Quercetin 2,3-dioxygenase mimicking ring cleavage of the flavonolate ligand assisted by copper. Synthesis and characterization of copper(I) complexes [Cu(PPh3)2(fla)] (fla = flavonolate) and [Cu(PPh3)2(O-bs)] (O-bs = O-benzoylsalicylate)

Article abstract of DOI:10.1021/ic990175d

Cu(PPh₃)₂(fla) has been prepared by reacting copper(I) chloride with sodium flavonolate in tetrahydrofuran solution. Crystallographic characterization of the complex (orthorhombic, P2₁2₁2₁, a = 9.588(1) ?, b= 17.364(3) ?, c = 24.378(3) ?, V = 4058.6(10) ?³, Z = 4, R = 0.049) has shown that the coordination geometry of the molecule is tetrahedral. Oxygenation of Cu(PPh₃)₂(fla) in a methylene chloride solution at ambient conditions gives the O-benzoylsalicylato copper complex Cu(PPh₃)₂(O-bs) and carbon monoxide. Labeling experiments with an ¹⁸O₂¹⁶O₂ mixture (1:4) evidenced the incorporation of both ¹⁸O atoms of ¹⁸O₂ into the O-bs ligand. IR and MS studies of labeled O-bs confirmed the incorporation of ¹⁸O₂ while the released CO remained unlabeled. Crystallographic characterization of Cu(PPh₃)₂(O-bs) on crystals obtained as the acetone solvate (triclinic, P1?, a = 13.154(1) ?, b = 17.991(1) ?, c = 20.495(1) ?, a = 80.01(1)°, β= 88.02(1)°, γ = 71.83(1)°, V = 4537.5(5) ?³, Z = 4, R = 0.0403) shows that the molecule has a distorted tetrahedral structure. The oxygenolysis was followed by spectrophotometry, and the rate constants were determined according to the rate law - d[Cu(PPh₃)₂(fla)]/dt = fa[Cu(PPh₃)₂(fla)][O₂]. The rate constant, activation enthalpy, and entropy at 363.16 K are as follows: k₂/M^-1 s^-1 = 4.16 ± 0.48, ΔH^?/kJ mol^-1 = 102 ±7, ΔS^?/J mol^-1 K^-1 = -13.0 ± 21. The reaction fits a Hammett linear free energy relationship for 4′-substituted flavonolates, and an increase of the electron density on copper makes the oxygenation reaction faster.

Full text of DOI:10.1021/ic990175d

Inorg. Chem. 1999, 38, 3787-3795
3787
Quercetin 2,3-Dioxygenase Mimicking Ring Cleavage of the Flavonolate Ligand Assisted by
Copper. Synthesis and Characterization of Copper(I) Complexes [Cu(PPh3)2(fla)] (fla )
Flavonolate) and [Cu(PPh3)2(O-bs)] (O-bs ) O-Benzoylsalicylate)
EÄ va Balogh-Hergovich,1a Jo´zsef Kaizer,1b Ga´bor Speier,*,1b Vilmos Fu1lo1p,1c and
La´szlo´ Pa´rka´nyi1c
Department of Organic Chemistry, University of Veszpre´m, 8201 Veszpre´m, Hungary, Research Group
for Petrochemistry of the Hungarian Academy of Sciences 8201 Veszpre´m, Hungary, and Central
Research Institute of Chemistry of the Hungarian Academy of Sciences, 1525 Budapest, Hungary
ReceiVed February 12, 1999
Cu(PPh3)2(fla) has been prepared by reacting copper(I) chloride with sodium flavonolate in tetrahydrofuran solution.
Crystallographic characterization of the complex (orthorhombic, P212121, a ) 9.588(1) Å, b ) 17.364(3) Å, c )
24.378(3) Å, V ) 4058.6(10) Å3, Z ) 4, R ) 0.049) has shown that the coordination geometry of the molecule
is tetrahedral. Oxygenation of Cu(PPh3)2(fla) in a methylene chloride solution at ambient conditions gives the
O-benzoylsalicylato copper complex Cu(PPh3)2(O-bs) and carbon monoxide. Labeling experiments with an 18O2-
16O2 mixture (1:4) evidenced the incorporation of both 18O atoms of 18O2 into the O-bs ligand. IR and MS studies
of labeled O-bs confirmed the incorporation of 18O2 while the released CO remained unlabeled. Crystallographic
characterization of Cu(PPh3)2(O-bs) on crystals obtained as the acetone solvate (triclinic, P1h, a ) 13.154(1) Å,
b ) 17.991(1) Å, c ) 20.495(1) Å, R ) 80.01(1)°, â ) 88.02(1)°, γ ) 71.83(1)°, V ) 4537.5(5) Å3, Z ) 4, R
) 0.0403) shows that the molecule has a distorted tetrahedral structure. The oxygenolysis was followed by
spectrophotometry, and the rate constants were determined according to the rate law -d[Cu(PPh3)2(fla)]/dt )
k2[Cu(PPh3)2(fla)][O2]. The rate constant, activation enthalpy, and entropy at 363.16 K are as follows: k2/M-1
s-1 ) 4.16 ( 0.48, ∆Hq/kJ mol-1 ) 102 ( 7, ∆Sq/J mol-1 K-1 ) -13.0 ( 21. The reaction fits a Hammett
linear free energy relationship for 4′-substituted flavonolates, and an increase of the electron density on copper
makes the oxygenation reaction faster.
Introduction
esses.10,11 The dioxygen chemistry of copper12-18 and iron19,20
and the coordination chemistry of some of the substrates help
in understanding the catalytic factors for enhanced reactivities.
There is vivid interest in iron and copper-containing mono-
oxygenase21-23 and dioxygenase enzymes24-27 and in their
structural and functional model systems. It has been shown that
in the case of catechol dioxygenase models of copper28 and
The fundamental nature of metalloenzymes is being widely
studied. Biological and biomimetic works aim to elucidate and
understand the structure of these enzymes and specially the role
of metal ions in the enzymatic process. Many of these
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active site, utilize molecular oxygen for the metabolism of
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10.1021/ic990175d CCC: $18.00 © 1999 American Chemical Society
Published on Web 08/03/1999

3788 Inorganic Chemistry, Vol. 38, No. 17, 1999
Kaizer et al.
