Photochemically-induced dioxygenase-type CO-release reactivity of group 12 metal flavonolate complexes

Article abstract of DOI:10.1039/c1cc13961d

Exposure of 3-hydroxyflavonolate complexes of the group 12 metals to UV light under aerobic conditions results in oxidative carbon-carbon bond cleavage and CO release. This reactivity is novel in that it occurs under mild reaction conditions and suggests that light-induced CO-release reactivity involving metal flavonolate species may be possible in biological systems.

Full text of DOI:10.1039/c1cc13961d

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COMMUNICATION
Photochemically-induced dioxygenase-type CO-release reactivity of
group 12 metal flavonolate complexesw
Katarzyna Grubel,a Brynna J. Laughlin,b Thora R. Maltais,b Rhett C. Smith,b Atta M. Arifc
and Lisa M. Berreau*a
Received 2nd July 2011, Accepted 27th July 2011
DOI: 10.1039/c1cc13961d
Exposure of 3-hydroxyflavonolate complexes of the group 12
metals to UV light under aerobic conditions results in oxidative
carbon–carbon bond cleavage and CO release. This reactivity is
novel in that it occurs under mild reaction conditions and
suggests that light-induced CO-release reactivity involving metal
flavonolate species may be possible in biological systems.
are lacking, and while the chemistry of copper flavonolate
species has been significantly advanced in recent years,7 far
fewer X-ray crystallographically characterized flavonolate
complexes of other metal ions have been reported.8 To address
this deficiency, we recently prepared and characterized the first
series of 3-Hfl complexes of the 3d metals, including a Zn(II)
derivative, [(6-Ph2TPA)Zn(3-Hfl)]ClO4 (1; 6-Ph2TPA, N,N-
bis((6-phenyl-2-pyridyl)methyl)-N-((2-
Flavonoids are a class of a naturally occurring, polyphenolic
substances produced in plants. They are of current interest as
potential therapeutic agents due to their anti-microbial, anti-
oxidative, and UV-protective activity.1 A prominent member
of this family of compounds is quercetin (Fig. 1), a natural
compound that is being investigated to prevent or treat a
variety of diseases.1a,2 Quercetin is found in an assortment of
foods including black and green tea, red onions, and many
other fruits and vegetables that are widely touted for their
beneficial health effects.
pyridyl)methyl)amine).9
Outlined herein is the first systematic study of the structural,
spectroscopic, and aerobic photochemical reactivity properties
of group 12 metal 3-Hfl complexes. Our results demonstrate
that all three group 12 metal ions form isolable flavonolate
complexes that can be characterized by X-ray crystallography,
and that each complex undergoes an aerobic photochemically-
induced dioxygenase-type reaction to release CO and form a
metal-depside complex. These results are novel for a number
of reasons. First, aerobic photoinduced flavonoid ring-opening
and CO release under mild conditions has not been previously
reported for any metal flavonolate complex. Second, the
observed dioxygenase reactivity for the complexes contrasts
with prior reports of Zn(II)-flavonolate species that exhibit
photoisomerization reactivity akin to that found for free
3-hydroxyflavonol.10
Studies of the interactions of flavonoids with metal ions are
essential toward understanding how complexation modulates
the reactivity properties of the flavonoid.3 Investigations of metal-
flavonoid species are also relevant toward understanding the
active site chemistry of quercetinases from fungi and bacteria that
catalyze oxidative cleavage of the C(2)–C(3) bond (a dioxygenase-
type reaction; Fig. 1) and CO release.4,5 In another area of
research, metal complexes of 3-hydroxyflavonol (3-Hfl, Fig. 1
(bottom)) are being used as model systems to evaluate inter-
eactions between components of soil organic matter and
bioavailable or contaminating heavy metal ions.6 To adequately
address these areas, systematic studies of structure/reactivity
relationships of metal flavonolate complexes are needed, including
studies involving environmentally toxic metals ions such as
Cd(II) and Hg(II). However, to date, such systematic studies
The Cd(II) and Hg(II) flavonolate complexes [(6-Ph2TPA)-
M(3-Hfl)]ClO4 (M = Cd(II), 2; M = Hg(II), 3) were prepared
a Department of Chemistry and Biochemistry, Logan,
UT 84322-0300, USA. E-mail: lisa.berreau@usu.edu;
Fax: 435-797-3390; Tel: 435-797-3509
b Department of Chemistry, Clemson University, Clemson, SC 29634,
USA
c Department of Chemistry, University of Utah, Salt Lake City, UT
84112, USA
w Electronic supplementary information (ESI) available: Details of
experimental procedures including synthetic and characterization data
for 2, 3, and 4–6; 18O2 labeling experiments for the reactions of 1 and
2. CCDC 832449–832452. For ESI and crystallographic data in CIF or
other electronic format see DOI: 10.1039/c1cc13961d
Fig. 1 Top: Structure of quercetin (including numbering of C–C
bond that undergoes oxidative cleavage) and the reaction catalyzed
by quercetinase enzymes. Bottom: Structure of 3-hydroxyflavonol
(3-Hfl) and labelling of rings.
c
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Chem. Commun., 2011, 47, 10431–10433 10431

