Synthesis and characterization of a symmetric bis(7-hydroxyflavylium) containing a methyl viologen bridge

Article abstract of DOI:10.1002/chem.201003726

A symmetric bis(flavylium) constituted by two 7-hydroxyflavylium moieties linked by a methylviologen bridge was synthesized. The thermodynamic and kinetics of the network of chemical reactions involving bis(flavylium) and the model compound 7-hydroxy-4′-methylflavylium was completely characterized by means of direct and reverse pH jumps (stopped flow) and flash photolysis. Both compounds follow the usual pH-dependent network of chemical reactions of flavylium derivatives. The equilibrium species of the model compound are the flavylium cation (acidic species) and the trans-chalcone (basic species) with an apparent pK′_a=2.85. In the case of the bis(flavylium) it was possible to characterize by ¹H NMR spectroscopy three species with different degrees of isomerization: all flavylium, flavylium-trans-chalcone, and all trans-chalcone. Representation of the time-dependent mole fraction distribution of these three forms after a pH jump from equilibrated solutions of all-flavylium cation (lower pH values) to higher pH values, shows that formation of trans-chalcone is not completely stochastic (two independent isomerizations), the isomerization of one flavylium showing a small influence on the isomerization of the other. The radical of the methyl viologen bridge is formed upon reduction of the bis(trans-chalcone) with dithionite. The system is reversible after addition of an oxidant in spite of the occurrence of some decomposition. Copyright

Full text of DOI:10.1002/chem.201003726

FULL PAPER
DOI: 10.1002/chem.201003726
Synthesis and Characterization of a Symmetric Bis(7-hydroxyflavylium)
Containing a Methyl Viologen Bridge
Ana M. Diniz, Carlos Pinheiro, Vesselin Petrov, A. Jorge Parola, and Fernando Pina*[a]
Abstract: A symmetric bis(flavylium)
constituted by two 7-hydroxyflavylium
moieties linked by a methylviologen
bridge was synthesized. The thermody-
namic and kinetics of the network of
chemical reactions involving bis(flavyli-
um) and the model compound 7-hy-
droxy-4’-methylflavylium was com-
pletely characterized by means of
direct and reverse pH jumps (stopped
flow) and flash photolysis. Both com-
pounds follow the usual pH-dependent
network of chemical reactions of flavy-
lium derivatives. The equilibrium spe-
cies of the model compound are the
flavylium cation (acidic species) and
the trans-chalcone (basic species) with
an apparent pK’a =2.85. In the case of
the bis(flavylium) it was possible to
characterize by 1H NMR spectroscopy
three species with different degrees of
isomerization: all flavylium, flavylium-
trans-chalcone, and all trans-chalcone.
Representation of the time-dependent
mole fraction distribution of these
three forms after a pH jump from equi-
librated solutions of all-flavylium
cation (lower pH values) to higher pH
values, shows that formation of trans-
chalcone is not completely stochastic
(two independent isomerizations), the
isomerization of one flavylium showing
a small influence on the isomerization
of the other. The radical of the methyl
viologen bridge is formed upon reduc-
tion of the bis(trans-chalcone) with di-
thionite. The system is reversible after
addition of an oxidant in spite of the
occurrence of some decomposition.
Keywords: electrochemistry · flavy-
lium · multistates · photochromism ·
viologen
Introduction
the 2-position of the flavylium cation. Tautomerization of
B2 leads to the formation of the cis-chalcone Cc, through a
ring-opening process, and finally, the cis/trans isomerization
results in the formation of the trans-chalcone Ct. The fol-
lowing set of equations [Eq. (1—4)] accounts for the se-
quence of reactions shown in Scheme 1.
Synthetic flavylium salts constitute a versatile family of com-
pounds possessing the same basic structure of anthocyanins,
the ubiquitous compounds responsible for most of the red
and blue colors of flowers and fruits.[1–5] Their physical–
chemical properties are greatly dependent on the nature
and position of the functional groups attached to the 2-
phenyl-1-benzopyrylium skeleton.[5] However, independent
on their structure and provenience, natural or synthetic, fla-
vylium derivatives follow in general the same network of
chemical reactions previously established by Dubois, Brouil-
lard, and McClelland, exemplified in Scheme 1 for 7-hy-
droxyflavylium.[6]
AHþ þ H2O Ð A þ H3Oþ
AHþ þ 2 H2O Ð B2 þ H3Oþ
Ka Proton transfer
Kh Hydration
ð1Þ
ð2Þ
ð3Þ
ð4Þ
B2 Ð Cc
Cc Ð Ct
Kt Tautomerization
Ki Isomerization
In acidic media, the flavylium cation, AH+, is the thermo-
dynamically stable species. When the pH is raised, other
species are formed: the quinoidal base A, which is generally
a transient species formed immediately upon deprotonation
of the phenol group, the hemiketal B2, through hydration in
Equations (1) to (4) can be substituted by a single acid–
base equilibrium.
½CBꢀ½H3Oþꢀ
AHþ þ H2O Ð CB þ H3Oþ
K0a
¼
ð5Þ
ð6Þ
½AHþꢀ
K0a ¼ Ka þ Kh þ KhKt þ KhKtKi
½CBꢀ ¼ ½Aꢀ þ ½B2ꢀ þ ½Ccꢀ þ ½Ctꢀ
[a] A. M. Diniz, Dr. C. Pinheiro, Dr. V. Petrov, Dr. A. J. Parola,
Prof. F. Pina
REQUIMTE
Departamento de Quꢀmica
Faculdade de CiÞncias e Tecnologia
Universidade Nova de Lisboa
2829-516 Caparica (Portugal)
Fax : (+35)1212948550
It is important to stress that in acidic and neutral media
the conversion of flavylium into the chalcones takes place
through the hydration reaction [Eq. (2)]. The neutral quinoi-
dal base A does not hydrate under these conditions (al-
though it can form the hemiketal in basic media by hydrox-
ylation) and thus it is a kinetic product that evolves towards
E-mail: fjp@dq.fct.unl.pt
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201003726.
Chem. Eur. J. 2011, 17, 6359 – 6368
ꢁ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
6359