Scheme 1
responsible for the oxidative process.37 Labeling experiments
with 18O2 proved the incorporation of both 18O atoms into the
substrate which is characteristic of dioxygenases.38 Purification
and characterization of the enzyme showed the copper to be in
the oxidation state CuII, but the ligand environment around CuII
has not been determined. Quercetin is believed to coordinate
to copper through the 3-hydroxy and 4-carbonyl groups.39-41
Model oxygenation reactions on quercetin and the parent
compound flavonol (1b) have been carried out in order to
understand the enzymic reaction. Base-catalyzed oxygenation
of quercetin and related 3-hydroxyflavones under aqueous42 and
nonaqueous43 conditions, photosensitized oxygenations,44 and
reactions with superoxide45 have been investigated. Metal
complexes of cobalt46-48 and copper49-51 have been found to
act as catalysts for the oxygenation reaction. Copper(I)52 and
copper(II)53 flavonolate complexes were also successfully used
for the oxygenation of flavonol.
Recent crystallographic studies of flavonolato complexes of
copper(I),52 copper(II),53 cobalt(III),54 and zinc(II)55 disclosed
the coordination mode of the flavonolate ligand, geometries
around the metal ions, and their influence on the delocalization
of π-electrons in the flavonolate ligand.
We have been concerned with the synthesis of copper
flavonolates and quercetin 2,3-dioxygenase mimicking oxygen-
ations.56-58 By the use of simple ligands we aimed to work on
synthetic analogues and synthesize stable flavonolato and
quercetin complexes of copper suitable for structural charac-
terization which bear close resemblance to the enzyme. In the
present paper, we report details for the synthesis and charac-
terization of Cu(PPh3)2(fla) (fla ) flavonolate, 3) and its
oxygenated product Cu(PPh3)2(O-bs) (O-bs ) O-benzoyl-
salicylate, 4), and details of the oxidative ring cleavage reaction
supported by 18O-labeling and kinetic experiments.
iron29 the oxidative intradiol cleavage of catecholates to muconic
acids proceeds through intramolecular redox steps, involving
catecholate (cat.) and semiquinone (SQ) ligands coupled with
metal ions of varying oxidation state (eqs 1 and 2). They are
FeIII(cat.) h FeII(SQ)
CuII(cat.) h CuI(SQ)
(1)
(2)
believed to be responsible for substrate activation. In these
reactions FeII or CuI and also the semiquinone ligand (SQ) may
react with dioxygen at ambient conditions.30,31 Both substrate
activation (intradiol cleavage) and dioxygen activation (extradiol
cleavage in the case of iron) have been established for the
mechanism of the enzyme reaction.32
In the microbial metabolism of rutin by Aspergillus or
Pulmallaria species, quercetin (3′,4′,5,7-tetrahydroxyflavonol,
1a) is oxidatively degraded into a depside (phenolic carboxylic
acid ester, 2) and carbon monoxide33-38 (Scheme 1). It has been
found that the copper-containing quercetin 2,3-dioxygenase is
Experimental Section
Materials and Methods. Solvents used for the reactions were
purified by literature methods59 and stored under argon. 3-Hydroxy-
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Quercetin 2,3-Dioxygenase
Inorganic Chemistry, Vol. 38, No. 17, 1999 3789
Table 1. Physical Properties and Analyses of Complexes
Cu(PPh3)2(4′-R-fla) (3a-e)
and dried under vacuum (5.12 g, 86%): IR (Nujol) 3614, 1740, 1627,
1447, 1406, 1256, 1207, 1094, 1056, 1014, 774, 700 cm-1
.
Anal. Calcd for C30H24O9Cu: C, 60.85; H, 4.08. Found C, 60.55;
H, 3.97.
C, %
H, %
yield,
%
a
cmpd
R
color
mp, °C
calcd found calcd found
Cu(PPh3)2(O-bs) (4a). Method A. Flavonolatobis(triphenylphos-
phine)copper(I) (0.82 g 1.0 mmol) in methylene chloride (10 mL) was
treated with dioxygen (0.1 MPa) at room temperature for 30 h (27 mL,
1.08 mmol) yielding a pale yellow solution. This was evaporated to
dryness giving a light yellow residue (0.65 g, 78%): mp 148-150 °C;
IR (Nujol) 1734, 1587, 1547, 1464, 1435, 1380, 1267, 1200, 1100,
3a
H
88 orange 153-155 74.21 74.30 4.76 4.67
84 pink 63-65 72.81 73.10 4.67 4.59
3c CH3 82 orange 142-147 74.41 74.18 4.92 4.84
3d NO2 76 orange >300 70.37 70.11 4.40 4.30
3e Cl 84 orange 68-70 71.24 70.92 4.45 4.53
3b OH
1067, 1027, 752, 700, 516, 500 cm-1
Anal. Calcd for C50H39O4P2Cu: C, 72.4; H, 4.74. Found C, 71.83;
H, 4.82.
.
a Isolated yields.
Table 2. Characteristic Absorption Bands of Complexes
Cu(PPh3)2(4′-R-fla) (3a-e)
Method B. Cu(O-bs)2‚C2H5OH (5.97 g, 10 mmol) and triphenyl-
phosphine (6.55 g, 25 mmol) were refluxed under argon in anhydrous
MeOH (200 mL) for 3 h. The colorless solution was cooled to room
temperature, evaporated to half volume under vacuum, and cooled in
a refrigerator for several hours. The white precipitate was filtered off,
washed with absolute methanol, and dried in a vacuum (7.1 g, 86%).
Cu(PPh3)2(O-bs)‚CH3COCH3 (4a‚CH3COCH3). Complex 4a (0.414
g, 0.5 mmol) was dissolved in boiling acetone (15 mL), and after
cooling, the solution colorless crystalline product was obtained (0.41
g, 92%): mp 180-182 °C; IR (KBr) 1738, 1710, 1584, 1551, 1476,
UV-vis
(DMF) λ[nm] (log ꢀ)
ν
(CdO) [cm-1
(Nujol)
] ∆ν(CdO)
complex
R
[cm-1
]
3a
3b
3c
3d
3e
H
1554
1549
1548
1549
1549
54
52
67
66
66
266.5 (4.38) 430.5 (3.89)
265.0 (4.45) 440.5 (3.95)
263.5 (4.39) 436.0 (3.87)
270.5 (4.30) 417.5 (3.88)
263.0 (4.31) 430.5 (3.60)
OH
Me
NO2
Cl
1429, 1393, 1267, 1196, 1093, 1059, 1023, 740, 694, 516, 505 cm-1
;
droxy-4′-chloroflavone,60 3-hydroxy-4′-nitroflavone,61 and O-benzoyl-
salicylic acid62 were prepared by literature methods. CuCl obtained from
Reanal (reagent grade) was washed with acetic acid on a filter several
times until the filtrate became colorless. The resulting white solid was
subsequently treated with distilled water, dried under vacuum, and
stored in a Schlenck tube under an atmosphere of argon. A sample of
18O2 was purchased from Pierce Inorganics B. V. Other reagents were
the highest grade commercially available and were used without further
purification. Diazomethane63 was freshly prepared according to the
literature in ether and immediately used for the methylation reactions.
