodeprotonation of the thione triazole in solution enables
II
II
II
the formation of the L:M = 1:1 species with Co , Ni and Zn , the 2:1
II
II
II
HL and HL alone indicated that the metal ions in 1, 2, and 3 are species with Co and Zn , and the 3:1 species with Zn . A distorted
chelated by two nitrogen atoms, N(4) of pyrazine and N(5) of triazole tetrahedral arrangement of the Cu complex was suggested on the ba-
in the thiol tautomeric form, whereas the Zn ion in 4 is coordinated
II
II
sis of EPR and Vis/NIR spectra.
action.[1] It is noteworthy that mercapto-triazoles can exist in
two major tautomeric forms; the thione/thiole tautomers exhi-
bit different reactivity, metal complexation, and substitution re-
actions.[ The relationship between their binding behavior
towards metal ions, either bidentate- or monodentate, and the
position, as well as the nature of the substituent at the triazole
ring has allowed 1,2,4-triazoles to find various functions in
coordination and bioinorganic chemistry.[ It has been re-
vealed that metal chelation is an advantageous factor in in-
creasing the antibacterial and antifungal activities of some tri-
azole derived compounds because it enhances effective pene-
tration through the lipid layer of the cell membrane.[
Introduction
Triazoles and thiadiazoles, as well as their derivatives, have
drawn a fair degree of scientific attention due to their structural
and biological activity. In particular, the 1,2,4-triazoles and
their derivatives are very important ligands with N,S-donor
centers giving a wide spectrum of possibilities for the synthesis
of subsequent compounds with different specificity or mode of
2]
3]
*
Prof. Dr. A. Kufelnicki
Fax: +48-42-678-8398
E-Mail: aleksander.kufelnicki@umed.lodz.pl
[
a] Department of Physical and Biocoordination Chemistry
Faculty of Pharmacy
4]
Medical University of Łódz´
The triazole rings are known to be pharmacologically impor-
tant scaffolds in a variety of drug categories.[ Their deriva-
tives and metal complexes have been reported as antimicro-
Muszy n´ skiego 1
5]
9
0–151 Łód z´ , Poland
[
b] Collegium Medicum in Bydgoszcz
Nicolaus Copernicus University in Torun´
Faculty of Pharmacy
[6,7]
[8]
[9–11]
[12]
bial,
antiviral, antitumor,
anticonvulsant,
antide-
pressant,[ analgestic,[14] and anti-inflammatory agents.
A series of 1,3,4-thiadiazole-2(3H)-thiones, 1,3,4-oxa-
diazole-2(3H)-thiones, and 4-amino-1,2,4-triazole-5(4H)-
thiones have been synthesized as potent new inhibitors of tyro-
sinase: a copper-containing enzyme responsible inter alia for
biosynthesis of the melanin pigment in skin, hair, and eyes of
humans. Kinetic and active site binding studies attribute their
potent inhibition to the monodentate binding of triazole rings
to the active site, the dicopper center of tyrosinase, and to the
enzyme’s hydrophobicity. Substitutions of the triazole ring
were found to play a major role in the high binding affinity to
tyrosinase.[
13]
[15]
Department of Inorganic and Analytical Chemistry
Jurasza 2
85–094 Bydgoszcz, Poland
[
[
[
[
c] Department of Organic Chemistry
Medical University of Lublin
Chod z´ ki 4a
20–093 Lublin, Poland
d] Institute of Applied Radiation Chemistry
Technical University of Łódz´
˙
Zeromskiego 116
0–924 Łód z´ , Poland
9
e] Faculty of Chemistry
University of Wrocław
1
5
4 F. Joliot-Curie Str.
0–383 Wrocław, Poland
16]
f] Department of Cosmetic Raw Materials Chemistry
Faculty of Pharmacy
1,2,4-Triazole derivatives have also been identified as prom-
Medical University of Łódz´
Muszy n´ skiego 1
ising antiacetylcholinesterase (AChE) agents due to their in-
9
0–151 Łód z´ , Poland
[17]
hibitory effect on AChE.
Cholinesterase inhibitors may be
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/zaac.201700102 or from the au-
thor.
[
18]
very important in the treatment of Alzheimer’s disease.
The
capacity of 4R-1,2,4-triazoles derived from amino acids and
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amino-acid esters to coordinate ZnII ions has been exploited
for their inhibition of metallo-β-lactamases. The activity re- stretching vibrations ν(N–H) of the triazole/triazolate in the
The IR spectra of all the metal complexes show signals of
–1
corded for the triazole derivative of methionine against the region 3292–3431 cm . The presence of a characteristic band
BcII enzyme showed modest inhibition of the BcII enzyme.[
19]
at 2359 cm due to ν(S–H) stretching and the disappearance
–1
–1
This paper reports the synthesis and physicochemical evalu- of the absorption band at ca 1103 cm corresponding to
ation of newly-obtained cobalt(II), nickel(II), copper(II), and ν(C=S) vibrations, shows that complexes 1, 2, and 3 exist in
zinc(II) complexes of the title triazole derivative. It also de- thiol form when in a solid state. The appearance of a C=S
scribes the interaction of this derivative with the same biomet- stretching band at 1107 cm and the absence of an absorption
als in solution. The results would highlight the possibility of band around 2300 cm–1 (which is connected with the S–H
using, and eventually modifying, the thione compound (also as group) suggest that for 4 the ligand coordinates in thione
a ligand coordinated by metal ions) with a pharmacologically form.[22]
–1
important triazole scaffold as a potential enzyme inhibitor.
