Structural and catalytic aspects of copper(II) complexes containing 2,6-bis(imino)pyridyl ligands

Article abstract of DOI:10.1080/00958972.2012.695017

The synthesis, structure, and ligand substitution mechanism of a new five-coordinate trigonal-bipyramidal copper(II) complex, [Cu ^II(py^tBuMe₂N₃)Cl₂] (1), with a sterically constrained py^tBu

Full text of DOI:10.1080/00958972.2012.695017

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Structural and catalytic aspects of
copper(II) complexes containing 2,6-
bis(imino)pyridyl ligands
S.Y. Shaban a b , A.M. Ramadan a & R. van Eldik b
a Chemistry Department, Faculty of Science , Kafrelsheikh
University , Kafrelsheikh , Egypt
b Department of Chemistry and Pharmacy , University of Erlangen-
Nuremberg , Egerlandsr. 1 , 91058 Erlangen , Germany
Accepted author version posted online: 29 May 2012.Published
online: 13 Jun 2012.
To cite this article: S.Y. Shaban , A.M. Ramadan & R. van Eldik (2012) Structural and catalytic
aspects of copper(II) complexes containing 2,6-bis(imino)pyridyl ligands, Journal of Coordination
Chemistry, 65:14, 2415-2431, DOI: 10.1080/00958972.2012.695017
To link to this article: http://dx.doi.org/10.1080/00958972.2012.695017
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Journal of Coordination Chemistry
Vol. 65, No. 14, 20 July 2012, 2415–2431
Structural and catalytic aspects of copper(II) complexes
containing 2,6-bis(imino)pyridyl ligands
S.Y. SHABAN*yz, A.M. RAMADANy and R. VAN ELDIK*z
yChemistry Department, Faculty of Science, Kafrelsheikh University,
Kafrelsheikh, Egypt
zDepartment of Chemistry and Pharmacy, University of Erlangen-Nuremberg,
Egerlandsr. 1, 91058 Erlangen, Germany
(Received 24 February 2012; in final form 26 April 2012)
The synthesis, structure, and ligand substitution mechanism of a new five-coordinate trigonal-
bipyramidal copper(II) complex, [CuII(pytBuMe2N3)Cl2] (1), with a sterically constrained
pytBuMe2N3 chelate ligand, pytBuMe2N3 ¼ 2,6-bis-(ketimino)pyridyl, are reported. The kinetics
and mechanism of chloride substitution by thiourea, as a function of nucleophile concentration,
temperature, and pressure, were studied in detail and compared with an earlier study reported for
the analogous complex [CuII(pytBuN3)Cl2] (2) [pytBuN3 ¼ 2,6-bis-(aldimino)pyridyl]. Catalysis
of the oxidation of 3,5-di-tert-butylcatechol to 3,5-di-tert-butylquinone by 1 and 2 was studied.
Correlations between the reactivity, chloride substitution behavior, and reduction potentials of
both complexes were made. These show that the rate of oxidation is independent of the rate of
chloride substitution, indicating that the substitution of chloride by catechol as substrate occurs
in a fast step. Spectral data show a non-linear relationship between the ability of the complexes to
oxidize 3,5-DTBC and the Lewis acidity of their copper(II) centers. Electrochemical data
demonstrate that the most effective complex 1 has a E0 value that approaches the E0 value of the
natural tyrosinase enzyme.
Keywords: Biomimetics; Structure; Imine complexes; Catalysis; Copper(II); Catecholase
1. Introduction
Oxidation of organic substrates by molecular oxygen under mild conditions is of great
interest for industrial and synthetic processes both from an economical and environ-
mental point of view [1]. Although the reaction of organic compounds with oxygen is
thermodynamically favored, it is kinetically hindered due to the triplet ground state of
dioxygen. The synthesis and investigation of functional model complexes for metallo
enzymes with oxidase or oxygenase activity is therefore promising for the development
of new and efficient catalysts for oxidation reactions. Catechol oxidase belongs, like
tyrosinase, to the polyphenol oxidases which oxidize phenolic compounds to the
corresponding quinones in the presence of oxygen. This reaction is of importance in
medical diagnosis for the determination of the hormonally active catecholamines
*Corresponding authors. Email: shaban.shaban@sci.kfs.edu.eg; vaneldik@chemie.uni-erlangen.de
Journal of Coordination Chemistry
ISSN 0095-8972 print/ISSN 1029-0389 online ß 2012 Taylor & Francis
http://dx.doi.org/10.1080/00958972.2012.695017

