Quercetinase model studies. The oxygenation of flavonol catalyzed by a cationic 2,2'-bipyridine copper(II) flavonolate complex

Article abstract of DOI:10.1016/S1381-1169(97)00208-2

The catalyst [Cu¹¹(bpy)(fla)]ClO₄, 1, was prepared from Cu(CH₃CN)₄ClO₄, 2,2'-bipyridine (bpy), flavonol (flaH), and dioxygen in acetonitrile at ambient conditions. The flavonolato copper complex 1 reacts with molecular oxygen slowly at room temperature but reasonably fast at around 100°C in acetonitrile or DMF to the O-benzoylsalicylato copper complex [Cu¹¹(bpy)(O-bs)]ClO₄ in good yield. Kinetics of the oxygenation of 1 shows that there are two kinetically not interpretable segments of the reaction, however 1 is a good catalyst for the oxygenation of flavonol to O-benzoylsalicylic acid (O-bsH) at around 100°C. Kinetic studies of the catalytic reaction resulted in the rate expression -d[flaH]/dt = k(obs)[flaH][catalyst]²[O₂]². The reaction constant at 100°C was found to be k(obs) = 7.20 ± 0.13 X 10¹⁰ mo1^-4 dm¹² s^-1, with activation parameters Δ H(+) = 80.83 ± 3.14 kJ mol^-1, ΔS(+) = 179.61 ± 8.82 J mol^-1 K^-1.

Full text of DOI:10.1016/S1381-1169(97)00208-2

Ž
.
Journal of Molecular Catalysis A: Chemical 130 1998 139–148
Quercetinase model studies. The oxygenation of flavonol
X
ž /
catalyzed by a cationic 2,2 -bipyridine copper II flavonolate
1
complex
)
Istvan Lippai, Gabor Speier
´
´
Department of Organic Chemistry, UniÕersity of Veszprem, 8200 Veszprem, Hungary
´
´
Received 5 November 1996; accepted 9 September 1997
Abstract
X
w
IIŽ .Ž .x
Ž
.
Ž
.
Ž
.
The catalyst Cu bpy fla ClO4, 1, was prepared from Cu CH3CN ClO4, 2,2 -bipyridine bpy , flavonol flaH , and
4
dioxygen in acetonitrile at ambient conditions. The flavonolato copper complex 1 reacts with molecular oxygen slowly at
room temperature but reasonably fast at around 1008C in acetonitrile or DMF to the O-benzoylsalicylato copper complex
w
IIŽ .Ž
.x
Cu bpy O-bs ClO4 in good yield. Kinetics of the oxygenation of 1 shows that there are two kinetically not interpretable
Ž
.
segments of the reaction, however 1 is a good catalyst for the oxygenation of flavonol to O-benzoylsalicylic acid O-bsH at
w
x
around 1008C. Kinetic studies of the catalytic reaction resulted in the rate expression yd flaH rdt s
2
kobs flaH catalyst O2 2. The reaction constant at 1008C was found to be kobss7.20"0.13=1010 moly4 dm12 sy1, with
w
xw
x w
x
activation parameters D H ‡s80.83"3.14 kJ moly1, DS‡s179.61"8.82 J moly Ky1. q 1998 Elsevier Science B.V.
1
Keywords: Copper; Dioxygenation; Quercetinase; Flavonolate
1. Introduction
important role, the understanding of the nature
of these reactions is of primary interest. Mecha-
nistic aspects of both areas may have common
basic chemistry and due to that interest in cop-
Many enzymes utilize molecular oxygen for
the biological degradation of organic substrates.
These enzymes usually contain redoxactive met-
als such as copper and iron ions at their active
center. Since oxidation reactions in biological
systems as well as in the industry play an
w
x
per-containing monooxygenase 1–4 and
w
x
dioxygenase enzymes 5–7 and their structural
and functional model systems are still under
w x
intense investigation 8 .
Aspergillus or Pullularia species oxidatively
X
X
Ž
degrade quercetin 3 ,4 ,5,7-tetrahydroxy-
.
Ž
flavonol into a depside phenolic carboxylic
)
Corresponding author. Tel.: q36-88-422022; fax: q36-88-
.
Ž
Ž ..
acid ester and carbon monoxide Eq. 1 .