The spectra of HL and complexes 1–4 also show bands in
the range 1575–1628 cm–1 resulting from stretching vibrations
–1
ν(C=N) and in 1053–1022 cm from stretching vibrations
Results and Discussion
[1]
ν(N–N). For the complexes, these characteristic bands are
shifted to higher, for ν(C=N), and lower, for ν(N–N), fre-
quencies in comparison with the spectrum of the ligand. This
IR Spectroscopic Characterization of Metal Complexes
The most probable structures of complexes 1–4 (Scheme 1) observation can be explained by the nitrogen atom of the tri-
were predicted on the basis of their IR spectra compared with azole ring coordinating with the metal ions in complexes 1–4.
An intensive band that appears for the ligand at 1172 cm–1 due
to the pyrazine ring, is shifted to lower wavelengths and ap-
pears in the spectra of complexes 1, 2, and 3 at about
that of the ligand.
–1
1
157 cm , thus indicating complexation of the metal atoms
[23]
via pyrazine nitrogen. However, in the spectrum of complex
4
, this band remains unshifted, suggesting that the pyrazine
[24]
nitrogen is not involved in coordination.
1H NMR Spectroscopy of the Zinc(II) Complex
1
II
The H NMR spectrum of the Zn complex was recorded
in [D ]DMSO (Figure S2, Supporting Information) and the
6
data is presented in the Experimental Section. The position
and intensity of the signals correspond to reagents used in the
synthesis. In the spectra, a signal was observed at δ = 1.22 ppm
for the proton of the –SH group. This signal is not shifted as
compared to the free ligand (Figure S3, Supporting Infor-
mation). Signals for the protons from the aromatic ring were
found at δ = 8.75 ppm and 9.18 ppm as singlets. The amine
protons of the triazoline ring were observed as two singlets at
δ = 13.90 and δ = 14.12 ppm. Because of the paramagnetic
Scheme 1. Synthesis of CoII (1), NiII (2), CuII (3) and ZnII (4) com-
plexes.
II
character of the Ni complex, the proton NMR spectrum was
unattainable (Figure S4, Supporting Information).
The IR data of the ligand and its metal complexes are listed
in Table 1. The ligand shows characteristic bands at 3294 and
ESI-MS Spectrometry
–
1
–1
3
066 cm due to ν(N–H) and at 2343 cm due to ν(S–H).
–
1
The absorption band at 1103 cm should be assigned as
ν(C=S) vibrations.[
Valuable information about the structure of newly-synthe-
6,20,21]
These results suggest that the 1,2,4- sized complexes 1–4 was obtained by mass spectrometric mea-
surements and is presented in the Experimental Section. The
triazole ligand exhibits thione-thiol tautomerism (Scheme 1).
–1
Table 1. FT-IR spectroscopic data /cm .
Compound
ν(N–H)triazole
ν(C=N)triazole
ν(N–N)triazole
ν(C=N)pyrazine
ν(C=S)triazole
ν(S–H)triazole
HL
1
2
3
4
3294, 3066
3390, 3373
3392,3377
3431, 3397
3292, 3211
1575
1616
1616
1618
1628
1053
1039
1039
1047
1016
1172
1157
1159
1155
1170
1103
–
–
–
2343
2359
2359
2357
–
1107
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peaks observed in the spectra of 1, 2, and 3 were assigned to from the ligand was around 10% lower than the number re-
the ions of parent complexes, whereas for 4, they were as- sulting from the total concentration value. Thus, it may be pre-
+
signed to the [Zn(HL) Cl] ion. The spectra of complexes 1– sumed that coordination occurs due to a dissociable proton of
3
+
4
exhibited peaks ascribed to the molecular ions [ML] (M = one of the tautomeric forms, most likely the thione form usu-
II
II
II
II
[25,26]
Co , Ni , Cu , Zn ). Additionally, the analysis of the spectra ally predominating in non-basic medium.
recorded allowed for the identification of the [Co(HL)Cl] ion ation constant of the ligand was confirmed with high accuracy,
for 1 and the [Zn(HL) Cl] and [Zn(HL) ] ions for 4. The pK = 5.76Ϯ0.01. The corresponding protonation constant log
The dissoci-
+
+
+
2
3
a
peaks at (m/z) 179 and 180 in the spectra of complexes 2 and 3 β011 = pK is found in Table 2.
a
correspond to the L and L+1H ions, respectively. The obtained
results are in good agreement with those derived using the
elemental analysis (see Experimental Section).
Table 2. Protonation constants, cumulative
[
β
mlh
=
[M
M] [L] [H] formation constants and UV/Vis/NIR spectroscopic data
in the metal(II) - 5-(pyrazin-2-yl)-2,4-dihydro-3H-1,2,4-triazole-3-
m l h
L H ]/
m
l
h
II
II
II
thione systems. For Co , Ni and Zn : solv. 10/90 (v/v) DMSO/H
I = 0.1 (KNO
2
O.