All reactions were performed by standard Schlenck technics under
argon.64
UV-vis (λmax, DMF) 264 nm (log ꢀ 4.35); 1H NMR (CDCl3, 20 °C) δ
2.16 (s, 6H, CH3), 7.05-7.45 (m, 38 H, ArH), 7.80-7.90 (m, 1H, ArH);
13C NMR (CDCl3, 22 °C) δ 206.8, 165.5, 149.8, 133.8, 133.7, 132.7,
132.4, 132.2, 131.5, 130.2, 129.7, 128.5, 127.8, 125.3, 122.9, 30.9;
13C NMR (DMSO-d6, 30 °C) δ 206.0, 170.2, 164.8, 149.9, 134.4, 134.2,
133.7, 133.5, 133.4, 131.6, 131.0, 130.3, 130.0, 129.7, 128.6, 125.5,
123.2, 31.0; 31P NMR (CDCl3, 22 °C) δ -3.2; 31P NMR (DMSO-d6,
22 °C) δ -6.16.
Anal. Calcd for C53H45O5P2Cu: C, 71.73; H, 5.11. Found C, 71.57;
H, 5.16.
Instrumentation. IR spectra were recorded in either Nujol or KBr
pellets on a Specord IR-75 (Carl Zeiss) spectrometer. Electronic spectra
were measured on either a Specord M-40 (Carl Zeiss) or a Shimadzu
UV-160 spectrometer using quartz cells. NMR spectra were recorded
Cu(PPh3)2(fla) (3a). To a stirred solution of flavonol (2.38 g, 10
mmol) in anhydrous tetrahydrofuran (100 mL) was added sodium (0.23
g, 10 mmol) under argon. After dissolution of the sodium, triphenyl-
phosphine (5.25 g, 20 mmol) and CuCl (1.0 g, 10 mmol) were added.
The mixture was stirred for 1 h, the solvent was evaporated in a vacuum,
and the residue was treated with ether and recrystallized from ether to
give orange diamagnetic crystals of 3a suitable for X-ray diffraction
experiments (7.26 g, 88%): mp 153-155 °C; UV-vis (λmax, CH2Cl2)
232 nm (log ꢀ 4.89), 272 (4.54), 426 (3.88); IR (Nujol) 1583, 1554,
1487, 1473, 1440, 1413, 1323, 1227, 1087, 1031, 1000, 757, 700, 521,
1
on a Varian Unity-300 spectrometer. H NMR shifts are reported as
values downfield from an external standard of Me4Si. 13C NMR spectra
were obtained at 75.4 MHz, reference was the center peak of
chloroform-d (77.0 ppm), or DMSO-d6 (39.7 ppm). 31P NMR spectra
were recorded at 121.4 MHz with H3PO4 as external reference with
downfield values reported as positive. The peak assignments were made
using DEPT and APT methods. Magnetic susceptibility were determined
by the Gouy method.65 GC analyses were performed on a HP 5830A
gas chromatograph equipped with a flame ionization detector and a
CP SIL 8CB column. GC-MS measurements were recorded on a HP
5890II/5971 GC/MSD at 75 EV.
1
513, 493 cm-1; H NMR (CDCl3, 22 °C) δ 7.19-8.44 (m, ArH); 31P
NMR (CDCl3, 22 °C) δ 29.62; 13C NMR (CDCl3, 22 °C) δ 161.8,
154.9, 145.1, 134.3, 134.0, 133.3, 132.5, 132.2, 132.0, 131.9, 129.3,
128.9, 128.6, 128.4, 127.8, 127.2, 125.4, 123.6, 120.8, 118.1; 13C NMR
(DMSO-d6, 30 °C) δ 174.6, 162.2, 154.6, 145.1, 141.8, 133.7, 133.5,
132.5, 131.7, 131.6, 129.7, 129.5, 128.9, 128.7, 128.5, 127.4, 124.8,
124.5, 118.5.
Kinetic Measurements. Reactions of Cu(PPh3)2(fla) with O2 were
performed in DMF solutions. In a typical experiment Cu(PPh3)2(fla)
was dissolved under argon atmosphere in a thermostated reaction vessel
with an inlet for taking samples with a syringe, and connected to
mercury manometer to regulate constant pressure. The solution was
then heated to the appropriate temperature. A sample was then taken
by syringe, and the initial concentration of Cu(PPh3)2(fla) was
determined by UV-vis spectroscopy measuring the absorbance of the
reaction mixture at 430 nm (log ꢀ 4.45) [λmax of a typical band of
Cu(PPh3)2(fla)]. The argon was then replaced with dioxygen, and the
consumption of Cu(PPh3)2(fla) was analyzed periodically (ca. every 5
min). Experimental conditions are summarized in Table 3. The
temperature was determined with an accuracy of (0.5 °C; the
concentrations of Cu(PPh3)2(fla) were measured with a relative mean
error of ca. (2%; the pressure of dioxygen was determined with an
accuracy of (0.5%. The O2 concentration was calculated from literature
data66 taking into account the partial pressure of DMF67 and assuming
the validity of Dalton’s law.
Anal. Calcd for C51H39O3CuP2: C, 74.21; H, 4.76. Found C, 74.30;
H, 4.67.
Cu(PPh3)2(4′R-fla) (3b-e). Complexes 3b-e were prepared by the
same method as that described above for the preparation of 3a.
Properties, analyses, and IR and UV-vis data of the complexes are
summarized in Tables 1 and 2.
Cu(O-bs)2‚C2H5OH (5). To a solution of Cu(OAc)2‚2H2O (2.00 g,
10 mmol) in ethanol (80 mL) was added benzoylsalicylic acid (4.84 g,
20 mmol) in ethanol (20 mL) with stirring at 40 °C. The solution was
stirred for 3 h and allowed to cool to room temperature. The blue
crystalline product was collected by filtration, washed with ethanol,
(60) Smith, M. A.; Newman, R. M.; Webb, R. A. J. Heterocycl. Chem.
1968, 5, 425.
(61) Reidel: L.; Hempel, G. Justus Liebigs. Ann. Chem. 1959, 625, 184.
(62) Einhorn, A.; Rothlauf, L.; Seuffert, R. Chem. Ber. 1911, 44, 3309.
(63) Arndt, F. In Organic Syntheses; Blatt, A. H., Ed.; John Wiley &
Sons: New York, 1943; Vol. 2, p 165.
