Ternary complexes containing Copper(II), L-Valinate and α, ?-bipyridyl or 1,10-phenanthroline: Synthesis, characterization, ligand substitution and oxidase biomimetic catalytic activity studies

Article abstract of DOI:10.1016/j.molstruc.2019.04.003

Ternary copper(II) complexes with the molecular formulae of [Cu^IILL′]X or [Cu^IILL′X]; L =L-Valinate; L′ = α, ?-bipyridyl or 1,10 - phenanthroline and X is Clˉ, Brˉ, NO₃ˉ, AcOˉ, ?SO₄ ^2? or ClO₄ˉ were synthesized. Elemental and thermal analysis in addition to electrochemical (molar conductance and cyclic voltammetry), magnetic moment measurements as well spectral (FT-IR, UV–Vis and ESR) techniques were used to characterize the complexes. The spectroscopic results suggested square pyramidal and square planar geometries for the five- and four-coordinate complexes respectively. Powder X-ray diffraction spectral data along with the structure solution program Expo 2014 has been used for structural elucidation of the sulfato complexes 1 and 5. Stopped follow technique was employed to study the substitution of the nonelectrolytic coordinately counter anion ligand by using thiourea (TU) as a function of nucleophile and a biphasic process is proposed. An initial fast reaction is followed by a slower one and the initial one was found to be counter ion dependent. Bio-mimicking the multicopper oxidase enzyme such as catechol oxidase and phenoxazinone synthase is a further goal of the present study. Catalytic examinations displayed that the present complexes are promising candidates as functional mimic of the examined enzymes and the probable mechanistic catalytic sequences are discussed.

Full text of DOI:10.1016/j.molstruc.2019.04.003

Accepted Manuscript
Ternary complexes containing Copper(II), l-Valinate and α, ά-bipyridyl or 1,10-
ortho-phenanthroline: Synthesis, characterization, ligand substitution and oxidase
biomimetic catalytic activity studies
A.M. Ramadan, S.Y. Shaban, M.M. Ibrahim, F.I. El-Shami, S.A. Al-Harbi
PII:
S0022-2860(19)30392-8
DOI:
https://doi.org/10.1016/j.molstruc.2019.04.003
MOLSTR 26375
Reference:
To appear in: Journal of Molecular Structure
Received Date: 18 November 2018
Revised Date: 23 March 2019
Accepted Date: 1 April 2019
Please cite this article as: A.M. Ramadan, S.Y. Shaban, M.M. Ibrahim, F.I. El-Shami, S.A. Al-Harbi,
Ternary complexes containing Copper(II), l-Valinate and α, ά-bipyridyl or 1,10-ortho-phenanthroline:
Synthesis, characterization, ligand substitution and oxidase biomimetic catalytic activity studies, Journal
of Molecular Structure (2019), doi: https://doi.org/10.1016/j.molstruc.2019.04.003.
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ACCEPTED MANUSCRIPT
Ternary Complexes Containing Copper(II), L-Valinate and
α,
ά
-Bipyridyl or
1
,10-ortho-phenanthroline: Synthesis, Characterization, Ligand Substitution
and Oxidase Biomimetic Catalytic Activity Studies
a
a
a
a
b
A. M. Ramadan , S. Y. Shaban , M. M. Ibrahim , F. I. El-Shami , S. A. Al-Harbi
a
Chemistry Department, Faculty of Science, Kafr El-Sheikh University, Kafr El-Sheikh Egypt
Chemistry Department, University College in Al-Jamoum, Umm Al-Qura University, 21955,
b
Makkah, Saudi Arabia.
Abstract
II
II
Ternary copper(II) complexes with the molecular formulae of [Cu LL′]X or [Cu LL′X]; L = L-
2
-
Valinate; L′ = α, ά-bipyridyl or 1,10 ortho - phenanthroline and X is Cl¯ , Br¯ , NO ¯ , AcO¯ , ½SO
3
4
or ClO ¯ were synthesized. Elemental and thermal analysis in addition to electrochemical (molar
4
conductance and cyclic voltammetry), magnetic moment measurements as well spectral (FT-IR,
UV–Vis and ESR) techniques were used to characterize the complexes. The spectroscopic results
suggested square pyramidal and square planar geometries for the five- and four-coordinate
complexes respectively. Stopped follow technique was employed to study the substitution of the
nonelectrolytic coordinately counter anion ligand by using thiourea (TU) as a function of
nucleophile and a biphasic process is proposed. An initial fast reaction is followed by a slower one
and the initial one was found to be counter ion dependent. Bio-mimicking the multicopper oxidase
enzyme such as catechol oxidase and phenoxazinone synthase is a further goal of the present study.
Catalytic investigations demonstrated that the present complexes are promising candidates as
functional mimic of the examined enzymes and the probable mechanistic catalytic sequences are
discussed.
-4
UV/Vis spectral changes recorded for the reaction of complex 1 (6 × 10 M) with (a) 3,5-di-tert-
-2
-2
butylcatechol (10 M) (b) o-aminophenol (10 M) in MeOH at 296 K. Inset shows the course of the
absorbance at 400 nm for 3,5-DTBC and at 432 for o-AP with time (in second).

ACCEPTED MANUSCRIPT
Ternary Complexes Containing Copper(II), L-Valinate and
α, ά-
Bipyridyl or 1,10-ortho-phenanthroline: Synthesis, Characterization,
Ligand Substitution and Oxidase Biomimetic Catalytic Activity Studies
a
a
a
a
b
A. M. Ramadan , S. Y. Shaban , M. M. Ibrahim , F. I. El-Shami , S. A. Al-Harbi
a
Chemistry Department, Faculty of Science, Kafr El-Sheikh University, Kafr El-Sheikh
Egypt
b
Chemistry Department, University College in Al-Jamoum, Umm Al-Qura University,
2
1955, Makkah, Saudi Arabia.
Abstract
Ternary copper(II) complexes with the molecular formulae of [Cu LL′]X or [Cu LL′X];
L = L-Valinate; L′ = α, ά-bipyridyl or 1,10 - phenanthroline and X is Cl¯ , Br¯ , NO ¯ ,
II
II
3
2
-
AcO¯ , ½SO4 or ClO ¯ were synthesized. Elemental and thermal analysis in addition to
4
electrochemical (molar conductance and cyclic voltammetry), magnetic moment
measurements as well spectral (FT-IR, UV–Vis and ESR) techniques were used to
characterize the complexes. The spectroscopic results suggested square pyramidal and
square planar geometries for the five- and four-coordinate complexes respectively.
Powder X-ray diffraction spectral data along with the structure solution program Expo
2
014 has been used for structural elucidation of the sulfato complexes 1 and 5. Stopped
follow technique was employed to study the substitution of the nonelectrolytic
coordinately counter anion ligand by using thiourea (TU) as a function of nucleophile and
a biphasic process is proposed. An initial fast reaction is followed by a slower one and
the initial one was found to be counter ion dependent. Bio-mimicking the multicopper
oxidase enzyme such as catechol oxidase and phenoxazinone synthase is a further goal of
the present study. Catalytic examinations displayed that the present complexes are
promising candidates as functional mimic of the examined enzymes and the probable
mechanistic catalytic sequences are discussed.
Keywords: α, ά -bipyridyl; L-Valinate; 1,10-phenanthroline, Copper(II) complex;
Powder XRD, Catechol oxidase, phenoxazinone synthase
1

