Design, synthesis, characterization and catechol oxidase activity of novel class of multi-tripodal pyrazole and triazole-based derivatives

Article abstract of DOI:10.1007/s11164-019-04044-3

A class of novel multi-tripodal ligands has been prepared via condensation reaction between pyrazole or triazole moieties and N′,N′-bis(2-aminoethyl)ethane-1,2-diamine. Spectroscopic techniques (¹H NMR, ¹³C NMR, IR and mass spectroscopy) have been used to characterize the compounds. The ability of the in situ ligand complexes to catalyze the oxidation reaction of catechol to o-quinone at ambient conditions has been studied. The study demonstrated that the concentration of the metal salt has a pronounced influence on the catalytic activity. Thus, the best result has been obtained with the in situ complex [2 + CuSO₄] with an oxidation rate of 21.60?μmol?l^?1?min^?1. Kinetic parameters of the in situ complexes have been also investigated.

Full text of DOI:10.1007/s11164-019-04044-3

Research on Chemical Intermediates
https://doi.org/10.1007/s11164-019-04044-3
Design, synthesis, characterization and catechol
oxidase activity of novel class of multi‑tripodal pyrazole
and triazole‑based derivatives
Abdelkhalek Zerrouki1 · Farid Abrigach1 · Mustapha Taleb2 · Sghir El Kadiri1
Received: 6 June 2019 / Accepted: 8 November 2019
© Springer Nature B.V. 2019
Abstract
A class of novel multi-tripodal ligands has been prepared via condensation reaction
between pyrazole or triazole moieties and N′,N′-bis(2-aminoethyl)ethane-1,2-di-
amine. Spectroscopic techniques (1H NMR, 13C NMR, IR and mass spectroscopy)
have been used to characterize the compounds. The ability of the in situ ligand
complexes to catalyze the oxidation reaction of catechol to o-quinone at ambient
conditions has been studied. The study demonstrated that the concentration of the
metal salt has a pronounced infuence on the catalytic activity. Thus, the best result
has been obtained with the in situ complex [2+CuSO4] with an oxidation rate of
21.60 µmol l−1 min−1. Kinetic parameters of the in situ complexes have been also
investigated.
Keywords Multi-tripodal · Pyrazole · Triazole · Catalysis · Dendrimers ·
Catecholase
Introduction
The catechol oxidase (catecholase) is one of the most metalloproteins investigated
due to its interesting biological properties. In fact, it is a dinuclear copper protein
well known as an exclusive catalyst of the oxidation reaction of a wide range of
catechols to the corresponding o-quinones with no action on monophenols [1]. Like
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s1116
4-019-04044-3) contains supplementary material, which is available to authorized users.
*
Sghir El Kadiri
s.elkadiri@ump.ac.ma
1
2
Laboratory of Applied Chemistry and Environment, Faculty of Sciences, Mohammed First
University, 60000 Oujda, Morocco
Laboratory of Engineering, Electrochemistry, Modeling and Environment, Faculty of Sciences,
University Sidi Mohamed Ben Abdellah, Fez, Morocco
Vol.:(0123456789)
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A. Zerrouki et al.
hemocyanin and tyrosinase, catecholase, also known as type-3 copper(II) protein,
active site consisting of two closely spaced copper ions each surrounded by three
imidazole nitrogen donor atoms of histidine residues [2]. For these reasons, several
mono, di- and polynuclear copper complexes were reported and used to mimic the
function of catechol oxidase enzyme [3, 4]. In this context, multi-tripodal systems
containing nitrogen donor atoms and embedded triazole or pyrazole cores have
been the subject of many studies in recent years. Actually, these skeletons have been
shown to possess a wide range of potential biological and environmental properties.
In addition, they present a very high importance in organometallic chemistry area,
especially that concerning the coordination with the transition metals. Indeed, pyra-
zole and triazole containing complexes show a high structural stability and catalytic
ability which is due probably to the strong efciency capacity of the ligands, in part,
to coordinate metals through diferent binding modes (monodentate, bidentate, tri-
dentate and tetradentate modes) and to the fexible N-donor bridging which allowing
the ligands to bend or rotate freely when interacting with the metals in other part
[5–7].
To this date, a large number and diferent types of multidentate ligands are
reported in the literature. Among these compounds, many mono-tripodal ligands
based on pyrazole and triazole (Fig. 1A) were synthesized and investigated for their
diferent biological, catalytic and anticorrosion properties by many reach groups
[8–17]. These structures are characterized in general by the presence of an electron-
rich cavity due to the three N-donor atoms, which facilitate the complexation with
metals and the binding with enzyme receptors in microorganisms. The studies dem-
onstrated that some of these derivatives are found to exhibit considerable antitumor,
antimicrobial, anticorrosion and catalytic activities. In contrast, a few numbers of
bis-tripodal pyrazole and triazole-based chelating ligands (Fig. 1B) were prepared.
Actually, since the frst synthesis reported by Driessen [18], very limited works
were directed toward the preparation and the evaluation of diferent applications of
this kind of compounds [16, 19–22]. Among the tested derivatives, some of them
showed a remarkable antifungal activity against budding yeast Saccharomyces cer-
evisiae. Besides, these molecules present an interesting template in the feld of the
A
B
Fig. 1 General structure of some current tripodal based compounds
1 3