O.
II
3
), temp. 25 °C. For Cu : solv. 40/60 (v/v) DMSO/H
2
Potentiometric Equilibrium Studies
Standard deviations in parentheses refer to random errors only.
–
1
–1
The titrations started to neutralize the excess inorganic acid Species
log(βmlh
)
λmax /nm
εmax /m ·cm
and ended in an alkali medium. A representative set of ti-
L a)
3
–
319
314
3.9ϫ10
6.6ϫ10
trations for ligand:metal = 2:1 is shown in Figure 1. In the case
3
LH
5.76(1)
of Cu , the share of DMSO in the solvent had to be increased Cu complexes b)
II
2+
CuL
CuL
6.24(2)
10.31(2)
770 c)
1.3ϫ10
5.6ϫ10
1.0ϫ10
2
2
3
to an optimum 40% (v/v), which led to entire transparency of
the forming brown solution. Even so, this did not enable fur-
ther titration at higher pH due to predominating hydrolytic ef-
c)
2
1050
≈
500 sh d)
Co2+ complexes
fects (cf. last part of the curve for Cu in Figure 1). Therefore, CoL
4.62(2)
8.50(3)
513c
2.0ϫ102
II
d)
3
351
9.9ϫ10
5.1ϫ10
1.3ϫ10
the formation constants of the Cu -HL complexes had to be
c)
2
CoL
2
≈508 sh
determined spectrophotometrically, as will be described later
d
4
324
(chapter “UV/Vis/NIR Studies”).
Ni2+ complexes
NiL
c)
c)
d)
2
5.59(3)
648
3.2ϫ10
2
6
3
94
48
3.1ϫ10
3
6.0ϫ10
Zn2+ complexes
ZnL
ZnL
ZnL
3.98(2)
7.84(1)
10.24(6)
–
–
–
–
–
–
2
3
–
a) L = L deprotonated ligand. b) Results obtained spectrophotometri-
cally. c) d-d transition. d) CT transition.
The potentiometric titrations in the presence of the metals
were also based on measurements below pH 7. These titration
Figure 1. Potentiometric titration of ligand HL and titrations in pres-
ence of the metal ion in an argon atmosphere. The negative values of
II
results indicate the formation of L:M = 1:1 species with Ni ;
II
base equivalent, a, correspond to HNO
3
in excess as related to the however, for Co , the refinements showed higher convergence
II
II
II
ligand. Solv. 10/90 (v/v) DMSO/water for Ni , Co , Zn and with the model involving 1:1 and 2:1 species of formation con-
4
4
0/60 (v/v) DMSO/water for Cu. Ligand-to-metal ratio 2:1. C
.0ϫ10–3 m.
L
=
II
stants presented in Table 2. In the case of Zn , the calculations,
particularly at excess of ligand, indicated also a 3:1 species.
The species distribution curves are shown in Figure 2.
Noteworthy is the agreement of the first step formation con-
It is visible that the base equivalent for the ligand alone
comes close to the end-point at ca 0.8, but does not attain 1.0,
which is due to precipitation occurring at pH Ͼ 7. Such an
effect indicates fair DMSO/water 10/90 (v/v) solubility of the
title triazole ligand in its monodeprotonated form. In contrast,
in the presence of the metals, the titration curves go nearer to
the base equivalent 1.0 as a result of the pH falling due to the
displacement of hydrogen ions by the metal ions. Moreover,
II
II
stants series with the Irving-Williams series (Cu Ͼ Ni
Co Ͼ Zn ).
Ͼ
II
II
UV/Vis/NIR Spectroscopy
The spectrophotometric titrations of the ligand (Figure 3)
these curves do not exhibit inflection after neutralization of the were carried out at concentrations one order of magnitude
excessive inorganic acid, which indicates a high complexing lower than in the potentiometric experiments as the molar ab-
–
affinity of the metal ions to the ligand already in acidic me- sorbances of the two ligand species (HL and L = L ) in the
3
4
–1
–1
dium. Hence, the refinements for ligand HL unambiguously UV reached 10 –10 m ·cm .
need to consider the presence of one dissociable proton of HL Consequently, the lowered concentrations were also used in
II
II
in the proton balance, irrespective of the protons from the ex- presence of the metals Co and Ni . By comparison with a
cessive inorganic acid. However, the analysis of all titrations similar benzene, 1,2,4-triazole derivative described in refer-
show that the refined number of accessible protons originating ence,[ the UV bands of both the ligand forms at 310–320 nm
26]
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are likely due to π Ǟ π* and n Ǟ π* chromophore transitions
of the thione group (Figure S1, Supporting Information). The
lower wavelength part of the total optical density should be
considered as an overall contribution of π Ǟ π* transitions in
the 1,2,4-triazole ring.