2416
S.Y. Shaban et al.
adrenaline, noradrenaline, and dopa [2]. For this reason studies on the coordination
chemistry of copper(II) complexes with chelates incorporating pyridine and imine
donors have been of significant interest in recent years due to their relevance to histidine
coordinated copper proteins, such as blue copper proteins, hemocyanin, tyrosinase, and
cytochrome c oxidase [3]. Also in the past decade, interest in the chemistry of imine-
based ligand systems has been revitalized by the discovery that their complexes may act
as supporting ligands for a variety of excellent catalysts with a range of applications [4].
The bis-imine pyridine ligand in particular has attracted considerable attention for its
ability to provide unprecedented Ziegler–Natta catalysts based on late transition
metals [4].
This study is a continuation of our work on the structure and mechanism of ligand
substitution of copper complexes derived from sterically demanding conjugated bis-
imine pyridines (figure 1). In the previous study [5], the crystal structure of
[CuII(pytBuN3)Cl2] showed the complex to be a five-coordinate species with trigonal-
bipyramidal geometry. The mechanism of the substitution of chloride in
[CuII(pytBuN3)Cl2] by a series of thiourea derivatives was studied and showed that
the mechanism is associative. To the best of our knowledge, only a few studies have
been performed on the mechanism of substitution in five-coordinate copper(II)
complexes and have shown the mechanism to be associative [6].
Most functional and structural models for metalloproteins have been prepared by
variation of the substituent on the ligands in order to match the spectral properties of
the metalloproteins [7]. For example, Gibson et al. [8] reported that a change in the
ligand environment [2,6-(ArNCR1)2C5H3] of the system resulted in changes in catalyst
productivity and polymer molecular weight. Changing the substituent on the imine
functional group from a ketimine (R1 ¼ CH3) to an aldimine (R1 ¼ H) resulted in
differences in productivity, molecular weight, and molecular weight distribution. It was
found to be advantageous to change the substituent on the imine functional group from
aldimine to ketimine, i.e., by using diacetylpyridine instead of diformylpyridine, and to
study the effect of methyl substituents on the electronic properties, ligand substitution
mechanism, and biomimetic catecholase activity. We report here a detailed mechanistic
study of the ligand substitution reactions of [CuII(pytBuMe2N3)Cl2] in methanol as a
function of the entering nucleophile concentration, temperature, and pressure. This
study also focuses on a detailed mechanistic analysis of the oxidation of 3,5-di-tert-
butylcatechol (3,5-DTBC) and the catecholase activity of the studied complexes.
R
R
N
N
N
X
X
N
N
N
X
X
1
3
2
Terpy
L , R = CH ; L , R = H; X = tert-butyl
Figure 1. Schematic structure and abbreviations for ligands analogous to terpyridine.

Copper(II) complexes
2417
In addition, electrochemical data were obtained in an attempt to correlate the reduction
potentials with the reactivity of the complexes.
2. Experimental
2.1. General
2,6-Diacetylpyridine was purchased from Aldrich Chemical Co. and 2,6-di-tert-
butylaniline was synthesized as described in the literature [5]. All other chemicals
were obtained commercially and used as received unless stated otherwise.
2.2. Instrumentation and measurements
Spectra were recorded on the following instruments: IR (KBr discs, solvent bands were
compensated): Mattson Infinity instrument (60 AR) at 4 cmꢀ1 resolution from 400 to
4000 cmꢀ1; NMR: Jeol-JNM-GX 270, EX 270, and Lambda LA 400 with the protio-
solvent signal used as an internal reference. Mass spectra: Jeol MSTATION 700
spectrometer; Elemental analyses: Carlo Erba EA 1106 or 1108 analyzer. Cyclic
voltammetry measurements were performed in a one-compartment three-electrode cell
using a gold working electrode (Metrohm) with a geometrical surface of 0.7 cm2
connected to a silver wire pseudo-reference electrode and a platinum wire serving as
counter electrode (Metrohm). Measurements were recorded with an Autolab PGSTAT
30 unit at room temperature. The working electrode surface was cleaned using 0.05 mm
alumina, sonicated, and washed with water every time before use. The working volume
of 10 mL was de-aerated by passing a stream of high purity N2 through the solution for
15 min prior to the measurements and then maintaining an inert atmosphere of N2 over
the solution during the measurements. All CVs were recorded for the reaction mixture
with a sweep rate of 50 mV sꢀ1 at 25ꢁC. Potentials were measured in 0.1 mol Lꢀ1 TBAP
electrolyte and are reported versus a Ag/AgCl electrode. Kinetic investigations of the
substitution of the dichloro complex by thiourea or tetramethylthiourea were
performed either in tandem cuvettes with a path length of 0.88 cm, thermally
equilibrated at 23.0 ꢂ 0.1ꢁC before mixing, using a Varian Cary 1G spectrophotometer,
or on an Applied Photophysics SX 18MV stopped-flow instrument (also thermostated
at 23.0 ꢂ 0.1ꢁC) with an optical pathlength of 1 cm at 394 nm.
For experiments at elevated pressure up to 150 MPa, a laboratory-made high-
pressure stopped flow instrument was used for fast kinetic measurements [9], whereas a
Shimadzu spectrophotometer equipped with a high pressure cell, combined with a pill-
box optical cell, was used for slow kinetic measurements [10]. The temperatures of the
instruments were controlled with an accuracy of ꢂ 0.1ꢁC. Thiourea was selected as
entering nucleophile since its high nucleophilicity prevents back reaction with chloride.
LiCl solutions (0.002 mol Lꢀ1) were used to avoid spontaneous solvolysis of the chloro
complexes. The ligand substitution reactions were studied under pseudo-first-order
conditions by using at least a 10-fold excess of thiourea. All listed rate constants
represent an average of at least three kinetic runs under each experimental condition.