Design, synthesis, characterization and catechol oxidase…
coordination chemistry due to the presence of two electron-rich cavities which can
complex two metal ions.
With the aim of developing new template of multi-tripodal compounds, we
reported here our contribution in preparation of some new ligands possessing three
tripodal unites based on pyrazole or triazole moieties. Indeed, to the best of our
knowledge, this is the frst report of this kind of compounds in the literature. In real-
ity, the purpose and the main objective of this part is to design novel dendrimer
architectures in the future with multiple tripodal units which can be acting as an
efcient template in the feld of the coordination chemistry, nanoscience and other
sectors.
Experimental section
Materials
Solvents (acetonitrile, diethyl ether, dichloromethane and methanol) and all other
chemicals (N′,N′-bis(2-aminoethyl)ethane-1,2-diamine, Na2SO4, catechol and metal-
lic salts) were of reagent grade and used as received from MERCK without further
purifcation. (1H-1,2,4-triazol-1-yl)methanol (a), 3,5-dimethyl-1H-pyrazol-1-yl)
methanol (b) and ethyl 1-(hydroxymethyl)-5-methyl-1H-pyrazole-3-carboxylate (c)
were synthesized according to the methods described in the literature after some
modifcations [4, 23, 24].
Physical measurements
Nuclear magnetic resonance (NMR) spectra were recorded using a Bruker-300
instrument (300 MHz for 1H, 75 MHz for 13C). Chemical shifts are reported in
parts per million (ppm) downfeld from an internal trimethylsilane (s: singlet, t: tri-
plet and m: multiplet). Fourier-transform infrared (FT-IR) spectra were recorded on
pressed KBr pellets (4500–500 cm−1) using a Shimadzu infrared spectrophotome-
ter (al: aliphatic and ar: aromatic). Mass spectrometry (MS) spectra were obtained
using electrospray ionization method. UV visible (UV–vis) absorption spectra were
recorded using a UV 1650 PC Shimadzu spectrophotometer using quartz cuvettes of
1 cm path length.
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A. Zerrouki et al.
Compounds synthesis
N′,N′‑bis((1H‑1,2,4‑triazol‑1‑yl)methyl)‑N″,N″‑bis(2‑(bis((1H‑1,2,4‑triazol‑1‑yl)
methyl) amino)ethyl)ethane‑1,2‑diamine (1)
0.36 g (2.5 mmol) of N′,N′-bis(2-aminoethyl)ethane-1,2-diamine was added to an ace-
tonitrile solution (25 ml) of (1H-1,2,4-triazol-1-yl)methanol (0.99 g, 10 mmol). The
mixture was stirred and heated under refux for 4 h, then dried over Na2SO4 and fltered.
After evaporation of the solvent under reduced pressure, the resulting product was dis-
solved in dichloromethane. The addition of diethyl ether yields 1 as a yellow oil. Yield:
60%. 1H NMR (300 MHz, CDCl3, δ, ppm): 8.54 (s, 6H, H14,20,27,33,40,46); 7.94 (s, 6H,
H12,18,25,31,38,44); 5.25 (s, 12H, H9,15,22,28,35,41); 2.77 (t, 6H, J=6.75 Hz, H5,6,7); 2.44 (t,
6H, J=6.75 Hz, H 2,3,4). 13C NMR (75 MHz, CDCl3, δ, ppm): 151.95 (C12,18,25,31,38,44);
144.65 (C14,20,27,33,40,46); 66.50 (C9,15,22,28,35,41); 52.17 (C2,3,4); 48.07 (C5,6,7). FT-IR
(KBr, cm−1): 3099 (νC–Har); 2997; 2955 (νC–Hal); 2912; 1506 (νC=N); 1373; 1354; 1338;
1273; 1192; 1136; 1012 (νC–N); 958; 877; 761 (δ C–Har); 678; 644.
1 3