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1
. Introduction
Copper is a fundamental metal for living systems having unique chemical properties
that allow it to plays divers roles in cellular functions chemistry [1]. Its biological
significance is ascribed to the capability of copper to catalyze oxidation reduction (redox)
chemistry [1]. In this context copper oxidases effecting either one electron or two
electron oxidation of substrates and these copper proteins react with O
2
to reduce it to
either H O or H O [2]. These blue copper proteins comprise catechol oxidase and
2
2
2
phenoxazinone synthase play significant roles in melanin pigment and antibiotic
production. The type 3 dinuclear copper protein namely catechol oxidase catalyzes the
four electrons oxidation of catechol to the corresponding light absorbing o-quinones.
Other concern copper enzyme is phenoxazinone synthase that catalyzes the production of
2
-aminophenoxazinone chromophore (APX) via a six-electron oxidation of o-
aminophenol (o-APH ) to APX with the concomitant reduction of aerobic 3/2 O to 3H O.
3
2
2
The active site has yet to be well characterized; although the enzyme appears to contain
several types of copper ions [3].
Model complexes have played a prominent role in elucidating the chemical principles
that may involved in the dioxygen chemistry of copper oxidase metalloenzymes. Study
the copper oxidase models have played a notable role to illustrate the chemical principles
that may involve in the activation of dioxygen or the substrate during the biological
oxidation processes [4-8]. The common metal donor atoms in metalloproteins are sulfur;
nitrogen and oxygen of the coordinated amino acids which provide coordination
chromophore facilitate the catalytic role of these enzymes. In this regard ternary
copper(II) complexes containing amino acid and nitrogen base afford donor sites which
match the native copper proteins. Among the studied nitrogen bases, α, ά -bipyridyl has
been the most attractive due to its various functions [9]. Furthermore, the ternary
copper(II) complexes can serve as oxidase models that provide a better understanding of
the catalytic pathway of the native copper-enzyme [10].
In our continuation study in the mimicking catechol oxidase and phenoxazinone
synthase, we provide herein study on a new series of ternary copper(II) complexes that
II
II
have the formula of [Cu LL′]X or [Cu LL′X]; L = L-Valinate; L′ = α,ά-bipyridyl or 1,10-
2

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-phenanthroline with various anion. As a further goal of the present study the lability of
the complexes were investigated and correlated with their catalytic activity.
2
. Experimental
2
.1. Materials
All chemicals used were of analytical grade. The ligand systems [LL′] that composed
of 1,10-phenanthroline, α, ά-bipyridyl and L-Valine obtained from Aldrich and were used
without further purification.
2
.2. Synthesis of copper(II) complexes
The amino acid L−Valine (1 mmol) was dissolved in an aqueous methanolic solution
(20 ml) containing NaOH (1 mmol). To this mixture a methanolic solution of copper(II)
salts, CuX nH O (1.0 mmol, X = NO , Br, Cl, ClO ) and CuSO in a small amount of
2
2
3
4
4
water was added and the reaction mixture was stirred for several minutes. Further
addition of the methanolic solution (1.0 mmol) of the nitrogen bases (1,10-
phenanthroline or α,ά–bipyridyl) with stirring at room temperature leads to the formation
of colored powder crystalline precipitates. The resulting products were filtered off,
washed several times with cold methanol and ether, and finally dried under vacuum for
one week.
2
.3. Physicochemical measurements
Physical measurements, kinetics and the catalytic experiments were carried out as
previously described [8c, d and 10c].
2
.4. Powder XRD
The powder X-ray diffraction spectra of the solid microcrystalline samples of the sulfato
copper(II) complexes 1 and 5 were performed using Shimadzu 6000 XRD spectrometer.
Measurements conditions are 45 kV, 30 mA and Cu Kα radiation with λ=1.54 Å at scan
range of 2θ = 5 – 80.
3

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3
. Results and Discussions
3
.1. Synthesis and characterization of ternary copper(II) complexes (CuLL'X)
The present ligand systems (LL') in which L is L-Valinate and L' is the bidentate,
nitrogen base 1,10-phenathroline or α, ά -bipyridyl afford a series of ternary copper(II)
complexes. Based on the counter anion incorporated in the complex molecule two
II
II
molecular formulae of [Cu LL′]X or [Cu LL′X] were obtained. This ligand system
coordinates to copper(II) ion as monobasic tetradentate via the coordination chromophore
3
N O (Scheme 1). The elemental analysis data and the molar conductance behavior of
these chelates in DMF solution suggested the assigned molecular formulae tabulated in
Table 1. Fully structural characterization was accomplished through further spectral
investigations, magnetic, thermal (TGA and DTG) and electrochemical measurements.
The solid chelates are colored microcrystalline and exhibit shades of green, blue,
violet and brown colors (Table 1). They show very good solubility in the aqueous
medium and the polar organic solvents such as MeOH, DMF and DMSO. All the
attempts made to separate suitable single-crystal for X-ray structural analysis were
unsuccessful.
−1
−1
2
The electrical molar conductivities values (15.00 - 44 ꢀ mol cm ) at room
-3
-1
temperature of 10 mol L in DMF solution of the chloro, bromo and acetato derivatives
indicate their nonelectrolytic behavior [11] and confirm the participation of the counter
anion in the coordination chromophore. The bridging coordination mode of the sulfato
counter anion was inferred from the low electrical conductance values (Table 1) of the
sulfato complexes 1 and 5. Spectral and magnetic investigations provide support for these
suggested dimeric structures of 1 and 5 complex species. Both perchlorate (4) and nitrate
−
1
−1
(
8) complexes exhibit relatively higher molar conductance values (66 – 105 ꢀ mol
2
cm ) assigned to 1:1 electrolytic behavior and this fact ruled out the participation of these
anionic groups in the coordination to copper(II) center.
4

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3
.2. Thermal analysis
3
.2.1. Thermal decomposition (TGA and DTG)
Thermal analysis (TGA and DTG) was carried out in order to identify the nature of
the water content of the studied copper(II) complexes. The obtained results are given in
Table 2 and the corresponding thermograms are given in the supplementary materials S1-
S4.
The hydrated complexes 1, 2, 3, 7 and 8 exhibit similar thermal degradation behaviors
as inferred from their TGA thermograms. The initial stage is ascribed to the dehydration
process which occurred between 50 180 °C with the maximum decomposition peaks
DTGmax within the temperature range of 55 - 155 °C. The observed low values of the
–
1
activation energy 7.23-13.40 kJ mol (S5) reveal the non-coordination nature of the
water content of these chelates. The next thermal pyrolysis stage is referring to the
complete elimination of the coordinated non-electrolytic counter anions in addition to the
full volatilization of the organic ligand system.
The thermal pyrolysis pattern of the bromo complex 6, referees to the thermal loss of
the water content and the coordinated bromo counter anion followed by the complete
removal of the coordinated organic chelators. The unhydrated sulfato complex 5 exhibits
thermal degradation corresponding to the complete ignition of the organic ligand system
in addition to elimination of the bridged sulfato group.
For all complexes the significant mass loss leads to formation of the copper oxide as a
final product. The calculated values of the metal content from the oxide residue are in
accordance with the analytical data given in Table 1.
3
.2.2. Thermal kinetic studies
Coats-Redfern equations [12] were employed to determine the various
thermodynamic parameters (E , ꢁH, ꢁS, and ꢁG) of the studied decomposition processes.
a
The following mathematical relations and their graphical treatments were hired to
account for the contained thermodynamic and kinetic parameters as shown in S5.
1
−n
Ea
.303RT
AR
1− (1− ∞)
2
RT
−
= log
log
[
]
[
1−
]
2
2
qEa
T (1− n)
Ea
for n ≠ 1
5

