Dinuclear complexes of copper and zinc with m-xylene/cyclohexane-linked bis-aspartic acids: Synthesis, characterization, dioxygen activation, and catalytic oxidation of nitrobenzene in pure aqueous solution

Article abstract of DOI:10.1039/c3dt50923k

Two new m-xylene/cyclohexane-linked bis-aspartic acid ligands, L _b and L_c, were synthesized via Michael addition in basic aqueous solution. Their structures were characterized by elemental analysis, NMR and MS spectrometry. Both ligands react with Cu(ii) and Zn(ii) to form dinuclear complexes, with M₂L(OH)^- the major species in neutral/weak basic aqueous solution. To quantify the relative interaction strength between a Lewis acid and base, a new parameter σ = log K/14 was proposed which compares the stability constant with the binding constant between H⁺ and OH^-. The dinuclear copper complexes (L _b-2Cu and L_c-2Cu) react with H₂O₂ in aqueous solution. The reaction in 0.020 M phosphate buffer at pH 7.5 is first-order for [L_c-2Cu], but second-order for [L_b-2Cu]. The oxidation products are oxygenated and/or dehydrogenated species. Radical trapping tests indicate that both complexes slightly scavenge the OH radical, but generate the H radical. L_c-2Cu generates the H radical much more effectively than that of L_b-2Cu when reacted with H₂O ₂. Both complexes are excellent catalysts for the oxidation of nitrobenzene in the presence of H₂O₂ in weakly basic aqueous solution. The oxidation follows the rate-law v = k[complex] [nitrobenzene][H₂O₂]. The k values in pH 8.0 phosphate buffer at 25 °C are 211.2 ± 0.3 and 607.9 ± 1.7 mol ^-2 L² s^-1 for L_b-2Cu and L _c-2Cu, respectively. The Arrhenius activation energies are 69.4 ± 2.2 and 70.0 ± 4.3 kJ mol^-1 for L_b-2Cu and L_c-2Cu, respectively, while the Arrhenius pre-exponential factors are 2.62 × 10¹⁴ and 1.06 × 10¹⁵, respectively. The larger pre-exponential factor makes L_c-2Cu more catalytically active than L_b-2Cu. These complexes are some of the most effective oxidation catalysts known for the oxidation of nitrobenzene. The Royal Society of Chemistry 2013.

Full text of DOI:10.1039/c3dt50923k

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Dinuclear complexes of copper and zinc with
m-xylene/cyclohexane-linked bis-aspartic acids:
Synthesis, characterization, dioxygen activation, and
catalytic oxidation of nitrobenzene in pure aqueous
solution†
Cite this: Dalton Trans., 2013, 42, 10898
Shourong Zhu,*a Zhixiang Qiu,a Tianjun Ni,*b Xiujuan Zhao,a Shikai Yan,c
Feifei Xing,a Yongmei Zhao,a Yueling Baia and Mingxing Lia
Two new m-xylene/cyclohexane-linked bis-aspartic acid ligands, Lb and Lc, were synthesized via Michael
addition in basic aqueous solution. Their structures were characterized by elemental analysis, NMR and
MS spectrometry. Both ligands react with Cu(II) and Zn(II) to form dinuclear complexes, with M2L(OH)−
the major species in neutral/weak basic aqueous solution. To quantify the relative interaction strength
between a Lewis acid and base, a new parameter σ = log K/14 was proposed which compares the stabi-
lity constant with the binding constant between H+ and OH−. The dinuclear copper complexes (Lb–2Cu
and Lc–2Cu) react with H2O2 in aqueous solution. The reaction in 0.020 M phosphate buffer at pH 7.5 is
first-order for [Lc–2Cu], but second-order for [Lb–2Cu]. The oxidation products are oxygenated and/or
dehydrogenated species. Radical trapping tests indicate that both complexes slightly scavenge the OH˙
radical, but generate the H˙ radical. Lc–2Cu generates the H˙ radical much more effectively than that of
Lb–2Cu when reacted with H2O2. Both complexes are excellent catalysts for the oxidation of nitrobenzene
in the presence of H2O2 in weakly basic aqueous solution. The oxidation follows the rate-law v =
k[complex][nitrobenzene][H2O2]. The k values in pH 8.0 phosphate buffer at 25 °C are 211.2 0.3 and
607.9 1.7 mol−2 L2 s−1 for Lb–2Cu and Lc–2Cu, respectively. The Arrhenius activation energies are 69.4
2.2 and 70.0 4.3 kJ mol−1 for Lb–2Cu and Lc–2Cu, respectively, while the Arrhenius pre-exponential
factors are 2.62 × 1014 and 1.06 × 1015, respectively. The larger pre-exponential factor makes Lc–2Cu
more catalytically active than Lb–2Cu. These complexes are some of the most effective oxidation catalysts
known for the oxidation of nitrobenzene.
Received 8th April 2013,
Accepted 17th May 2013
DOI: 10.1039/c3dt50923k
www.rsc.org/dalton
1. Introduction
The synthesis of amino acids is of great importance. Non-
aDepartment of Chemistry, College of Sciences, Shanghai University, Shanghai
200444, China. E-mail: shourongzhu@shu.edu.cn; Fax: +86-21-60947570;
Tel: +86-21-66132403
bDepartment of Chemistry, Xinxiang Medical University, East of Jinsui Road,
Xinxiang, Henan 453003, China
cSchool of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China
proteinogenic α-amino acids are important in biological,
medicinal and synthetic chemical applications.1 The most
effective carbon–nitrogen bond formation is by simple addition
of amines to carbon–carbon double bonds.2 Although the
Mannich reaction is an effective method to form C–N bonds,
Michael addition is a common approach for the synthesis of
amino acids and their derivatives with 100% atom efficiency
and without any byproduct formation.3 The direct addition of
†Electronic supplementary information (ESI) available: Synthetic procedure of
ligand Lb and Lc. IR spectra of ligand Lb and Lc. NMR of Lb and Lc in D2O. EI-MS
spectra of Lc and Lc in aqueous solution. pH titration curve of 1.000 × 10−3
M
Cu2-Lc in absence and presence of 10.00 eq. H2O2 at 25.0 0.1 °C, I = 0.10 M
KNO3. Time dependences of 400 nm absorbance for the reaction of nitrobenzene amines to inactivated alkenes is very difficult to accomplish,4
and H2O2 in the presence of dinuclear copper complexes. Plot of the observed
although the direct amination of α,β-unsaturated carboxylic
acids can readily be effected.5 Amination of unsaturated di-
second-order rate constants determined at 360 nm as a function of [H2O2] for Lc-
2Cu complexes. Radical scavenging spectra. Positive mass spectra of dinuclear
carboxylic acids, such as maleic and fumaric acid, is most suc-
cessfully performed by aspartase enzymes.6 However, there is
no general one-step method for the synthesis of N-substituted
copper complexes. X-band EPR spectra of 2.5 × 10−3 M copper(II) complex in the
absence and presence of 80 equivalent H2O2 at different pH at −60 °C. First-
order and second-order rate constants. See DOI: 10.1039/c3dt50923k
10898 | Dalton Trans., 2013, 42, 10898–10911
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functionalized aspartic acids had been reported until 2005.5 complex and found the product was xylyl hydroxylation.21
While aspartic acid synthesis in the presence of aspartate Some similar results were reported later,21,22 and ligand
ammonia lyase,7 and the conjugate addition of N-nucleophiles hydroxylation was also found to occur in iminodiacetate sub-
to substituted fumaric acids using methylaspartase are enantio- stituted analogs.23 Ligand structure has a subtle influence on
specific,8 chemical addition of amine to CvC bond will the dioxygen activation of their complexes. For example,
generate racemic products.8,9 Therefore, development of less m-xylyl bridged bis-iminodiacetate iron complex can activate
expensive, simpler, “greener” methods for the reactions is still dioxygen, but m-xylyl bridged bis(2-pyridylmethyl) amine iron
highly desirable. Liang et al. showed that the K2CO3 supported complex cannot.23 Most of the dioxygen activation studies are
catalysts were very efficient for the reactions, but the product in non-aqueous solution at low temperature. Aqueous solution
was racemic.2 The enantioselective synthesis of amino acids is dioxygen activation is more desirable for practical usage, but
of great interest and there is no precedence for the synthesis of on the whole, there are few reports of dioxygen activation in
bis-aspartic acids.