(65) Carlin, R. L. Magnetochemistry; Springer-Verlag: Berlin, 1986; p 311.
(66) Kruis, A. In Landolt-Bo¨rnstein; Board 4, Teil 4., Springer-Verlag:
Berlin, 1976; p 269.
(64) Shriver, D. F.; Drezdzon, M. A. The Manipulation of Air-sensitiVe
Compounds; John Wiley & Sons: New York, 1986.
(67) Ram, G.; Sharaf, A. R. J. Ind. Chem. Soc. 1968, 45, 13.

3790 Inorganic Chemistry, Vol. 38, No. 17, 1999
Kaizer et al.
Table 3. Kinetic Data for the Oxygenation of Cu(PPh3)2(fla) in DMF Solution
expt no.
temp, °C
103[O2], mol L-1
104[Cu], mol L-1
104k′, s-1
R, %a
103k, s-1 mol L-1
108d[Cu]/dt, mol L-1 s-1
1
2
3
4
5
6
7
8
9
90
90
90
90
90
90
90
90
90
90
90
90
1.96
3.52
5.93
7.84
9.01
10.18
12.52
7.84
7.84
7.84
7.84
7.84
2.02
2.04
2.04
1.77
1.94
2.06
2.06
3.00
5.00
7.57
10.00
15.00
0.06 ( 0.001
0.11 ( 0.003
0.26 ( 0.007
0.47 ( 0.016
0.56 ( 0.015
0.60 ( 0.003
0.82 ( 0.026
0.17 ( 0.003
0.30 ( 0.008
0.38 ( 0.004
0.18 ( 0.007
0.16 ( 0.007
99.85
99.43
99.79
99.31
99.50
99.81
99.80
99.82
99.69
99.94
99.01
99.36
3.05 ( 0.05
3.01 ( 0.08
4.35 ( 0.12
5.99 ( 0.21
6.21 ( 0.17
5.89 ( 0.03
6.56 ( 0.21
2.20 ( 0.04
3.77 ( 0.10
4.90 ( 0.05
2.25 ( 0.09
1.98 ( 0.09
4.16 ( 0.48b
13.66 ( 0.40
26.82 ( 1.22
62.91 ( 4.62
0.12 ( 0.004
0.26 ( 0.008
0.62 ( 0.050
0.88 ( 0.071
1.09 ( 0.074
1.24 ( 0.036
1.69 ( 0.102
0.52 ( 0.008
1.48 ( 0.057
2.42 ( 0.065
2.72 ( 0.110
3.55 ( 0.119
10
11
12
13
14
15
100
110
120
7.70
6.82
6.06
1.96
2.15
2.20
1.05 ( 0.030
1.83 ( 0.083
3.82 ( 0.280
99.53
99.28
98.86
a Correlation coefficients of least-squares regressions. b Mean value of the kinetic constant k and its standard deviation σ(k) were calculated as
k ) (∑iwiki/∑iwi) and σ(k) ) (∑iwi(ki - k)2/(n - 1)∑iwi)1/2, where wi ) 1/σi2.
Table 4. Crystallographic Data for Cu(PPh3)2(fla) (3a) and
displacement parameters, hydrogen atom positions, bond lengths, and
bond angles are available as Supporting Information.
Cu(PPh3)2(O-bs)‚CH3COCH3 (4a‚CH3COCH3)a
a
3a
4a‚C3H6O
Results
formula
fw
cryst syst
space group
a, Å
b, Å
c, Å
R, deg
â, deg
γ, deg
V, Å3
C51H39CuO3P2
825.30
C53H45CuO5P2
887.37
The sodium salt of flavonols react with cuprous chloride to
give copper flavonolate complexes. In the presence of phosphine
coligand tetrahedral CuI(PR3)2(fla)52 products are obtained; with
nitrogen-donor coligands octahedral [CuI(fla)3]2- or planar
Cu(fla)2 products are formed.56,53 Reactions carried out in the
presence of triphenylphosphine have been found to give
CuI(PPh3)2(fla). In a similar way, starting from the sodium salt
of 4′-chloro-, 4′-hydroxy-, 4′-methyl-, and 4′-nitroflavonol, the
corresponding products obtained are Cu(PPh3)2(4′-R-fla). Char-
acterization of the complexes is given in Tables 1 and 2.
Oxygenation of Cu(PPh3)2(fla) in dichloromethane solution at
room temperature and 0.1 MPa dioxygen pressure have been
found to give Cu(PPh3)2(O-bs) and carbon monoxide contami-
nated with a small amount of CO2. Both complexes have been
fully characterized, and the results of this investigation are
described below.
Cu(PPh3)2(fla). Crystallographic characterization has shown
that Cu(PPh3)2(fla) is tetrahedral. A view of the coordination
geometry is given in Figure 1, and selected bond lengths and
bond angles are listed in Table 5. It shows a distorted tetrahedral
coordination geometry around the metal ions. The O(2)-Cu-
O(3) angle within the chelate ring is 79.3(2)°, and the P(1)-
Cu-P(2) angle is opened to 124.50(7)°. The Cu-O(3) bond
length is 0.1 Å longer than the Cu-O(2) bond.
Copper oxygen bond distances are longer than those found
in [Cu4(OBut)4] [Cu-Oav ) 1.854(9) Å],68 in [Cu2Cl2(OMe)2-
(py)2] [1.932(4) and 1.940 Å],69 and in [Cu(PPh3)2(PhenSQ)]
[2.082(7) and 2.111(8) Å].70 The C(2)-O(2) distance is shorter
while the C(3)-O(3) distance is longer than those in the
uncoordinated flavonol [1.357(3) and 1.232(3) Å].71 Due to
coordination to the copper ion there is a change in the bond
lengths of the pyranone ring. The O(1)-C(1) [1.369(3) Å] and
C(1)-C(2) [1.363(4) Å] bond distances become longer, and the
C(2)-C(3) bond distance [1.457(4) Å] shorter, which may be
assigned to delocalization of the π-system over the whole
molecule. The Cu-P bond distances are somewhat longer [Cu-
orthorhombic
P212121
9.588(1)
17.364(3)
24.378(3)
90.000
90.000
90.000
4058.6(10)
4
293(2)
1.351
1712
1.848
3.12-74.83
0.40 × 0.35 × 0.20
3358
triclinic
P1h
13.154(1)
17.991(1)
20.495(1)
80.01(1)
88.02(1)
71.83(1)
4537.5(5)
4
Z
temp, K
293(2)
1.299
1848
1.723
2.62-72.95
0.30 × 0.23 × 0.12
18 134
D
calcd, g cm-3
F(000)
abs coeff, mm-1
Θ range, deg
cryst size, mm
reflns collected
independent refltns
[R(int))0.000]
final R
3358
18 134
0.0403
0.1167
1.047
0.0496
0.1238
1.007
final Rw
GOF on F2
a Radiation Cu KR (λ 1.541 84 Å); temp 293-298 K; R )Σ||Fo| -
|Fc||/Σ|Fo||; Rw ) [Σw(|Fo| - |Fc|)2/Σw|Fo| ]1/2
.