ACCEPTED MANUSCRIPT
AR
log[ −
log(1 − ∞)
2RT
Ea
=
log
]
[
1−
]
−
2
qEa
T
Ea
2.303 RT
for n = 1
ꢁS = 2.303 R [log (Ah/KT) – 1]
ꢁ
H = E – RT
a
ꢁG = ꢁH – TꢁS
Definition the various terms such as α, t, T, q, A, n, R, K, E , ꢁH, ꢁS, ꢁG and h in these
a
mathematical relations is include with keys of S5.
The values of both the pre-exponential factor (A) and the entropy of activation (ꢁS)
exhibit no clear direction of the different thermal degradation stages while a definite
trend is reported for the activation energy values (see S5). In this regards the activation
energy values of successive stages follow the order first < second < third. The positive
sign of ꢁG indicates the non-spontaneous trend for the current decomposition processes
and also to the fact that the initial compound has lower free energy than that of the final
residue. In most thermal degradation steps the value of ꢁG increase through the
successive stages of degradation indicating that the rate of elimination of the water
content and the coordinated anions is lower than that of the organic ligand system (LL′).
The negative values of ꢁS (S5) indicate that the reactants have less ordered structure than
the activated one.
3
.3. Mode of bonding
The FTIR spectra of the free components of the in situ synthesize copper(II)
complexes were compared to get information about the coordination behavior of this
ligand system with copper(II) ion. The data obtained are given in Table 3 while the charts
of the spectra are given in the supplementary materials (S6-S17). The strong to medium
-1
bands appearing between 3224 and 3367 cm are assigned to the stretching frequencies
-1
of the coordinated amino group (NH ). The bands around 1586 and 1440 cm are
2
–
–
ascribed to the frequencies of υasym(COO ) and υsym(COO ) respectively of the free L-
Valine. These characteristic frequencies were appeared in the corresponding complexes
-1
at range of 1577 - 1598 and 1443 - 1459 cm , in pointing out to the participation of
6

ACCEPTED MANUSCRIPT
–
-1
-1
(
COO ) in coordination to copper(II) center [13]. The values of ꢁυ cm (124 - 155 cm )
–
indicate the monodentate mode of (COO ) [14] and the bidentate pattern of L-Valine
[15]
.
For the coligands 1,10- phenanthroline and α,ά-bipyridyl the observed and recorded
shift in their characteristic frequencies on the complex formation point out to their
participation in coordination to copper(II) ion [16,17,18,19]. The spectra of all complexes
-1
exhibit new medium bands at 505 - 547 and 410-430 cm can be assigned to Cu-N and
Cu-O, respectively and this finding is a further spectral evidence for the formation of the
complexes. Concerning the hydrated complexes the broad band appear at about 3400
−
1
cm and assignable to the υ(OH) of H O is spectral evidence for the presence of lattice
2
−
1
water. The spectrum of the acetato complex exhibits new bands at 1430 cm and 1496
−
1
–
–
cm assigned to υ (CH COO ) and υ (CH COO ) confirms the coordination of the
asym
3
sym
3
acetato anion to copper(II) center [20]. The ionic nature of both NO and ClO ¯ groups is
3
4
–
1
inferred from its IR spectral features at 1383 and 1116 cm respectively [20,21]. For
halogeno complexes the nonelectrolytic halogen exhibits far IR absorptions assignable to
the coordinated halide ion [20].
For the sulfato derivatives 1 and 5 their spectra displayed vibrational bands
corresponds to the bridging fashion of the sulfato group of C symmetry [20] similar to
2
v
that reported for the analogous oxidovanadium(IV) picolyl hydrazones [22a]. These
spectral features and the molar conductance results emphasize the dimeric structure of
complexes 1 and 5 that contain the nonelectrolytic bridging sulfato group [22b].
3
.4. Electronic absorption spectra
Study the electronic transitions in the ultra violate and visible regions of the metal
chelates furnish easy and valuable information about the stereochemistry and the
electronic properties of the central metal ion in its coordination environment. In this
regard a saturated solutions of the inspected copper(II) were prepared in DMF as suitable
solvent and the distinguishing electronic absorption spectra were measured by using the
double beam spectrophotometer at the ambient temperature. The recorded absorption
energies of the various electronic transitions are listed in Table 4. The data in Table 4
indicate the spectral similarity for the four– coordinated complexes 4 and 8. Their spectra
7

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comprise three weak d-d transitions in the low energy visible region assignable to the
2
2
2
2
2
2
three spin allowed transitions: B1 → B , B → A and B → E , respectively
g
2g
1g
1g
1g
g
[23,24,25]. The band energy and position point out to the square-planar environment
around copper(II) center [26,27]. The non-detection of any electronic transitions at a
-1
value of lower than 10,000 cm , excluded the tetrahedral or the pseudo-tetrahedral
stereochemistries in these ternary copper(II) complexes [23].
Concerning the five coordinate copper(II) complexes, halogeno and sulfato in
addition to acetato complex 9, their electronic absorption spectra exhibit three weak
absorptions having low frequency values. These spectral features could be ascribed to the
2
x
2
2
x
2
y
2
z
2
x
2
y
d-d electronic transitions namely d , d → d – , d → d – and d → d – which
xz yz
y
xy
corresponds to the square-pyramidal environment (C4v) for copper(II) ion [23]. The
present spectral investigations results confirm the square-pyramidal geometry for the
inspected five coordinate copper(II) complexes based on their noticeable similarity with
the analogues five-coordinate square-pyramidal copper(II) complexes [28]. This
stereochemistry visualization finds support from the ESR spectra measurements.
3
.5. ESR spectra and magnetic moment measurements
Room temperature magnetic moments in B.M. of the investigated copper(II) chelates
were determined to further elucidate the their structural features. The results obtained are
recorded in Table 5 which demonstrates the magnetic dilute status of all complexes
except the sulfato derivatives. The observed magnetic moments for all complexes except
sulfato complexes fall in the range 1.94 – 2.15 BM (Table 5) and indicate the monomeric
nature of the complexes in a tetragonal geometry. This results excluded any metal – metal
interaction since the reported ꢀeff values are slightly higher than the spin only (S=1/2)
9
behavior of 1.73 B.M. for d configuration in a magnetically dilute environment. The
clear resolution of the EPR spectra of these copper(II) complexes further confirmed this
finding.
The binuclear sulfato complexes 1 and 5 are magnetically concentrated and exhibit
magnetic moment per copper(II) ion close to the spin-only value of the magnetically
dilute copper(II) complexes. This result reveal that there is no secondary magnetic
interaction between the neighboring copper(II) centers in their binuclear structure in the
8