During the spectrophotometric titrations in the presence of
II
II
Co and Ni , the absorbance evidently increased, as compared
to the ligand alone, around 400 nm due to the rising contri-
bution of the complex species and their CT bands (Figure 4a
for Co and Figure 5a for Ni). The absorbance plotted against
pH shows buffer zones within the main range of complex for-
II
mation. For Co , the absorbance increases more visibly due to
the rising contribution of the CoL2 species (Figure 4b),
II
whereas for Ni , the absorbance within the buffer zone is due
only to the NiL contribution moderately rising starting from
pH 3.5 (Figure 5b). The maximum wavelengths and calculated
molar absorbances obtained by HypSpec deconvolution are
found in Table 2 (both for the ligand and the complexes with
II
II
Co and Ni ). The values for the ligand field d-d transitions in
the visible part, which are characteristic of pseudo-octahedral
symmetry, are also reported in Table 2. The expected lower
II
d-d transition wavelength of the Ni -L complex around
390 nm was invisible; it was overlapped by the neighboring,
strong CT band.
Figure 2. Species distribution curves as a function of pH in the H+/
Metal ion/HL systems in 10/90 (v/v) DMSO/water solutions·L:M = 2:1
II
II
II
for Co , Ni and L:M = 4:1 for Zn .
+
II
Figure 4. (a) UV/Vis spectra of the H /Co /HL system in an argon
atmosphere recorded by means of a 5 mm dip probe between pH 3.25
and 8.10 (pH values shown for corresponding curves). (b) Absorbance
–
4
–4
at 400 nm as a function of pH. CCo = 1.0ϫ10 m, C
L
= 2.0ϫ10 m.
Solv. 10/90 (v/v) DMSO/water.
II
As it follows from the potentiometric results for Cu , the
spectrophotometric investigations had to be carried out as
batch file titrations at constant pH in 40/60 (v/v) DMSO/water
solutions (Figure 6a). The absorption spectra taken at constant
metal concentration and varying L:M concentration ratio
showed broad low-energy absorption bands moving from 800
to 1050 nm, apparently due to d-d transitions, and finally an
Figure 3. UV/Vis spectrophotometric titration of ligand HL in an ar-
gon atmosphere. Fibre optics dip probe 5 mm (i.e. path length 10 mm).
Characteristic pH values shown for corresponding curves. C
1
L
=
.0ϫ10–4 m. Solv. 10/90 (v/v) DMSO/water.
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EPR Studies
The CoII and NiII complexes appeared to be EPR silent
when the conventional X-band frequency (about 9.6 GHZ) was
II
used at 295 and 77 K. The magnetic measurement of Ni com-
plex gave magnetic moment per individual molecule of 3.09
B.M at 100 K, which corresponds to a high spin (S = 1) 3d8
electron configuration, strongly indicating that the geometry of
the coordination sphere is close to tetrahedral.
The EPR spectrum of the powdered complex CuLCl re-
2
veals a symmetrical, isotropic line at g = 2.12, the same at
295 K and 77 K (Figure 7, spectrum 1). This spectrum feature
is unusual for copper(II) complex, which symmetry of coordi-
nation sphere must be at least axial leading to the anisotropic
spectrum consisting of two signals at different g tensor compo-
nents g = g ϶ g . The symmetrical line can be related to
x
y
z
averaging of the anisotropic g tensor due to the intramolecular
exchange interaction between spin centers at close positions.
The isotropic spectrum agrees with an unresolved spectra aris-
ing from distorted tetrahedral environment associated with e.g.
II
[29]
Cu sites [(H pyimH)[CuCl ],
(
and in CunicX complexes
2
2
4
nic = nicotnic acid, X = Cl or Br).[
30]
+
II
Figure 5. (a) UV/Vis spectra of the H /Ni /HL system in an argon
atmosphere recorded by means of a 5 mm dip probe between pH 3.18
and 8.28 (pH values shown for corresponding curves). (b) Absorbance
at 400 nm as a function of pH. CNi = 1.0ϫ10–4 m, C
= 2.0ϫ10 m.
–4
L
Solv. 10/90 (v/v) DMSO/water.
inflection at 500 nm most likely assigned to a LMCT πN Ǟ
Cu transition.[
27,28]
2
Figure 7. The EPR spectra of CuLCl measured for powdered sample
at 77 K (1) and frozen solution in DMF, at 77 K, (2) which is compared
with the spectrum (sim2) simulated using the EPR parameters given
in the text. The EPR spectrum (3*) was obtained by subtracting (2)
from (3) (see text).
The EPR spectra of frozen solutions of CuLCl in DMF or
2
DMSO show poorly resolved splitting due to hyperfine inter-
Figure 6. (a) UV/Vis spectra of Cu /HL recorded at various ligand- action between the spins of unpaired electron and copper nu-
II
to-metal concentrations (shown for corresponding curves). pH = 2.9–
clei (I = 3/2); the resolution was improved considerably after
3
.0. CCu = 1.0ϫ10–3 m. Solvent 40/60 (v/v) DMSO/water: (b) Calcu-
adding about 30 vol% of ethyl glycol, which efficiently pre-
2
+
lated absorption spectra of the individual complex species: 1 - Cu
II
vents the aggregation of Cu ions (Figure 7). It is not possible
2
solv.; 2 - CuL; 3 - CuL .