2
Crystallographic Structure Determinations Cu(PPh3)2(fla). Crys-
tals obtained from an ether solution formed as orange prisms. Cu(PPh3)2-
(fla) indicated orthorhombic symmetry, and the centered settings of
25 reflections gave the unit cell dimensions listed in Table 4. Data
were collected by ω/Θ scans on a Enraf-Nonius CAD-4 diffractometer
within the angular range of 3.12-74.83°. The space group was found
to be P212121, and the structure was solved by the heavy atom method.
Final cycles of refinement, including fixed contributions for the
hydrogen atoms, converged with discrepancy indices of R ) 0.0496
and Rw ) 0.1238. Tables containing atom positions, anisotropic
displacement parameters, hydrogen atom positions, bond lengths, and
bond angles are available as Supporting Information.
Cu(PPh3)2(O-bs). Crystals obtained by recrystallization from acetone
formed as colorless blocks. The complex indicated triclinic symmetry,
and the centered settings of 25 reflections gave the unit cell dimensions
listed in Table 4. Data were collected by ω/Θ scans on an Enraf-Nonius
CAD-4 diffractometer within the angular range of 2.62-72.95°. The
space group was found to be P1h, and the structure was solved by direct
methods. Final cycles of refinement, including fixed contributions for
the hydrogen atoms, converged with discrepancy indices of R ) 0.0403
and Rw ) 0.1167. Tables containing atom positions, anisotropic
(68) Grezier, T.; Weiss, E. Chem. Ber. 1976, 109, 3142.
(69) Willett, R. D.; Breneman, G. L. Inorg. Chem. 1983, 22, 326.
(70) Speier, G.; Hendrickson, D. N. Unpublished results.
(71) Etter, M. C.; Urbanczyk-Lipkowska, Z.; Baer, S.; Barbara, P. F. J.
Mol. Struct. 1986, 144, 155.

Quercetin 2,3-Dioxygenase
Inorganic Chemistry, Vol. 38, No. 17, 1999 3791
Table 6. Selected Bond Lengths and Angles for
Cu(PPh3)2(O-bs)‚CH3COCH3 (4a‚CH3COCH3)
Bond Lengths (Å)
Cu(1)-O(10)
Cu(1)-P(1)
Cu(1)-P(2)
Cu(1)-O(11)
P(1)-C(1A)
P(1)-C(3A)
P(1)-C(2A)
Cu(2)-O(20)
Cu(2)-O(21)
Cu(2)-P(3)
Cu(2)-P(4)
P(3)-C(8A)
P(3)-C(9A)
P(3)-C(7A)
2.148(2) C(10)-C(11)
2.2262(6) O(13)-C(17)
2.2389(6) O(11)-C(10)
2.280(2) O(10)-C(10)
1.826(2) P(2)-C(5A)
1.825(2) P(2)-C(4A)
1.829(2) P(2)-C(6A)
2.183(2) C(20)-C(21)
2.226(2) O(20)-C(20)
2.2360(6) O(23)-C(27)
2.2435(6) O(21)-C(20)
1.827(2) P(4)-C(12A)
1.829(2) P(4)-C(11A)
1.830(2) P(4)-C(10A)
1.513(3)
1.205(3)
1.244(3)
1.250(3)
1.824(2)
1.821(2)
1.821(2)
1.510(3)
1.246(3)
1.212(4)
1.245(3)
1.828(2)
1.824(2)
1.811(2)
Bond Angles (deg)
O(10)-Cu(1)-P(1) 119.68(5)
O(11)-C(10)-O(10) 122.8(2)
O(10)-Cu(1)-P(2) 110.01(5)
O(10)-C(10)-C(11) 118.3(2)
C(10)-O(11)-Cu(1) 86.12(13)
O(10)-Cu(1)-O(11) 59.16(6)
C(10)-O(10)-Cu(1) 91.95(14)
P(1)-Cu(1)-P(2)
129.06(2)
P(1)-Cu(1)-O(11) 106.59(5)
P(2)-Cu(1)-O(11) 107.72(5)
C(6A)-P(2)-Cu(1) 113.77(7)
C(4A)-P(2)-Cu(1) 119.34(7)
C(5A)-P(2)-Cu(1) 111.21(7)
O(20)-Cu(2)-O(21) 59.42(6)
O(20)-Cu(2)-P(3) 119.20(5)
O(21)-Cu(2)-P(3) 108.40(5)
O(20)-Cu(2)-P(4) 109.31(5)
O(21)-Cu(2)-P(4) 111.96(5)
C(8A)-P(3)-Cu(2) 110.13(7)
C(9A)-P(3)-Cu(2) 118.11(7)
C(7A)-P(3)-Cu(2) 115.97(7)
C(1A)-P(1)-Cu(1)
C(2A)-P(1)-Cu(1)
C(3A)-P(1)-Cu(1)
116.46(7)
111.44(7)
115.24(7)
C(20)-O(21)-Cu(2) 87.86(14)
C(20)-O(20)-Cu(2) 89.82(14)
O(21)-C(20)-O(20) 122.6(2)
O(20)-C(20)-C(21) 118.5(2)
Figure 1. Molecular structure and atomic numbering scheme for
Cu(PPh3)2(fla) (3a). Ellipsoids are drawn at the 50% probability level.
P(3)-Cu(2)-P(4)
127.86(2)
C(10A)-P(4)-Cu(2) 111.67(8)
C(11A)-P(4)-Cu(2) 112.86(7)
C(12A)-P(4)-Cu(2) 119.94(7)
Table 5. Selected Bond Lengths and Angles for Cu(PPh3)2(fla) (3a)
Bond Lengths (Å)
Cu-O(2)
Cu-O(3)
Cu-P(2)
Cu-P(1)
O(2)-C(2)
O(3)-C(3)
2.056(4) P(1)-C(41)
2.164(5) P(1)-C(31)
2.240(2) P(1)-C(21)
2.282(2) P(2)-C(51)
1.293(7) P(2)-C(71)
1.265(8) P(2)-C(61)
1.823(4)
1.827(4)
1.841(3)
1.820(4)
1.834(3)
1.836(4)
[2.237(1) Å].72 The carboxylate bite is 59.16(6)° compared to
58.9(1)° in [Cu(PPh3)2(4-NO2C6H4CO2)],72 and all other angles
involving the Cu atom are close to that of a regular tetrahedron.