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solid state. It may be worthwhile to point out that, in most bridged bimetallic
coordination complexes, the shell of the bridging ligand surrounding the metal ion in
such that a long metal-metal distance is usually maintained. This prevents the magnetic
dipoles of the metal ions from influencing one another, thus ensuring a magnetically
dilute system. Thus the antiferromagnetic exchange pathways are highly sensitive to the
metal – metal distance in the magnetically dilute systems. This explanation is further
supported from the computed value of the ESR spectral parameter G (Table 5); G values
of these sulfato complexes are greater than 4.
X-band ESR spectrometer technique was used to measure the EPR spectra of the
powder samples of the inspected copper(II) complexes. A frequency around 9100
megacycles per second and magnetic field strength of 3100 gauss and scan rate of 1000
were employed at room temperature. Representative spectra are given in S18-24 and the
computed spectral parameters such as g||
present four- and five-coordinated copper(II) complexes their EPR spectral features are
of the axial symmetry fashion. The trend of g|| gꢀ > 2.0023 is characteristic of the axial
symmetry with elongation of axial bonds and the orbital d – is the ground state.
, gꢀ, gav and G are given in Table 5. For the
>
2
2
y
x
Concerning the five coordinate complexes, their ESR data point out to excluding the
trigonal–pyramidal while the square pyramidal geometry is the more expected geometry.
[
30]. Based on Kivelson and Neiman hypothesis the trend g (2.248– 2.271) > g (2.042 –
||
ꢀ
2
.054) is characteristic of the axial symmetry and confirm the presence of the unpaired
9
2
2
y
electron of the d configuration is localized in d – orbital for copper(II) ion in the
x
square pyramidal stereochemistry [31].
The present ESR together with the position of the d–d absorption bands point out to a
square planar and square-pyramidal structures and comparable with analogous copper(II)
complexes having the same stereochemistries [32,33].
The gav values were calculated using the relation; gav =1/3(g|| + 2g ) and their values
ꢀ
point out to the covalency prevailing in the bonding between the central metal and the
donor sites of the ligand system [34]. The mathematical relation [35]: G = (g - 2)/(g - 2)
|
|
ꢀ
was used to determine the EPR parameter G which measure the spin-spin interaction
between the copper(II) centers in the polycrystalline solid complexes. The recorded G-
9

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values in Table 5 excluded any spin – spin interaction between the copper(II) centers in
the solid complexes [36].
3
.6. Electrochemical studies:
Our kinetic investigations of the catalytic oxidation of the studied substrates
II
I
3
demonstrated the reduction of Cu to Cu by 3,5-DTBC or o-APH followed by the
oxidation of Cu(I) by the atmospheric dioxygen during the catalytic oxidation cycle. In
this context, electrochemical behavior of the inspected copper(II) chelates was examined,
because the redox potential is an important parameter in electron transfer processes and
in our catalytic systems. Methanol was the suitable solvent for performing the cyclic
+
voltammetric measurements versus the reference electrode Ag/Ag and representative
voltammograms are given in S25 and S26. All complexes exhibit a quasi-reversible peak
in the region 310 - 450 mV regenerating from a one-electron reduction of copper(II) to
+
2+
copper(I) followed by the corresponding oxidation of Cu to Cu . In this situation the
II
I
couple Cu /Cu is present as a redox centre. Most of the complexes undergo reduction are
completely regenerated following electrochemical oxidation, as shown in S25 and S26.
II
I
The chemically reversibility for one-electron transfer process in the case of Cu /Cu
centre is evidenced from the ratio of the peak currents where i /i is ≈1.0. The limiting
pa pc
p p
peak-to-peak separation values (ꢁE , 60 - 86 mV), approach the referenced value (ꢁE , is
6
0 mV) for a reversible one-electron redox process. This result demonstrate that the
present ligand system facilitate the reversibility of electron-transfer process in these
complexes is and the mass transfer is limited [37a,b]. In addition this reversible one-
electron redox process doesn’t accompanied by stereochemical reorganization [37c]. In
this regard the electrode cyclic oxidation reduction processes can be represented as
follows:
II
I
Cu + e
Cu
An additional one-electron reduction followed by the corresponding oxidation in the
region of 150 - 225 mV has been observed for the studied complexes (Table 6). The
observed E1/2 values of 149 - 229 mV rang can not ascribe to redox behaviour of metal
centre and could be arising from other redox couple in the medium such solvent
molecule. In this regard the i /i value is far from unity, with a relatively higher ꢁEp
pa pc
1
0

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value ≈ 120 mV, indicating that these redox centres undergo structural reorganization on
electron transfer.
Powder X-ray Diffraction
Despite the significant effort for growing a suitable single crystal for structural
determination of the current copper(II) complexes we could not. Anyway the field of
crystal structure determination from powder diffraction data is scientific technique which
has been widely and successfully applied for organic, inorganic and organometallic
molecules with low molecular mass [38]. In this context we have succeeded for preparing
good quality microcrystalline powder sample of the sulfato complexes 1 and 5 and their
structure have been determine by using the Rietveld profile refinement technique. The
Rietveld method is a computational treatment of diffraction data that separates
overlapping data from a typical powder x-ray diffraction pattern and allows accurate
determination of the structure of a compound. In this regard a computer program namely
Expo 2014 was employed to carry out all the steps of the structure solution process by
powder diffraction data by Rietveld technique [39].
The powder XRD patterns (Figure 1 and S27) of the inspected sulfato copper(II)
complexes 1 and 5 are greatly similar demonstrating their structural similarity and
indicate the microcrystalline nature of the solid state of these copper(II) chelates. The
quality of fit between the experimental powder XRD patterns and the calculated data in
the final Rietveld refinement is shown in Figure 2. The crystallographic data, selected
bond angle and bond lengths are given in Tables 7, 8, 9 and 10 respectively. Generally,
the obtained results reveal that the inspected complexes crystallized in the monoclinic
space group P 1 21/a 1 for complex 1 and P 1 21 in the case of complex 5 with unit cell
dimensions, a =11.33215 Å, b = 9.89238 Å, c = 5.20312 Å, α = 90°, β = 102.853° and γ =
9
0° for complex 1 while for complex 5, a = 13.23850 Å, b = 7.32726 Å, c = 6.78498 Å, α
90°, β = 97.953° and γ = 90°. The optimized structures of the sulfato derivatives
=
copper(II) chelates 1 and 5 are depicted in Figure 3 which demonstrates that the
investigated complexes have the molecular formula [(CuLL′) SO ]. For both complexes
2
4
L is L-Valinate and L′ is the bidentate nitrogen base, 1,10-phenathrolene or α, ά -
bipyridyl for complexes 1 and 5 respectively. For both complexes the sulfato group
behaves as bidentate ligand in a bridge fashion between the two complex entities
1
1