to assign the parameters, g = 2.397, g = 2.075 and A =
|
|
Ќ
||
The UV/Vis/NIR parameters following from the absorption 138ϫ10–4 cm , derived by simulation of the experimental
–1
spectra (Figure 6b) of the two individual complex species CuL EPR spectrum 2 (Figure 7), to axial local symmetry of the cen-
II
II
and CuL , accepted by HypSpec, are shown in Table 2. The tral Cu ion realized in chelating Cu xy plane through two
2
presence of a radical red shift accompanied by consecutive nitrogen donors of one ligand. The A values are usually much
|
|
II
predomination of CuL indicates a consecutive change in com- larger and g much smaller for the typical in-plane Cu coordi-
2
||
2
+
plex structure from a solvated Cu ion to a pseudotetrahederal nation by two nitrogen donors, provided by e.g. one ethyl-
–1 [31]
structure of CuL2.
enediamine with g = 2.283, g = 2.060, 183ϫ10–4 cm .
||
Ќ
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Hence, the observed EPR spectral parameters suggest a geom- analyzer. ESI-MS were recorded with a Varian 500-MS LC ion-trap
mass spectrometer and a Bruker, AmaZon Speed ETD. The experi-
ments were performed in positive ion mode.
etry distorted towards tetrahedral in agreement with those
II
found for the frozen solutions of Cu dihalide adducts with
nicotine acid[
30]
or bis(2-benzimidazolyl)ethane
[27]
being a
The spectrum 2 is close to
that obtained for CuCl in DMF/H O or DMSO/H O frozen
All reagents and solvents used for synthesis of the ligand were pur-
chased from either Lancaster or Sigma Aldrich and used without fur-
ther purification. Melting points were determined with an Electrother-
II
[28]
model of Cu blue proteins.
2
2
2
solutions, which is expected considering the coordination of mal IA9100 apparatus and are presented without corrections. Elemen-
only one ligand and replenishment of the remaining coordina- tal analyses were performed with an AMZ 851 CHX analyzer and the
1
tion sites by solvent molecules and/or counter anions, together results were within Ϯ0.4% of the theoretical value. The H NMR
spectra were recorded with a Bruker Avance 300 MHz instrument
with a distorted arrangement. The results of analysis of d-d
6
using [D ]DMSO as a solvent and TMS as an internal standard. IR
electronic transitions strongly support this finding (Figure 6b).
The EPR spectrum 3 (Figure 7) was detected for frozen
DMSO/water solution containing 2:1 molar ratio of ligand to
–
1
spectra (ν in cm ) were recorded in KBr with a Specord IR-75 spec-
trophotometer.
Cu(ClO ). It is composed of two spectra, a dominant is similar
4
Preparation and Spectroscopic Characterization of Metal(II)
to 2 and new one is distinctly seen as additional line at the Complexes: Ligand 5-(pyrazin-2-yl)-2,4-dihydro-3H-1,2,4-triazole-3-
highest magnetic field. By subtracting the spectrum 2 from 3 thione (HL) was synthesized according to the procedure described be-
the resulting one, 3*, with poorly resolved hyperfine splitting low. The ligand formed solid complexes 1–4 in reactions with co-
balt(II), nickel(II), copper(II), and zinc(II) salts. The triazole derivative
HL reacted with cobalt(II), nickel(II), and copper(II) chloride hexahy-
drate in a 1:1 molar ratio in dichloromethane/methanol mixture yield-
may be simulated approximately using g = 2.305, g = 2.065,
|
|
Ќ
–
4
–1
A = 160ϫ10 cm . They differ significantly from those
|
|
–
4
–1
(
g = 2.207, g = 2.040, A = 198ϫ10 cm ) characteristic
of a Cu complex with two ethylenediamines.
|| Ќ ||
ing complexes 1, 2, and 3 of general formula [MLCl
anhydrous zinc(II) chloride in acetonitrile/methanol solution formed
complex 4 of [M(HL) Cl ] type, irrespective of a L:M molar ratio (1:1
or 2:1), in which the reaction proceeded.
2
]. The ligand and
II
[31]
This fact
again indicates a geometry close to tetrahedral in the formed
3
2
CuL species, which is in very good agreement with the sig-
2
nificant red shift of the d-d transition to about 1050 nm corre-
sponding to CuL complex (Figure 6b). Such low-energy ab- Preparation of 5-(Pyrazin-2-yl)-1,2,4-triazole-5-thione (HL): 4-
2
Benzoyl-1-(pyrazin-2-ylcarbonyl)-thiosemicarbazide (0.01 mol) was
sorption bands are commonly found in pseudotetrahedral cop-
per(II) complexes.[
27,28]
dissolved in 2% sodium hydroxide solution (10 mL) and the mixture
was heated under reflux for 4 h. After cooling, the solution was neu-
tralized with dilute hydrochloric acid. The precipitate was filtered off
and then crystallized from 95% ethanol. The melting point of the ob-
Conclusions
[
34]
tained compound is known to be 278–280 °C,
however, our present
The results indicate that the title ligand displays a high affin-
1
result was 282–285 °C. Yield: 89%. H NMR ([D ]DMSO): δ = 8.78
6
II
II
II
II
ity to the transition metals, Co , Ni , Cu , and Zn . The chela- (s, 2 H, 2ϫCH); 9.20 (s, 1 H, 1ϫCH); 13.96 (s, 1 H, NH); 14.17 (s,
tion effect is confirmed by the obtainment of the corresponding 1 H, NH) ppm. IR (KBr): ν˜ = 3294, 3066, 2924, 2850, 2762, 2343,
solid complex compounds. The ligand creates neutral, pseudo- 1641, 1575, 1489, 1216, 1172, 1135, 1103, 1020, 973, 855, 756, 707,
–
1
II
583, 551, 411 cm .