The overall feature of the structures suits the general geometry
of a distorted tetrahedron as found earlier for mononuclear
copper(I) carboxylates.73-75
Kinetic Measurements. Cu(PPh3)2(fla) forms stable solutions
at room temperature in DMF under dinitrogen or argon but under
dioxygen slow oxygenation occurs. The kinetics of the oxy-
genation was followed by determining the concentration of
Cu(PPh3)2(fla) in the reaction solutions as a function of time
by electron spectroscopy at 430.5 nm. Experimental conditions
are summarized in Table 3. The measured absorption spectra
for Cu(PPh3)2(fla) dissolved in DMF (7.57 × 10-4 M) at 363.16
K are shown in Figure 3, with time range being 6 h.
To determine the rate dependence on the two reactants,
oxygenation runs were performed at different dioxygen pressures
(Table 3, experiments 1-7) and various initial Cu(PPh3)2(fla)
concentrations (Table 3, experiments 8-12). A simple rate law
for the reaction between Cu(PPh3)2(fla) and O2 is as shown in
eq 3.
Bond Angles (deg)
O(2)-Cu-O(3)
O(2)-Cu-P(2)
O(3)-Cu-P(2)
O(2)-Cu-P(1)
O(3)-Cu-P(1)
P(2)-Cu-P(1)
C(71)-P(2)-Cu
79.3(2)
C(3)-O(3)-Cu
109.5(4)
120.82(14) C(2)-O(2)-Cu
109.2(2)
109.82(14) C(41)-P(1)-Cu
112.4(4)
116.4(2)
115.6(2)
114.3(2)
119.2(2)
110.2(2)
C(21)-P(1)-Cu
100.7(2)
124.50(7)
117.5(2)
C(31)-P(1)-Cu
C(51)-P(2)-Cu
C(61)-P(2)-Cu
O(2)-C(2)-C(1) 122.6(6)
O(2)-C(2)-C(3) 118.8(6)
O(3)-C(3)-C(4) 121.6(6)
O(3)-C(3)-C(2) 119.5(6)
Pav ) 2.261(2) Å] than those in [Cu(PPh3)2(PhenSQ)] [Cu-
Pav ) 2.240(3) Å] and in [Cu(PPh3)2(4-NO2C6H4CO2)] [Cu-
Pav ) 2.237(1) Å].72
Cu(PPh3)2(O-bs). Crystallographic characterization of 4a has
shown that it contains two slightly different Cu(PPh3)2(O-bs)
molecules with a distorted tetrahedral geometric arrangement
as shown in Figure 2, with selected bond lengths and bond
angles listed in Table 6.
The elemental cell contains four molecules of [Cu(PPh3)2-
(O-bs)], of which two are identical and show slight differences
in bond distances and angles compared to the others as shown
in Figure 2 (molecules 1 and 2). In both molecules the
carboxylato group of the O-benzoylsalicylate ligand is bidentate
with somewhat different [2.226(2) and 2.280(2) Å] and very
similar [2.148(2) and 2.183(2) Å] Cu-O distances. The Cu-P
-d[Cu(PPh3)2(fla)/dt ) d[Cu(PPh3)2(O-bs)]/dt
) k[Cu(PPh3)2(fla)]m[O2]n
(3)
Under pseudo first-order conditions at constant dioxygen
concentration (keeping dioxygen pressure constant) for the
experiments the concentrations of [Cu(PPh3)2(fla)] were meas-
ured. A typical time course and first-order plot of the oxygen-
distances are close in both molecules 1 and 2 [Cu-Pav
2.2326(6) (molecule 1) and 2.2398(6) Å (molecule 2)]. This
fits well to Cu-Pav distances in [Cu(PPh3)2(4-NO2C6H4CO2)]
)
(73) Mehrotra, R. C.; Bohra, R. Metal Carboxylates; Academic Press:
London, 1983; pp 286-295.
(74) Pa´rka´nyi, L.; Speier, G. Z. Kristallogr. 1995, 210, 307.
(75) Speier, G.; Selmeczi, K.; Pinte´r, Z.; Huttner, G.; Zsolnai, L. Z.
Kristallogr. 1998, 213, 263.
(72) Cabras, M. A.; Naldini, L.; Zoroddu, M. A.; Cariati, F.; Demartin, F.;
Masciocchi, N.; Sansoni, M. Inorg. Chim. Acta 1985, 104, L19.

3792 Inorganic Chemistry, Vol. 38, No. 17, 1999
Kaizer et al.
Figure 2. Molecular structure and atomic numbering scheme for Cu(PPh3)2(O-bs)‚CH3COCH3 (4a‚CH3COCH3). Ellipsoids are drawn at the 50%
probability level.
Figure 3. Spectral changes accompanying the oxygenation of Cu(PPh3)2-
(fla) during experiment 9 in Table 3. For simplicity only a few spectra
are shown, taken at 0, 65, 125, 185, 340, and 455 min.
Figure 5. Plot of initial oxygenation rate of Cu(PPh3)2(fla) versus the
initial Cu(PPh3)2(fla) concentration (experiments 4, 8-12, Table 3).
Figure 4. The time course for oxygenation of Cu(PPh3)2(fla) monitored
at 430.5 nm (O), and plot of log[Cu(PPh3)2(fla)] versus reaction time
for the oxygenation of Cu(PPh3)2(fla) (experiment 4, Table 3) (]).
Figure 6. Plot of d[Cu(PPh3)2(fla)]/dt versus O2 pressure for experi-
ments 1-7 in Table 3.
ation of Cu(PPh3)2(fla) is shown in Figure 4 for experiment 4;
the reaction remains first order in Cu(PPh3)2(fla) for the whole
time in which the experiment was followed (62% conversion,
5.2 h). The first-order dependence of the reaction rate on
Cu(PPh3)2(fla) could be also confirmed by plotting the initial
reaction rate -d[Cu(PPh3)2(fla)]/dt versus substrate concentra-
tion (Table 3, experiments 8-12). The straight line so obtained
as shown in Figure 5 validates the first-order dependence in
Cu(PPh3)2(fla) with a slope k′ ) (2.58 ( 0.27) × 10-5 s-1 and
a correlation coefficient of 97.38%. Columns k, k′ (k′ ) pseudo-
first-order rate constant), and R in Table 3 report the slopes
and correlation coefficients obtained from least-squares method
for these linear regressions.
dependence. A plot of -d[Cu(PPh3)2(fla)]/dt versus [O2] for
the above experiments gave a straight line with a slope of
k[Cu(PPh3)2(fla)] ) (1.22 ( 0.11) × 10-6 s-1 and a correlation
coefficient of 99.34% (Figure 6).