Quercetin 2,3-dioxygenase, a copper-containing
metalloenzyme, is responsible for the oxygena-
425196; e-mail: speier@almos.vein.hu
1 Dedicated to Professor Gottfried Huttner on the occasion of
his 60th birthday.
1381-1169r98r$19.00 q 1998 Elsevier Science B.V. All rights reserved.
Ž
.
PII S1381-1169 97 00208-2

(
)
140
I. Lippai, G. SpeierrJournal of Molecular Catalysis A: Chemical 130 1998 139–148
w
x
tion reaction 9–13 . Previous studies have
shown that the copper is in the cupric form in
the resting state of the enzyme, its ligand envi-
ronment is still obscure, and quercetin coordi-
nates probably through its 3-hydroxy and 4-
yses were performed on a Carlo Erba 1108
CHNS-O instrument. IR spectra were obtained
Ž
.
on a Specord 75 IR Carl Zeiss, Jena and ESR
spectra on a JEOL JES-FEr3X ESR spectrome-
ter. GC-MS determinations were performed on
a Hewlett Packard 5890 Series II gaschromato-
graph and magnetic measurements on a Bruker
B-E 10b8 magnetic balance.
w
x
carbonyl group to the copper ion 14–16 .
2.2. Materials
Ž
.
Solvents acetonitrile, diethyl ether and DMF
Some model reactions on the oxygenation of
quercetin and flavonol have been carried out to
gain information about this curious reaction.
Base catalyzed oxygenation of quercetin and
Ž
.
were purchased from Reanal Budapest in ana-
lytically pure quality. Acetonitrile was refluxed
on P2O5, distilled, then redistilled from K2CO3
under argon or dinitrogen. Diethyl ether was
distilled from K–Na amalgam under Ar atmo-
sphere. DMF was distilled with benzene and
water 250 g DMF, 20 g benzene and 10 g
water and stored under nitrogen in the dark to
avoid direct light. Purified, water- and oxygen-
free solvents were stored under argon or dinitro-
gen. 2,2X-bipyridine was purchased from Reanal
w
x
related 3-hydroxyflavones under aqueous 17
w
x
and non-aqueous 17 conditions, photosensi-
w
x
tized oxygenations 18 , and reactions with su-
peroxide ion 19 have been studied. Metal com-
plexes of cobalt 18 and copper 20 have been
found to act as catalysts for the oxygenation
Ž
w
x
.
w
x
w x
Ž .
w
x
Ž . w x
reaction. Copper I 21 and copper II 16
flavonolate complexes were also successfully
Ž
.
Budapest and used without further purifica-
tion. Flavonol 22,23 , Cu CH3CN ClO4 24
x w IŽ
.
x
w x
used for the oxygenation of flavonol.
w
4
Recently we have been concerned with the
synthesis of copper flavonolate complexes and
their oxygenation reactions as well as using
them as catalyst for the oxygenation of flavonol
w
x
and O-benzoylsalicylic acid 25 were obtained
by literature methods. Gaseous oxygen from
Messergriesheim was 99.60% and passed
through P2O5 and Blaugel in order to remove
traces of water and other impurities.
w
x
16,21 . In the present paper we report details
for the synthesis and characterization of
w
IIŽ
.Ž
.Ž
.x
Cu bpy fla ClO4 and its oxygenated product
II
w
IIŽ
.x
[
(
)( )]
2.3. Cu fla bpy ClO4
Cu bpy O-bs ClO4, and kinetic studies on
the stoichiom etric oxygenation of
w
IIŽ
.Ž
.x
Cu bpy fla ClO4 and the catalytic oxygena-
tio n o f fla v o n o l c a ta ly z e d b y
Ž
.
To a solution of 0.149 g 0.456 mmol
Cu CH3CN ClO4 in 5 cm acetonitrile 0.109
g 0.455 mmol flavonol and 0.071 g 0.456
mmol 2,2 -bipyridine were added. The reaction
3
w
IŽ
. x
4
w
IIŽ
.Ž
.x
Cu bpy fla ClO4.
Ž
.