100% aqueous solution. In this paper, we present a facile one-
Our goal is to synthesis bis-aspartic acids ligand that can step, aqueous method for the preparation of N-substituted,
form dinuclear complexes to investigate their dioxygen acti- functionalized bis-aspartic acids, pH titration studies of the
vation and catalytic oxidation. Oxidative transformations use ligands and their copper(II) and zinc(II) complexes, dioxygen
dioxygen or H2O2 as an inexpensive, environmentally friendly activation by the complexes and catalytic oxidation of
oxidant in contrast to toxic chemical oxidants, and they exceed nitrobenzene substrates in the presence of H2O2 in aqueous
their chemical equivalent in regiospecificity and enantio- solution.
selectivity.10 The development of transition metal complexes
as effective catalysts for a wide range of oxidative transform-
ation reactions and the understanding of the latter processes
2. Experimental section
Materials and methods
still represent a fundamental challenge to inorganic che-
mists.11 Inspired by biological systems, and in consideration
All chemicals were of reagent-grade quality, obtained from
of environmental aspects, the complexes of choice contain an
iron, copper or manganese active site.12 Although there are a
commercial sources and were used as received without further
purification. Elemental analyses were determined using a
large number of papers published on dioxygen activation or
catalytic oxidation,13 greener amino acid complexes for use as
Vario EL III elemental analyzer. The IR spectra were recorded
in the 4000–400 cm−1 region using KBr pellets and a Nicolet
catalysts in these reactions are still scare. Recently, chloro-
AVATAR-370 spectrometer. NMR spectra were recorded on a
methylated polystyrene supported alanine-dihydroxylbenzalde-
BRUKER AV 500 MHz spectrometer. UV-vis spectra were
hyde Schiff base and 1,10-phenanthroline metal complexes for
recorded on a Puxi general TU-1900. Optical rotations were
the oxidation of cumene by molecular oxygen have been
reported.14 Catalytic oxidation of substrates with Mn,16 Ru,
measured on Rudolph Research Analytical Autopol IV-T
and Cu17 amino acid complexes have also been reported. The
polarimeter.
most relevant study with respect to the work presented herein
is the enantio-differentiating catalytic oxidation of reactive
ESI-MS analysis
ESI-MS analysis was performed on an Agilent-1100 HPLC
system with a LC/MSD Trap XCT mass spectrometer (Agilent
Corporation, MA, USA). The ESI-MS spectra were acquired in
both positive and negative ion mode with the following con-
ditions: drying gas N2 at 10 L min−1; temperature 350 °C;
pressure of nebulizer 30 psi; capillary voltage 2500 V. Analyses
were performed in the full scan mode (50–1500 m/z) with
auto fragmentation. Data acquisition was performed using
Chemstation software (Agilent Techniques, MA, USA).
HPLC-MS was measured on a Shimadzu LC-MS 2020 instru-
ment with a C18 column at 25 °C, eluted with 70% methanol–
30% H2O. Column temperature was 40 °C. To 2.0 mL of
Lb–2Cu or Lc–2Cu (pH 9.5) was added 20 μL of 30% H2O2, and
the mixture was stirred for 1 h. K2S solution (0.08 M, 50 μL)
was added to the solution. The mixture was left at room temp-
erature for half an hour and centrifuged to remove CuS.
L- and D-dihydroxyphenylalanine (Dopa) by a biomimetic tri-
nuclear copper complex containing two L-histidine residues.
This reaction depends on the anchoring of the substrate pro-
vided by the third copper center which does not participate in
the catalytic reaction and which recognizes the chirality of the
substrate.15
We chose nitrobenzene as an organic substrate because
nitrobenzene is an environmental pollutant which is quite
difficult to oxidize. Nitrobenzene oxidation has been studied
by Lu et al. via the Fenton reaction and other techniques.16
Some other green oxidation catalysts have been reported,17
such as a Mn-complex which catalyzed the oxidation of
organic substrates in the presence of H2O2.18 However, metal
complex catalyzed oxidation of nitrobenzene is rare. One
requirement for catalytic oxidation of an organic substrate is
dioxygen activation, and complexes of dinuclear copper19 or
iron20 are the most popular. Binuclear complexes, where the
two tridentate donor groups are separated by an m-xylyl bridge,
Radical formation/scavenging test
are somewhat similar to the active center of hemerythrin and Two methods were used to scavenge radicals. (a) 1,1-Diphenyl-
hemocyanin. In 1984, Karlin et al. reported dioxygen activation 2-picrylhydrazyl (DPPH) free radical scavenging activity assay:24
by a bis(2-pyridylmethyl) amine substituted xylene copper(I) dicopper(II) complex (Lb or Lc), dissolved in deionized water
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(2 mL), was mixed with 2 mL of methanolic solution contain- Na2HPO4 and 0.025 mol L−1 KH2PO4 mixture) and 9.322
ing DPPH radicals, resulting in a final concentration of 1.00 × (0.010 mol L−1 disodium tetraborate), respectively. All pH
10−4 M DPPH and 1.67 × 10−4 M copper(II) complex. The titration experiments were run at least in duplicate to ensure
mixture was shaken vigorously and left to stand for 30 min in reliability of the data. Data were acquired with TIMAO soft-
the dark, and the absorbance was then measured at 545 nm ware. Ligand titrations were performed in the pH range
against a blank. The percentage of released radical was ∼2.5–12 and titrations on complexes in the pH range 3–11.
calculated as a formation ratio = {[1 − (A1 − A2)/A0]} × 100% Titration data were fitted with the program SCMAR (Newton–
where A0 was the absorbance of the control (without Gauss nonlinear least-squares).26 The activity coefficient of H+
copper complex), A1 was the absorbance in the presence of the and OH− were taken from literature.27
complex, and A2 was the absorbance without DPPH. (b)
OH˙scavenging assay: OH˙ scavenger ability was measured
Synthesis of Lb
according to a literature procedure.24c OH˙ radicals were gen- To 10.0 g (0.10 mol) of maleic anhydride suspended in 30 mL
erated from FeSO4 and H2O2, and detected by their ability to water was slowly added 0.20 mol NaOH (in 5 mL water) at
hydroxylate salicylate. The reaction mixture (3 mL) contained 75–85 °C to dissolve the maleic anhydride. 1,3-Xylenediamine
1 mL FeSO4 (1.5 mM), 0.7 mL H2O2 (6 mM), 0.3 mL sodium (6.47 mL, 6.81 g, 50 mmol) was added to the solution. The
salicylate (20 mM) and 1.0 mL 2.5 × 10−4 M Lb–2Cu or Lc–2Cu. mixture was refluxed for 3 days and the color changed from
The absorption spectra were measured immediately and after colorless to yellow–green. Maleic anhydride, disodium salt
30 min at 25 °C. The percentage of radical released was calcu- (5 g) was added to the solution, and the mixture was refluxed
lated (500 nm absorption) in the same way as the DPPH for an additional 2 days. The mixture was cooled to room
method.
temperature and filtered. To the filtrate was added a solution
of 16.65 g (0.15 mol) of CaCl2 in 20 mL water and the mixture
was stirred overnight at room temperature. The newly precipi-
Reaction with H2O2 in aqueous solution
To a 2.00 mL of 0.050 M KH2PO4–NaOH solution at specific tated solid was isolated by filtration and washed with water
pH was added 2.00 mL of water, 1.00 mL of 2.5 × 10−3
and ethanol to yield the calcium salt of the ligand Lb (20.84 g).