On the basis of the results above, one can conclude that the
reaction follows rate law (3) with m ) n ) 1, from which a
mean value of the kinetic constant k of 4.16 ( 0.48 × 10-3
mol L-1 s-1 at 363.16 K was obtained (Table 3).
The activation parameters for the present oxygenation reaction
were determined from the temperature dependence of the kinetic
constant k. The temperature-dependent reaction rate measure-
ments in the range of 363.16-393.16 K (experiments 1-12,
13, 14, and 15 in Table 3) resulted in a straight line in the Eyring
plot (Figure 7), with a correlation coefficient of 99.5% and
activation parameters ∆Hq ) 102 ( 7 kJ mol-1, ∆Sq (363.16
K) ) -13 ( 21 J mol-1 K-1, and ∆Gq (363.16 K) ) 106 ( 14
kJ mol-1, respectively. Reaction rates on the oxygenation of
4′-substituted flavonolato copper complexes Cu(PPh3)2(4′R-fla)
Experiments made at different dioxygen pressures (0.022,
0.040, 0.067, 0.092, 0.106, 0.120, and 0.148 MPa) show that
PO appreciably influences the rate of the reaction (Table 3,
2
experiments 1-7). Kinetic measurements of the reaction rate
with respect to the dioxygen concentration indicate a first order

Quercetin 2,3-Dioxygenase
Inorganic Chemistry, Vol. 38, No. 17, 1999 3793
Scheme 2
Figure 7. Eyring plot of rate constant, k, for the oxygenation of
Cu(PPh3)2(fla).
peak at m/z 225 (M - 31), peaks at 227 (M - 33) and 229 (M
- 31) are present.
Discussion
All of the experimental data reported in the previous sections
can be used for the interpretation of the mechanism of copper(I)
assisted oxygenolysis of coordinated flavonolate to O-benzoyl-
salicylate. Dioxygenase enzymes seem to have reactive sub-
strates, and copper(I) complexes have a rich dioxygen chem-
istry.76,77 One can put the question forward: what is the role of
the metal? The requirement of a redox metal at the active site
of the enzymes, e.g., iron or copper, may have the function either
to activate dioxygen and/or activate the substrate by changing
the electron density either by withdrawing or releasing electrons
or just to deprotonate the substrate. In the tetrahedral copper
flavonolate complexes 3 the structural data indicate that the
electron distribution in the coordinated flavonolate differs only
slightly from that of the free ligand. Flavonolate as a chelating
ligand forms stable complexes with copper ions. In most cases
they are stable toward dioxygen in solid form and even in
solution at ambient conditions. The reactivity of copper(I) in 3
is also low due to the stabilizing effect of the phosphine
ligands.78 Compounds 3 are smoothly oxygenated under ambient
conditions giving the copper(I) complexes 4 with the new ligand
of O-benzoylsalicylate formed in the enzyme-like reaction. At
elevated temperature the reaction proceeds reasonably fast.
However it is interesting to note that copper(I) is not oxidized
to copper(II) even under more severe conditions, and the
geometry around the copper is tetrahedral as found by other
mononuclear copper(I) carboxylate complexes.73-75
Figure 8. Hammett plot for the oxygenation of Cu(PPh3)2(4′-R-fla)
complexes.
(3a-e) (eq 4) under identical conditions were determined (with
various electron-withdrawing or releasing substituents R) in
order to find out electronic effects on the reaction rate.
The Hammett plot obtained is shown in Figure 8. Electron
realizing substituents enhanced the reaction rate, and the reaction
constant F was found to be -1.32.
18O2 labeling experiments on the oxygenation of 3a revealed
that both 18O-atoms of the 18O2 molecule are incorporated into
the substrate and the extruded carbon monoxide does not contain
18O, mimicking the enzyme action (eq 4).38
18O2 Labeling Experiments. Oxygenation of flavonolatobis-
(triphenyl phosphine) copper(I) was also carried out with a
mixture of 16O2 and 18O2 (4:1). After 20 h of stirring the reactants
at 25 °C, GLC-MS analysis of the gas phase showed only the
presence of unlabeled CO. The pale yellow solution was
evaporated to dryness, giving a mixture of Cu(PPh3)2(16O-bs)
A reaction mechanism that nicely fits the chemical, spectro-
scopic, labeling, kinetic, and thermodynamic data is shown in
Scheme 2. Kinetic studies on the oxygenation of the flavonolato
complexes 3 established a second-order overall rate expression,
indicating that the rate-determining step must be bimolecular,
namely the reaction of 3 with dioxygen or a unimolecular
process such as the formation of the trioxametallocycle (7) or
the endoperoxide (8). The intramolecular electron shift 5 h 6
is probably very fast, but either k3 or k4 may be rate-determining.
In the latter case the dioxygen-uptake is a fast preequilibrium,
and the formation of the trioxametallocycle (7) or the endo-
peroxide (8) is the rate-determining step. Both mechanistic
assumptions satisfy the kinetic data, but we believe that the
and Cu(PPh3)2(18O-bs): IR (Nujol) ν(C18O) 1714 cm-1
,
ν(C16O18O) 1514, 1364 cm-1, ν(C16O) 1734 cm-1, ν(C16O2)
1547, 1380 cm-1. The GLC-MS analysis of the residue, after
treated with Etheral diazomethane, shows the presence of 16O-
and 18O-benzoylsalicylic acid methyl ester in the appropriate
ratio: m/z 260(M+, 0.4), 256(M+, 1.8), 229(0.11), 227(0.17),
225(1.0), 107(25), 105(100). The 18O-benzoylsalicylic acid
derivative gave a molecular ion at m/z 260 (256 + 4;
C15H1216O218O2), showing that both 18O atoms of 18O2 are
incorporated into the carboxylic acid from molecular oxygen.
The relative abundance of m/z 260 to that at m/z 256 parallels
the 18O2 enrichment used in the experiment. The same is
observed for the base peak, m/z 107 (105 + 2). Instead of the
(76) Kitajima, N.; Moro-oka, Y. Chem. ReV. 1994, 94, 737.
(77) Tyekla´r, Z.; Karlin, K. D. Acc. Chem. Res. 1989, 22, 241.