ACCEPTED MANUSCRIPT
2 3
[CuLL′] . The mixed ligand system chromophore N O occupies the equatorial plane of
these five coordinated complexes while the apical position is occupied by the oxygen
atom of the sulfato bridge. The indexed geometrical quotient, (τ), is beneficial distinguish
geometry for the penta coordinated copper(II) complexes [40] where τ is defined as τ =
(β−α)/60; where α and β being the two largest angles around the central atom. For the
perfect square-pyramidal environment around copper(II) center, τ is zero, while for a
perfect trigonal-bipyramidal geometry, τ becomes 1.0 [40]. The obtained values of
0
.1285 (Cu1) and 0.3136 (Cu2) for complex 1 and 0.0193 (Cu1) 0.1693 (Cu2) in the case
of complex 5 for the geometrical index τ are characteristic to the distorted square-
pyramidal stereochemistry for the copper(II) center. The comparative analysis of the
powder XRD patterns spectra of the polycrystalline complexes 1 and 5 and spectroscopic
data shows the presence of a significant structural agreement.
The bond angles (Tables 8 and 9) around the copper(II) central ion in the equatorial
and the apical positions are in an almost agreement with those reported for the analogous
copper(II) chelates [10c, 41]. The distance of Cu-N (Table 10) of the nitrogen donors of
2
NH and nitrogen base, 1,10-phenathrolene or α, ά -bipyridyl are within the normal bond
distances of Cu-N [42]. As well the copper oxygen bond length (Cu-O) (Table 10) of the
oxygen donor of the carboxylate of L-valinate or the sulfato bridge is in the usual values
[10c,41,42].
3
.7. Kinetic studies on ligand substitution reactions
Prior investigations on copper(II) catechol oxidase models suggest the bounding of
2
-
the deprotonated divalent catecholate anion (3,5-DTBC ) to copper(II) center of the
copper(II) oxidase model [43,44]. Consequently, an exchange interaction between the
fifth ligand of the oxidase model with the deprotonated divalent catecholate ion is the
initiation step of the catalytic oxidation cycle. In this context the lability of the reported
copper(II) complexes is a key factor of the catalytic activity of the present candidate
copper(II) oxidase models. To shed more light on the catalytic capacity of the copper(II)
complexes under study a detailed kinetic study was carried out to assess the lability
character of the present copper(II) oxidase model. In this regard kinetic investigations for
the coordinated counter anion substitution by using thiourea (TU) were accomplished for
1
2

ACCEPTED MANUSCRIPT
the copper(II) oxidase model.
Thiourea was selected as entering nucleophile because of
its high nucleophilicity that will prevent back reaction with the coordinated counter
anion.
Interactions of the present copper(II) complexes with thiourea can be followed
spectrophotometrically at wavelength ca. 300-400 nm and the substitution reactions were
performed in methanol as a function of thiourea concentration. Figure 4 describes the
spectral changes of complexes 2 and 3 in the UV-Vis region as representative kinetic
traces recorded at 300 nm using stopped-flow instrument. Rate constants of the current
ligand substitution reactions were determined by using concentration of the metal
-3
complex 10 fold lower than the total concentration of thiourea which was 1 × 10 - 2.5 ×
-2
1
0 M. Under the present prevailing reaction conditions, equation (1) can be employed to
fit the kinetic (absorbance/time) traces at the studied wavelength:
-k
obsd1
t
-k
obsd2
t
A = a1e
+ a2e
+ A0
(1)
The overall reactions in all cases are biphasic in which the initial fast reaction is
followed by a slower one and characterized by the rate constants kobs1 and kobs2 for the
fast and slow reactions respectively. kobs1 and kobs2 increase linearly with TU
concentration as shown in Figures 5 and 6 leading to rate constants of the second-order.
Kinetic investigations demonstrated that the studied ligand substitution reactions proceed
in two stages.
For the five coordinated complexes their kinetic behavior can be accounted for in
terms of two subsequent substitution reactions (see equation 2 and 3). The first and fast
reaction is the displacement of the nonelectrolytic counter anion ligand (X) by one TU
characterized by the second-order rate constant k . The second substitution reaction can
1
be ascribed to the substitution of one arm of the coordinated ligand. We do not have
evidence for which arm is de-coordinated but according to the polarization theory,
nitrogen atom is more polarizable donor of the ligand system than the oxygen and as a
result the nitrogen binds stronger than oxygen. So we expect to be the oxo-arm of the
amino acid bidentate ligand is the flexible site. The second substitution reaction can be
1
3

ACCEPTED MANUSCRIPT
ascribed to the displacement of one arm of the coordination chromophore by a second
molecule of TU also characterized by the second order rate constant k2.
k1
+
[CuLL'TU] + X
(
2)
[
CuLL'X] + TU
+
k2
+
[
CuLL'TU] +
TU
[CuLL'(TU)2]
(3)
¯
The rate effect of only one variable, X , for the five coordinated copper(II) complexes
[Cu(II)(L-Val)(Phen)X], (2, X = Br; 3, X = Cl) or [Cu(II)(L-Val)(Bpy)X] (6, X = Br; 7, X
=
Cl) is given in Table 11. Complex 5 ([Cu(Val)(Phen)H O]NO ) was used from
2 3
reference number (10c) for comparison with its analogous complexes 1-4. The results
obtained show that the first reaction rates in methanol are in the order of Br¯ > NO ¯ >
3
C1¯ . This finding measures the coordination binding of the respective counter anion
towards the copper(II) center and this means that the greater the coordination affinity of
the counter anion ligand, the slower the substitution rate. The second reaction rates are at
the almost identical fast for most copper(II) complexes and this can be explained as the
substitution is taking places for the same arm of the ligand (see Table 11).
As shown in Figures 5 and 6, in the absence of a back reaction kobs1 and kobs2 should
1 1 2
depend linearly on the concentration of the entering TU such that k = k [TU] and k =
k2[TU]. The data in Table 11 reveal that the rates of the second substitution reactions
with thiourea for all studied complexes are much slower than the first one (by about ten
times slower). This arises due to replacement of the smaller size counter anion X by the
much more bulk thiourea molecule which causes steric hindrance on the copper(II)
center.
The four coordinated complex species [Cu(II)(L-Val)(Phen)]ClO and [Cu(II)(L-
4
Val)(Bpy)]NO are square planer arrangement and since the present ligand system is
3
tetradentate donors accordingly their counter anions are expected to be situated in the
outer coordination sphere. We expect that this type of complexes will behave in different
behavior than that of the five coordinated complexes discussed before. The studied
kinetic behavior can be accounted for two subsequent substitution reactions (see equation
4
-6). The first and fast reaction is the displacement of solvent molecule (methanol) by
1
4