Design, synthesis, characterization and catechol oxidase…
N′,N′‑bis(2‑(bis((3,5‑dimethyl‑1H‑pyrazol‑1‑yl)methyl)amino)ethyl)‑N″,N″‑bis((3,5‑di
methyl‑1H‑pyrazol‑1‑yl)methyl)ethane‑1,2‑diamine (2)
A solution of 3,5-dimethyl-1H-pyrazol-1-yl)methanol (1.26 g; 10 mmol) and
N′,N′-bis(2-aminoethyl)ethane-1,2-diamine (0.24 g; 1.6 mmol) in acetonitrile
(25 ml) was refuxed and stirred for 4 h. The mixture was dried over Na2SO4,
fltered and evaporated at reduced pressure. The obtained product was extracted
three times with diethyl ether. The organic layer was dried again over Na2SO4,
and the solvent was removed. The fnal product was recuperated as a white oil.
1
Yield: 71%. H NMR (300 MHz, CDCl3, δ, ppm): 5.75 (s, 6H, H13,19,30,36,47,53);
4.78 (s, 12H, H9,15,26,32,43,49); 2.59 (t, J = 7.5 Hz, 6H, H5,6,7); 2.19 (t, J = 7.5 Hz,
6H, H2,3,4); 2.13(s, 18H, H21,22,38,39,55,56); 2.10 (s, 18H, H23,24,40,41,57,58). 13C NMR
(75 MHz, DMSO, δ, ppm): 147.32 (C12,18,29,35,46,52); 139.57 (C14,20,31,37,48,54);
105.77 (C13,19,30,36,47,53); 65.48 (C9,15,26,32,43,49); 51.89 (C2,3,4); 47.25 (C5,6,7);
13.41 (C23,24,40,41,57,58); 10.85 (C21,22,38,39,55,56). FT-IR (KBr, cm−1): 3132
(νC–Har); 2922 (νC-Hal); 1556 (νC=N); 1458 (νC=C); 1421; 1375; 1317; 1247;
1099; 1030 (νC–N); 977; 781 (δ C–Har). MS (ESI): m/z calcd: [M + H]+ = 795.5,
[M + Na]+ = 817.5; found: [M + H]+ = 795.5, [M + Na]+ = 817.3.
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A. Zerrouki et al.
Hexaethyl‑1,1′,1′′,1′′′,1′′′′,1′′′′′‑(((nitrilotris(ethane‑2,1‑diyl))tris(azanetriyl))hexakis
(methylene))hexakis(5‑methyl‑1H‑pyrazole‑3‑carboxylate) (3)
Ethyl 1-(hydroxymethyl)-5-methyl-1H-pyrazole-3-carboxylate (1.84 g; 10 mmol)
dissolved in 25 ml of acetonitrile was mixed with 0.24 g (1.6 mmol) of N′,N′-bis(2-
aminoethyl)ethane-1,2-diamine. After stirring and refuxing for 5 h, the solvent
was evaporated in vacuo and the residue was extracted three times with diethyl
ether. The organic phase was dried over Na2SO4, and the solvent was removed to
obtain a yellow oil. Yield: 63%. 1H NMR (300 MHz, CDCl3, δ, ppm): 6.50 (s, 6H,
H13,19,30,36,47,53); 5.01 (s, 12H, H9,15,26,32,43,49); 4.34–4.22 (m, 12H, H61,69,78,80,72,75);
2.80–2.51 (m, 6H, H5,6,7); 2.28–2.19 (m, 6H2,3,4); 2.20–2.04 (m, 18H,
H21,22,38,39,55,56); 1.35–1.26 (m, 18H, H62,70,73,76,81,82). 13C NMR (75 MHz, CDCl3,
δ, ppm): 162.38 (C23,24,40,41,57,58); 142.59 (C12,18,29,35,46,52); 140.66 (C14,20,31,37,48,54);
108.75(C13,19,30,36,47,53); 66.48 (C9,15,26,32,43,49); 60.89 (C61,69,72,75,78,80); 51.81 (C2,3,4);
47.51 (C5,6,7); 14.31 (C62,70,73,76,81,82); 10.86 (C21,22,38,39,55,56). FT-IR (KBr, cm−1):
3134; 2982 (νC-Hal); 2935; 1716 (νC=O); 1683; 1653 (νC=N); 1541 (νC=C); 1446;
1 3