Ž
X
.
mixture was stirred for 2 h at room temperature
under dioxygen atmosphere. The green precipi-
tate formed was filtered, washed several times
with diethyl ether and dried to give green pow-
der. Crystals were obtained from acetonitrile as
2. Experimental
2.1. Instrumentation
Ž
.
UV-VIS spectra were obtained on a Shi-
madzu UV-160A spectrophotometer. CHN anal-
green prisms. Yield: 0.230 g 90.76% . Anal.
Found: C, 55.20; H, 2.49; N, 5.32. Calc.: C,

(
)
I. Lippai, G. SpeierrJournal of Molecular Catalysis A: Chemical 130 1998 139–148
141
Ž
.
w
IŽ
that prepared from Cu CH3CN ClO4 and
. x
4
53.95; H, 3.06; N, 5.04%. IR KBr : 1540s,
1485s, 1445s, 1420s, 1090s, 1055s, 755s,
1310m, 1225m, 1200m, 615m, 3045w, 900w,
Ž
.
O-benzoylsalicylic acid 2.4 .
875w, 570w, 480w cmy1. UV-VIS DMF :
426.5 log ´ 4.26 , 312.0 4.27 , 265.5 4.30
Ž
.
.
II
[
(
)( )]
2.6. Oxygenation of Cu bpy fla ClO4 in
DMF
Ž
.
Ž
.
Ž
Ž
.
Ž
.
and 637.0 2.30 nm. ESR acetonitrile : gs
2.124, As77.68 G. Molar magnetic suscepti-
Ž
.
w
IIŽ .Ž
.x
bility: xs2.660=10y c.g.s. unit, meff s2.06
6
1.362 g 2.45 mmol Cu fla bpy ClO4 was
dissolved in 20 cm3 DMF and refluxed for 9 h
under dioxygen atmosphere. 2 cm3 diazo-
BMrCuII.
Ž
.
methane solution in diethyl ether was added to
II
2.4. Cu O-bs bpy ClO4
1 cm3 of the reaction mixture at room tempera-
[
(
)( )]
Ž
.
ture and N,N-dimethylbenzamide 17.90% ,
Ž
.
Ž
.
salicylic acid 29.06% , benzoic acid 18.39% ,
Ž
.
To a solution of 0.932 g 2.871 mmol
Ž
.
Cu CH3CN ClO4 in 30 cm3 acetonitrile
w
IŽ
. x
and O-benzoylsalicylic acid 23.73% was de-
4
termined by GC-MS.
Ž
.
0.695 g 2.872 mmol O-benzoylsalicylic acid
X
Ž
.
and 0.448 g 2.872 mmol 2,2 -bipyridine were
added. The reaction mixture was stirred for 1 h
at room temperature under dioxygen atmo-
sphere. The blue precipitate was filtered, washed
several times with diethyl ether and dried to
2.7. Catalytic oxygenation of flaÕonol catalyzed
II
[
(
)( )]
by Cu fla bpy ClO4
Ž
.
1.1249 g 4.72 mmol flavonol and 0.0537 g
Ž
.
give blue powder. Yield: 0.703 g 82.01% .
Anal. Found: C, 52.30; H, 3.59; N, 7.26. Calc.:
Ž
.
w
IIŽ .Ž
.x
0.10 mmol Cu fla bpy ClO4 was dissolved
and stirred at reflux temperature in 15 cm3
DMF for 10 h under dioxygen atmosphere. 2
Ž
.
C, 51.91; H, 3.33; N, 6.99%. IR KBr : 1725s,
1600s, 1435s, 1250s, 1080s, 1560m, 1465m,
1385m, 1310m, 1020m, 760m, 700m, 620m,
3050w, 850w, 740w, 660w cmy1. UV-VIS
cm3 diazomethane solution in diethyl ether
Ž
.
was added to 1 cm3 of the reaction mixture at
room temperature and the amount of N,N-di-
methylbenzamide 22.78% , salicylic acid
43.20% , benzoic acid 28.36% , and O-benzo-
ylsalicylic acid 2.76% was determined by GC-
Ž
Ž
.
Ž
.
Ž
.
DMF : 302.5 log ´ 4.13 , 262.5 4.00 , 312.0
Ž
.
.
Ž
.
Ž
.
4.09 and 670.0 1.58 nm. ESR toluene :
Ž
.