ACCEPTED MANUSCRIPT
1
one TU characterized by the second-order rate constant k . An evidence for the solvation
process and coordination of methanol is that the UV-spectra of these complexes are
solvent dependent as shown in Figure 7.
+
+
(4)
[
CuLL'] + CH OH
[CuLL'CH OH]
3
3
k1
+
+
[
CuLL'CH OH]
[CuLL'TU]
(5)
3
+ TU
+ CH OH
3
k2
+
+
+
TU
[CuLL'(TU)2]
[
CuLL'TU]
(6)
The overall reactions are also biphasic and the substitution reactions proceed as
previously mentioned for the five coordinate complexes. As well the second substitution
reaction can be ascribed to the substitution of one arm of the ligand as discussed above
for the five coordinated complexes. Similar to that reported for the five coordinated
complexes the data in Table 11 show that the second substitution reactions with thiourea
are slower than the first one (by more than ten times slower). As discussed before this
may arise due to the steric hindrance on the copper(II) center caused by the displacement
of methanol by thiourea. As well as the lability potency of the methanol co-ligand
compared to the strong coordination affinity of the donor arm of the ligand.
1
The observed greater value of k of the four coordinated complexes as compared to
the five coordinated complexes can be ascribed to the weaker coordinating affinity of the
coordinated methanol molecule as compared to the corresponding nonelectrolytic counter
anions. A comparison of k and k of the five coordinated complexes demonstrates that
1
2
the counter ion have a significant effect on the substitution process. A possible
explanation for this is that the mechanism is probably dissociative and as a result, the
natures of the counter ions are affecting the rate.
A comparison of k and k of both 1,10- phenanthroline and α,ά-bipyridyl derivatives
1
2
indicates that the ligand structure shows tangible effect on the substitution process as the
kinetic behavior is dependent mainly on the lability of the leaving group. Another
influential structural factor is: the complexes have phenanthroline moiety in their
structures are faster in both steps than complexes containing bipyridyl compartment. This
1
5

ACCEPTED MANUSCRIPT
can be attributed to the fact that the ligand structure does sensible effect on the electronic
character of copper(II) centre. In this context, the bipyridyl moiety may enhance the
Lewis acidity on the metal centre than the phenanthroline and as a result the bipyridyl
derivatives exhibit greater nucleophilic character.
Effect of the complex concentration on the rate of the present ligand substation
process was also examined. Figure 8 is an example for the representative kinetic traces
recorded at 350 nm using stopped-flow instrument. Similar to that reported for studying
the effect of TU concentration, under the prevailing reaction conditions, equation (1) can
be employed to fit the kinetic (absorbance/time) traces at the studied wavelength. The
overall reactions in all cases are also biphasic in which the initial reaction is fast while the
subsequent reaction is the slower on. This substitution process is characterized by the
1 2
initial rate constants k and k for the fast and slow reactions respectively. In this context,
for both the fast and slow steps our kinetic measurements demonstrated first-order
dependence on the complex concentration (Figure 9 and S28).
3
.8. Oxidase biomimetic catalytic activity study
Study the oxidase biomimetic catalytic activity of some copper containing protein
models such as phenoxazinone synthase and catechol oxidase is a further goal of the
present work. Catechol oxidase is a type-3 copper(II) enzyme catalyzes the aerobic
oxidation of many o-diphenol and its derivatives, to o-quinones [1,2]. Throughout this
catalytic process O
2
acquire four electrons to produce 2H
2
O (see reaction 7).
OH
O
Catalyst
(7)
2
2
+
2H O
2
O2
OH
O
3
,5-DTBQ
3
,5-DTBC
Another copper containing protein is the phenoxazinone synthase an oligomeric
multicopper oxidase that catalyzes oxidative dimerization of a wide range of o-
aminophenol (o-APH ) or its derivatives to the o-amino-3H-phenoxazine-3-ones (APX)
3
core [43,44] (see reaction 8). This complex six-electron oxidative dimerization reaction
1
6

ACCEPTED MANUSCRIPT
constitutes the final step in the bacteria synthesis of the naturally occurring antibiotic
Actinomycin D.
OH
N
NH2
Catalyst
2
+
3/2 O2
3H O
2
+
(8)
NH2
O
O
OAP
APX
Thus, it is interesting to investigate the ability of the present copper(II) oxidase
models to promote the oxidation of both o-APH to the light absorbing APX core and
3
3
,5-di-tert-butylcatechol (3,5-DTBCH ) to 3,5-di-tert-butyl-o-quinone (3,5-DTBQ). In
2
-2
this regard, 10 M methanolic solution of the respective substrate was mixed separately
-4
with 10 M solution of complex, and the oxidation process was proceed for two hours at
room temperature. The electron-transfer reaction between the electron donors 3,5-
DTBCH2 or o-APH3 and the synthesized copper(II) complexes can follow
spectrophotometrically by monitoring the characteristic absorption of 3,5-DTBQ and
APX at 400 and 433 nm respectively. Representative spectral profiles of these aerobic
catalytic oxidations are shown in Figure 10.
Blank experiments in an identical catalytic reaction conditions were done to get a
perception of the catalytic behavior of the studied oxidase models. The results obtained
revealed that the amount of the oxidation products, 3,5-DTBQ or APX, of the non-
catalyzed substrate autoxidation is not significant and can be neglected when compared
with those catalyzed. On the other hand the obtained results of the essential catalytic
experiments indicate that the examined copper(II) chelates are worthy models of catechol
oxidase and phenoxazinone synthase. In this context, the tested models exhibited a
differentiated catalytic ability to oxidize 3,5-TBCH to 3,5-DTBQ as a single oxidation
2
product. This noticed stability of 3,5-DTBQ under the previewing experimental
conditions suggest that this catalytic oxidation reaction proceed in a single pathway with
the exclusion further oxidative cleavage of 3,5-DTBQ.
Early catalytic investigations for oxidation of 3,5-TBCH or o-APH emphasized that
2
3
formation of a copper-substrate intermediate is the master step in the catalytic process
8c,d,43,44]. Subsequently binding of 3,5-DTBCH to the copper(II) centers as a
[
2
1
7

ACCEPTED MANUSCRIPT
dicopper(II)-catecholate intermediate should definitely be considered as the first rapid
step. Due to the developing product peak in the UV/Vis spectrum of the catalytic
oxidation reaction (Figure 10), it is difficult to make a clear picture about the nature of
binding of the 3,5-DTBCH
spectrophotometer. We have therefore used stopped-flow techniques to study the rapid
reaction of the present oxidase models with 3,5-DTBCH and o-APH in more detail.
2
to copper(II) center by using normal UV/Vis-
2
3
Upon mixing the substrate and catalyst solutions the recorded spectrum of the tested
complex changes dramatically during the first 30 seconds as shown in Figure 11. Kinetics
of these reactions could be followed at 400 and 433 nm in the case of 3,5-DTBCH and
2
o-APH respectively (Figure 10) with applying the initial rate method.
3
The results in Figure 11 show that the absorbance versus time plot at 400 nm after
addition of 3,5-DTBCH proceeds in two steps. The second step cannot be observed
2
when the experiment is repeated under inert atmosphere (i.e. in the absence of oxygen),
indicating that the growing band at 400 nm is due to quinone formation. More
information on the first reaction step could be obtained from stopped-flow measurements
over the first few seconds at 400 nm for complexes as shown in Figure 12. Similar
behavior was observed at 433 nm during the catalytic oxidation experiments of the
related substrate o-APH as shown in Figure 13.
3
Any way the present kinetic investigations demonstrated that the catalytic oxidation
of the studied substrates proceeds in two steps. The reversible first step is fast and
corresponding to the formation of the catalyst substrate intermediate which proceed via
2
-
coordination of the non protonated 3,5-DTBC or o-APH ¯ to the catalyst. The resulting
2
1 1 1
experimental values of K (K = k /k-1) measure the binding affinity or coordination
affinity of the examined substrates as shown in Tables 12 and 13. The second step is slow
and irreversible that proceeds in successive stages to produce the oxidation products.
From this perspective this slow step undoubtedly is the rate-determining step.
To examine the effect of the substrate concentration on the reaction rate, a constant
-4
concentration solution of the catalyst (10 M) was treated with multiple concentrations of
the studied substrates. The obtained results demonstrate first-order for the first step (see
1
8