Design, synthesis, characterization and catechol oxidase…
1217 (νC-O); 1107; 1030 (νC-N); 842; 779 (δ C–Har). MS (ESI): m/z calcd: [M+H]+
=1143.6, [M+Na]+ =1165.6; found: [M+H]+ =1143.3, [M+Na]+ =1166.1.
Catalysis study
The catechol oxidase activity of the in situ complexes was investigated spectro-
photometrically under aerobic conditions at room temperature monitoring the
increase in the o-quinone absorbance rate, using the experimental process described
previously after some simple modifcations [17]. Briefy, the metal complexes
were prepared in situ in a quartz cuvette of 1 cm path length mixing 0.15 ml of a
2×10−3 mol l−1 solution of manganese (II) acetate salt or copper (II) salts CuX2,
−
nH2O (with X=CH3COO−, Cl−, NO3 , SO42−) with 0.15 ml of ligand solution at
2×10−3 mol l−1, then 2 ml of a 10−1 mol l−1 fresh catechol solution were added in
the cuvette. All solutions were prepared in methanol 99.99%, and the absorbance
evolution of the formed o-quinone was followed at 390 nm for one hour.
Results and discussion
Compounds chemistry
The target ligands 1, 2 and 3 were prepared in one pot 6:1 condensation reaction
of diferent 1-hydroxypyrazoles or triazole on N′,N′-bis(2-aminoethyl)ethane-1,2-di-
amine in acetonitrile and under refux as outlined in Scheme 1. The primary precur-
sors a, b and c were previously prepared via a Mannich reaction from pyrazole or
triazole derivatives and formaldehyde. The structures of the new ligands were estab-
lished by diferent spectroscopic techniques such as 1H and 13C NMR, IR and mass
spectroscopy.
Generally, we were able to assign all the corresponding signals to the difer-
ent types of protons of these macromolecular compounds. The proportionality
between the signal’s integrality and the number of chemically equivalent protons
1
was respected. According to H NMR analyses, all the spectra of the fnal products
showed the presence of the characteristic signal of the –N–CH2–N– bridge which
remained the mean index indicating the formation of our ligands. For all com-
pounds, the signal was appeared as a singlet integrate 12 protons and with chemi-
cal shifts of 5.25, 4.78 and 5.01 ppm for 1, 2 and 3, respectively. In general, the
observed diferences in chemical shifts of the signal under study can be explained
by the shielding and deshielding efect of CH2 protons which is due to the diferent
electronic efects introduced by the substituent groups on the pyrazole and triazole
rings. In fact, the presence of electron donating groups (R2 =CH3) on the positions
3 of pyrazole rings leads to an increase of the electron density on –N–CH2–N– pro-
tons which make them more shielded than the protons in the case of compound 3,
where the same positions of the pyrazole moieties are substituted by electron with-
drawing groups (R2 =CO2Et). As a simple comparison with chemical shift values of
–N–CH2–N– protons of similar compounds in the literature, our results were found
1 3