(78) Hathaway, B. J. In ComprehensiVe Coordination Chemistry; Wilkinson,
G., Gillard, R. D., McCleverty, J. A., Eds.; Pergamon Press: Oxford,
1987; Vol. 5, p 536.

3794 Inorganic Chemistry, Vol. 38, No. 17, 1999
Kaizer et al.
Table 7. Hammet Data for the Oxygenation of Cu(PPh3)2(4′-R-fla)
bimolecular reaction between 3 and O2 is more probably the
slow step. The following data favor this assumption. The
moderate negative ∆Sq value (-13 ( 21 J mol-1 K-1) of the
oxygenation step favors a bimolecular reaction, despite the fact
that this value is somewhat less than expected for a bimolecular
step from theoretical considerations.79 This is also supported
by the Hammett correlation (Figure 8, Table 7), which stresses
that the higher electron density on the copper results in higher
reaction rates. The crucial evidence for a bimolecular reaction
step is the reaction constant F, which was found to be -1.32.
This value is very similar to that we have found earlier for the
oxygenation of CuCl in pyridine (F ) -1.24),80 and this
indicates an electrophilic attack of dioxygen on copper(I).
Mononuclear superoxo copper(II) complexes have been prepared
and characterized already, and their high reactivity has been
demonstrated.81-84 Further possible fast reaction steps of the
copper(II) superoxide complex 5 leading to the endproduct 4
are as shown in Scheme 2. It is reasonable to assume steps that
may require an electron flow from the flavonolato ligand to
copper(II) in 5, resulting in the copper(I) superoxide complex
6 with flavonolate radical coordinated to the copper ion. This
is then converted via an intramolecular radical radical reaction
to the trioxametallocycle 7. A deprotonated 2-hydroperoxide 7
is able to attack the 4-CdO carbon in a nucleophilic attack to
form the copper(I) endoperoxide complex 8. A breakdown of
8 with concomitant loss of CO results in the final product,
O-benzoylsalicylatobis(triphenylphosphine)copper(I) (4). The
mechanism of the breakdown of the endoperoxide is not known
and to our knowledge no investigations have been done on this
type of reactions.85 A homolytic cleavage of the O-O bond
seems to be reasonable, followed by the extrusion of carbon
monoxide. The breakdown of this type of endoperoxides (9) to
the metal complex of O-benzoylsalicylate (10) (eq 5) shows
some formal similarities to the transformation of trioxametal-
lacycles (11) to anhydrides and oxometal compounds (eq 6)
proposed for catechol dioxygenase mimicking reactions, as
adapted from the Criegee-type rearrangement of peroxides.86
complex
R
σ
102k, s-1 mol L-1
3a
3b
3c
3d
3e
H
0.000
-0.370
-0.170
0.710
6.291
15.138
7.270
0.625
1.497
OH
Me
NO2
Cl
0.227
first step is probably the homolytic scission of the O-O bond87
followed by the CO elimination step. More research is necessary
for the clarification of this type of cleavage mechanism.
A [3 + 2] dipolar addition of triplet dioxygen to the
coordinated flavonolate ligand, as a formal alternate reaction
path, seems highly improbable for the cyclic endoperoxide 8
and can be excluded for several reasons (thermodynamic and
symmetry considerations). Thus stepwise formation of the
endoperoxide 8 from the dioxygen adduct may be concluded
with certainty. The nucleophilic attack of the bound peroxide
could, however, also take place on the 3-CdO group as well,
giving rise to a 1,2-dioxetane intermediate. The absence of
chemiluminescence during the reaction, which is very charac-
teristic for the decomposition of 1,2-dioxetanes to carbonyl
compounds, seems to render this pathway unlikely.88-91 This
may be due to less steric strain in the five-membered cyclic
peroxide compared to that in the four-membered 1,2-dioxetane,
or may have also an electronic explanation due to higher electron
density on the 3-CdO carbon than in the case of 4-CdO carbon
accessible in the nucleophilic attack. Unfortunately, efforts to
isolate the peroxide species in the oxygenation reactions at
ambient conditions failed. This supports the assumption in the
mechanism that either steps after the formation of 5 are fast or
one of the following steps leading to transformation of 5 to the
endoperoxide is rate-limiting.
So far the role of copper ion in these oxygenation reactions
is difficult to assess with certainty. Flavonolate ion can be
oxygenated under protic conditions42 or by the use of singlet
oxygen44 to O-benzoylsalicylate. In the oxygenation of Co(fla)-
(salen) complexes dissociation of the flavonolate ion from the
cobalt has been proved, and the reaction between the free ligand
and dioxygen assumed.48 Nonetheless we believe that the copper
ions in the enzyme and also in model reactions act as an electron
buffer, due to their ability to accept or donate electrons. In this
sense the reactivity of the flavonolato ligand is transformed to
a radical anion, and the copper(I) formed can activate dioxygen.
It is important however to tress that oxygenation studies to
further copper-based model reactions are necessary to elucidate
these points, and the interception of some of the peroxide species
is necessary to have a clearer picture of the mechanism of the
oxidative scission reaction and especially of the role of copper
in these reactions. We aware of the fact that similar studies on
models with copper(II) ions will be more apropiate, since that
matches better the situation in the enzyme; however, if redox
changes of the metal ion are important then the redox equilibria
may be similar not depending on the starting complex.
The exact nature of this rearrangement is not known, but the
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(83) Harata, M.; Jitsukawa, K.; Masuda, H.; Einaga, H. Chem. Lett. 1996,
813.
Acknowledgment. We thank Dr. G. Szalontai for help with
NMR spectra. Financial support of the Hungarian National
Research Fund (OTKA T-7443, T-030400, and T-016285) is
gratefully acknowledged.
(84) Wada, A.; Harata, M.; Hasegawa, K.; Jitsukawa, K.; Masuda, H.;
Mukai, M.; Kitagawa, T.; Einaga, H. Angew. Chem. 1998, 37, 798.
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Wiley: Chichester, 1992; p 225.
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Natural Products; Zechmeister, L., Herz, W., Grisebach, H., Kirby,
G. W., Eds.; Springer-Verlag: Wien, 1981; pp 191-265.
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Quercetin 2,3-Dioxygenase
Inorganic Chemistry, Vol. 38, No. 17, 1999 3795
Supporting Information Available: Details of the X-ray structure
determination for Cu(PPh3)2(fla) and Cu(PPh3)2(O-bs)‚CH3COCH3. This
material is available free of charge via the Internet at http://pubs.acs.org.
X-ray crystallographic files, in CIF format, for the structure determi-
nation of Cu(PPh3)2(fla) and Cu(PPh3)2(O-bs) are available on the
Internet only.
IC990175D