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light for 490 days. However, exposure of aerobic CH3CN
solutions of 1–3 to UV light (Rayonet, 300 nm irradiation) at
ambient temperature results in high-yield dioxygenase-type
reactivity to give the depside complexes [(6-Ph2TPA)M(O-bs)]-
ClO4 (M = Zn (4), Cd (5), Hg (6); O-bs = O-benzoylsalicylate)
and CO.13 Each reaction proceeds with a high quantum yield
at 300 nm: 1 (F = 0.9), 2 (F = 1.0), and 3 (F = 0.8). The lower
reaction quantum yield of the Hg(II) complex is due to enhanced
spin–orbit coupling.14 Use of 18O2 in the reactions of 1 and 2
resulted in quantitative incorporation (498% as determined
by mass spectrometry and FTIR) of two labeled oxygen atoms
into the depside ligand. Comparison of the fully assigned
13C NMR spectra of 2, 5 and [(6-Ph2TPA)Cd(CH3CN)](ClO4)2
(7, Fig. S5–S7; Supporting Informationw) clearly show that the
carbon lost as CO is derived from the C(31)–O(1) unit (Fig. 2).
Complexes 4 and 5 were characterized by X-ray crystallo-
graphy, elemental analysis, NMR and IR spectroscopy, and
mass spectrometry. Complex 6 was characterized by NMR
and IR spectroscopy, and mass spectrometry. The cationic
portions of 4 and 5 are shown in Fig. 3. In 415 the zinc center
has a nearly trigonal bipyramidal geometry,16 with the O-bs
ligand coordinated in a monodentate fashion in an axial
position.17 In 5, the depside is coordinated as a bidentate
ligand.17,18 The spectroscopic properties of the depside
complexes 4 and 5 are as expected (Fig. S8). We note that
1H NMR spectra of 6 give evidence for a small amount of loss
of the 6-Ph2TPA ligand in CD3CN solutions of this complex.19
The results presented herein are novel when considered in
the context of the previously reported photochemistry of
3-Hfl. Irradiation of a pyridine solution of 3-Hfl using a
300 W tungsten lamp, in the presence of a photosensitizer
(bengal rose), has been reported to result in the formation of
the photooxygenation products depside (O-bs) and CO.20 This
reaction involves the generation of 1O2 which reacts with
ground state 3-Hfl. Studer, et al. reported that photooxygenation
of 3-Hfl occurs in O2-saturated nonpolar solvents in the
absence of a photosensitizer.21 In this case, photooxygenation
Fig. 2 Thermal ellipsoid drawings of the cationic portions of 2 and 3.
Ellipsoids are plotted at the 50% probability level. Hydrogen atoms
are omitted for clarity.
in a similar manner to the Zn(II) analog.9 Each complex was
characterized by X-ray crystallography, elemental analysis,
IR, multinuclear NMR, UV-vis, and fluorescence. While the
Zn(II) center of 1 has a coordination number of five in the solid
state, the Cd(II) and Hg(II) analogs 2 and 3 exhibit a distorted
octahedral geometry (Fig. 2).11 In both complexes the ketone
oxygen of the C ring is coordinated trans to the tertiary amine
nitrogen of the chelate ligand. The average M–O distance
involving the flavonolate oxygen atoms increases down the
group (1: 2.03 A; 2: 2.25 A; 3: 2.30 A),12 and the asymmetry of
the flavonolate coordination (DM–O) is largest for the Zn(II)
and Hg(II) derivatives (0.17 and 0.21 A, respectively). The
flavonolate moiety in 2 and 3 is positioned between the phenyl
appendages of the 6-Ph2TPA ligand (Fig. 2). The average
distance between the centroid of ring C of the flavonolate and
the centroids of the aryl rings of the chelate ligand is B4.0 A.
Comparison of the 1H NMR spectra of 1–3 (Fig. S1,
Supporting Informationw) shows that each complex has effective
Cs symmetry in solution with equivalent phenyl-appended
pyridyl appendages. There are interesting differences in the
1H NMR spectra of this series of complexes in terms of the
chemical shifts of proton resonances associated with the
phenyl appendages of the 6-Ph2TPA ligand. Namely, in 2
and 3 the resonances of the meta and para protons of the
phenyl appendages are shifted upfield, which is consistent with
p-stacking involving the C ring of the flavonolate. Additionally,
the signal for the C(1)-H of the unsubstituted pyridyl ring in 2
and 3 is shifted downfield by B0.9 ppm relative to the same
signal in 1. We attribute this deshielding to the presence of close
contact between C(1)-H of the unsubstituted pyridyl ring and
the carbonyl O(2) atom of the coordinated flavonolate (for both
complexes 2 and 3 the C(1)Á Á ÁO(2) distance is B3.0 A).
The band I transition of the flavonolate moiety of 2 is found
at 430 nm and is red-shifted relative to that of 1 (420 nm) and 3
(415 nm). Fluorescence emission spectra of the complexes show
a Stokes shift of 60 nm for 1 and 3, and 46 nm for 2 (Fig. S2–S4,
Supporting Informationw). The excited states associated with
these emissions have lifetimes of B2.0 ns (1: 2.0(1) ns; 2: 1.7(1) ns;
3: 2.0(1) ns). The fluorescence quantum yields for 1–3 are 0.18,
0.06, and 0.02, respectively. We note that the complexes
presented herein have lower fluorescence quantum yields than
that previously reported for [Zn(3-Hfl)]+ (0.38), albeit the
structure of this species has not been determined.10
Fig. 3 Thermal ellipsoid drawings of the cationic portions of 4 and 5.
Ellipsoids are plotted at the 50% probability level. Hydrogen atoms
are omitted for clarity.
The divalent metal flavonolate complexes 1–3 are stable
with respect to exposure to oxygen in the solid state under room
c
10432 Chem. Commun., 2011, 47, 10431–10433
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was suggested to result from reaction between a triplet tautomer
state, wherein the C(3) hydroxyl proton has been transferred
to the C(4)-carbonyl moiety in a zwitterionic structure, and
ground state 3O2. We note that this chemistry is solvent
dependent, as in CH3OH, CH3CN, or CH2Cl2, photooxygenation
does not happen and instead photorearrangement to give
3-phenyl-3-hydroxy-1,2-inandione occurs.22,23
8 (a) G. Barath, J. Kaizer, G. Speier, L. Pa
A. Vertes, Chem. Commun., 2009, 3630–3632; (b) J. Kaizer,
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rkanyi, E. Kuzmann and
´ ´
´
10 S. Protti, A. Mezzetti, C. Lapouge and J. P. Cornard, Photochem.
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11 2: C45H35CdClN4O7, M = 891.62, monoclinic, a = 11.4616(2),
= 16.3861(3), c = 20.8770(4) A, U =
3905.89(12) A3,
Previously, the presence of metal ions was reported to
prevent the photoinduced rearrangment of neutral 3-Hfl, or
have no effect on the photochemical reaction.10,23a However, the
results presented herein show that metal 3-hydroxyflavonolate
complexes can undergo photoinduced dioxygenase-type
CO-release reactivity when irradiated with UV light. In these
complexes the coordinated flavonolate anion is akin to the
tautomeric structure of 3-Hfl,21 thereby enabling photo-
induced photooxygenation and CO-release reactivity. Notably
this reactivity occurs under conditions that are considerably
milder than those reported for thermal dioxygenase-type reactions
of Cu(3-Hfl) complexes.7 Overall, the results presented herein
suggest that the formation of metal-flavonolate species in
nature may enable light-induced dioxgyenase-type CO-release
reactivity under mild conditions.
b
T = 151(1)K,space group P21/n, Z = 4, 15965 reflections measured,
8943 unique (Rint = 0.0303) which were used in all calculations.
The final R values (I 4 2s(I)) are R1 = 0.0364 and wR2 = 0.0765.
3: C45H35HgClN4O7, M = 979.81, monoclinic, a = 11.4117(2),
b
= 16.3761(2), c = 20.9794(3) A, U =
3905.65(10) A3,
T = 151(1)K, space group P21/n, Z = 4, 16 904 reflections
measured, 8946 unique (Rint = 0.0366) which were used in all
calculations. The final R values (I 4 2s(I)) are R1 = 0.0364 and
wR2 = 0.0883.
12 The average M–N distance involving the chelate ligand increases
by Z 0.3 A for the Cd(II) and Hg(II) derivatives relative to 1
(avg. M–N: 1: 2.11 A; 2: 2.41 A; 3: 2.46 A).
13 CO formation was detected via GC and the PdCl2 method.
T. H. Allen and W. S. Root, J. Biol. Chem., 1955, 215, 309–317.
CO2 formation was minimal and within the error range of the GC
analysis.
14 (a) A. Tamayo, B. Pedras, L. Lodeiro, L. Escriche, J. Casabo,
J. L. Capelo, B. Covelo, R. Kivekas and R. Silanpaa, Inorg. Chem.,
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2007, 46, 7818–7826; (b) C. N. Burress, M. I. Bodine, O. Elbjeirami,
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We acknowledge support from the National Science
Foundation (Grants CHE-0848858 to LMB and CHE-0847132
to RCS).
¨
15 4: C45H35F3N4O7SZn, M = 898.20, monoclinic, a = 10.1785(2),
b = 16.3337(5), c = 24.1620(5) A, U = 4016.34(17) A3, T =
151(1)K, space group P21/c, Z = 4, 15 119 reflections measured,
9139 unique (Rint = 0.0342) which were used in all calculations.
The final R values (I 4 2s(I)) are R1 = 0.0432 and wR2 = 0.0883.
16 4t5 = 0.92; t5 is a parameter that describes the geometry of a five-
coordinate metal center. A trigonal bipyramidal geometry corre-
lates with t5 = 1, whereas a square pyramidal geometry has t5 = 0.
A. W. Addison, T. N. Rao, J. Reedijk, J. van Rijn and
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c
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Chem. Commun., 2011, 47, 10431–10433 10433