A. Zerrouki et al.
Scheme 1 Synthesis route of the tris-tripodal compounds
to be in good accordance with the described fndings in these works, especially in
the case of compound 2 which showed a chemical shift of 4.78 ppm very close to
that shown by compound 4a (4.74 ppm) in our previous work [19] and compound 6b
(4.76 ppm) as described by Driessen [18]. 13C NMR chemical shifts, IR and mass
spectra were also in good agreement with the proposed structures.
Catalytic and kinetic studies
In the latest years, many in situ copper complexes have been investigated for their
catalysis power toward diferent catechol derivatives in order to develop new model
systems for mimicking catecholase enzyme activity [17, 25–27]. In our case, a
series of manganese(II) and copper(II) complexes was prepared in situ from sev-
eral metallic salts and the two ligands 2 and 3, and investigated toward the aerobic
1 3

Design, synthesis, characterization and catechol oxidase…
oxidation of catechol at room temperature. Evaluation of the catecholase activity of
these complexes was made spectrophotometrically by following the appearance of
the maximum absorbance of the corresponding o-quinone at 390 nm over time. The
results are illustrated in Fig. 2, showing the change in absorbance at 390 nm versus
time for 60 min.
In addition, catechol oxidizes very slowly in contact with air oxygen under stand-
ard conditions of pressure and temperature (25 °C, 1 bar). Under the experimen-
tal conditions used, the spectrum obtained for catechol alone showed practically no
absorbance as a function of time, the same result is observed with ligands alone, and
also with salts of metals alone in the presence of catechol, which means the absence
of o-quinone formation and any signifcant catalytic activity.
In general, tripods based on triazole units lead to a precipitation in the cuvette
with the transition metals; for this reason, the catecholase activity of compound 1
has not been studied.
The plots A and B (Fig. 2) recorded at the concentration of one equivalent
of ligand and three equivalents of metallic salts reveal clearly that absorb-
ance of the o-quinone formed after the catalysis reaction by the complexes
Fig. 2 The absorbance plots vs time for the aerobic oxidation of catechol to the corresponding o-quinone
performed at 25 °C in MeOH and catalyzed by the complexes prepared in situ with 2 and 3 and diferent
transition metallic salts. A and B present the absorbance plots of complexes prepared, respectively, with
2 and 3 at the molar ratio 1:3 (ligand/Metal), while C and D present the absorbance plots of the same
complexes in the same order at the molar ratio 1:6 (ligand/Metal)
1 3