2418
S.Y. Shaban et al.
2.3. Catecholase biomimetic catalytic activity
The catecholase catalytic activities of the copper(II) complexes (1 mmol Lꢀ1 in 25 mL
methanol) were performed for the oxidation of catechol at room temperature, under
atmospheric air as well as under inert atmosphere (N2), where the electronic spectra
were recorded at different time intervals. The oxidation of catechol was detected by
spectrophotometric monitoring the appearance of o-quinone at 400 nm.
2.4. Synthesis
2.4.1. Synthesis of 2,6-diacetylpyridinebis(3,5-di-tert-butylanil) (L1). 2,6-Diacetylpyridine
(0.135 g, 1.0 mmol) and 3,5-di-tert-butylaniline (0.410 g, 2.0 mmol) were stirred in
methanol (25 mL) for 6 h in the course of which a yellow solid was formed. The solid
was filtered off, washed with cold methanol, and dried in vacuum to give 1ꢃCH3OH in
96% yield. Anal. Calcd for C38H55N3O (%): C, 80.09; H, 9.73; N, 7.37. Found (%): C,
80.01; H, 9.46; N, 8.52. 1H NMR (CDCl3, 400 MHz): ꢀ, ppm 8.76 (s, 2H, HC¼N), 8.35
(d, J ¼ 7.5, 2H, Hꢁ pyridine), 7.85 (t, J ¼ 7.2, 1H, Hꢂ pyridine), 7.25 (s, 2H, Harom), 7.15
(s, 4H, Harom), 2.43 (s, 6H, 2CH3), 1.33 (s, 36H, (C(CH3)3)). 13C NMR
(CDCl3, 100 MHz): ꢀ, ppm 167.2, 156.3, 152.1, 151.1, 137.2, 122.2, 119.2, 118.9,
(Carom), 114.3 (CH¼N), 35.0 (CH3), 32.1 (C(CH3)3), 16.5 (C(CH3)3). IR (KBr): ꢃ, cmꢀ1
3062 (s, C–Harom), 2962 (s, C–Haliph), 1626 (m, C¼N), 1595, 1585, 1523 (s, C¼Carom).
MS (FDþ, EtOH): m/z ¼ 538 [M]þ.
2.4.2. Synthesis of 2,6-diacetylpyridinebis(3,5-di-tert-butylanil)CuCl2 [Cu(pyMet2BuN3)
Cl2] (1). CuCl2 ꢃ 2H2O (0.511 g, 0.3 mmol) was added to a suspension of 2,6-bis(3,5-di-
tert-butylphenylimino-1-ethyl)pyridine (L1) (1.53 g, 0.3 mmol) in methanol and the
mixture was stirred for 5 h. The resultant orange-brown product was filtered off,
washed with cold methanol (5 mL), and dried in vacuum to give 1.CH3OH in 75%
yield. Anal. Calcd for C39H59Cl2CuN3O2 (734.33) (%): C, 63.61; H, 8.08; N, 5.71.
Found (%): C, 63.32; H, 7.21; N, 5.75. IR (KBr): ꢃ, cmꢀ1 3070 (s, C–Harom), 2960, 2904
(s, C–Haliph), 1650 (m, C¼N). MS (FDþ, CH3OH): m/z ¼ 675 [M]þ.
3. Results and discussion
3.1. Synthesis and characterization
2,6-Bis-(ketimino)pyridine, L1, was synthesized in high yield via Schiff-base conden-
sation of one equivalent of 2,6-diacetylpyridine with two equivalents of 3,5-di-tert-
butylaniline. L1 behaves as a neutral tridentate chelating agent and its copper(II)
complex, 1, was synthesized by treating with CuCl2 in methanol (scheme 1). FAB mass
spectrum and microanalysis of
1
confirmed the suggested formula
[CuII(pytBuMe2N3)Cl2]. The azomethine band ꢃ(C¼N) in 1 undergoes a remarkable
shift to higher wavenumbers as a result of coordination of the nitrogen to the metal ion
[11]. The in-plane ring deformation band ꢀ(py) at 585–624 cmꢀ1 in the spectrum of the