ACCEPTED MANUSCRIPT
Figures 12, 13, 14, 15, S28 and S29) while at high substrate concentrations saturation
kinetics was observed. This finding suggests rapid pre-equilibrium involving ligand
exchange reaction between the tested complex and the studied substrates resulting in
2
-
adduct formation. In this situation the deprotonated substrate, catecholate (3,5-DTBC )
¯
2
or o-aminophenolate (o-APH ), behave as nucleophile coordinates to the catalyst as
shown in the reactions 9 and 10.
k1
O2
II
II
2
[Cu LL'X] 3,5-DTBC
[Cu LL') -3,5-DTBC]
3,5-DTBQ H O
(9)
+
2
+
2
2
k-1
k2
O
k1
O2
k2
II
o-APH3
II
H O
2
(10)
[
Cu LL'X]
[(Cu LL')-o-APH ]
+
2
+
2
k-1
NH
o-BQMI)
(
The irreversible conversion into the oxidation products is the rate-determining step,
i.e. k << k-1 and K = k /k-1. Similar results have been observed by our group and
reported recently [8c,d,10c].
2
1
1
Concerning o-aminophenol the previous studies demonstrated that o-benzoquinone
monoimine (o-BQMI) is the precursor to the APX formation. Further conversions for o-
BQMI to reach into the final product APX can access it by the reactions described in the
reference [45] and show in Scheme III.
The present kinetic investigations demonstrated that the studied catalytic oxidation
reactions proceed via catalyst substrate intermediate formation rout. Thus Michael
Menten approach is agreeable for determination the catalytic kinetic parameters such as
V
max, kcat, K
M
and kcat/K
M
-1
(Tables 12 and 13). Also the molar absorbance value of 1900
4
-1
and 2.33 × 10 M cm of 3,5-DTBQ [46] and APX [43b] respectively was used to
determine the produced amounts of 3,5-DTBQ and APX. By comparison with other
analogous models [43] the present copper(II) complexes demonstrate to be promising
catalysts for transformation of the studied substrates to 3,5-DTBQ and APX. The results
evaluated from Michael Menten plots for the catechol oxidase mimetic activity and the
-1
-4
phenoxazinone like activity respectively are (kcat = 2.0 - 9.3 s , K = 3.5 – 35.30 × 10
M
3
3
-1 -1
-1
M, and k /K = 1.0 × 10 – 12.5 × 10 M s ) and (k = 0.22 - 6.4 s , K = 1.6 – 54.3
cat
M
cat
M
1
9

ACCEPTED MANUSCRIPT
-4
2
3
-1 -1
×
M
10 M, and kcat/K = 1.75 × 10 – 12.857 × 10 M s ) (Tables 12 and 13). These
results are comparable to those values reported for other copper(II) complexes [43].
Effect of complex concentration on the rate of the studied catalytic oxidation
reactions was also examined. Kinetic runs under an atmospheric oxygen pressure
constant substrate concentration with variable concentrations of the catalyst showed the
dependence of the initial reaction rate on the catalyst concentration (see Figure 16 and
S30). Checking Figure 16 and S30 indicate that in the absence of the catalyst there is no
measurable reaction rate since the curve passes through the origin in addition to absence
of the intercept. These findings are consistent with the results obtained before in the case
of the blank experiments.
The data in Tables 12 and 13 show inequality in the reactivity of the present oxidase
models. There is no single factor could be account to explain the observed difference of
the oxidase mimetic activity of the inspected oxidase models. This notable variation in
the catalytic activity can be correlated with the different structural parameters,
electrochemical properties and electronic features around the copper(II) ion and these
factors will be considered sequentially.
The obtained kinetic results demonstrated that the catalytic oxidation reactions of the
studied substrates proceed via catalyst substrate intermediate formation rout. The results
measured for both substrates show that, for the most examined copper(II) complexes the
coordination affinity of 3,5-DTBCH (K = k /k ) lie in the range of 331 – 1040 is lower
2
1
1
-1
3
than of o-APH that are 610 - 1250 as observed in Tables 12 and 13. An explanation for
-1
this finding can be attributed to the higher basicity of o-APH2 in methanol compared to
2
-
2-
-1
3
,5-DTBC and also the high steric hindrance of 3,5-3,5-DTBC compared to o-APH .
2
For a given ligand system the structure effect of the counter anion (X¯ ) as only one
variable, is considered for assessment the catalytic efficiency of the investigated
copper(II) complexes. The results obtained show that the coordination affinity of 3,5-
2
-
DTBC in methanol (K
1
1
= k /k-1) towards the examine copper(II) complexes are in the
¯
¯
¯
4
¯
order of C1 > NO3 > SO ¯ ¯ > ClO > Br . With exception of sulphato and chloro
4
derivatives the same order holds for the catalytic efficiency towards 3,4-DTBCH and o-
2
APH . This greater catalytic efficiency in the case of the homobinuclear sulphato
3
2
0

ACCEPTED MANUSCRIPT
derivative could be attributed to influence of the structural and the electronic features
around the copper(II) ions. For the other group of the complexes 6, 7 and 8 their
¯
¯
coordination affinity towards the studied substrates follow the order Br > NO > C1¯ .
3
With exception of chloro derivatives the same order holds for the catalytic efficiency
towards 3,4-DTBCH and o-APH . These results confirm that the catalytic activity of the
2
3
current oxidase models is dependent on either the rate of ligand displacement from the
copper(II) complex or the difference in the dissociation constants for the loss of the
counter anion ligand. This suggests that displacement of the counter anion by the anionic
forms of the studied substrates may be involved in the slow pre-equilibrium step of the
overall reaction sequence outlined in (9) and (10).
The results in Tables 12 and 13 show that, complexes of 1,10-phenanthroline
3
derivatives exhibit lower catalytic activity for the oxidation of o-APH compared to that
of 3,5-DTBCH which have also greater activity than the native enzyme itself [43]. On
2
contrary the data in Tables 12 and 13 demonstrate that, except for complex 8, complexes
6
and 7 are highly reactive towards the aerobic catalytic oxidation of o-APH as
3
compared to 3,5-DTBCH2.
Reduction of copper(II) to copper(I) by the studied substrates, 3,5-DTBCH or o-
2
3 2
APH , and the subsequent reoxidation of copper(I) by O is a master key to maintain the
studied catalytic oxidation cycles. In this regard the redox potentials (E ) of
1
/2
representative copper(II) complexes have been obtained to determine if there is a
correlation between E1/2 of the current copper(II) complexes and the rate of oxidation of
3
,5-DTBCH or o-APH . Initially, the nitrato derivative, [Cu(L-Val)(Phen)H O]NO has
2 3 2 3
a redox potential value (394 mV) which equals the E° of the natural enzyme but there is
no obvious correlation between the redox potential and the reactivity. On contrary, the
notable difference in the catalytic activity of the perchlorate complex (4) (404 mV) as
compared to the bromo (2) (475 mV) and chloro (3) (430 mV) derivatives can be
correlated to their E
perchlorate complex (4) has redox potential value (E
of the native copper protein (394 mV) while the E
far from the E of the natural enzyme. The same trend is observed for the complexes (6),
°
values. This explanation finds support from the fact that the
= 404 mV) close to the reported E
values of complexes (2) and (3) are
°
°
°
°
2
1