A. Zerrouki et al.
[2 + Cu(CH3COO)2] and [2 + CuSO4] is higher than the absorbances found by
all other complexes including that of compound 3. Comparing these results to
that found at the concentration of one equivalent of ligand and six equivalents of
metallic salts (Fig. 2C, D), the absorbance resulted by the complex [2+ CuSO4]
is increased by double after 60 min. While the complex [3 + Cu(CH3COO)2]
showed a fnal absorbance seven times higher than one found in the frst case.
The other complexes showed slight change in the absorbance except complex
[2 + Cu(CH3COO)2] which did not show any absorbance.
As previously shown in Scheme 1, the studied ligands are characterized by
the presence of three chelation centers which made them capable of establish-
ing coordination bonds with three equivalents of metal salts. These tricentric
ligands difer from each other by the substituents borne by the pyrazole nucleus.
The ligand 2 has methyl electron donating inductive efect groups, while the
ligand 3 has electron withdrawing mesomeric efect groups (CO2Et). The nature
of the pyrazole substituents explains the diference in catalytic activity exhibited
by these complexes. In fact, the presence of electron donating groups like CH3
increases the electronic richness of the coordination sites, which promotes the
complexation of the ligand with the metal salts. In contrast, the electron with-
drawing groups such as CO2Et make the opposite efect. In addition to the elec-
tronic character, the steric hindrance efect of the groups on the pyrazole rings is
another important factor which can be afecting both the formation of the metal
complex and the accessibility of the substrate (catechol) to the metal ion [4].
More particularly, the complex of 2 with CuSO4 shows the high catalytic activity
with a rate reaches 15.86 µmol l−1 min−1 and catalytic activity concentration of
about 121.61 µmol l−1 min−1 at the molar ratio 1:3 (Ligand/Metal) (Table 1). This
result refects that the complex–catechol interactions are stronger, and the power
of transformation of catechol into o-quinone is very efcient and fast. In addition,
Table 1 Catalytic activity of complexes prepared in situ with compounds 2 and 3 at diferent molar ratio
of ligand and metal
Ligand (L)
Metallic salts (M)
1:3 (L/M)
1:6 (L/M)
R2
V
b
R2
V
b
2
Cu(CH3COO)2
Mn(CH3COO)2
CuSO4
Cu(NO3)2
CuCl2
Cu(CH3COO)2
Mn(CH3COO)2
CuSO4
0.97
0.96
1.00
0.98
0.75
0.97
0.96
1.00
0.98
0.75
10.76
5.25
15.86
0.19
0.08
2.81
4.20
4.58
0.60
0.11
82.51
–
–
–
40.25
121.61
1.44
0.96
1.00
0.98
0.75
0.97
0.96
1.00
0.98
0.75
10.54
21.60
0.72
0.52
10.16
7.46
11.36
0.34
0.35
80.79
165.60
5.55
4.00
0.58
3
21.56
32.20
35.08
4.60
77.91
57.21
87.11
2.58
Cu(NO3)2
CuCl2
0.86
2.68
V (average rate) and b (catalytic activity concentration) are in µmol l−1 min−1
1 3

Design, synthesis, characterization and catechol oxidase…
it has been shown that dinuclear complexes are generally more active than mono-
nuclear complexes [28].
Furthermore, the efect of the concentration of the metal salts allows a consider-
able increase in the reaction rate. The oxidation rate of the complex [2+CuSO4] was
increased from 15.86 to 21.60 µmol l−1 min−1, whereas that of complex [3+CuSO4]
was augmented by twice from 4.58 to 11.36 µmol l−1 min−1. These fndings can
be explained essentially by the increase in the concentration of complexes formed
in situ. On the other hand, the oxidation rates remain low for the complexes con-
taining the nitrate or chloride anions, which can be due to the high afnity of these
counter anions in solution toward the metal center, and thereafter disfavor the com-
plex–substrate interactions. Additionally, many previous studies mentioned that the
catalytic activity can also be infuenced by the nature of the solvent used [29, 30].
Moreover, to understand more the extent of the catalytic efciency of the com-
plexes prepared in situ of 2 and 3 ligands with the metal salts Cu(CH3CO2)2,
Mn(CH3CO2)2 and CuSO4 in methanol, kinetic studies determined by the initial rate
method were performed. The experiments were carried out in methanol, by main-
taining the concentration of each in situ catalyst to a specifc value of 1×10−3 M and
varying the concentration of the substrate 1,2-dihydroxybenzene (catechol) from
1×10−2 to 2×10−1 M. The initial rates were determined by linear regression from
the slope of the tangent to the absorbance vs time curve after the induction period
(t=3 min). Figure 3A and B represents the dependence of the initial rate on the con-
centration of catechol. The appropriate catalytic rate constant VM and the Michae-
lis–Menten constant KM were determined from the reciprocal Lineweaver–Burk
plots (Fig. 3a, b). Kinetic data are given in Table 2.
Kinetic studies of air oxidation of catechol catalyzed by the in situ complexes
showed curves of hyperbolic nature which fnally tends toward stabilization. From
the obtained results, in situ complexes of the tricentric ligand 2 demonstrate a
signifcant afnity toward catechol compared to the in situ complexes of the tri-
centric ligand 3; nevertheless, they exhibit good maximum reaction velocities.
The best afnity was obtained by the in situ complex [2+Cu(CH3COO)2] with a
Michaelis constant KM of 0.005 M and a maximum reaction velocity VM equal to
138.37 mM min−1, which confrms that this in situ complex presents a strong intro-
ductory activity and gave a better result for the oxidation of catechol. Considering
this fnding, the factor acting on the catalytic activity seems rather to be the trans-
formation of the intermediate (complex-catecholate) into the fnal product than its
dissociation. This refects the good afnity of the in situ complex, as well as its high
catechol oxidation power in terms of initial velocity.
1 3