Copper(II) complexes
2419
N
tBu
tBu
N
tBu
But
O
N
N
O
H2N
2
(a)
L1
tBu
tBu
(b)
N
tBu
But
N
Cl
N
Cu
Cl
tBu
tBu
1
Scheme 1. Synthesis of L1 and its copper(II) complex 1; (a) MeOH, 65ꢁC, 10 h; (b) CuCl2, MeOH, 65ꢁC, 7 h.
free ligand is shifted 612–650 upon complexation due to bonding through the pyridyl
nitrogen [12].
Due to the lack of an X-ray structure of the reported copper(II) complex
[CuII(pytBuMe2N3)Cl2] (1), comparative spectral and magnetic investigations were
carried out with the related copper(II) complex [CuII(pytBuN3)Cl2] (2) [5]. X-ray
structural analysis demonstrated that 2 consists of a five-coordinate trigonal bipyra-
midal copper(II) [5]. The room temperature magnetic moments of 1 and 2 in the solid
state, 1.9 and 1.88 BM, respectively, are consistent with the formulation of the
complexes as copper(II) monomers with one unpaired electron. The spectra of both
complexes in methanol exhibit broad asymmetric absorption bands at ꢄ720 nm
(ꢄ ¼ 1200 L molꢀ1 cmꢀ1), which are in the range expected for the d–d transition of the
tetragonal distorted copper(II) complex [13]. In addition, a strong absorption in the low
energy region can be assigned to the n ! ꢅ* transition that originates from the
azomethine linkage of the imine moiety of the ligand [14].
The position and intensity of this band depends on the type of substituent within the
carbonyl moiety of the Schiff-base ligands. The increasing energy of this band from 1 to
2 (figure 2) reflects the decreasing order of the Lewis acidity of the copper(II) center
[11]. The presence of the electron-donating group (CH3) in L1 shifts the n ! ꢅ* band of
C¼N to higher energy compared to the hydrogen in L2.
The X-band ESR spectra of 1 and 2 were measured at room temperature. The
spectral features are similar and exhibit intense ESR signals that are characteristic of the
rhombic symmetry with three g-values. The observed g-values (g1, g2, and g3 in the
order of decreasing magnitude) were computed from the spectra using DPPH
(g ¼ 2.0023) as g marker. In the rhombic symmetry, all orbital degeneracy must
disappear. The presence of a relatively weak rhombic distortion is apparent in the
splitting of the perpendicular resonance into two closely spaced components (g2 and g3)
in all cases. For the five-coordinate copper(II) complexes the probable configurations,
namely square pyramidal and trigonal bipyramidal, are characterized by the ground-
state dx2ꢀy2 and dz2 orbitals, respectively. ESR spectra for the five-coordinate copper(lI)
complexes provide a very good basis for distinguishing between these two states. For
systems with gl 4 g2 4 g3, the ratio of (g2 ꢀ g3)/(gl ꢀ g2) ¼ R is very useful. If the ground

2420
S.Y. Shaban et al.
1.4
1.2
1.0
0.8
0.6
0.4
0.2
0.0
1
2
300
350
400
450
500
550
600
λ (nm)
Figure 2. UV-Vis spectra recorded for 1 (—) and 2 (ꢃ ꢃ ꢃ) (0.5 ꢅ 10ꢀ4 mol Lꢀ1) in methanol at 296 K.
state is dz2 the value of R is larger than 1. On the other hand, if the ground state is dx2ꢀy2
the value of R is less than 1 [11]. The five-coordinate copper(II) complexes under study
show values of R larger than 1, thus indicating a five-coordinate trigonal bipyramidal
geometry. On the basis of these arguments, a five-coordinate trigonal bipyramidal
structure may be assigned for 1.
The electrochemical behavior of 1 was studied and compared with that of 2 to provide
more information on the nature of the complex in solution. Cyclic voltammograms were
recorded in MeOH versus a Ag/Agþ reference electrode (figure 3). In contrast to the
analogous complex 2, compound 1 exhibits only one peak. One-electron oxidation occurs
at 0.51 V and the corresponding reduction at 0.38 V. The peak at 0.51 V has the typical
symmetrical shape of an adsorption phenomenon. This may explain the ipa/ipc value 4 1.
The relatively high DEp value of 126 mV may suggest that a Eqrev or Eirrev electrochemical
mechanism is operating (i.e., slow electron transfer related to heavy structural
reorganization after the electron transfer, without chemical complications) [15]. On the
basis of the former data, the overall redox process may simply be the chemically
reversible, but electrochemically quasi-reversible and adsorption-complicated Cu(II)/
Cu(I) reduction [16]. The effect of chlorides (added as LiCl) may simply be to interfere
with this adsorption, ‘‘cleaning’’ the diffusion peak below.
A comparison of 1 with that found for the analogous [CuII(pytBuN3)Cl2] complex
indicates that the introduction of two methyl substituents into the bis-imine moiety
shifts E to a more positive value (from 44 mV for 1 to 70 mV for 2). An explanation
½
for this is most likely related to electron donation of the methyl substituent that leads to
an increase in the electron density on the metal center.
3.2. Kinetic studies on ligand substitution
Previous studies on copper(II) catecholase functional models demonstrated that the
exchange interaction between the catecholase anion radical with a good leaving group