tetrahedral complexes of the general type M(HL)Cl with Co ,
2
II
II
II
Ni , Cu ions. In the case of the Zn complex, monodentate
binding of 1,2,4-triazole-3-thione to the metal ion and forma-
2 2
Synthesis of Complex 1: Cobalt(II) chloride hexahydrate CoCl ·6H O
(
43.0 mg, 0.18 mmol) was dissolved in methanol (2.0 mL) and was
added dropwise at room temperature to a stirred solution of HL
32.4 mg, 0.18 mmol) in dichloromethane (8.0 mL). The reaction mix-
ture was stirred for 12 h at room temperature. The resulting green
tion of the complex M(HL) Cl are observed. The L:M = 3:1
3
2
coordination is also fully accepted in the solution equilibrium
(
II
model. The ligand’s exceptionally high affinity towards Cu
in DMSO/water solutions indicates the necessity for further powder of 1 was obtained by evaporation under reduced pressure
experimental studies on inhibition of the o-diphenolase activity to dryness. Yield: 47.4 mg (74%). M.p. 306.7–307.3 °C.
–
1
6 5 5 2 2
C H N SCoCl ·2·5H O (354.02 g·mol ): calcd. C 20.36; H 2.85; N
of tyrosinase by the 5-(pyrazin-2-yl)-2,4-dihydro-3H-1,2,4-tri-
azole-3-thione.
1
3
7
9.78%; found: C 20.19; H 2.51; N 19.98%. FT-IR (KBr): ν˜ = 3390,
373, 2359, 2330, 1616, 1550, 1489, 1288, 1157, 1060, 856,
61 cm . ESI-MS (m/z): [Co(HL)Cl
Co(HL)Cl] 273 (10%), [Co(HL)] 240 (70%).
–
1
2
+
2H] 310 (100%),
+
+
[
Experimental Section
Materials and Methods of Product Identification: All substances
2 2
Synthesis of Complex 2: Nickel(II) chloride hexahydrate NiCl ·6H O
were used without further purification. Cobalt(II) chloride hexahy- (51.2 mg, 0.22 mmol) was dissolved in methanol (2.0 mL) and was
drate, nickel(II) chloride hexahydrate, copper(II) chloride dihydrate added dropwise at room temperature to a stirred solution of HL
and zinc(II) chloride anhydrous were purchased from Aldrich. Solvents
for synthesis of the complexes (acetonitrile, dichloromethane, diethyl
ether and methanol) were reagent grade or better and were dried ac-
(39.2 mg, 0.22 mmol) in dichloromethane (12.0 mL). The reaction
mixture was stirred for 12 h at room temperature. A yellow-orange
solid product was obtained, filtered off and dried in vacuo. Yield:
[
33]
cording to standard protocols.
6 5 5 2 2
The melting points were determined 30.0 mg (41%). M.p. dec. Ͼ 320 °C. C H N SNiCl ·1·75H O
–
1
using an Electrothermal IA9100 apparatus and they are uncorrected. (335.77 g·mol ): calcd. C 21.46; H 2.40; N 20.86%; found: C 21.39;
The IR spectra were recorded as KBr pellets with a FT-IR-8400S Shi- H 2.68; N 20.33%. FT-IR (KBr): ν˜ = 3392, 3377, 2359, 2322, 1616,
–
1
madzu spectrophotometer. For the new compounds, elemental analyses
C, H and N) were obtained with a Perkin-Elmer PE 2400 CHNS
1550, 1489, 1288, 1159, 1062, 852, 763 cm . ESI-MS (m/z):
+
(
[Ni(HL)Cl
2
+ 1H] 309 (80%), [Ni(HL)] 238 (100%).
Z. Anorg. Allg. Chem. 0000, 0–0
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6
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Journal of Inorganic and General Chemistry
ARTICLE
Zeitschrift für anorganische und allgemeine Chemie
Synthesis of Complex 3: Copper(II) chloride dihydrate CuCl
59.8 mg, 0.35 mmol) was dissolved in methanol (2.0 mL) and was amounted to 4.0ϫ10 m. The metal–ligand interaction was studied at
added dropwise at room temperature to a stirred solution of HL ligand-to-metal ratios 1:1, 2:1 and 4:1.