ACCEPTED MANUSCRIPT
(7) and (8) of the other ligand system L-Valinate and α,α′-bibyridyl. For this group of
complexes the notable greater catalytic efficiency of the nitrate complex can be attributed
to its E value (405 mV) which is in a proximity to the E value of the native
metalloenzyme (394 mV). For bromo (466 mV) and chloro (344 mV) complexes which
exhibit lower reactivity than the nitrate complex (8) their E values are far from the
reported E of the natural enzyme (394 mV). Based on the present results a direct
°
°
°
°
correlation between the catalytic activity and the redox potential of the studied complexes
is difficult to be assigned. Malachowski and co-workers, reported similar observations
and mentioned that the electrochemical potential displays a secondary role in determining
the catalytic oxidation activity of copper(II) complexes [47].
In the light of the present kinetic investigations we suggest that schemes II and III meet
acceptance of description the catalytic oxidation pathways in the case of o-APH and 3,5-
3
DTBCH respectively.
2
II
II
o-APH + [LL′Cu X] → HX + [(o-APH )- Cu LL′]
(1)
(2)
(3)
(4)
(5)
(6)
3
2
II
I
[
[
[
[
(o-APH )- Cu LL′] → [(o-APSQH )- Cu LL′]
2 2
I
II
(o-APSQH )- Cu LL′] + O → [(o-APSQH - Cu LL′)-O ]
2
2
2
2
II
II
(o-APSQH
2
- Cu LL′)-O
2
] → o-BQMIH + [LL′Cu (O
2
H)]
II
II
LL′Cu (O
2
H)]+ HX → [LL′Cu X] + H
2
O
2
+ o-BQMIH
o-BQMIH + o-APH
3 2 2
+ O → → → APX + H O
Scheme II: The suggested catalytic pathway for conversion of o-APH
3
to APX
2
2

ACCEPTED MANUSCRIPT
k1
II
II
2HX + [(Cu LL) -3,5-DTBC]
(1)
[Cu LL'X] 3,5-DTBC
+
2
2
k-1
II
I
[
(Cu LL) -3,5-DTBC]
2[Cu LL'] + 3,5-DTBQ
(2)
(3)
(4)
2
II
I
[(Cu LL') -O ]
2
[Cu LL']
+
O2
2
2
II
[
3,5-DTBC-(Cu LL') -O ]
2 2
II
[
(Cu LL') -O ] + 3,5-DTBC
2
2
k2
II
(5)
II
2 [Cu LL'X]
3,5-DTBQ + H O2
+
2
[
3,5-DTBC-(Cu LL') -O ]
2
2
2
HX
Scheme III: The suggested catalytic pathway for conversion of 3,5-DTBC to 3,5-DTBQ
Conclusion
In summary, a new group of ternary copper(II) complexes of the type [CuLL′X] or
[CuLL′]X where L is L-Valinate and L′ is 1,10-phenanthroline or α, ά -bipyridyl and X is
2
-
Cl¯ , Br¯ , NO
3
¯ , ClO
4
¯ , ½SO
4
or AcO¯ have been isolated and their structures and
properties were determined via several analytical, electrochemical and spectroscopic
techniques. The coordination geometry around copper(II) centers is most probably square
pyramidal and square planar stereochemistries of the complex species [CuLL′X] and
[CuLL′]X respectively. The influential structural factor on the present copper(II) chelates
is the nature of counter anions incorporated in the complex molecule which modify the
coordination environment around the copper(II) centre and their physiochemical
properties. Crystalline powder X-ray diffraction technique combined with Rietveld
structure determination method were applied for conformation the final structure of the
sulfato derivatives copper(II) complexes 1 and 5. The lability characters of the inspected
copper(II) complexes was checked via examination the substitution of the coordinately
counter anion by using thiourea (TU) as a function of nucleophile by employing the
stopped follow technique. Catalytic measurements show that the studied copper(II)
2
chelates are promising oxidase models. Their catalytic activities are k /K = 1.75 × 10
cat
M
3
-1 -1
–
12.857 × 10 M s for the oxidative coupling of o-APH to aminophenoxazin-3-one
3
3
3
-1 -1
M 2
and kcat/K = 1.0 × 10 – 12.5 × 10 M s for the aerobic oxidation of 3,5-DTBCH to
3
3
,5-DTBQ. The detailed kinetic investigations reveal that the reported oxidation products
,5-DTBQ and APX are produced via a potential complex-substrate intermediate.
2
3

ACCEPTED MANUSCRIPT
Reactivity of the complexes has been correlated with their electrochemical, electronic,
geometry, coordination affinity of the studied substrates towards the examine catalysts
and the rate of decoordination of the leaving coordinated counter anion. The plausible
mechanistic pathways of the studied catalytic reactions were discussed.
References
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Table 1: Molecular formulae, physical prosperities and elemental analytical of copper(II) complexes
Found (calcd.)
Complex
Color
Λ
M
cm mol
-
1
2
-1
ꢀ
%
C
%H
%N
%M
1
2
3
4
5
6
7
8
9
.[(CuLL') SO ].2H O
Pale blue
Grey
12
48.28
4.25
(4.47)
9.58
(9.89)
15.15
(14.96)
2
4
2
(
(
(
(
(
(
(
(
(
48.38)
.[ CuLL' Br].H
2
O
41
20
66
25
54
40
87
20
44.86
44.68)
4.15
(4.16)
9.08
(9.20)
14.27
(13.91)
.[CuLL' Cl].H
2
O
Pale green
Blue
49.36
49.50)
4.69
(4.61)
10.15
(10.19)
15.67
(15.41)
.[CuLL'].ClO H O
46.62
46.51)
4.29
(4.33)
12.50
(12.77)
14.56
(14.48)
4
2
. [(CuLL') SO ]
Pale blue
Brown
47.45
47.87)
4.55
(4.44)
10.64
(10.98)
16.95
(16.60)
2
4
. [ CuLL' Br].H O
41.36
41.61)
4.35
(4.39)
9.66
(9.71)
14.90
(14.68)
2
. [CuLL' Cl].H
2
O
H
Green
46.11
46.38)
4.73
(4.89)
10.45
(10.83)
16.59
(16.37)
. .[CuLL'].NO
3
2
O
Dark blue
Pale violet
43.12
43.41)
4.49
(4.58)
13.32
(13.51)
15.89
(15.32)
. [CuLL' AcO]
49.32
49.56)
5.49
(5.58)
10.11
(10.21)
15.59
(15.43)
For all complexes L = L-Valinate; for complexes 1 – 4, L' = 1,10-phenathroline; for complexes 5 – 9, L' =
α, ά -bipyridyl