Copper(II) complexes
2421
5
4
50mV
50mVLiCl
0.506 V
3
2
1
0
-1
-2
-3
0.380 V
0.4
0.2
0.3
0.5
0.6
0.7
E[V]
Figure 3. (a) Cyclic voltammograms of [CuII(pytBuMe2N3)Cl2] (1) (— before and - - - after addition of
0.1 mol Lꢀ1 LiCl). Measurements were performed on a Pt working electrode vs. a non-aqueous Ag/Agþ
reference electrode; add 544 mV [300 mV, Ag/Agþ to SCE; þ244 mV, SCE to SHE] to convert to standard
hydrogen electrode (SHE); Fc/Fcþ couple in CH3CN, E , 0.414 V (CV); supporting electrolyte 0.1 mol Lꢀ1
½
NBu4PF6, scan rate ¼ 50 mV sꢀ1, potentials given in V, complex concentration 0.2 mmol Lꢀ1
.
incorporated in the complex initiates the catalytic oxidation cycle. If the coordinating
groups are stronger ligands than the catecholate, no oxidation will be observed for the
five-coordinate copper(II) catecholase models. To further elucidate the biomimetic
catalytic activity of the reported copper(II) catecholase models 1 and 2, a detailed
kinetic study on chloride substitution of 1 was carried out and compared with that for 2.
Thiourea was selected as entering nucleophile because of its high nucleophilicity that
will prevent back reaction with chloride. Furthermore, it was selected as a neutral
entering ligand such that the overall reaction is accompanied by charge creation, and
the formation of the transition state may involve changes in dipole moment [5, 17].
Reactions of 1 with thiourea can be monitored kinetically in the range of ca 360–
400 nm. Solutions were prepared by dissolving known amounts of 1 in methanol in the
presence of 0.002 mol Lꢀ1 LiCl to prevent the spontaneous solvolysis reaction. The
substitution reactions were studied as a function of TU concentration, temperature, and
pressure in methanol. Figures 4 and 5 show UV-Vis spectral changes and representative
kinetic traces, respectively.
Rate constants for the reactions were determined by using total TU concentrations of
0.001ꢀ0.25 mol Lꢀ1, i.e., always at least in 10-fold excess over the Cu(II) complex.
Throughout the nucleophile concentration range it was possible to fit the absorbance/
time traces to a two-exponential function by using the following equation:
obsd1t
obsd2t
A ¼ a1eꢀk
þ a2eꢀk
þ A0
ð1Þ
The overall reaction is biphasic and in line with that reported for 2. An initial fast
reaction (rate constant kobsd1) is followed by a much slower one (rate constant kobsd2).
kobsd1 increases linearly with TU concentration (figure 6), which leads to the second-
order rate constant k1 ¼ 3.6 ꢂ 0.1 (mol L
)
ꢀ1 ꢀ1 sꢀ1. Rate constant kobsd2 also depends
linearly on the TU concentration with second-order rate constant
k2 ¼ (3.8 ꢂ 1.1) ꢅ 10ꢀ2 (mol L
)
ꢀ1 ꢀ1 sꢀ1 (figure 6). The rate constants demonstrate that

2422
S.Y. Shaban et al.
Figure 4. UV-Vis spectral changes recorded for the reaction of 1 (0.5 ꢅ 10ꢀ4 mol Lꢀ1) with thiourea
(250 mmol Lꢀ1) in methanol at 296 K: (a) spectrum before the reaction; (b) spectrum obtained a few seconds
after mixing of the reactants; (c) spectrum obtained after 100 min.
Figure 5. Absorbance-time traces at 350 nm for the reaction of 1 (0.5 ꢅ 10ꢀ4 mol Lꢀ1) with thiourea
(250 mmol Lꢀ1) in methanol at 296 K (solid line obtained by fitting the data with a double exponential
function according to equation (1)). The inset represents the kinetic trace of the fast reaction measured by
stopped-flow instrument.
the second substitution is slowed by two orders of magnitude due to the displacement of
one chloride by thiourea.
The observed kinetic behavior can be accounted for in terms of two subsequent
substitution reactions (equation (2)) in which the two chlorides are sequentially displaced
by TU characterized by the second-order rate constants k1 and k2, respectively.
Â
Ã
Â
Ã
TU
TU
0
2þ
CuðLÞðClÞ2 ꢀꢀ! ½CuðLÞðClÞTUꢆþꢀꢀꢀ! CuðLÞðTUÞ2
ð2Þ
k1
k2