62.8 mg, 0.135 mmol) in dichloromethane (15 mL). The reaction mix-
2
·2H
2
O
HySS 2009.[40] The total concentration of the ligand in each sample
–
3
(
(
UV/Vis/NIR Spectroscopy: For spectrophotometric investigation of
ture was stirred for 12 h at room temperature. A green-brown solid
the equilibrium systems simultaneously with the potentiometric mea-
surements, the UV/Vis absorption spectra were recorded with a Cary
50 Bio spectrophotometer equipped with a fiber-optic device, in an
oxygen-free atmosphere (argon). A fiber-optic probe (5 mm), corre-
sponding to a path length of 1 cm, was dipped directly into the titration
product 3 was obtained, filtered off and dried in vacuo. Yield:
5
(
2.7·mg (48%). M.p. 262.3–262.8 °C.
C
6
H
5
N
5
SCuCl
398.53 g·mol ): calcd. C 21.10; H 1.77; N 17.57%; found: C 20.79;
H 1.85; N 17.74%. FT-IR (KBr): ν˜ = 3431, 3397, 3096, 2357, 1618,
2 2 2
·CH Cl
–1
–1
1
496, 1421, 1384, 1286, 1155, 1047, 856, 756 cm . ESI-MS (m/z):
–
5
+
vessel (initial volume 25.0 mL, total cobalt concentration 5.0ϫ10 or
2
[Cu(HL)Cl –1H] 312 (15%), [Cu(HL)] 242 (7%), [L] 179 (40%).
–
4
–4
–4
1
.0ϫ10 m, total nickel concentration 1.0ϫ10 or 2.0ϫ10 m). For
optimum absorbance measurements, the ligand:metal molar ratio was
54.52 mg, 0.40 mmol) was suspended in methanol (10 mL) and was 2:1, and the temperature was 25.0Ϯ0.1 °C. To avoid interference from
added dropwise at room temperature to a stirred solution of HL the absorption by the nitrate ion at ca. 300 nm, the UV experiments
71.68 mg, 0.40 mmol) in acetonitrile (12.0 mL). The reaction mixture
were carried out with perchlorates (basic electrolyte NaClO ). Perchlo-
Synthesis of Complex 4: Zinc(II) chloride anhydrous ZnCl
2
(
(
4
was stirred and refluxed for 6 h. A yellow micro-crystalline product rate salts are potentially explosive and were handled only in small
was obtained, filtered off and dried. Yield: 61.3 mg (62%). M.p. quantities with care. The ionic strength in aqueous phase was 0.5, i.e.
–
1
2
99.0–302.0 °C. C18
H
15
N
15
S
3
ZnCl
2
·0·5H
2
O (682.76 g·mol ): calcd.
higher than in the solely potentiometric measurements, to avoid unde-
sired dilution of samples during titration with 0.1 m NaOH. The used
alkali (0.5 m NaOH carbonate-free) was added from a 0.250 mL cal-
C 31.67; H 2.36; N 30.77%; found: C 31.91; H 1.88; N 30.52%. FT-
IR (KBr): ν˜ = 3292, 3211, 3070, 2762, 1575, 1521, 1489, 1384, 1294,
–1 1
1170, 1051, 889, 856, 756 cm . H NMR (300 MHz, [D
6
]DMSO): δ ibrated micro syringe. After each base increment added, the pH and
=
1.22 (s, 1 H, SH); 2.16 (s, 3 H, CH
3
(Ar); 8.75 (s, 2 H, Ar); 9.18
EMF were recorded with a Molspin titrator with a combined InLab
(
(
[
(
s, 1 H, Ar); 13.90 (s, 1 H, NH); 14.12 (s, 1 H, NH) ppm. ESI-MS Semi-Micro (METTLER TOLEDO) electrode. The reference half-cell
+
+
®
m/z): [Zn(HL)
3
Cl]
Cl] 459 (30%), [Zn(HL)
100%), [L + 1H] 180 (40%).
638 (20%), [Zn(HL)
3
] 600 (20%),
was filled with a polymer XEROLYT EXTRA electrolyte instead of
+
+
+
Zn(HL)
2
2
]
423 (22%), [Zn(HL)] 242 KCl due to the insolubility of KClO . A time delay was given to equili-
4
brate the system. After each point or set of points, the process was
–
1
paused and the spectrum was recorded at a slow scan (300 nm·min ).
Following the collection of a consecutive curve, new aliquots of base
were added and the procedure repeated. It was therefore possible to
collect a spectrum at each titration point or at each chosen pH. The
molar absorbances of species were calculated after deconvolution by
HypSpec (part of Hyperquad 2008 suite, Protonic Software). In the
Materials and Physical Measurements: All reagents and solvents
were purchased from commercial sources and were used as received.
The standard solutions of cobalt(II), nickel(II), and copper(II) salts
were titrated with disodium salt of EDTA in the presence of murexide.
In turn, the standard solution of Zn(NO ) was also determined with
3 2
EDTA but in the presence of eriochrome black (EBT).
II
spectrophotometric batch file titrations of the equilibrium Cu -HL sys-
tem, the UV/Vis/NIR absorption spectra were read with a Varian Cary
Potentiometric Measurements: pH-Potentiometric equilibrium stud-
ies were carried out with a Molspin automatic titration kit equipped
with a combined Russell CMAWL/4/5/S7 microelectrode. All the ex-
periments were carried out at a constant temperature of 25.0Ϯ0.1 °C.