M
Lb–2Cu or Lc–2Cu aqueous solution. The pH was adjusted to To the calcium salt was added 100 mL of water and 0.15 mol
7.50 with 1.0 M NaOH or HNO3. The final concentration of Cu H2C2O4, and the mixture was stirred overnight. The CaC2O4
complex was 5.00 × 10−4 M and the H2O2 concentrations that formed was removed by filtration and the remaining solu-
varied from 0.10 to 0.50 M. The solution (2.0 mL) was equili- tion was concentrated to 10 mL under reduced pressure.
brated in a 1.00 cm cell at 25.0
0.1 °C for 10 min. The Acetone (∼50 mL) was added to the residue and two layers
required amount (20–80 μL) of 30% H2O2 was added to the were obtained. The upper acetone layer was discarded and the
solution, and absorbance of the solution was measured at bottom layer (oil) was washed several times with 10 mL of
360 nm with 0.020 M buffer solution as a reference.
ethanol. The oil was vacuum dried at 80 °C. It contained con-
siderable water and foamed during vacuum drying. This com-
pound was very hygroscopic. Yield 65%. Mp. 267–269 °C. IR
Catalytic oxidation
Nitrobenzene (6.0 μL) was dissolved in 40 mL of 0.2 M νmax 3429, 3020, 2825, 1722, 1626, 1406, 1221, 1057, 876, 706,
of KH2PO4–NaOH buffer (pH = 8.00) with stirring to give a 638 and 526 cm−1 1H NMR (500 MHz, D2O) δ 7.45 (s, 4H,
;
1.47 × 10−3 M nitrobenzene solution. The nitrobenzene solu- aromatic proton), 4.25 (q, J = 13 Hz, 4H, Ar-CH2-), 3.90 (t, J =
tion (3.0 mL) was placed in a 1.0 cm quartz cell and thermally 2.8 Hz, 2H, N-CH), 2.90 (s, 4H, CH2COO). αD(18.5C) = 21.54.
equilibrated at 25 °C for 5 min. Various amounts of Lb–2Cu or Elemental analysis found (calculated) for Ca0.5C16H19N2O8·
Lc–2Cu and H2O2 (30%) were added to the solution. The total 0.2H2O: C 49.38 (49.16); H 5.15 (5.00); N 6.92 (7.16).
volume was 3.0–3.1 mL. Reaction kinetics were monitored at
Synthesis of Lc
400 nm with buffer as the reference.
To a 50 mL round bottom flask was added maleic anhydride
(1.0 g, 10 mmol) and 10 mL water. The mixture was warmed to
pH titration
The stability constants of the binary complexes were deter- 75–85 °C and 2.0 mL of 10 M NaOH (20 mmol) was added. 1,3-
mined by pH-metric titrations on a Metrohm Titrando 809 Bis(aminomethyl)cyclohexane 0.71 g (5.0 mmol) was added
equipped with a 800 Dosino and 6.0263.100 pH electrode. The and the solution was stirred for 3 days. The color gradually
samples contained either Cu(NO3)2 or Zn(NO3)2 and a ligand changed to light yellow. To make full use of the 1,3-bis(amino-
in a 2 : 1 mole ratio. The titration sample was 1.000 × 10−3
M
methyl)cyclohexane, another 5 mmol of disodium maleate was
in ligand. Pure, moist N2(g) was bubbled through the sample added. After stirring the mixture for 2 days, the color became
to ensure the absence of O2(g) and CO2(g) and to stir the solu- deep yellow. The solution was filtered and to the filtrate was
tions. All pH titrations were carried out with 20 mL samples at added CaCl2 (1.6 g, 15 mmol) in 5 mL of water. The mixture
298.0 0.1 K and a constant ionic strength of 0.10 M NaNO3. was stirred for 4 h, after which the white precipitate of the
Carbonate-free NaOH was used for all titrations as described calcium salt of the ligand and any unreacted calcium maleate
previously.25 The pH meter was calibrated at 4.003 (0.050 mol L−1 were removed by filtration. The solid was suspended in 10 mL
potassium hydrogen phthalate), 6.864 (0.025 mol L−1 water containing H2C2O4 (1.83 g, 15 mmol) and stirred for 5 h.
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The CaC2O4 was removed by filtration and washed with water.
The aqueous solution was concentrated to 2 mL under
reduced pressure, and acetone was added to give two layers.
The upper acetone layer was discarded to remove H2C2O4 and
maleic acid. The bottom layer was washed with ethanol until it
was colorless. The oil was vacuum dried at 80 °C. Pure Lc was
obtained in ∼60% yield. IR (cm−1): 3429, 2929, 2856, 1716,
1629, 1389, 1081, 1043, 871, 652 and 546. 13C NMR (500 MHz,
D2O): 176, 172, 58, 52, 34.5, 34, 33, 28, 24. MS (ESI) calcd
for C16H26N2O8 (M + H)+, 375, found 375. αD(18.5C) = 152.4.
Elemental analysis found (calculated) for Ca0.5(C16H25N2O8)·
3.5H2O (FW = 456.4): C, 41.95 (42.10); H, 6.92 (7.06); N, 6.39
(6.13).
Fig. 1 ESI-MS spectrum of ligand Lc in the negative ion mode.
that concentration to a very small volume resulted in a color-
less viscous oil, which still contained H2C2O4. This was
removed by washing with acetone. H2C2O4 is a strong acid
compared to aspartic acid, its pKa1 and pKa2 are 1.25 and 3.81
respectively. Theoretically, excess H2C2O4 can fully protonate
aspartate to form neutral aspartic acid. Beyond our expec-
tation, from elemental analysis and pH titration, there were
still calcium ions associated with the ligands; both of the bis-
aspartic acids contained 0.5 calcium ion per molecule. The
purity of N,N′-(m-phenylenedimethylene)bis-aspartic acid (Lb)
3. Results and discussion
Synthesis of ligands
Reports of bis-aspartic acids are quite rare28 except for some
patents.29 We chose flexible diamines, namely, 1,3-cyclohexane-
dimethanamine and 1,3-benzenedimethanamine to react
with inexpensive maleic anhydride in basic aqueous solution
for the synthesis of N,N′-(m-phenylenedimethylene) bis-aspar-
tic acid and N,N′-(1,3-cyclohexanedimethylene) bis-aspartic
acid, respectively (Scheme 1). Although Lb has been mentioned
in patents,30 and Kezerian also mentioned this compound in a
report,31 no synthetic details were provided. However, the reac-
tion of primary amines with electron-deficient alkenes has
been studied by several authors.2,32 Due to their highly hydro-
philic properties and very poor solubility in organic solvents,
we encountered great difficulty in the purification of the pro-
ducts, but we found that the bis-aspartic acids formed calcium
salts that were insoluble in aqueous solution. Removal of the
1
was confirmed by a very clean H NMR spectrum in D2O solu-
tion (Fig. s2†). However, N,N′-(1,3-cyclohexanedimethylene)
1
bis-aspartic acid (Lc) had a very complicated H NMR in D2O
solution, possibly due to the presence of four chiral carbon
atoms in Lc. To further clarify the composition, ESI-MS was
used. Lc produced a very clean spectrum (Fig. 1).
From the MS spectrum, the parent ion peak, H3Lc (M−)
−
was located at 373.1, which is similar to the calculated value of
373.16. Its isotope pattern was also identical to the theoretical
simulation. The second strong peak at 785.2 is [Ca(H3Lc)2
−
H+]−. Positive spectra also coincided well with the structure
(Fig. s5 and s6 in ESI†). Both ligands have optical rotation,
which indicate both ligands are not a racemic mixture.
Ca as CaC2O4 resulted in the acid form of the products. pH titration
However, the acid form of the bis-aspartate was so hydrophilic
Data for the titration of 1.00 × 10−3 M ligand in the absence
and presence of 2 eq. Zn(NO3)2 or Cu(NO3)2 in I = 0.10 M
KNO3 are presented in Fig. 2. Computer simulation was
used to obtain the ligand protonation constants and complex
stabilities, which are summarized in Table 1. Although there
is 0.5 Ca2+, the interactions of Ca2+, as well as Na+ and K+, with
ligands are omitted.
From the titration curves (Fig. 2), both Lb and Lc exhibit pH
jumps at H2L2−. This indicates that the last two protons dis-
sociate at a much higher pH than the others. The titration
curve of Lb is below that of Lc at pH 7 or higher, which means
that the protonation constant of Lc is higher than that of Lb.
Table 1 lists the cumulative protonation constants of Lb and Lc
at 25 °C, I = 0.10 M KNO3. Aspartic acid has three deprotona-
tion processes; its stepwise protonation constants are pKa1
=
9.66, pKa2 = 3.71, pKa3 = 1.95.33 Sajadi recently reported 9.90,
3.72 and 1.99 respectively at 25 °C.34 Our data indicate that the
bis-aspartic acids have six protonation processes. The Ka1 and
Ka2 correspond to the first pKa of the two aspartic acids in the
ligand. They are 10.28 and 8.82 for Lb and 10.54 and 9.84 for
Lc. The pKa1 of Lb and Lc are obviously larger than that of free
aspartic acid. When statistical factors (concentration effect, 0.3
Scheme 1 Synthetic procedure of the ligands.
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difference in pKa) are taken into account, the pKa1 of Lb is com-
parable with that of free aspartic acid. The pKa1 of Lc is larger,
possibly due to the electron donating effect of the alkyl substi-
tuent. The difference between the pKa1 and pKa2 which corres-
ponds to the interaction between the two aspartates in a
ligand, is 1.46 and 0.7 for Lb and Lc, respectively. If there
were no interaction between the two aspartic moieties, the
theoretical pKa difference would be 0.3. The pKa differences
in Lb and Lc are larger than 0.3, indicating that the mono-
protonated aspartic acid interacts with the other aspartate in
Lb. The pKa3 and pKa4 of Lb and Lc correspond to pKa2 of free
aspartic acid. They are 4.19 and 3.62 and 3.93 and 3.15 for Lb
and Lc, respectively, which is similar to 3.71 in free aspartic
acid. The second protonation constant of aspartate in Lb is
slightly larger than that in Lc. The pKa5 and pKa6 for Lb is 2.75
and 2.39. When the concentration effect is taken into consider-
ation, they are almost the same, which indicates that the fully
protonated aspartates in Lb have no interaction with each
other. The pKa5 and pKa6 in Lc are smaller than 2.0 (third
protonation constant of free aspartic (1.9)), therefore, the log
β5 and log β6 have a much larger error than any of the other
protonation constants. The pKa5 and pKa6 of Lc are so close
that protonation takes place simultaneously. The protonation
Scheme 2 Protonation process of Lb in aqueous solution at 25 °C, I = 0.10 M
KNO3.
process is illustrated in Scheme 2. The distribution diagrams
are shown in Fig. 3.
The titration curves in the presence of 2 eq. Zn2+ or Cu2+
are significantly different from those in the absence of metal
ions (Fig. 2). Upon removal of all protons from the ligand at
B/L = 3, the pH is roughly 6 and 8 in the presence of 2 eq.
Cu(II) and 2 eq. Zn(II), respectively. With further addition of
base, the pH did not increase sharply, which indicates that
OH− is coordinated to the metal ion. Both complexes have a
pH jump at B/L = 5, which means two more protons from each
ligand are dissociated in the presence of 2 eq. of metal ions.
These two protons must come from coordinated water mole-
cules. If the complex species MpLqHr are represented by pqr,
ˉ
species (212) exists in weak basic solutions. Scmar simulations
reveal that the two ligands formed dinuclear complexes with
different protonation modes. The formation constants (log K)
of species MpLqHr, are summarized in Table 2. Note that r can
be a negative integer, which means r extra protons have disso-
ciated from the species. These stability constants are compar-
able with those reported recently by Miličević35 for Zn(II)–
aspartic acid complexes with log K110 = 5.42. Claridge reported
the log K110 of aspartate–copper(II) complex to be 8.84 in
I = 0.1 M KNO3 at 25 °C.36 These data are comparable with
recently reported data by Sajadi.34
The log K of Lb complex 210 is 17.25 and 11.93 for Cu2+ and
Zn2+, complexes, respectively, which are roughly similar to
Fig. 2 pH titration curve of 1.000 × 10−3 M ligand in the absence and presence complexes of free aspartic acids. These data are 17.54 and
10.57 for Lc Cu2+ and Zn2+ complex. For both ligands, the titra-
tion curves of Cu(II) complexes are always below those of Zn(II)
complexes (Fig. 2). The titration curves of Lb and its complexes
are given later of corresponding Lc analogs in B/L < 3. At B/L = 3
or higher, the relative position of the titration curves are
of 2.000 eq. metal ions at 25.0 0.1 °C, I = 0.10 M KNO3. B/L is the molar ratio
of base to ligand. Lines are simulated data, symbols are experimental. (a) 1.000
× 10−3 M Lb; (b) 1.000 × 10−3 M Lc; (c) 1.000 × 10−3 M Lb and 2.000 × 10−3
M
Cu(NO3)2; (d) 1.000 × 10−3 M Lc and 2.000 × 10−3 M Cu(NO3)2; (e) 1.000 × 10−3
Lb and 2.000 × 10−3 M Zn(NO3)2; (f ) 1.000 × 10−3 Lc and 2.000 × 10−3
Zn(NO3)2.
M
Table 1 The cumulative protonation constants of ligands at I = 0.10 M KNO3, 25 °C
Ligand
log β1
log β2
log β3
log β4
log β5
log β6
Lb
Lc
10.28(02)
10.54(06)
19.10(03)
20.38(05)
23.29(05)
24.31(07)
26.91(05)
27.46(07)
29.66(07)
NAa
32.05(09)
31.94(13)
a The error in β5 is much larger than any other species.
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Fig. 3 Distribution curve of 1.00 × 10−3 M ligands (top) and their copper(II) complexes (2.00 × 10−3 M Cu(NO3)2) (bottom) in aqueous solution at 25 °C, I = 0.10 M
KNO3.
Table 2 Species and their stability constants (log K) of Lb and Lc complexes at
25 °C, I = 0.10 M KNO3
Species (pqr)a
2Cu–Lb
2Zn–Lb
2Cu–Lc
2Zn–Lc
211
210
21
22.84(03)
17.25(09)
9.67(10)
0.88(09)
−10.62(15)
NA
19.66(09)
11.93(13)
4.08(05)
−4.92(09)
−15.58(11)
−26.38(14)
36.66(09)
21.75(09)
17.54(04)
10.86(07)
3.88(07)
−5.34(19)
−16.98(34)
NA
18.72(08)
10.57(09)
ˉ
212
−5.16(05)
−15.44(06)
−25.95(08)
NA
ˉ
213
ˉ
214
421
44.28(10)
Scheme 3 The coordination process of Lb with Cu2+ in aqueous solution at
25 °C, I = 0.10 M KNO3.
a Species MpLqHr is presented as pqr.
reversed. This phenomenon is observed because the co- can be considered as the interaction strength between the
ordinated water molecule has a lower pKa in Lc complexes than Lewis acid and the Lewis base. Sigel et al. have published
many papers that deal with pKa and/or stability constants.38
in Lb complexes. The log K difference between adjacent
ˉ
species, such as log K (210) and log K (211), is the pKa of the Although, the pKa or log K value is the absolute interaction
coordinating water molecule. The coordinated water molecules strength, there are still no relative criteria to characterize how
strong the interaction is between acid and base. Here we
in 2Cu–Lb have pKa of 7.58 and 8.79 (Scheme 3), while 2Cu–Lc
complex have pKa 6.68 and 6.98 respectively. For 2Zn–Lb propose a parameter that can easily characterize the relative
complex, they are 7.85 and 9.00. The species distribution is strength of an acid or base. The most common substance
related to acid–base chemistry is water. The binding constant
shown in Fig. s7–s10.† There is some dimerized species (421)
for Lb–2Cu complex in weakly acidic solution (Fig. 3).37 We between a standard acid, H+, and a standard base, OH−, is
have tried different methods to isolate a solid complex, but 1.0 × 1014. Other ligands (bases) bind to protons in the same
way but with a different binding constant. The binding con-
unsuccessfully. The complexes are highly soluble in water in
pH 7–9 region, but insoluble in organic solvents.
stant is a measurement of the interaction between the acid
Based on the titration data, the coordination process and the base. We define the binding constant 1.0 × 1014, as the
binding strength between a standard base (ligand) and a stan-
and the pKa of coordinated species are summarized in
Scheme 3.
dard acid (metal ion) (Scheme 4). Then σ = log K/14 represents
Acid–base has been a common term in chemistry for a long the binding strength between an acid and a base (Scheme 4).
Especially, when the acid is H+, the log K/14 represents the
time. For Lewis acid–base adducts, their stability constants
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Scheme 4 The definition of relative binding strengths.
basicity of a ligand. When the base is OH−, the log K/14 rep-
resents the acidity of a cation (metal ion). According to this
definition, the basicity of acetate (pKa = 4.75) is 0.339, or the
binding strength between a proton and acetate is 33.9% that
of the HO–H bond. For Lb, the pKa1 is 10.28, equivalent to σ =
4−
0.734, which indicates that the Lb has 73.4% the basicity of
OH−. For Lc, the pKa3 is 4.19, which indicates that H2Lc has
−
29.9% the basicity of OH−. The pKa1 and pKa2 difference
(corresponding to the pKa1 difference in the two aspartates in
a ligand) is 1.46 and 0.70 for Lb and Lc, respectively. Taking
the concentration effect (log 2 = 0.30) into account, the differ-
ence is 1.06 and 0.40, or σ = 0.076 and 0.029 in Lb and Lc,
respectively. This means that the interaction between the
mono-protonated aspartate and un-protonated aspartate is
7.6% and 2.9% the strength of H+ and OH− in Lb and Lc
respectively.
The linear free energy relationship (LFER) exists in coordi-
nation chemistry, which is expressed as log KML = alog KHL + b,
where KML is the stability constant of complex ML, KHL is the
protonation constant of ligand L, a and b are constants. This
relationship can be re-written as: σML = aσHL + b/14, which
indicate the binding strength between ligand and metal ion is
proportional to the binding strength of ligand and proton.
Explaining LFER with relative binding strength is more under-
standable and meaningful.
Fig. 4 Spectral changes recorded for the reaction of 1.5 × 10−3 M Lb–2Cu with
0.08 M H2O2 in pH = 7.50, 0.2 M KH2PO4–NaOH-solution at room temperature.
absorbance. The 360 nm absorbance coefficient is 660 L mol−1
cm−1 at 0.20 M pH 7.5 phosphate buffer. At pH 9.0 tetraborate
buffer, the oxidized product has an absorbance coefficient
∼3.2 × 104 L mol−1 cm−1. Phosphate buffers significantly
decrease the absorbance of the oxidized product. The 360 nm
absorbance also decreases with the decrease of pH. This is
possibly due to phosphate acting as a ligand that prevents it
from binding to H2O2. The 360 nm absorbance decreases in
the presence of buffers, whether phosphate or borax compared
with the same pH without buffer. Borax buffer decreases the
360 nm absorbance less significantly than that of phosphate
buffer at the same pH. Although the spectra change is much
more obvious without any buffers, but H2O2 reaction with
dinuclear copper(II) complex will decrease the pH of the solu-
tion 0.8–1 units, so all the reactions were run in buffer solu-
Reaction with H2O2 in aqueous solution
tion (Fig. s8†). Lc–2Cu complex has
a similar reaction
except the 360 nm peak is not that obvious (Fig. s9†) in pH 7.5
As shown in Fig. s8,† in the presence of H2O2, the solution
pHs are lower (the titration curve is in the bottom) than in the phosphate buffer, but the 360 nm peak is much more obvious
in pH 8.5 borax buffer.
absence of H2O2. This indicates that more protons are disso-
ciated and H2O2 reacted with the complex. H2O2 cannot react
The 360 nm absorbance increase in the presence of excess
with the dinuclear complex if the pH is less than 6.3. There- H2O2 in phosphate buffers (Fig. s10†). The equation for a first-
order reaction is kt = ln[(A∞ − A0)/(A∞ − At)], where kobs is
the observed rate constant, A∞, At and A0 are the 360 nm absor-
fore, the reaction of H2O2 and copper complex was studied in
weak basic solution.
m-Xylyl bridged dinuclear complexes are somewhat similar bance at time ∞, t and 0. Plots of ln[1/(A∞ − At)] vs. t give
straight lines, where the slope of the line is the first-order rate-
to the active center of hemerythrin and hemocyanin. It was
constant kobs. The catalytic oxidation is first-order to Lc–2Cu
found that dioxygen activation of the di(2-pyridylmethyl)
amine substituted xylene copper(I) complex led to ligand complex which can be expressed as v = kobs[Lc–2Cu]. However,
hydroxylation.21 Some similar results were also reported
for the Lb–2Cu complex, this plot is not linear. For the Lb–2Cu
later.21,22 Ligand hydroxylation also takes place in iron com-
complex, the plot 1/(A∞ − At) vs. t gives a very good straight
plexes of iminodiacetate substituted analogs.23 Fig. 4 shows line, which indicates the oxidation is second-order to Lb–2Cu
complex, i.e. v = kobs′[Lb–2Cu]2. Tables 3 and 4 listed the
the UV-vis spectral changes after adding H2O2 to 1.50 × 10−3
M
observed second-/first-order rate constants for 5 × 10−4
essentially colorless. After adding H2O2, it becomes yellow. A Lb–/Lc–2Cu in 0.02 M phosphate buffer at 25 °C, pH = 7.50.
M
Cu2–Lb complex at pH 7.5 aqueous solution. The complex is
Not only do complex concentrations have an influence on
the reaction rate, but also on H2O2. For complex Lc–2Cu, the
new absorption band appeared at 360 nm. This peak is possi-
bly the ligand hydroxylated complex.39 The intensity of the
peak depends on pH. High pH will increase the 360 nm observed first-order rate constants kobs increase linearly with
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Table 3 The observed second-order rate-constant (L mol−1 s−1) of 5 × 10−4 M Lb–2Cu in 0.02 M phosphate buffer at pH 7.5, 25 °C at different H2O2 concentrations
[H2O2]
0.0015
0.025
0.10
0.18
0.25
0.40
2nd-order kobs′
0.037 0.0001
0.16 0.0005
0.25 0.001
0.30 0.003
0.32 0.002
0.33 0.002
Table 4 The observed first-order rate-constant (s−1) of 5 × 10−4 M Lc–2Cu in 0.02 M phosphate buffer at pH 7.5, 25 °C at different H2O2 concentrations
[H2O2]
0.1
0.175
0.25
0.325
0.4
1st-order kobs
(8.1 0.02) × 10−4
(2.9 0.006) × 10−3
(4.4 0.02) × 10−3
(7.6 0.02) × 10−3
(8.4 0.06) × 10−3
Table 5 H˙a and OH˙b radical scavenging/formation data of the dinuclear
the increase of H2O2 concentrations (Table 4). The rate law for
Lc–2Cu complex was:
complexes
c
d
e
v ¼ k½H2O2ꢀ½Lc–2Cuꢀ; k ¼ 0:02294 + 0:00231 L molꢁ1 sꢁ1
:
A0
A1
A2
Radical increased (%)
DPPH radical Lb–2Cuf 0.755 0.736 0.003
Lc–2Cuf 0.755 0.421 0.006
2.9
45.0
−4.2
−2.6
−4.7
ð1Þ
While for Lb–2Cu, v = kobs′[Lb–2Cu]2. The kobs′ vs. [H2O2]
is not a straight line (Fig. s11†). However, the plot of 1/kobs′
vs. 1/[H2O2] is a straight line (Fig. s11†). That is 1/Kobs′
a + b/[H2O2], where a and b are the intercept and slope of the
OH radical
Lb–2Cug 1.022 1.156 0.091
Lc–2Cug 1.022 1.124 0.075
Lb–2Cuf 0.827 1.011 0.145
=
Lc–2Cuf 0.827 1.043 0.119 −11.7
a 545 nm absorbance of 1.33 × 10−2 M H2O2, 1.0 × 10−4 M DPPH,
1.67 × 10−4 M L–2Cu in methanol–H2O (1 : 2). b 500 nm absorbance of
5.0 × 10−4 M FeSO4, 1.4 × 10−3 M H2O2, 2.0 × 10−3 M sodium salicylate
and 8.3 × 10−5 M L–2Cu mixture. c A0 was the absorbance of the
control (without copper(II) complex). d A1 was the absorbance in the
presence of the copper(II) complex. e A2 was the absorbance without
sodium salicylate/DPPH. f Measured after 30 min in dark. g Measured
immediately after mixing.
line.
Rearranging:
kobs′ ¼ ½H2O2ꢀ=ðb þ a½H2O2ꢀÞ ¼ ½H2O2ꢀ=ð0:087 þ 2:89½H2O2ꢀÞ
The rate-law for the reaction of Lb–2Cu with H2O2 in
0.020 M pH 7.5 phosphate buffer can be written as:
2
2
v ¼ kobs′½Lb–2Cuꢀ ¼ ½Lb–2Cuꢀ ½H2O2ꢀ=ð0:087 þ 2:89½H2O2ꢀÞ
scavenged are 4.7% and 12% for Lb–2Cu and Lc–2Cu respecti-
ð2Þ vely (Table 5). Lc–2Cu can scavenge twice as many OH˙ radi-
cals than that of Lb–2Cu in the presence of H2O2.
The rate-law for the reaction of Lb–2Cu and Lc–2Cu with
H2O2 is different, which indicates a different mechanism. pH
has a great influence on the reaction rate. Increasing pH will
increase the 360 nm absorbance of the products. Increasing
pH will also make the reaction faster between dinuclear
copper(II) complexes and H2O2. The reaction is too fast to
study the kinetics by UV-vis in pH > 9. After a longer reaction
time at high pH precipitation will occur. The reaction mechan-
ism needs further exploration.
DPPH assay is routinely used for assessment of the free
radical scavenging potential of an antioxidant molecule and
considered as one of the standard and easy colorimetric
methods for the evaluation of antioxidant properties.40 The
highly reactive H˙ radical can react with DPPH radical by
donating hydrogen to a free DPPH radical and hence its
reduction to an unreactive colorless species.41 Addition of
hydrogen removes the odd electron feature which is respon-
sible for radical reactivity (DPPH color fades, Fig. s14†). The
Lb–2Cu complex fades 2.9% of DPPH absorbance at 545 nm.
While Lc–2Cu complex decreases 45% of the DPPH radical
absorbance. These data indicate that both complexes scavenge
the OH˙ radical, but generate the H˙ radical. Lc–2Cu can gene-
rate the H˙ radical much more effectively than that of the
Lb–2Cu complex when reacted with H2O2. This may explain
why the reaction kinetics of the two dinuclear complexes is
different.
We expect there should be some OH˙ radical generated
upon reaction with H2O2.19g,42 However, the sodium salicylate–
Fe(II) system gives a negative result. EPR spectra indicate that
reactive oxygen species (ROS) can generate H˙ radical.43
Recently, Yuzawa44 proposed a H˙ radical generation mechan-
ism in acidic and basic aqueous solution. ROS (S⋯H–O˙,
where S is organic substrate) gives an electron to H+ to
Radical trapping test
The very high reactivity of the OH˙ radical enables it to react
with a wide range of molecules found in living cells, such as
sugars, amino acids, lipids and nucleotides. Although OH˙
formation can occur in several ways, by far the most important
mechanism in vivo is the Fenton reaction, where a transition
metal is involved as a pro-oxidant in the catalyzed decompo-
sition of superoxide and hydrogen peroxide. With this assay,
the 500 nm absorbance changed due to hydroxyl radical sca-
venges/releases in the presence of copper(II) complexes than in
the absence of the copper(II) complexes (Fig. s13†). OH˙
radical scavenged 4.2% and 2.6% in the presence of Lb–2Cu
and Lc–2Cu respectively (the spectra were measured immedi-
ately, Table 5). After 30 min reaction in dark, radicals
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generate the H˙ radical. From literature data, H˙ does exist in
the presence of ROS.
The MS spectra of Lc–2Cu complex is quite complicated
(Fig. s16†). In contrast to the Lb–2Cu complex, no mono-
oxygenated peaks (+16) were present, but instead dehydro-
genation of the cyclohexane occurred in the presence of H2O2.
Ligand hydroxylation is common in xylyl-containing ligands,
but is impossible in cyclohexane-containing ligands within
several minutes. Ligand dehydrogenation takes place in air
without adding H2O2. This might explain why the Lc–2Cu
complex decreased the DPPH absorbance much more effec-
tively than the Lb–2Cu complex.
Mass spectra
The UV-vis spectra indicate that dinuclear copper(II) complexes
of Lb and Lc react with H2O2 in neutral or basic aqueous solu-
tion. Radical scavenging/formation tests, as discussed above,
showed that the reaction mechanism is different for the two
complexes. The likely product was possibly a xylyl hydroxylated
species. The reaction was monitored by MS spectroscopy.
The negative ion ESI-MS of Lb–2Cu complex in aqueous
solution at pH 7 and 9 before and after adding H2O2 are
Analysis of fully oxidized products
shown in Fig. 5. The main peaks are essentially the same at The mass spectra (Fig. 5 and s16†) discussed in the previous
pH 7 and 9 except the 606 and 608 peak in pH 7 did not section are those of the complexes obtained immediately
appear in pH 9. The strongest peak at 561 and 563 is after adding H2O2. To investigate the final products of H2O2
[Cu2Lb(OH)(H2O)3]− (M−), and has an isotope pattern identical oxidation, 20 μL of 30% H2O2 was added to 2.0 mL of dinuc-
to simulation. This formula agrees well with the pH titration lear copper(II) complex of Lb and Lc (pH 9.0). After stirring the
data. Besides these peaks, the Lb–2Cu complex also shows mixture for 1 h, 50 μL of 0.08 M K2S solution was added.
M− − 3H2O peaks at 505 and 507; M− + KNO3 at 662 and 664; The mixture was left at room temperature for 1/2 h. CuS was
M− + 2KNO3 at 763 and 765. The 606 and 608 peak is [Cu2Lb removed by centrifugation before HPLC-MS measurements
(NO3)(H2O)3]−. The 707 and 709 peak in pH 7 is [Cu2Lb(NO3)- were obtained. Although there are more than 2 oxidized
(H2O)3]− + KNO3. After adding H2O2, the dinuclear complex species for Lb complex, HPLC was not able to separate them
revealed the presence of corresponding Cu2L + O (+16) peaks. well and only one peak appeared in the HPLC. However, the
This is possibly due to the replacement of OH− by HOO−, or oxidized form of Lc was separated in two parts in a 2 : 1 ratio.
the hydroxylation of the phenyl in the 2-position to form the The major part of the oxidized form of Lc was identical to the
phenol group. Ligand hydroxylation in the presence of H2O2 is oxidized form of Lb (Fig. 6).
well established in xylyl-containing dinuclear iron(III) and
Aspartic acid oxidation is a common phenomenon that
Cu(II) complexes.23,45 The same conclusions were drawn from takes place in biological systems. The product of aspartic acid
the positive ion spectra (Fig. s18†), and this also agrees well oxidation is the keto acid,46 and the intermediate is an imino
with the distribution curve of the system.
compound. Amino hydroxylation was also reported recently.47
Fig. 5 Lb–2Cu negative ion mass spectrum (a) pH 7, (b) pH 9, (c) pH 7 – H2O2 (d) pH 9 – H2O2.
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dehydrogenation of the cyclohexyl group will generate Lb in its
oxidized form. Incomplete oxidation of Lc will generate decar-
boxylated and oxygenated products. We tried our best to separ-
ate these mixtures by chromatography, but failed. Possible
oxidation products are illustrated in Scheme 5.
Catalytic oxidation of nitrobenzene
Considering its high oxidation potential, it would appear
unlikely that activation of nitrobenzene would proceed by
oxidation via electron transfer. In fact, nitrobenzene has been
observed to be a mild oxidative dehydrogenating agent under
both acidic and basic conditions.48 The oxidation of nitro-
benzene is quite difficult. A Scifinder search gives 17 references
on nitrobenzene oxidation into nitrophenol. The most closely
related studies to our work are the vanadium(V)-substituted
polyoxometalates49 and iron-catalyzed50 oxidation of nitro-
benzene into nitrophenol. Both reactions are heterogeneous
with long reaction times and low conversions (<10%), and a
free radical mechanism is proposed. Anodic oxidation can also
oxidize nitrobenzene into nitrophenol with 18% yield.51 Cumyl
hydroperoxide52 can oxidize nitrobenzene in strong basic
media with yield 45%. The reaction proceeds via an addition-
base-induced β-elimination pathway analogous to that of
vicarious nucleophilic substitution. Most of the oxidations are
non-selective even protein engineering.53 D’Oliveira found that
UV-illuminated TiO2 in the presence of O2 (air) can oxidize
nitrobenzene into nitrophenol.54 To our knowledge, investi-
gations of the reaction kinetics are still rare and ambiguous.
Upon addition of H2O2, nitrobenzene is oxidized quickly
to nitrophenol as indicated by its absorbance at 400 nm. In
0.20 M phosphate buffer, no observable pH change was
observed before and after catalytic oxidation. Fig. 7 illustrates
the spectral changes that occurred during catalytic oxidation
of 0.80 × 10−3 M nitrobenzene by 0.1667 M H2O2 in 0.2 M
KH2PO4 buffer at pH = 8.00, by 2.08 × 10−5 M Lc–2Cu complex.
Fig. 6 The MS of Lb– and Lc–2Cu after oxidation overnight in the presence of
excess H2O2. Cu(II) was removed by K2S. (top) Lb; (bottom) Lc minor part.
Scheme 5 Proposed ligand oxidation products and their m+/z values.
+
For Lb–2Cu complex, the un-oxidized ligand had K3H2Lb
peaks at 483, K3H2Lb+–H2O at 465, K2H3Lb+–H2O at 427 and
+
KH4Lb at 407. The strongest peak at 419 is the mono-oxyge-
nated form of the ligand, [KH4LbO]+–2H2, whose structure is
illustrated in Scheme 5. The 416 peak is KH3LbO*–3H2 radical.
Peaks at 475 and 588 are the doubly oxygenated species,
+
+
K2H3LbO2 –H2 and K3H2LbO2 –2CH2, respectively (Scheme 5).
Dehydrogenation of an alkyl group will generate a double
bond, the position of the double bond is not clear yet. The pro-
posed structures are similar to those reported by Zhu et al.19g
The amount of minor HPLC band of the oxidized form of Lc is
roughly 1/2 that of the major band. Because the MS of the
major band was identical to the MS of Lb, it was concluded
that the cyclohexane moiety of Lc had been oxidized to a
phenyl ring. The MS spectrum of the minor part indicated the
presence of a different structure. The base peak at 448 is
K2H2Lc*+–H2. The decarboxylated form (–CH2) is located at
+
399, which corresponds to KH4Lc –CH2. The 516 peak is attrib-
+
uted to the double oxygenated form, K3HLcO2 –2H2. Isotope
patterns are identical to the theoretical simulations. According
to the above discussion, Lb hydroxylation at the 2-position of
the xylyl is the predominant species. Ligand Lb can be doubly
oxygenated and dehydrogenated as well. While for Lc, full
Fig. 7 Spectral changes with time recorded for the reaction of 0.8 × 10−3
M
nitrobenzene and 2.08 × 10−5 M Lc–2Cu with 0.1667 M H2O2 in pH = 8.00,
0.2 M KH2PO4–NaOH-solution at 25 °C.
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different rate formulae for nitrobenzene oxidation via the
Fenton process (v = 0.259[Fe2+]1.02[H2O2]0.34[NB]−0.094, where
NB represents nitrobenzene, which is different from ours).16
Our dinuclear copper(II) complexes have obvious advances over
the Fenton process. Firstly, the catalytic reaction takes place
in weak basic aqueous rather than the Fenton process at
pH 2.4–3.6.16 Secondly, the k for our complexes (200–600) is
much larger than that of the Fenton process (0.259). Although
the nitrobenzene concentration was not very high, our
complexes can convert all of the nitrobenzene substrate into
nitrophenol. The full conversion of nitrobenzene can be
proved by the 400 nm absorbance plateau (A∞). The plateau is
irrelevant to complex (catalyst) concentrations in the experi-
ments (Fig. 8). All other known catalytic systems have a much
lower nitrobenzene conversion.49–52
The oxidation rate increased with an increase in the reac-
tion temperature (Fig. s19,† Table 7). The Arrhenius activation
energies, obtained from a plot of ln k vs. 1/T, are 69.4 2.2 and
70.0 4.3 kJ mol−1 for Lb and Lc dicopper complexes, respecti-
vely (Fig. s20†). These values are essentially the same and also
the same as 378 to 600 °C supercritical water oxidation
Fig. 8 Kinetic traces recorded at 400 nm for the catalyzed oxidation of nitro-
benzene. Reaction conditions: pH = 8.00, 0.2 M KH2PO4–NaOH, 1.47 × 10−3
M
nitrobenzene, 0.1667 M H2O2, 25 °C. (a) No complex. (b) 5.00 × 10−6 M Lc–2Cu,
(c) 1.25 × 10−5 M Lc–2Cu, (d) 2.50 × 10−5 M Lc–2Cu, (e) 3.75 × 10−5 M Lc–2Cu,
(f) 5.00 × 10−5 M Lc–2Cu.
in the absence of oxygen 68.0
9.0 kJ mol−1 55
. However,
the Arrhenius pre-exponential factors are 2.62 × 1014 and
1.06 × 1015 respectively. These pre-exponential factors are sig-
nificantly larger than that for supercritical water oxidation.55 It
is the larger pre-exponential factor that make the Lc–2Cu
complex more active than the Lb–2Cu complex in nitrobenzene
catalytic oxidation.56
The rate of nitrobenzene oxidation is also affected by pH of
reaction solution (Table 8). An increase in the reaction pH sig-
nificantly increased the oxidation rate. This phenomenon
agrees well with the reaction between the complexes and H2O2,
indicating that dioxygen activation is the first step in the cata-
lytic oxidation.
The absorbance at 400 nm increased during the oxidation
process. The oxidation is first order in nitrobenzene.
Kinetic traces recorded at 400 nm for the catalyzed oxi-
dation of nitrobenzene at different complex concentrations are
shown in Fig. 8. The first-order rate constant linearly increases
with an increase in dicopper(II) complex concentration (Fig. 8
and Tables s1 and s2†), as well as with H2O2 concentration
(Fig. s18, Tables s3 and s4†). Although Lb–2Cu and Lc–2Cu
follow a different rate law for their reaction with H2O2, for the
catalytic oxidation process, both complexes follow the rate law
(data listed in Table 6):
v ¼ k½complexꢀ½nitrobenzeneꢀ½H2O2ꢀ
4. Conclusions
This agrees well with the polyoxometalate catalyzed
oxidation of nitrobenzene.49b The k values are 211.2 0.3 and Two new bis-aspartic acid ligands were synthesized via
607.9 1.7 L2 mol−2 s−1 at pH 8.0 for Lb–2Cu and Lc–2Cu, Michael addition in aqueous solution. Both ligands react with
respectively. For the same reaction under the same conditions, Cu(II) and Zn(II) to form dinuclear complexes. pH titration, as
k was 45.01 0.06 L2 mol−2 s−1 when the Cu complex of 1,3- well as ESI-MS indicates that M2L(OH)− is the major species in
N,N,N′,N′-xylylenediamine tetraacetate was the catalyst. This neutral/weak basic aqueous solution. The dinuclear copper
agrees well with the radical generation ability of the dicopper(II) complexes react with H2O2 in aqueous solution. The reaction
complexes. As shown in Fig. 8, even at the very low complex mechanism of the two Cu complexes differs greatly in 0.020 M
concentration of 5.00 × 10−6 M, which is 1/294 of the nitro- pH 7.5 phosphate buffer. The oxidation products were oxyge-
benzene concentration, the maximum absorbance at 400 nm nated and/or dehydrogenated species in neutral and basic
is the same as in the presence of 5.00 × 10−5 M complex con- aqueous solution. Both complexes can trap/scavenge OH˙
centration. These data indicate that the complex is a catalyst, radical, but generate H˙ radical when reacting with H2O2,
not a reactant.
especially the Lc–2Cu complex. Both complexes can catalyze
The pathway for the completion of the reaction, nitro- nitrobenzene oxidation in the presence of H2O2 in weak basic
benzene to nitrophenol is still unclear.49b According to radical aqueous solution. The two complexes follow the same rate-law.
trapping data, we believe that the oxidation of nitrobenzene The catalytic rate constant of Lc–2Cu is 3 times that of the
occurs via an H˙ radical mechanism, different from the OH˙ Lb–2Cu complex. It is the larger pre-exponential factor that make
radical mechanism proposed by Jin Anotai et al. in acidic Lc–2Cu complex more active than Lb–2Cu complex in nitro-
aqueous solution.16 This can also be further proved by benzene catalytic oxidation. Both complexes can convert all
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Table 6 The first order kobs × 104 (s−1) for oxidation of 1.47 × 10−3 M nitrobenzene in the presence of 0.1667 M H2O2 in 0.2 M KH2PO4 buffer at pH = 8.00, 25 °C
[Complex]
5.00 × 10−6
1.25 × 10−5
2.50 × 10−5
3.75 × 10−5
5.00 × 10−5
No complex
Lb–2Cu
Lc–2Cu
2.25 0.004
4.21 0.003
4.56 0.006
11.3 0.02
8.73 0.009
26.9 0.06
13.2 0.02
38.0 0.1
16.9 0.04
50.0 0.2
0.622 0.0001
0.622 0.0001
Table 7 Rate-constants k (L2 mol−2 s−1) for the oxidation of nitrobenzene by H2O2 catalyzed by dicopper(II) complexes in 0.20 M phosphate buffer at pH = 8.00
Temp
5 °C
15 °C
25 °C
35 °C
45 °C
La–2Cua
Lb–2Cu
Lc–2Cu
11.71 0.01
23.36 0.02
94.51 0.2
18.37 0.02
76.76 0.09
174.4 0.3
45.01 0.06
211.2 0.3
607.9 1.7
159.0 0.3
442.3 1.3
1496 4.1
347.1
1078
3780 40
1
5
a La is 1,3-N,N,N′,N′-xylylenediamine tetraacetate.
Table 8 The k (L2 mol−2 s−1) for oxidation of nitrobenzene in the presence of
H2O2 in 0.2 M KH2PO4 buffer at pH = 8.00, 25 °C
2 X. Z. Liang, N. N. Quan, J. Wang and J. G. Yang, Sci. China,
Ser. B: Chem., 2009, 52, 874–878.
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pH
7.00
7.50
8.00
8.50
a
La
Lb
Lc
28.64 0.03
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53.17 0.08
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1152 3.6
a La is 1,3-N,N,N′,N′-xylylenediamine tetraacetate.
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Acknowledgements
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The project was supported by the National Natural Science
Foundation of China (grant No. 20971084 and 21001073).
We are also in debt to Prof. Judith Walmsley for her careful
proof reading and revision. We thank Instrumental
Analysis and Research Center of Shanghai University for
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