Copper(II) complexes
2423
1.0
0.8
0.6
0.4
0.2
0.0
1.0
0.8
0.6
0.4
0.2
0.0
0.00 0.05 0.10 0.15 0.20 0.25
0.00 0.05 0.10 0.15 0.20 0.25
[TU], M
[TU] M
Figure 6. Plots of kobsd vs. thiourea concentration for 1 in methanol at 296 K (left: first reaction step; right:
second reaction step). Experimental conditions: [1] ¼ 0.5 ꢅ 10ꢀ4 mol Lꢀ1, 0.002 mol Lꢀ1 LiCl.
Table 1. Summary of the rate and activation parameters for the substitution of the chloride ligands in
[CuII(pytBuMe2N3)Cl2] (1) and [CuII(pytBuN3)Cl2] (2) by TU in methanol in the presence of 2 mmol Lꢀ1 LiCl.
Complex
k296 ((mol L
)
ꢀ1 ꢀ1 sꢀ1
)
DH# (kJ molꢀ1
)
DS# (JKꢀ1 molꢀ1
)
DV# (cm3 molꢀ1
)
1
First step
Second step
3.6 ꢂ 0.1
40 ꢂ 1
ꢀ100 ꢂ 5
ꢀ172 ꢂ 3
ꢀ14.0 ꢂ 0.3
ꢀ19.3 ꢂ 0.6
(3.8 ꢂ 1.1) ꢅ 10ꢀ2
35.6 ꢂ 0.8
2a
First step
Second step
918 ꢂ 30
42 ꢂ 2
ꢀ46 ꢂ 7
ꢀ6.5 ꢂ 0.2
1.62 ꢂ 0.06
58 ꢂ 2
ꢀ47 ꢂ 6
ꢀ5.3 ꢂ 0.7
aRef. [5].
It follows from this reaction scheme that kobs1 and kobs2 should depend linearly on the
entering TU concentration in the absence of a back reaction as shown in figure 6, such
that kobs1 ¼ k1[Nu] and kobs2 ¼ k2[Nu]. The rate constants in table 1 show that the
second substitution reaction with thiourea is much slower than the first one. This can be
ascribed to steric hindrance on the Cu(II) center caused by the displacement of chloride
by thiourea. A comparison of k1 and k2 with that found for the analogous
[CuII(pytBuN3)Cl2] complex indicates that the introduction of two methyl substituents
on the bis-imine slows the first reaction 250 times and the second reaction 40 times at
296 K. A likely explanation for this decrease in rate is related to two factors: (i) the
electron donation of the methyl substituents leads to an increase in the electron density
at the metal center and hence a decrease in electrophilicity; (ii) the steric factor arising
from the two methyl groups attached directly to the imine linkage limits the freedom of
rotation of the aryl ring substituents [8, 18].
Since activation parameters such as DS# and DV# are sensitive probes that reflect the
nature of the transition state of a given reaction, their determination serves as a useful
mechanistic tool in assigning the mechanism of the TU substitution reaction. The
temperature and pressure dependences of the substitution rate constants were studied
by stopped-flow and spectrophotometric techniques from 12ꢁC to 28ꢁC (limited due to
low solubility of the complex) and pressure range 10–150 MPa, respectively. The
observed temperature and pressure dependencies are presented in figures 7 and 8,
respectively, and the plots are linear over the ranges studied. From these plots the
activation parameters for the TU substitution reaction were estimated, and the data are

2424
S.Y. Shaban et al.
Figure 7. Temperature dependence of the reactions of 1 with thiourea in methanol (left, first reaction step;
,
right: second reaction step). Experimental conditions: [1] ¼ 0.5 ꢅ 10ꢀ4 mol Lꢀ1
[TU] ¼ 0.25 mol Lꢀ1
,
0.002 mol Lꢀ1 LiCl.
Figure 8. Pressure dependence of the reaction of 1 with thiourea in methanol (g first reaction step, ꢇ second
reaction step). Experimental conditions: [1] ¼ 0.1 mmol Lꢀ1, [TU] ¼ 0.015 mol Lꢀ1, 296 K, 0.002 mol Lꢀ1 LiCl.
summarized in table 1. The values of DS# and DV# are much more negative than those
reported for [CuII(pytBuN3)Cl2], supporting an associative mechanism for both reaction
steps in reaction (2) rather than an associative interchange (Ia) mechanism [19]. In this
case, the transition state of the process is expected to have six-coordinate character on
forming a bond between the five-coordinate Cu(II) complex and the entering
nucleophile. The activation parameters reported in table 1 also support this suggestion.
3.3. Kinetic studies on the reaction with 3,5-DTBC
In most catecholase-like activity studies of synthetic model complexes, 3,5-DTBC has
been employed as substrate. The product 3,5-di-tert-butyl-o-quinone (3,5-DTBQ) is

Copper(II) complexes
2425
Figure 9. UV-Vis spectral changes recorded for the reaction of 1 (0.1 mmol Lꢀ1) with 3,5- DTBC
(100 mmol Lꢀ1) in MeOH at 296 K. Inset shows the course of the absorbance at 400 nm with time (in
minutes).
stable and has a strong absorption at ꢆmax ¼ 400 nm [20]. Therefore, activities and
reaction rates can be determined using electronic spectroscopy by following the
appearance of the absorption maximum of the quinone. The reactivity studies were
performed in methanol and THF solutions because of the good solubility of the
complexes, the substrate (3,5-DTBC) and its product (3,5-DTBQ) in these solvents.
Prior to a detailed kinetic study, it was first necessary to estimate approximately the
ability of the complexes to oxidize catechol. For this purpose, 0.1 mmol Lꢀ1 solutions of
1 and 2 in methanol were treated with 100 mmol Lꢀ1 of 3,5-DTBC in the presence of air.
The course of the reaction was followed by UV-Vis spectroscopy over the first 200 min.
The results indicate that the reactivity of 1 is higher than that of 2, and can be expressed
in turnover numbers of 30 minꢀ1 for 1 versus 12 minꢀ1 for 2. The course of the
catecholase reaction with a solution of 1 is shown in figure 9 for the reaction in
methanol.
It is clear from the results in figure 9 that the addition of 100 mmol Lꢀ1 of 3,5-DTBC
to the complex has an immediate influence on the UV-Vis spectrum. The bands in the
charge-transfer region as well as the d–d bands change with respect to position and
intensity. Therefore, binding of 3,5-DTBC to copper(II) should be considered as the
first rapid step. Due to the developing product bands in the UV-Vis spectrum of the
complex, it is difficult to make a clear statement about the nature of the coordination of
catechol to the metal center. We have therefore used stopped-flow techniques to study
the rapid reaction with 3,5-DTBC in more detail. The complex spectrum changes
dramatically upon the addition of 3,5-DTBC during the first 30 s, as shown in figure 10.
The kinetics of this reaction could be followed at 400 nm. The kinetics of the subsequent
slow reaction was studied by the initial rate method by monitoring the absorbance
change at 400 nm (see inset in figure 9).
The same reaction in THF occurs orders of magnitude faster and the results
in figure 11 show that the absorbance versus time plot at 400 nm after the addition of

2426
S.Y. Shaban et al.
0.56
0.52
0.48
0.44
0.40
1.0
0.8
0.6
0.4
0.2
0.0
0
30
60
90
120
150
180
Time, s
300
350
400
450
[λ] nm
500
550
600
Figure 10. UV-Vis spectral changes recorded for the first reaction step of 1 (0.1 mmol Lꢀ1) with 3,5-DTBC
(18 mmol Lꢀ1) in MeOH at 296 K. Inset: representative kinetic trace obtained by stopped-flow spectro-
photometry monitored at 400 nm.
0.85
1.2
0.80
0.75
0.9
0.70
0.65
0.6
0.60
0
40
80
[Time] s
120
160
200
0.3
0.0
300
400
500
600
λ, nm
Figure 11. UV-Vis spectral changes recorded for the reaction of 1 (0.5 ꢅ 10ꢀ4 mol Lꢀ1) with 3,5 - DTBC
(225 mmol Lꢀ1) in THF at 296 K. Inset: kinetic trace of the overall reaction between 3,5-DTBC and 1 in THF
monitored by stopped-flow spectrophotometry at 400 nm. Experimental points superimposed with the best
single-exponential fit.
3,5-DTBC also proceeds in two steps, namely a fast decrease in absorbance in the first
step followed by an increase in absorbance in the second step. The second step cannot
be observed when the experiment is repeated under inert atmosphere (i.e., in the absence
of oxygen), indicating that the growing band is due to quinone formation. More
information on the first reaction step could be obtained from stopped-flow measure-
ments over the first few seconds at 400 nm as shown in figure 12.

Copper(II) complexes
2427
Figure 12. Representative kinetic trace for the first reaction step between 3,5-DTBC and 1 in THF obtained
by stopped-flow spectrophotometry monitored at 400 nm. Experimental points superimposed with the best
single-exponential fit. Conditions: T ¼ 296 K; [1] ¼ 0.5 ꢅ 10ꢀ4 mol Lꢀ1 and [3,5-DTBC] ¼ 75 mmol Lꢀ1
.
To determine the dependence of the observed reactions on the substrate concentration,
solutions of 1 were treated with different concentrations of 3,5-DTBC in both methanol
and THF. For the first step, a first-order dependence on the substrate concentration was
observed in both cases (figures 13 and 14). Thus, we propose a rapid pre-equilibrium
involving adduct formation between the Cu(II) complex and 3,5-DTBC (equation (3)).
The results obtained in both solvents show that the coordination affinity of 3,5-DTBC
in
THF
(K1 ¼ k1/k ¼ 7.3 (mol Lꢀ1 ꢀ1
)
)
is
smaller
than
in
MeOH
ꢀ1
(K1 ¼ k1/k ¼ 11.3 (mol L
)
ꢀ1 ꢀ1) (figures 13 and 14, respectively). The reason for this
can be traced to the higher basicity of methanol which can assist in the deprotonation of
3,5-DTBC.
ꢀ1
k1
O2
Cu -DTBC adduct ꢀꢀ! Cu complex þ DTBQ ð3Þ
II
II
II
ꢀꢀ!
Cu complex þ 3,5-DTBC
ꢀꢀ
k2
kꢀ1
For the second step of the reaction between 3,5-DTBC and 1 in methanol, a first-
order dependence on the substrate concentration was observed at low concentrations of
3,5-DTBC. At higher substrate concentrations, saturation kinetics was observed
(figure 15). The irreversible conversion into the quinone product is considered to be the
rate-determining step, i.e., k2 ꢈ k and K1 ¼ k1/kꢀ1. Although a much more compli-
ꢀ1
cated mechanism may be involved, the results show that this simple model is sufficient
for a kinetic description. The rate law for the reaction sequence in (3) is given by (4):
Ã
Â
where V is the rate of product formation, which can be rewritten as
k2k1 CuIIcomplex ½3,5-DTBCꢆ
1 þ k1½3,5-DTBCꢆ
Â
Ã
d½DTBQꢆ
dt
V ¼
¼ k2 CuIIcomplex ꢀ adduct ¼
V
k2k1½3,5-DTBCꢆ
Â
à ¼
ð4Þ
CuIIcomplex
1 þ k1½3,5-DTBCꢆ