A. Zerrouki et al.
Fig. 3 A and B illustrate the variation of the initial rate vs catechol concentration of the complexes of 2
and 3, respectively. a and b show reciprocal Lineweaver–Burk plots for the same complexes respectively
Table 2 Catalytic parameters of
Ligand
Metallic salts
R2
KM (M)
VM (mM min−1
)
the complexes prepared in situ
with 2 and 3
2
Cu(CH3COO)2
Mn(CH3COO)2
CuSO4
Cu(CH3COO)2
Mn(CH3COO)2
CuSO4
0.67
0.96
0.96
0.69
0.98
0.96
0.005
0.034
0.034
0.010
0.043
0.360
138.37
173.92
68.28
84.42
185.99
3
43.64
Perspectives: dendrimers and dendrimers complexes design
As previously mentioned, one of the main purposes of this work is to launch an idea
concerning the preparation of novel class of dendrimers with pyrazole, pyridine or
triazole tripod units on their surface. As it is well known, dendrimers are globular
macromolecules or monodisperse polymers with a caulifower shape. They can be
prepared by iterative reactions using diferent pathways but mainly two, the diver-
gent and the convergent methods [31]. Their unique structure and special chemi-
cal and biological properties such as the number and the type of surface functional
groups, the high solubility and the high molecular weight make them of signifcant
scientifc interest [32–34]. These properties and others allow the application of
1 3

Design, synthesis, characterization and catechol oxidase…
Fig. 4 Example of complex that can be formed with prospective dendrimers based on tripodal pyrazole
ligands
dendrimers in several scientifc felds such as biology, medicine, biosensors, cataly-
sis, environmental protection, electronic devices and nanotechnology [35–39].
The possibility to modify dendrimers periphery can greatly expand their applica-
tions; in this way, the complexation of the proposed dendrimers with metallic ions
is one of the most suitable tasks that we propose due principally to the presence of
many chelating sites on the surface. Actually, many works have been studied the
complexation of dendrimers [40–44], but the particularity of our proposed dendrim-
ers is their capacity to coordinate many metallic ions as displayed in Fig. 4.
Conclusion
In summary, a class of novel multi-tripodal ligands has been synthesized by the
condensation of pyrazole or triazole moieties with N′,N′-bis(2-aminoethyl) ethane-
1
1,2-diamine. H NMR, 13C NMR, IR and mass spectroscopy techniques have been
1
used to confrm the structures of the new compounds. H NMR analysis revealed
that chemical shift of the N–CH2–N bonds is very depending on the nature of the
substituents on pyrazole cores. The prepared compounds can be useful in the design
1 3

A. Zerrouki et al.
of new dendrimers of high interest. The catalytic activities of the complexes formed
in situ of studied ligands, and several metallic salts were found to be very infuenced
by the nature of the ligand, the counter anion and the concentration of metallic salts
used. The in situ [2+CuSO4] complex showed the best catecholase activity for the
oxidation reactions rate, which attain 21.60 µmol l−1 min−1. However, the kinetic
investigation results determined by the initial rate method showed that the highest
activity, in the reactions of the catechol oxidase, is obtained by the in situ complex
[2+Cu(CH3COO)2].
Compliance with ethical standards
Confict of interest The authors declare no confict of interest.
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