The ligand (insoluble in water) was initially dissolved in of DMSO
5000 spectrophotometer in sealed 1 cm quartz cuvettes and 10.0 mL
flasks for a series of solutions of known concentration.
EPR Spectroscopy and Magnetic Measurement: The EPR spectra
were measured with a Bruker ELEXYS E500 spectrometer equipped
with an NMR teslameter (ER 036TM) and frequency counter at X-
band. The experimental spectra were analyzed using the programs
WINEPR SimFonia, version 1.25 and DoubletExact (S = 1/2) written
by Dr Andrew Ozarowski from NHMFL, University of Florida, with
resonance field calculated by full diagonalization of energy matrix. A
magnetic susceptibility measurement at temperature 100 K was per-
formed at a magnetic field of 0.5 T with a Quantum Design SQUID
MPMSXL-5 magnetometer. Correction for the sample holder and the
diamagnetic corrections to the magnetic susceptibility, which were es-
timated from the Pascal constants, were applied.
(1 mL) and added to a 10 mL flask filled with an aqueous solution
containing HNO in excess, in regards to the ligand, and KNO . Water
3
3
solutions of the cobalt(II), nickel(II), and zinc(II) nitrates were added
to the acidified ligand solution and next titrated with alkali solution.
The ionic strength of the final 10/90 (v/v) DMSO/water solution was
3
0.1 (KNO ). The addition of copper(II) nitrate to the same ligand solu-
tion gave a brown precipitate. A transparent brown solution was ob-
tained only by using a higher share of DMSO in the solvent mixture,
optimal at 40/60 (v/v) DMSO/water, however further titration with
alkali led to the formation of insoluble hydrolytic products.
The protonation and formation constants were determined by pH-met-
ric titrations of 4.0 mL samples. Alkali (0.1 m NaOH carbonate-free)
was added by a 0.500 mL calibrated micro syringe. The measurement
Supporting Information (see footnote on the first page of this article):
UV/Vis/NIR studies are presented in Figure S1. H NMR spectra are
presented in Figures S2–S4.
1
+
cell was calibrated daily with 0.1 m NaOH vs. –log[H ] by titration of
0.005 m HNO
3 3
in 10/90(v/v) DMSO/water solution (containing KNO
up to I = 0.1). The calculated ionic product for this solution was 14.06 Acknowledgements
[
35]
(
close to the value 14.04 reported in ), but the ionic product in 40/
6
0(v/v) DMSO/water solution amounted to 14.64, quite close to the Financial support from Medical University of Łód z´ (Grant No. 503/3–
[
36]
[37]
literature data under similar conditions: 14.98, 14.42. The overall 066–02/503–31–001 to Department of Cosmetic Raw Materials Chem-
m
l
h
concentration formation constants (βmLh = [M
m
L
l
H
h
]/[M] [L] [H] )
and then by HYPER- Physical and Biocoordination Chemistry) and the Collegium Medicum,
QUAD 2013.[ The graphical simulation of speciation diagrams on Nicolaus Copernicus University in Toru n´ (Grant No. 411 to Depart-
the basis of these determined constants was carried out by ment of Inorganic and Analytical Chemistry) is gratefully acknowl-
istry and Grant No. 503/3–014–02/503–31–001 to Department of
[
38]
were initially calculated by SUPERQUAD
39]
Z. Anorg. Allg. Chem. 0000, 0–0
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7
© 0000 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Journal of Inorganic and General Chemistry
ARTICLE
Zeitschrift für anorganische und allgemeine Chemie
edged. This work was partly financed by a subsidy for statutory ac-
[18] D. G. Wilkinson, P. T. Francis, E. Schwam, J. Payne-Parrish,
Drugs Aging 2004, 21, 453–478.
19] A. D. Naik, J. Beck, M. M. Dîrtu, C. Bebrone, B. Tinant, K. Rob-
eyns, J. Marchand-Brynaert, Y. Garcia, Inorg. Chim. Acta 2011,
tivity from Ministry of Science and Higher Education of the Republic
of Poland for Faculty of Chemistry, University of Wrocław. Authors
[
´
wish to thank Dr Mirosława Swi a˛ tek for cooperation in the HypSpec
368, 21–28.
calculations.
[
[
[
[
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Keywords: S ligand; Divalent metals; Spectroscopic and
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Received: March 30, 2017
Published Online: ᭿
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© 0000 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Journal of Inorganic and General Chemistry
ARTICLE
Zeitschrift für anorganische und allgemeine Chemie
A. Kufelnicki,* J. Jaciubek-Rosi n´ ska, M. Sobiesiak,
A. Paneth, J. Jezierska, E. Budzisz .................................. 1–9
Metal(II) Ion Complexes with 5-(Pyrazin-2-yl)-2,4-dihydro-
3H-1,2,4-triazole-3-thione; Synthesis, Structural Characteriza-
tion, Acid-base, and Complexing Properties in Solution
Z. Anorg. Allg. Chem. 0000, 0–0
www.zaac.wiley-vch.de
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© 0000 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim