Copper catalyzed oxidation of amino acids

Article abstract of DOI:10.1016/j.poly.2014.02.007

Copper(II) chloride and novel bis(1-amino(cyclo)alkane-1-carboxylato- κ²N,O)copper(II) complexes as catalysts were studied in relation with enzymatic oxidation of amino acids. The oxidation of aminophosphonate derivative: (1-amino-1-methyl)ethylphosphonic acid was also investigated. Two bis(1-aminocycloalkane-1-carboxylato-κ²N,O) copper(II) complexes were structurally characterized. Surprisingly, while the 1-aminocyclobutane-1-carboxylate complex has square planar (SP-4) copper(II) center with trans-orientated ligands, the 1-aminocyclohexane-1-carboxylate complex has μ-carboxylato dimeric structure with square pyramidal (SPY-5) sites, one with cis- and one with trans-orientated ligands. Redox behavior of the bis(1-amino(cyclo)alkane-1-carboxylato-κ²N,O)copper(II) complexes was also investigated. Catalytic oxidations were carried out in alkaline DMF-water mixtures using H₂O₂ as oxidant and the complexes as catalysts. The observed potentials for the irreversible current peaks associated with the Cu(II) to Cu(I) reduction and the rates of the amino acid oxidations show inverse trend. This suggests that the Cu(II)/Cu(I) redox cycling due to the presence of H₂O₂ plays important role in the peroxide/copper activation that in turn provides the observed products.

Full text of DOI:10.1016/j.poly.2014.02.007

Polyhedron 73 (2014) 37–44
Contents lists available at ScienceDirect
Polyhedron
journal homepage: www.elsevier.com/locate/poly
Copper catalyzed oxidation of amino acids
Szabina Góger a, József S. Pap a, Dóra Bogáth a, A. Jalila Simaan b, Gábor Speier a, Michel Giorgi c,
József Kaizer a,
⇑
a Department of Chemistry, University of Pannonia, H-8200 Veszprém, Hungary
b Aix Marseille Université, CNRS, Centrale Marseille, iSm2 UMR 7313, 13397 Marseille, France
c Aix-Marseille Université, FR1739, Spectropole, Campus St. Jérôme, Avenue Escadrille Normandie-Niemen, 13397 Marseille cedex 20, France
a r t i c l e i n f o
a b s t r a c t
Copper(II) chloride and novel bis(1-amino(cyclo)alkane-1-carboxylato-j
2N,O)copper(II) complexes as
catalysts were studied in relation with enzymatic oxidation of amino acids. The oxidation of
Article history:
Received 27 November 2013
Accepted 5 February 2014
Available online 18 February 2014
aminophosphonate derivative: (1-amino-1-methyl)ethylphosphonic acid was also investigated. Two
bis(1-aminocycloalkane-1-carboxylato-
Surprisingly, while the 1-aminocyclobutane-1-carboxylate complex has square planar (SP-4) copper(II)
center with trans-orientated ligands, the 1-aminocyclohexane-1-carboxylate complex has -carboxylato
dimeric structure with square pyramidal (SPY-5) sites, one with cis- and one with trans-orientated
ligands. Redox behavior of the bis(1-amino(cyclo)alkane-1-carboxylato-
2N,O)copper(II) complexes
j
2N,O)copper(II) complexes were structurally characterized.
Keywords:
l
Biomimetic oxidation
Oxidase activity
Kinetic studies
Amino acids
j
was also investigated. Catalytic oxidations were carried out in alkaline DMF-water mixtures using
H2O2 as oxidant and the complexes as catalysts. The observed potentials for the irreversible current peaks
associated with the Cu(II) to Cu(I) reduction and the rates of the amino acid oxidations show inverse
trend. This suggests that the Cu(II)/Cu(I) redox cycling due to the presence of H2O2 plays important role
in the peroxide/copper activation that in turn provides the observed products.
Copper(II)
Ó 2014 Elsevier Ltd. All rights reserved.
1. Introduction
carbonyl compounds [7,8] (Scheme 1), mimicking the action of
the non-heme iron enzyme 1-aminocyclopropane-1-carboxylic
The oxidative degradation of organic substances such as amino
acids under mild conditions is of great interest for industrial and
synthetic processes both from an economical and environmental
point of view. Amino acids may form potentially harmful disinfec-
tion byproducts during the conventional treatment of water and
wastewater [1,2]. Removal of these parent compounds by the use
of the environmental-friendly oxidant, ferrate(VI) was assessed
by studying the kinetics of the oxidation of glycine [3]. Previously,
kinetics and mechanism of oxidation of neutral L-amino acids by
sodium N-chloro-p-toluene sulfonamide in acid [4,5] and alkaline
medium [6] have been reported.
Metal ion-catalyzed oxidations (MCO) of amino acids were also
performed by researchers to mimic the deamination of bioactive
molecules catalyzed by enzymes. The first example of a biomimetic
mononuclear iron complex, ([FeIII(Salen)Cl] (Salen = N,N0-bis
(salicylidene)-ethylenediaminato) was described, that highly
selectively and efficiently catalyzes the oxidation of a series of
acyclic and cyclic amino acids to ethylene or the corresponding
acid oxidase (ACCO) [9]. Kinetics and mechanism of the oxidation
of -amino acids by peroxomonosulphate (PMS) in acetic acid/so-
dium acetate buffered [10–16], and alkaline medium were also re-
a
ported [17].
Besides enzymatic reactions, the oxidation of amino acids or
amino acid residues in living organisms may occur either by reactive
oxygen species (ROS) [18] or as a MCO process [19]. ROS-indicated
oxidation reactions of amino acids and the products formed are
well described, and understood [20]. Much less is known this far
about MCO, however metal-based oxidants have far greater
potential [21]. MCO gives rise to highly reactive intermediates such
as hydroxyl radicals, which lead to damage in bio-molecules such
as proteins that are implicated in aging and the pathogenesis of
neurodegenerative diseases, including Alzheimer’s disease [22,23].
Here we describe a new copper(II)-catalyzed (Table 1) system
for a series of acyclic (a-amino-isobityric acid (AIBH), D,L-alanine
(D,L-ALAH)) and cyclic amino acids (1-aminocyclopropane-
1-carboxylic acid (ACCH), 1-amino-1-cyclobutanecarboxylic acid
(ACBCH), 1-aminocyclopentanecarboxylic acid (ACPCH), and 1-
aminocyclohexanecarboxylic acid (ACHCH)), and
phonic acid ((1-amino-1-methyl)ethylphosphonic acid (AMEP))
a-aminophos-
⇑
Corresponding author. Tel.: +36 88 624 720; fax: +36 88 624 469.
E-mail address: kaizer@almos.vein.hu (J. Kaizer).
http://dx.doi.org/10.1016/j.poly.2014.02.007
0277-5387/Ó 2014 Elsevier Ltd. All rights reserved.

38
S. Góger et al. / Polyhedron 73 (2014) 37–44
Scheme 1. Pathways leading to different products by ACCO.
Table 1
commercial products and were used as received without further
Summary of the isolated complexes.
purification. The Cu(ClO4)2ꢀ6H2O and the amino acid substrates
Amino acid (AA)
[CuIIn(AA)2n]ꢀmH2O
and AMEPH were purchased from commercial sources.
ACBC
ACPC
ACHC
AIB
1 (n = 1, m = 0)
2 (n = 1, m = 1)
3 (n = 2, m = 2)a
4 (n = 1, m = 0)
5 (n = 1, m = 1)
2.2. Analytical and physical measurements
D,L-ALA
Infrared spectra were recorded on an Avatar 330 FT-IR Thermo
Nicolet instrument using samples mulled in in KBr pellets. UV–Vis
spectra were recorded on a Cary 60 spectrophotometer equipped
with a fiber-optic probe with 1 cm pathlength. Microanalyses were
done by the Microanalytical Service of the University of Pannonia.
Cyclic voltammograms (CV) were taken on a VoltaLab 10 potentio-
stat with VoltaMaster 4 software for data process. The electrodes
were as follows: glassy carbon (working), Pt (auxiliary), and
Ag/AgCl in 3 M KCl (reference). The potentials were referenced
vs. the ferrocenium ferrocene redox couple (+416 mV in methanol
in our setup). The crystal evaluations and intensity data collections
were performed on a Bruker-Nonius Kappa CCD single-crystal
a
one water molecule is coordinated.
as surrogates for the corresponding
(Scheme 2, Table 1).
a-aminocarboxylic acids
2. Experimental
2.1. Materials
Solvents used for the reactions were purified by literature
methods [24] and stored under argon. All other chemicals were
diffractometer (1, 3) using Mo K
a radiation (k = 0.71070 Å) at
Scheme 2. Structures and abbreviated names of the substrates used in this study.

S. Góger et al. / Polyhedron 73 (2014) 37–44
39
Table 3
296, 293, and 203 K, respectively. Crystallographic data and details
Selected bond lengths (Å) for 1 and 3.
of the structure determination are given in Table 2, whereas se-
lected bond lengths and angles are listed in Tables 3–6. SHELX-97
[25] was used for structure solution and full matrix least squares
refinement on F2. CIF files are available in the CCDC database: CCDC
941371–941372 (1, 3). GC measurements were performed on a HP
5890 gas chromatograph equipped with a 30 m Supelcowax
coloumn.
1
Cu1–N1
1.987(6)
Cu1–O1
1.968(5)
3
Cu1–N1
Cu1–N2
Cu1–O1
Cu1–O3
Cu1–O5
1.984(3)
1.988(3)
1.959(2)
1.942(3)
2.349(2)
0.34
Cu2–N3
Cu2–N4
Cu2–O1
Cu2–O6
Cu2–O8
1.978(2)
1.977(3)
2.537(2)
1.944(2)
1.927(2)
0.11
2.3. Synthesis of [CuII(ACBC)2] (1)
s(Cu1)
s(Cu1)
A 5 mL aqueous solution of ACBCH (0.69 g, 6 mmol) was mixed
with CuCl2ꢀ2H2O (0.51 g, 3 mmol) in 15 mL CH3OH and triethyl-
amine (0.84 mL, 6 mmol) was added slowly to the mixture. Forma-
tion of a purple-blue crystalline precipitate was observed following
the disappearance of a transient lilac colour. Yield: 0.56 g (64%).
Anal. Calc. for C10H16CuN2O4: C, 41.16; H, 5.53; N, 9.60. Found: C,
41.4; H, 5.6; N, 9.8%. FT-IR bands (KBr pellet, cmꢁ1) 3285 (m),
3238 (m), 3126 (w), 2974 (w), 2950 (w), 2868 (w), 1619 (vs),
1391 (s), 1272 (s), 1158 (s), 1070 (m), 751 (w), 690 (w), 571 (w).
Table 4
Selected bond angles (°) for 1 and 3.
1
N1–Cu1–O1
N1–Cu1–N1
83.7(2)
180.0(3)
N1–Cu1–O1
C3–C2–C5
96.3(2)
87.1(6)
3
N1–Cu1–N2
N1–Cu1–O1
N1–Cu1–O5
N2–Cu1–O3
O1–Cu1–O3
O1–Cu1–O5
C2–C1–C6
175.2(1)
83.4(1)
91.8(1)
N3–Cu2–O1
N3–Cu2–O6
N3–Cu2–O8
N4–Cu2–O1
N4–Cu2–O6
N4–Cu2–O8
88.42(9)
85.0(1)
178.2(1)
87.3(1)
171.9(1)
85.3(1)
UV–Vis (CH3OH/water) [kmax, nm (loge)] 243 (4.00), 611 (2.06).
Crystals suitable for X-ray structural determination were obtained
from CH3OH–water solvent mixture.
83.8(1)
154.7(1)
103.88(9)
110.4(3)a
Complexes 2–5 were synthesized analogously to 1.
a
Average of the four corresponding angles is 110.4(6).
2.4. Synthesis of [CuII(ACPC)2].H2O (2)
Yield: 0.71 g (74%). Anal. Calc. for C12H22CuN2O5: C, 42.66; H,
6.56; N, 8.29. Found: C, 42.7; H, 6.6; N, 8.4%. FT-IR bands (KBr pel-
let, cmꢁ1) 3446 (m), 3284 (m), 3248 (m), 2959 (w), 2870 (w), 1625
(vs), 1583 (s), 1374 (s), 1326 (w), 1186 (m), 1148 (m), 821 (m), 645
(w), 596 (w). UV–Vis (CH3OH) [kmax, nm (loge)] 245 (3.89), 594
(1.94).
Table 5
Assignment of the
the solid complexes.
m
(CO2)as and
m
(CO2)s stretching frequencies for
Complex
m
(CO2)as (cmꢁ1 (CO2)s (cmꢁ1
)
m
)
1
2
3
4
5
1619
1625
1612
1627
1626
1391
1374
1369, 1343
1390, 1363
1394, 1354
2.5. Synthesis of [CuI2I(ACHC)4(H2O)].H2O (3)
Yield: 0.65 g (62%). Anal. Calc. for C28H52Cu2N4O10: C, 45.95; H,
7.16; N, 7.66. Found: C, 46.3; H, 7.2; N, 7.8%. FT-IR bands (KBr
pellet, cmꢁ1) 3441 (m), 3320 (m), 3250 (m), 3147 (w), 2929 (s),
2859 (s), 1612 (vs), 1603 (s), 1453 (m), 1369 (s), 1343 (s), 1175
(m), 1098 (m), 983 (w), 814 (m), 757 (w), 670 (w), 561 (w).
Table 6
Electrochemical data for Cu(AA)2 complexes in DMF (the E°01/2 of
ferrocene was 490 10 mV) at 100 mV/s scan rate.
UV–Vis (CH3OH) [kmax, nm (loge)] 245 (3.84), 595 (1.85). Crystals
Complex
E°0pa
E°0pc
1
2
ꢁ84
ꢁ55
ꢁ80
ꢁ80
ꢁ63
ꢁ659
ꢁ692
ꢁ754
ꢁ735
ꢁ620
Table 2
Crystal structure details for 1 and 3.
3
4*
5
Compound reference
1
3
Chemical formula
Formula mass
Crystal system
a (Å)
b (Å)
c (Å)
C5H8Cu0.5NO2
145.89
monoclinic
10.381(1)
5.1906(5)
9.912(1)
90
90.345
90
534.08(9)
293(2)
P21/c
C28H52Cu2N4O10
731.82
*
Solubility of the complex was limited.
monoclinic
10.733(1)
13.629(1)
22.776(3)
90
100.41(5)
90
3276.8(6)
293(2)
suitable for X-ray structural determination were obtained from
CH3OH–water solvent mixture.
a
(°)
b (°)
(°)
2.6. Synthesis of [CuII(AIB)2] (4)
c
Unit cell volume (Å3)
T (K)
Yield: 0.59 g (73%). Anal. Calc. for C8H16CuN2O4: C, 35.88; H,
6.02; N, 10.46. Found: C, 35.4; H, 6.1; N, 10.2. FT-IR bands (KBr
pellet, cmꢁ1) 3273 (m), 3240 (m), 3142 (w), 2974 (m), 2933 (w),
1627 (vs), 1588 (m), 1474 (m), 1390 (s), 1363 (m), 1221 (s), 1097
(m), 1087 (m), 893 (w), 817 (w), 782 (m), 691 (w), 576 (w).
Space group
Number of formula units per unit cell, Z
P21/c
4
Mo Ka
4
Radiation type
Mo K
a
Absorption coefficient (l )
/mmꢁ1
No. of reflections measured
No. of independent reflections
Rint
Final R1 values (I > 2
Final wR values (I > 2
Final R1 values (all data)
Goodness of fit (GOF)
CCDC number
5465
1293
38240
7987
0.081
0.0524
0.1291
0.1185
1.028
UV–Vis (CH3OH) [kmax, nm (loge)] 244 (3.84), 600 (1.88).
0.1051
0.0587
0.1369
0.1379
0.971
r
r
(I))
(I))
2.7. Synthesis of [CuII(D,L-ALA)2].H2O (5)
Yield: 0.58 g (81%). Anal. Calc. for C6H14CuN2O3: C, 27.96; H,
5.48; N, 10.87. Found: C, 28.2; H, 5.5; N, 11.0%. FT-IR bands (KBr
941371
941372

40
S. Góger et al. / Polyhedron 73 (2014) 37–44
Fig. 1. X-ray structure of 1 and 3. Ellipsoids are plotted at 30% probability level, hydrogen atoms are omitted for ACHC for clarity.
pellet, cmꢁ1) 3395 (m), 3267 (m), 3158 (w), 2970 (m), 2935 (w),
2877 (w), 1626 (vs), 1591 (s), 1451 (m), 1394 (s), 1354 (m), 1301
(m), 1160 (s), 1120 (s), 1062 (w), 857 (m), 789 (w), 672 (w), 566
and the evolved product(s) were measured by removing 250 lL of
the headspace by GC analysis. The concentration of products in the
head space are linearly proportional to the concentration of those
in the reaction mixture.
(m). UV–Vis (CH3OH/water) [kmax, nm (loge)] 239 (3.86), 610
(1.81).
3. Results and discussion
2.8. Determination of products and kinetic measurements
3.1. Synthesis and characterization of the complexes
Kinetic studies on the catalytic oxidation of amino acids by
CuCl2 or Cu(AA)2 complexes were performed in a 3:1 DMF–water
mixture at 35 °C. Assays were performed as follows: respective
amino acid (3.6 ꢂ 10ꢁ4 mol) was dissolved in 10 mL of the solvent
mixture in a sealable tube of 20 mL. To the mixture were then
The complexes were synthesized in methanol. Crystalline prod-
ucts were obtained by slow evaporation of the methanol from the
reaction mixture. An overview of the isolated and characterized
compounds is given in Table 1, crystal structure details for 1 and 3
are given in Table 2, the single crystal structures are shown in Fig. 1.
Selected bond lengths and angles are listed in Tables 3 and 4.
The ligand geometry in 1 is SP-4 and the ACBC ligands are located
added MeCN (10
l
L) as internal standard, the catalyst (7.2 ꢂ 10ꢁ8
mol) and NH4OH (3.6 ꢂ 10ꢁ4 mol). Hydrogen peroxide (32
lL,
3.6 ꢂ 10ꢁ4 mol) was then added through the septum with a syringe

S. Góger et al. / Polyhedron 73 (2014) 37–44
41
Fig. 3. Reaction of AIBH (j) and AIBH in the presence of AMEP (ꢂ) in DMF/water
(3:1) at 35 °C. [CuCl2]0 = 7.2 ꢂ 10ꢁ6 M, [AIBH]0 = 3.6 ꢂ 10ꢁ2 M, [AMEPH]0 = 0 or
3.6 ꢂ 10ꢁ3 M, [H2O2]0 = 3.6 ꢂ 10ꢁ2 M, [NH4OH]0 = 3.6 ꢂ 10ꢁ2 M.
Fig. 2. Cyclic voltammograms of the AA complexes (DMF, 1 mM complex, 0.1 M
TBAP electrolyte, at 100 mV/s scan rate).
in trans-arrangement. Thus the Cu(II) ions represent the inversion
centre of the molecule and occupy face-centred positions of the
centrosymmetric unit cell. The bond lengths are all below 2.0 Å.
Remarkably the geometry lacks any distortions. Although the O2
atom of a neighboring complex is found 2.83 Å from Cu1 at the ax-
ial site, this contact is too long to be considered as a metal–ligand
interaction. Weak H-bonds are listed in Fig. S1. In contrast, 3 is
dinuclear with two different SPY-5 sites. Regarding the equatorial
planes, Cu1 is surrounded by two ACHC ligands in trans-, whereas
Cu2 binds two ACHC ligands in cis-configuration. The O1 atom
forms a bridge between Cu1 and Cu2, for the latter as an axial
ligand. Finally, the axial site at Cu1 is occupied by a water
molecule. The dimer is remarkably rich in H-bonds that are shown
(Table 3), yet both are best described as distorted square
pyramidal. The configuration descriptors for the two centers are
SPY-5-21 for Cu1 and SPY-5-12 for Cu2.
It is out of the scope of this study to consider the presumable
role of the H-bonds and ring size of the amino acid R-group in
the favored trans- vs. cis- arrangement of the ligands.
The IR spectral analysis of the solid complexes can be useful,
since the characteristic m(CO2)as and m(CO2)s stretching frequencies
for the carboxylate groups should be sensitive to coordination
modes. According to the X-ray structures, between two Cu(II)
centers a
1 and 3. The complexes exhibit relatively great difference between
the (CO2)as and
(CO2)s frequencies in the range 220–270 cmꢁ1
l-carboxylato-jO,jO’-bridge exists in the solid state in
m
m
in Fig. S2. The
s values are somewhat different for the two sites
that is in accordance with their bridging position (bands are listed
Table 7
Kinetic data for the oxidation of amino acids.a
Substrate
Product(s)
CuCl2
Cu(AA)2
ꢁd[S]/dt (10ꢁ7 Msꢁ)
0.04
TOF (hꢁ1
2
)
TOF (hꢁ1
–
)
BDEN–H (kcal/mol)
97.4
b
-
ethylene
CO2
+
NH3
ACCH
-
cyclobutanone, dehydroproline, butyronitrile
cyclopentanone
2.40
4.52
103
150
166
175
–
–
CO2
+
NH3
ACBCH
-
CO2
NH3
+
ACPCH
-
cyclohexanone
formaldehyde
16.85
2.20
809
9
–
–
CO2
+
NH3
ACHCH
-
14
98.8
CO2
+
H
NH3
ALAH
CO2
-
acetone
acetone
19.60
1.26
853
98
860
–
100
–
+
NH3
AIBH
-
CO2
NH2
+
MAIBH
a
In DMF/water (3:1) at 35 °C. [CuCl2]0 = 7.2 ꢂ 10ꢁ6 M, [S]0 = 3.6 ꢂ 10ꢁ2 M, [H2O2]0 = 3.6 ꢂ 10ꢁ2 M, [NH4OH]0 = 3.6 ꢂ 10ꢁ2 M.
b
From Ref. [27].

42
S. Góger et al. / Polyhedron 73 (2014) 37–44
Table 8
Kinetic data for the oxidation of AIBH and ACCH by CuCl2 in DMF/water (3:1).
AIBH
ACCH
kcat (sꢁ1
KM (mM)
SIE
)
1.25
110
3.14
0.0007
4.5
1.44
Fig. 4. Reaction of AIBH or AMEPH in DMF/water (3:1) at 35 °C. [CuCl2]0 = 1.8 ꢂ
10ꢁ3 M, [AIBH]0 (or [AMEPH]0) = 3.6 ꢂ 10ꢁ2 M, [H2O2]0 = 3.6 ꢂ 10ꢁ2 M, [NH4OH]0
3.6 ꢂ 10ꢁ2 M.
=
Fig. 7. Progress of the oxidation reaction of AIBH in DMF/water (j) and DMF/
deuterium-oxide (N) (3:1) at 35 °C. [AIBH] = 3.6 ꢂ 10ꢁ2 M, [CuCl2] = 7.2 ꢂ 10ꢁ6 M,
[NH4OH] = 3.6 ꢂ 10ꢁ2 M.
Fig. 5. (a) Changes in the rate of the reaction of AIBH with the initial substrate
concentration in DMF/water (3: 1) at 35 °C, [CuCl2]0 = 7.2 ꢂ 10ꢁ6 M, [H2O2]0 = 3.6 ꢂ
10ꢁ2 M, [NH4OH]0 = 3.6 ꢂ 10ꢁ2 M; (b) Lineweaver–Burk plot. (For data see
Table S1).
Fig. 8. Progress of the oxidation reaction of ACCH in DMF/water (j) and DMF/
deuterium-oxide (N) (3:1) at 35 °C. [ACCH] = 3.6 ꢂ 10ꢁ2 M, [CuCl2] = 7.2 ꢂ 10ꢁ6 M,
[NH4OH] = 3.6 ꢂ 10ꢁ2 M.
in Table 5). However, without isotope labeling the assignment of
the m(CO2)s stretching for the [Cu(AA)2] complexes can be ambigu-
ous due to the presence of two bands in the concerned 1400–
1300 cmꢁ1 region. Nevertheless, considering the lowest possible
m
(CO2)s, the m(CO2)as–m
(CO2)s difference is still >200 cmꢁ1 in each
spectrum. The multiple frequencies of symmetric stretching modes
may originate from the different binding positions for the carbox-
ylates in structures similar or identical to that of 3.
3.2. Redox properties of Cu(AA)2 (1–5) complexes
Fig. 6. (a) Changes in the rate of the reaction of ACCH with the initial substrate
concentration in DMF/water (3: 1) at 35 °C, [CuCl2]0 = 7.2 ꢂ 10ꢁ6 M, [H2O2]0 = 3.6 ꢂ
The electrochemical properties of the Cu(AA)2 complexes 1–5
were studied by cyclic voltammetry (CV) to the cathodic direction,
in DMF, at room temperature under argon. The CV curves are
10ꢁ2 M, [NH4OH]0 = 3.6 ꢂ 10ꢁ2
M (b) Lineweaver–Burk plot. (For data see
Table S2).

S. Góger et al. / Polyhedron 73 (2014) 37–44
43
shown in Fig. 2 and the observed peak potentials are listed in
Table 6. The CVs all show one irreversible cathodic reduction peak
that varies with the AAs (between ꢁ620 and ꢁ754 mV), except for
the alanine complex that exhibits a pre-peak shoulder, too. The
irreversibility may be associated with a geometric change in the
coordination sphere to achieve stabilization from square planar
for Cu(II) to tetrahedral for Cu(I) as supported by DFT calculations
that have previously been carried out on similar Cu-AA complexes
[26], or other changes in the ligand environment induced by the
gained negative charge. Whichever is the case, the reverse scan
to the anodic direction yields a peak that is non-Nernstian in its
profile suggestive of an ECE mechanism that necessarily precludes
any type of further straightforward analysis at this level.
3.3. Catalysis
Toward an efficient catalytic system we first started studies using
directly CuCl2 as catalyst in DMF/H2O (3:1) mixtures at 35 °C with
1:5000:5000 [Cu]:[substrate]:[H2O2] ratios and by adding 5000
equivalents of ammonium hydroxide as base. The results from the
experiments are summarized in Table 7. The highest TOF values
were observed with ACHCH among the cyclic and AIBH among acy-
clic substrates. It is remarkable that the N-methyl group in MAIBH
causes roughly an order of magnitude decrease in the reaction rate.
When AMEPH is present in the catalytic system (500 equiva-
lents is added to the 1:5000:5000 Cu:AIBH:H2O2 mixture) the reac-
tion is completely inhibited and no acetone can be detected (Fig. 3).
However, if we made an experiment with an increased copper con-
centration (250:5000:5000) and only AMEPH present, the conver-
sion of AMEPH to acetone was 12% corresponding to a TON of 2.4.
In comparison, AIBH is converted by 60% to acetone among the
same conditions, corresponding to a TON of 12 (see Fig. 4 for more
details). Moreover, pseudo-first-order rate constants could be
obtained for both reactions: k0AIBH = (1.60 0.05) ꢂ 10ꢁ4 sꢁ1 and
k0AMEPH = (0.35 0.02) ꢂ 10ꢁ4 sꢁ1. These give a k0AIBH/k0AMEPH = krel
of 4.6, a significant lowering in reaction rate that fits well the ratio
of the corresponding TON’s. These results explain the inhibition of
the AIBH oxidation when AMEPH is present.
Fig. 9. (a) Progress of the oxidation reaction of ACBH in DMF/water (3:1) at 35 °C.
[ACBCH] = 3.6 ꢂ 10ꢁ2 M, [CuCl2] = 7.2 ꢂ 10ꢁ6 M, [H2O2]0 = 3.6 ꢂ 10ꢁ2 M, [NH4OH]0
=
3.6 ꢂ 10ꢁ2 M. Cyclobutanone (ꢂ), dehydroproline (j), n-butyronitrile (N), (b)
Proportion of the products.
In two cases (ACCH and AIBH) the substrate dependence was
also investigated. The saturation kinetics (Figs. 5 and 6) suggest a
pre-equilibrium between the substrate and the catalyst. From the
Lineweaver–Burk plots the KM and kcat parameters could be deter-
mined (Table 8). These are in accordance with the much higher
reactivity of the AIBH than ACCH as experienced with 5 and 1
and similarly in the Fe-based catalytic systems [8].
Fig. 10. (a) Progress of the oxidation reaction of CuII(ACBC)2 (6) in DMF/water (3:1)
at 35 °C. [CuII(ACB)2] = 3.6 ꢂ 10ꢁ2 M, [H2O2]0 = 3.6 ꢂ 10ꢁ2 M, [NH4OH]0 = 3.6 ꢂ
10ꢁ2 M. Cyclobutanone (ꢂ), dehydroproline (j), n-butyronitrile (N), (b) Proportion
of the products.
The BDE values for the N–H bonds of the amino acids are very
similar and do not correlate with the reactivity order (Table 7). SIE’s
were investigated for AIBH and ACCH and the low values (Figs. 7
and 8, Table 8) are in the range typical for an ET-PT mechanism. It
seems likely that the formation of the imine radical (the generally
assumed initiating step of the ACCO reaction) from the coordinated,
anionic amino acids, takes place via an ET-PT mechanism.
ACBCH deserves more detailed discussion as this substrate is
unique considering its dual degradation pathway. Three products
were observed during catalysis (Figs. 9 and 10): dehydroproline
and n-butyronitrile (according to pathway C in Scheme 1), and
cyclobutanone (according to pathway B in Scheme 1). While the
latter is analogous to the degradation of AIBH and cyclic AAs with
n > 2 the former products correspond to the ACCH degradation. It
can be said that the major product is cyclobutanone in both cases
with similar proportion. In all other cases the reactions selectively
provided the ketone products.
Fig. 11. The log(Vi) values as a function of E°0pc of the corresponding Cu(AA)2
complexes. Insert: TOF values with CuCl2 (green) or Cu(AA)2 (orange) as catalyst
among identical conditions. Data are listed in Tables 6 and 7, log(Vi) values in this
figure are identical to the logarithm of corresponding ꢁd[S]/dt values in Table 7.
(Colour online.)
Since Cu(AA)2 complexes are well known it seemed reasonable that
during the catalysis such bis-chelate complexes may occur. To check
this possibility we used the synthesized Cu(AA)2 complexes includ-
ing our new bis(1-amino(cyclo)alkane-1-carboxylato-j
2N,O)copper(II)

44
S. Góger et al. / Polyhedron 73 (2014) 37–44
complexes as catalysts and determined the TOF values for the reac-
tions with 1, 2, 4 and 5 (Table 7). Only minimal differences be-
tween the TOFs of runs conducted with Cu(AA)2 and CuCl2 were
found (Fig. 11 insert) indicating that the dominant form of the cat-
alyst may be the same. Moreover, when the logarithm of the initial
rate of the reactions (based on product analysis) is plotted against
the E°’pc of the Cu(AA)2 complexes a correlation with negative slope
can be obtained (Fig. 11). On thermodynamic grounds this allows
the conclusion that among the various amino acids those will be
oxidized the most efficiently by hydrogen peroxide, which are
the stronger reducing agents in their Cu(I) form.
Cambridge CB2 1EZ, UK; fax: (+44) 1223-336-033; or e-mail:
deposit@ccdc.cam.ac.uk. Supplementary data associated with this
article can be found, in the online version, at http://dx.doi.org/
10.1016/j.poly.2014.02.007.
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Catalytic systems using Cu(II) were first tested as ACCO models.
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Acknowledgments
Financial support of the Hungarian National Research Fund
(OTKA K108489), TÁMOP-4.2.2.A-11/1/KONV-2012-0071, TÁMOP
4.2.4.A/2-11-1-2012-0001 (S. Góger), TÁMOP-4.2.2/B-10/1-2010-
0025, and COST CM1003 is greatfully acknowedged. This project
was also supported by the János Bolyai Scolarship of the Hungarian
Academy of Sciences (J. S. Pap).
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Appendix A. Supplementary data
CCDC 941371 and 941372 contains the supplementary crystal-
lographic data for 1 and 2. These data can be obtained free of
charge via http://www.ccdc.cam.ac.uk/conts/retrieving.html, or
from the Cambridge Crystallographic Data Centre, 12 Union Road,
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