Ž
.
gs2.138, As61.22 G. Molar magnetic sus-
Ž
.
ceptibility: xs1.619=10y c.g.s. unit, meff s
6
MS.
1.71 BMrCuII.
2.8. Kinetic oxygenations
II
[
(
)( )]
2.5. Oxygenation of Cu fla bpy ClO4 in
acetonitrile
Reactions were carried out at controlled tem-
Ž
perature in a thermostated glass reactor 50
IIŽ .Ž
.
x
.
0.011 g 0.20 mmol Cu fla bpy ClO4
dissolved in 5 cm3 acetonitrile was stirred in a
stainless steel pressure vessel for a week at
room temperature under dioxygen at 92 bar.
The solvent was then evaporated in vacuum, the
residue was washed several times with diethyl
cm3 provided with an electronically controlled
Ž
.
w
magnetic stirrer connected to a manometer con-
taining dioxygen of various pressure. The con-
centration of the complex Cu fla bpy ClO4
and flavonol was followed spectrophotometri-
cally by taking samples at regular time inter-
vals, diluted them to appropriate concentration,
w
IIŽ .Ž
.x
w
IIŽ
.Ž
.x
.
ether and dried to give Cu O-bs bpy ClO4
as blue powder. Yield: 0.010 g 93.51% . The
spectral and magnetic features were identical to
Ž
Ž .
and monitored at 426.5 log ´s4.26 and 342.5
Ž
.
log ´s4.24 nm.

(
)
142
I. Lippai, G. SpeierrJournal of Molecular Catalysis A: Chemical 130 1998 139–148
3. Results and discussion
After establishing the stoichiometry of the
reaction kinetic studies on the oxygenation of
II
[
(
)( )]
w
IIŽ
.Ž
.x
3.1. Oxygenation of Cu bpy fla ClO4
Cu bpy fla ClO4 were carried out in DMF at
1008C and atmospheric dioxygen pressure. The
reaction was monitored by electron spec-
troscopy at 426.5 nm. A typical oxygenation
experiment can be seen in Fig. 2. Plotting the
time dependence of the concentration of
T he structure of the com plex
w
IIŽ
.Ž
.x
Cu bpy fla ClO4 has been determined by
X-ray crystallography, and was found to exhibit
a square pyramidal geometry around the CuII
w
x
w
IIŽ
.Ž .x Ž .
Cu bpy fla ClO4 Fig. 3 shows two seg-
ion 26 . The N-atoms of bpy and the O-atoms
of the 3-OH and 4-C5O groups of flavonolate
are in the basal plane, while the perchlorate
ments, indicating that there are at least two
processes occurring consecutively. The initial
gradient hints to a slower process, while the
second one may be considered as the actual
oxygenation process of the coordinated flavono-
late ligand. The first one is believed to corre-
spond to a slow conversion of the complex to
another one, which then reacts with dioxygen to
Ž
.
O-atom occupies the apical position Fig. 1 .
Ž .
The oxygenation of the copper II flavonolate
w
IIŽ
.Ž
Ž .
.x
complex Cu bpy fla ClO4 to the O-benzo-
w
IIŽ
.Ž
ylsalicylato copper II complex Cu bpy O-
.
x
bs ClO4 either in acetonitrile or DMF at room
temperature and atmospheric dioxygen pressure
is negligible. However if the reaction is carried
the endproduct.
A
conversion of
Ž
.
w
IIŽ IIŽ
.Ž .x .Ž
Cu bpy fla ClO4 to Cu bpy fla may be
.
out at elevated dioxygen pressure 92 bar at
room temperature in a pressure vessel for one
2
the case, as found with the similar complex
w
IIŽ
.Ž
Ž
.
week in acetonitrile the yield on Cu bpy O-
bs ClO4 is over 90%. In a similar fashion the
oxygenation of Cu bpy fla ClO4 in DMF at
1008C results in the O-benzoylsalicylato cop-
ligated by tmeda. Here Cu fla could be iso-
.
x
w
Ž
2. Ž
.x
lated and the formation of Cu fla tmeda ClO4
2
w
IIŽ
.Ž
.
x
w x
was assumed on the basis of kinetic data 27 .
Efforts to fit the curve or parts of it, in order to
establish the reaction order with respect to the
copper flavonolate complex, failed. The reason
for that may lay in the complexity of the reac-
tion, or the starting complex serves only as a
Ž .
per II complex in 89% yield. In both cases
carbon monoxide formation contaminated with
a small amount of carbon dioxide has been
observed.
w
IIŽ .Ž .x
Fig. 1. The X-ray structure of Cu bpy fla ClO4.

(
)
I. Lippai, G. SpeierrJournal of Molecular Catalysis A: Chemical 130 1998 139–148
143
Fig. 4. Spectral changes accompanying the oxygenation of flavonol
w
IIŽ .Ž .x
catalyzed by Cu bpy fla ClO4 at 1008C, 1 bar dioxygen pres-
sure and 1.15=10y5 mol dmy3 catalyst concentration.
Fig. 2. Spectral changes accompanying the oxygenation of
w
IIŽ .Ž .x
Cu bpy fla ClO4 in DMF at 1008C and 1 bar dioxygen pres-
sure.
vated temperature the reaction progressed well,
and the disappearance of the flavonol and the
concentration of the catalyst could be monitored
conveniently by electron spectroscopy. The
spectral characteristics of a DMF solution of the
precursor for other active species, giving rise to
the complexity of the system.
w
IIŽ
.Ž
.x
Cu bpy fla ClO4 complex and its oxy-
genated product have been established. The
3.2. Oxygenation of flaÕonol catalyzed by
II
[
(
)( )]
Cu bpy fla ClO4
w
IIŽ
.Ž
.x
complex Cu bpy fla ClO4 exhibits absorp-
tion at 426.5 nm. Flavonol shows absorbance at
Since for the enzymatic reaction of quercetin
2,3-dioxygenase it has been assumed that
w
x
342.5 nm 28,29 . Spectral changes accompany-
ing addition of dioxygen to the DMF solution
show that the absorption peaks at 306.5 and
343.0 nm decrease, while that at 426.5 nm
increases with time and at 381.0 nm there is an
Ž .
quercetin binds to copper II through its 3-hy-
w
x
droxy and 4-keto groups 14–16 , and structural
model studies with simple copper compounds
and flavonol evidenced this type of coordination
Ž
.
isosbestic point Fig. 4 .
w
x
14–16 we attempted as a key model reaction
the oxygenation of flavonol by the copper
In order to understand the reaction of the
oxygenation of flavonol catalyzed by
w
IIŽ
.Ž
.x
flavonolate complex Cu bpy fla ClO4. The
oxygenation did not proceed fast enough in
acetonitrile or other solvents at room tempera-
ture as already established for the stoichiometric
oxygenation reaction. In DMF however at ele-
w
IIŽ
.Ž
.x
Cu bpy fla ClO4 the kinetics of the reaction
was investigated. The reaction could be fol-
lowed easily by electron spectroscopy. Flavonol
has absorptions in DMF at 340.0 nm and the
Fig. 3. Time dependence of the oxygenation of
Fig. 5. Time dependence of the catalytic oxygenation of flavonol
IIŽ .Ž .x
Ž
.
w
IIŽ .Ž .x
Žw
x
Cu bpy fla ClO4 and excess dioxygen PO2 s1 bar in DMF
catalyzed by Cu bpy fla ClO4 flaH 0 s5.10=10y4 mol
w
monitored at 426.5 nm Cu 0 s4.17=10y4 mol dmy3, ts
dmy3
,
Cu s1.15=10
mol dmy3, ts1008C, O2 s7.37=
w x
y5
Žw
x
w
x
y3
w
x
.
.
1008C, O2 s2.54=10
mol dmy3
10y3 mol dmy3
.
.

(
)
144
I. Lippai, G. SpeierrJournal of Molecular Catalysis A: Chemical 130 1998 139–148
w
x
Fig. 6. The plot of the log flaH vs. time for the
Fig. 8. Initial rate of reaction plotted against the second power of
IIŽ .Ž .x
Žw
x
y3
w
IIŽ .Ž .x
Ž
w
x
w
Cu bpy fla ClO4-catalyzed oxygenation of flavonol flaH 0 s
Cu bpy fla ClO4 concentration ts1008C, O2 s7.37=10
5.10=10y4 mol dmy3, Cu s1.15=10 mol dmy3, ts1008C,
y5
mol dmy3, flaH 0 s3.25=10y4 mol dmy3
.
.
w
x
w
x
y3
mol dmy3
.
.
w
x
O2 s7.37=10
of the oxygenation versus the catalyst concen-
tration a parabolic curve was obtained, indicat-
ing that the reaction order with respect to the
catalyst is two. Plots of the reaction rate against
the square of the catalyst concentration resulted
flavonolato complex shows charge transfer
bands in DMF at 426.5 nm. In the presence of a
large excess of flavonol and constant dioxygen
pressure the decrease of the flavonol concentra-
tion takes the course as shown in Fig. 5. Plot-
ting the logarithm of the flavonol concentration
against the time a straight line was obtained as
shown in Fig. 6, indicating that the rate of the
reaction is first order with respect to the sub-
strate. The first order dependence in the sub-
strate flavonol could also be established by
plotting the initial reaction rate of the oxygena-
tion of flavonol against the initial concentration
Ž
.
in a straight line Fig. 8 , and similarly by
2
w
x
plotting the reaction rate against O2 again a
straight line was established Fig. 9 . The rate
expression therefore has the form
Ž
.
2
2
d flavonol rdtskobs catalyst flavonol O2
2
Ž .
w
x
where catalyst is the initial concentration of
the complex. The value of kobs is calculated as
Ž
.
of flavonol giving again a straight line Fig. 7 .
The rate of oxygenation of flavonol at different
catalyst concentration and at various dioxygen
7.20"0.13=1010 dm12 moly sy at 1008C.
Details and data of the kinetic measurements are
compiled in Table 1. By measuring the reaction
rate of the Cu bpy fla ClO4-catalyzed
flavonol oxygenation at temperatures of 90 and
4
1
Ž
.
pressure assuming the validity of Dalton’s law
w
IIŽ
.Ž
.x
was also determined. Plotting the reaction rate
Fig. 7. Initial rate of reaction as a function of the flavonol
y3
2
concentration ts1008C, O2 s7.37=10
mol dmy3, Cu s
Fig. 9. Initial rate of reaction as a function of O2
Ž
w
x
w
x
w
x
Ž
ts1008C,
1.15=10y5 mol dmy3
.
Cu s1.15=10 mol dmy3, flaH 0 s5.96=10y4 mol dmy3
y5
.
w
x
w
x
.
.

Table 1
Kinetic data for the oxygenation of Cu bpy fla ClO4 and the catalytic oxygenation of flavonol catalyzed by Cu bpy fla ClO4
w
Ž
.Ž .x
w
Ž
.Ž .x
2
2
2
6
Ž
.
w
x
w
x
w
x
w
x w
x
w
x
Reaction
No.
t 8C
O2
Ž
flaH
Ž
d flaH rdt
k Cu O2
k O2
Ž
kobs
Ž
=10 mol dmy3
=10 mol dmy3
=10 mol dmy3 sy1
=10 sy1
=10 moly2 dm6
=10 moly4 dm12 sy1
y3
y4
y7
y4
10
.
.
Ž
.
Ž
.
.
.
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
100
100
100
100
100
100
100
100
100
100
100
100
100
90
1.47
7.37
7.37
7.37
7.37
7.37
7.37
7.37
7.37
7.37
7.37
7.37
7.37
7.23
7.18
9.23
6.249
6.416
1.797
2.671
2.248
3.956
5.102
2.632
2.416
3.080
3.252
2.942
2.894
7.445
7.545
5.960
6.038
6.314
0.129
3.497
0.937
1.255
1.105
2.116
2.798
1.299
4.165
9.246
3.056
6.392
7.613
1.774
6.600
4.947
7.236
1.621
0.206
5.450
5.214
4.699
4.915
5.349
5.484
4.940
1.725
3.004
9.403
2.174
2.632
2.383
8.748
8.300
1.198
2.567
0.156
4.114
3.936
3.547
3.710
4.038
4.139
3.729
4.081
3.873
3.762
4.099
4.070
1.799
6.603
6.265
9.042
1.938
7.211"0.119
7.569"0.043
7.242"0.360
6.526"0.033
6.826"0.123
7.429"0.074
7.615"0.152
6.861"0.139
7.509"0.229
7.126"0.083
6.922"0.151
7.542"0.168
7.489"0.091
3.442"0.091
108
100
100
100
12.801"0.139
7.352"0.099
7.504"0.060
6.451"0.104
10.98
5.481

(
)
146
I. Lippai, G. SpeierrJournal of Molecular Catalysis A: Chemical 130 1998 139–148
Ø
w
IŽ
. Ž
.
x
w
IŽ
.
2 xq
fla and Cu bpy as indicated
Cu fla
Ž .2
in Eq. 4 .
K2
q
CuI flaØ bpy qflaH | CuI flaØ fla
Ž
.Ž
.
Ž
.2Ž
.
q CuI bpy qqHq
4
Ž .
Ž
.
2
The equilibrium is again shifted much to the
left side with a small value for K2. The com-
Ø
w
IŽ
. Ž
.x
pound Cu fla
fla is probably octahedral
2
w
IŽ
.
2 xq
and Cu bpy
is tetrahedral as evidenced in
Fig. 10. Arrhenius plot for the catalytic oxygenation of flavonol
IŽ
.
x w IŽ
. x
3
y5
w
IIŽ .Ž .x
Žw
.
x
w
catalyzed by Cu bpy fla ClO4 Cu s1.15=10
mol dmy3
,
the similar complex Cu bpy
Cu fla from
2 2
flaH 0 s7.75=10y4 , O2 s1 bar .
w
x
w
x
w
x
which an X-ray structure is also available 30 .
Among the products of equilibrium
Ž .
4
Ø
w
IŽ
. Ž
.
x
w
IŽ
.
2 xq
Cu fla
fla has three and Cu bpy
one
2
redoxactive center. All redoxactive centers may
react with dioxygen, however the very clean
second order dependence of the reaction rate on
1088C the Arrhenius plot shown in Fig. 10 has
been obtained. The activation parameters calcu-
lated from Fig. 10 for the catalytic oxygenation
of flavonol gave the following values: D H ‡ s
the dioxygen concentration makes an assump-
P
w
IŽ
. Ž
.x
tion plausible that probably Cu fla fla re-
1
80.83"3.14 kJ moly and DS‡ s179.61"
2
acts with two moles of dioxygen in the rate-de-
1
1
8.82 J moly Ky
.
Ž .
termining step as a radical radical reaction 5 to
The high complexity of the rate equation
suggests that the mechanism of the catalytic
oxygenation of flavonol in the presence of
P
w
IŽ
.Ž
.x
the primary product Cu flaO2 fla , which is
transformed in fast consecutive steps to
Cu bpy O-bs and CO. Flavonol replaces
then the O-benzoylsalicylato ligand again in a
w
IIŽ
.Ž
.
xq
w
IIŽ
.Ž
.x
Cu bpy fla ClO4 is rather complicated com-
pared to that of the similar N,N,NX,NX-tetra-
fast reaction.
Ž
.
methylethylene tmeda copper complex where
an overall third order rate expression could be
k3
CuI flaØ fla q2O ™ CuI flaOØ fla
Ž
.2Ž
.
Ž
.
2Ž
.
2
2
w
x
established 27 . We suggest in the case with the
bpy ligand reaction steps, which are in agree-
ment with the kinetic data obtained. In the
slow
5
Ž .
The activation parameters of the oxygenation
reaction based on an observed reaction constant
kobs should be considered with caution. The
overall fifth order rate dependence of the reac-
tion on the reactants shows a complex molecu-
larity of the catalytic cycle and the kobs values
determined do contain the preequilibrium con-
stants K1 and K2 together with the k3 value,
assumed as the rate-determining step. Since the
absolute value of these constants could not be
determined the activation parameters should be
handled with care. The value of the enthalpy of
activation and the free enthalpy of activation are
responsible for the relatively slow reacton rate
however they are smaller than those obtained
using the similar tmeda complex. These differ-
w
IIŽ
.Ž
.x
Cu bpy fla ClO4 complex there may be an
intramolecular electron transfer from the
Ž
.
Ž .
flavonolate ligand fla to Cu II yielding
Ø
w
IŽ
.Ž
.
x
Ž .
Cu bpy fla ClO4 as shown in Eq. 3 .
Ž .
3
The value of K1 is probably very small. Two
Ø
w
IŽ
.Ž
.x
moles of Cu bpy fla ClO4 may react then
with flavonol in reversible step to
a

(
)
I. Lippai, G. SpeierrJournal of Molecular Catalysis A: Chemical 130 1998 139–148
147
Scheme 1.
ences are in agreement with the kinetic data
ence as we believe is the soft bpy ligand. Bpy
Ž
.
greater initial velocity under similar conditions
obtained. According to the transition state the-
lends the driving force to the formation of
Ø
Cu bpy fla
from Cu bpy fla q and the
w .Ž
IIŽ
w
IŽ
.Ž
.
xq
.x
2
y
w
x
w
IŽ
.3x
ory 31 the formation of the activated complex
formation of Cu fla
with the counter ion
Ž
w
Ž
.
xq
as a result of the intramolecular electron trans-
of Cu bpy
species as have been shown
w
x 2
Ž .
fer from the flavonolate ligand to the copper
earlier 30 , and this octahedral copper II
flavonolate species serves as a key intermediate
in the present system. The whole catalytic cycle
may be drawn as shown in Scheme 1. Scheme 1
is based on the kinetic data and suggests that
due to intramolecular electron transfer in
ion, and possibly the coordination of more
flavonolate ligands to copper is more favorable
.
in the presence of the soft bpy ligand than in the
case of tmeda. The relatively great positive
entropy of activation suggests that the activated
complex does not have too much steric con-
strains and, since the entropy of the activated
complex is greater than that of the reactants, the
w
IIŽ
.Ž
.
xq
Ž .
3
Cu bpy fla
according to Eq.
.
xq
Cu bpy fla is formed in a fast preequilib-
Ø
w
IŽ
.Ž
rium, and two of them react with flaH re-
w
x
complex must be very loosely bound 31 .
versibly to form the key compound
Ø
Ø
w
IŽ
. Ž
.
x
Ž
Ž ..
w
IŽ
. Ž
fla reacts
2
.x
Cu fla
fla Eq. 4 . Cu fla
2
then in the slowest step with two dioxygen
4. Summary
molecules to yield the oxygenated primary
Ø
w
IŽ
. Ž
.x
product Cu flaO2 fla . Due to a reverse di-
2
In contrary to the oxygenation of
rected intram olecular electron shift
w
w
IŽ
. Ž
.
x w
x
w
IIŽ
.
x w
x
w
IIŽ
y. Ž
.
xy
Cu PPh3 2 fla
21 , Cu fla
16 , and
Cu flaO2 fla species are formed, which
2
2
IIŽ
.Ž
.
x
w x
Cu tmeda fla ClO4 27 where the stoichio-
via an intramolecular nucleophilic attack on 4-
C5O yield the endoperoxide first and then the
decomposed products with O-benzoylsalycilate
ligand and carbon monoxide. Ligand substitu-
tion by flaH ends up then the catalytic cycle.
metric oxygenation showed simple overal sec-
ond order rate expressions, and by their use as
catalyst for the oxygenation of flavonol overall
third order reaction rate equations were found
Ž .
the copper II flavonolate complex with bpy
w
IIŽ
.Ž
.x
Cu bpy fla ClO4 shows significant differ-
ences. The complexity of the reaction kinetics
with the overall fifth order reaction rate expres-
sion suggests a different reaction rate with dif-
ferent molecularity. The reason for the differ-
Acknowledgements
We thank the Hungarian Science Fund
Ž
.
OTKA T 016285 and the Fund of the Ministry

(
)
148
I. Lippai, G. SpeierrJournal of Molecular Catalysis A: Chemical 130 1998 139–148
w
x
13 T. Oka, F.J. Simpson, H.G. Krishnamurthy, Can. J. Micro-
Ž
.
for Culture and Education a 624 for financial
support.
Ž
.
biol. 16 1977 493.
w
w
x
Ž
.
14 K. Takamura, M. Ito, Chem. Pharm. Bull. 25 1977 3218.
15 G. Speier, V. Fulop, L. Parkanyi, J. Chem. Soc. Chem.
x
¨ ¨
´ ´
Ž
.
Commun. 1990 512.
´
x
w
w
w
w
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