2428
S.Y. Shaban et al.
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0.0
0.00
0.04
0.08
0.12
0.16
0.20
[3,5-DTBC] M
Figure 13. Plot of kobs1 vs. 3,5-DTBC concentration for the first reaction step between 3,5-DTBC and
1
0.5 ꢅ 10ꢀ4 mol Lꢀ1
in MeOH at 296 K. The reaction was monitored at 400 nm (K1 ¼ k1/
k
¼ 11.3 (mol L
)
ꢀ1 ꢀ1).
ꢀ1
6
5
4
3
2
1
0
0.0
0.1
0.2
0.3
0.4
[3,5-DTBC] M
Figure 14. Plot of kobs1 vs. 3,5-DTBC concentration for the first reaction step between 3,5-DTBC and
0.5 ꢅ 10ꢀ4 mol Lꢀ1 1 in THF at 296 K (K1 ¼ k1/k ¼ 7.3 (mol L
)
ꢀ1 ꢀ1).
ꢀ1
The maximum rate constant, k2, is reached when the catalyst is completely saturated
with 3,5-DTBC, i.e., at high [3,5-DTBC]. At a V/[CuIIcomplex] value of k2/2, the
[3,5-DTBC] ¼ 1/k1, which according to figure 15 results in k1 ꢉ 10 (mol Lꢀ1 ꢀ1
)
for the
reaction in methanol. This value is indeed very close to that found for k1 in figure 13
and illustrates the validity of the kinetic model.
The greater catalytic activity of 1 compared to 2 can be correlated with their redox
potentials. It should be noted that the enzyme tyrosinase, which catalyzes the aerobic

Copper(II) complexes
2429
1000
800
600
400
200
0
−1
k = 960 s
2
1/K = 0.098
1
0.0
0.1
0.2
[3,5-DTBC], M
0.3
0.4
Figure 15. Dependence of the initial rate of the oxidation reaction of 3,5-DTBC on the concentration of the
substrate 3,5-DTBC catalyzed by 1 in methanol. The concentration of 1 was 0.5 ꢅ 10ꢀ4 mol Lꢀ1 and the
reaction was followed at 400 nm.
oxidation of catechol to the light absorbing o-quinone, has a reported E0 value of 0.36 V
versus the standard calomel reference electrode [8]. It is obvious, however, that the
enzyme is able to balance successfully the requirements of the different oxidation states
of the metal, Mnþ ÐM(nꢀ1)þ, in performing its catalytic tasks. The balance between the
ease of reduction of copper(II) and subsequent re-oxidation of copper(I) by molecular
oxygen must be maintained for efficient catalysis to occur. E of 1 (0.44 mV)
½
approaches the reported E value of the natural enzyme whereas that of 2 (0.71 mV) is
½
much higher [21, 22]. Several studies on catechol oxidation demonstrated that for five-
coordinate copper(II) complexes with tetradentate ligands, the degree of lability of the
fifth donor has an effect on the rate of catalysis [23]. In addition, it has been shown that
electron transfer from catechol to copper(II) can begin only after catechol and the
copper(II) species form a copper(II)-catecholate intermediate as suggested in reaction
(3) [24]. Such an intermediate can easily be formed as mentioned above, which clearly
showed that both 1 and 2 undergo associative ligand substitution reactions of the
coordinated chloride ligands. The kinetic results showed that the order of lability of the
coordinated chloride ligands is 1 5 2, but the opposite order holds for their reaction
with 3,5-DTBC. These results thus confirm that the catecholase mimetic activity is
independent of either the rate of ligand displacement from the copper(II) complex or
the difference in the dissociation constants for the loss of the chloride ligand. This
suggests that displacement of chloride by catechol as substrate must be involved in a
rapid pre-equilibrium step of the overall reaction sequence outlined in (3).
4. Conclusion
A new sterically constrained N3 donor L1 was synthesized with the aim to understand
the effect of ligand substituents in terms of electronic and steric factors on the structure,

2430
S.Y. Shaban et al.
spectral behavior and consequently the catecholase biomimetic catalytic activity of its
copper(II) complex. Based on the elemental analysis, mass spectra, and the results from
different physicochemical techniques employed in this study, a five-coordinate trigonal-
bipyramidal geometry was proposed for the newly synthesized [CuII(pytBuMe2N3)Cl2]
(1). To confirm the proposed structure, comparative spectral and magnetic investiga-
tions were carried out with the previously prepared copper(II) complex
[CuII(pytBuN3)Cl2] (2). The ability of 1 and 2 to oxidize 3,5-DTBC was studied and
the results demonstrated that there is no correlation between the rate of chloride
substitution and the observed catalytic activity. In assessing whether there is a
correlation between the Lewis acidity of the central copper(II) ion and catalytic
properties, no trend was observed for these complexes. Although 1 is the catalytically
most active species, its Lewis acidity is lower than that of 2. It appears that both the
Lewis acidity of the central copper(II) and redox potentials are of secondary importance
to chloride substitution in determining the catalytic properties of these complexes.
Acknowledgments
Kafrelsheikh University, Kafrelsheikh, Egypt, the University of Erlangen-Nuremberg,
Erlangen, Germany, and the Deutsche Forschungsgemeinschaft are thanked for
financial support.
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