Scheme 1. Chemical reaction network of flavylium salts exemplified for 7-hydroxyflavylium.
chalcones only through the hydration of the flavylium
cation.
Results and Discussion
In contrast with anthocyanins, in which CB is mainly con-
stituted by the species B2,[7] in many synthetic flavylium
compounds Ct is the major species at moderately acidic to
neutral solutions, which has led to the exploitation of these
compounds as photochromic systems.[5,8] In the case of 7-hy-
droxyflavylium, as in most flavylium compounds, irradiation
of Ct leads to the primary photochemical product Cc.[6] The
primary photoproduct tends to revert back to Ct (in the ab-
sence of a cis/trans isomerization barrier) or to give the col-
ored species AH+ or A, depending on pH. The efficiency of
the photochromic system (considering formation of colored
species) is thus dependent on the competition between a for-
ward reaction to give AH+ or A and a backward reaction to
recover Ct. The colored species resulting from the irradia-
tion revert back to the equilibrium defining a photochromic
system. However, some flavylium compounds exhibit high
cis/trans isomerization barriers facilitating the efficiency of
the appearance of AH+/A and leading to high lifetimes of
the photochemical products by preventing or retarding the
thermal back reaction. In this last case, the system can be
viewed as a model for optical memories capable of read–
write–erase.[9–13]
Synthesis: The synthesis of flavylium compounds is usually
achieved through the acid-catalyzed condensation of aceto-
phenones with benzaldehydes, by following a method early
introduced by Robinson[14] and slightly modified by Katritz-
ky et al.[15] The synthetic pathway to obtain de desired bis-
AHCTUNGTREG(NNNU flavylium) 3 is described in Scheme 2. Bromination of 4’-
methylacetophenone yielded 4’-bromomethylacetophenone
that was reacted with 4,4’-bipyridine to give bis(acetophe-
none) 2 in 83% yield. The synthesis of 2 was adapted from
a procedure previously described by Porter et al.[16] to pre-
pare extended viologens. Initially, only the symmetric com-
pound was synthesized but by monoalkylation of 4,4’-bypiri-
dine, unsymmetrical moieties could be obtained (not studied
in this work). Compound 2 was condensed with 2,4-dihy-
droxybenzaldehyde under strongly acidic conditions[14,15] to
give the desired viologen-bridged bis(flavylium) 3 with a
global yield of 48%.
Besides their role as biological dyes, the flavylium chro-
mophores have acquired importance in materials science ap-
plications. In this framework, it would be interesting to
extend the network of reactions to include a redox respon-
sive moiety. The viologen was selected due to its well-char-
acterized reversible redox behavior that would allow the en-
largement of the possible number of available states and to
respond to electric stimuli. In this work, a bis(flavylium)
compound possessing two 7-hydroxyflavylium units linked
by a methyl viologen bridge in the 4’-position was synthe-
sized to study the mutual effect of two covalently linked
photochromic systems and to characterize the redox behav-
ior of the viologen bridge.
Scheme 2. Synthesis of bis(flavylium) 3 containing a viologen bridge:
i) NBS/AIBN/CCl4, 83%; ii) DMF/reflux, 96%; iii) CH3COOH/H2SO4,
60%. NBS=N-bromosuccinimide; AIBN=azobisisobutyronitrile.
6360
www.chemeurj.org
ꢁ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2011, 17, 6359 – 6368

Symmetric Bis(7-hydroxyflavylium) Containing a Methyl Viologen Bridge
FULL PAPER
Figure 1. UV/Vis spectral variations occurring upon a pH jump from a stock solution of the model compound 4 at pH 1 (6.4ꢂ10ꢁ5 m) to higher pH
values: Spectra recorded immediately after the pH jump (<1 min after adding base) (A) and upon thermodynamic equilibrium being reached
(~24 h) (B). Spectral variations upon reverse pH jumps of a solution at pH 12 (Ct2ꢁ) to less basic pH values leading to the protonation of the trans-chal-
*
cones are shown in (C). Insets: fittings (c) of the absorbance values ( ) at the specified wavelengths superposed to the mole fraction distribution of
species (a).
For comparative studies, the model compound 7-hydroxy-
4’-methylflavylium tetrafluoroborate (4) salt was prepared
by condensation of 2,4-dihydroxybenzaldehyde with 4’-
methylacetophenone in the presence of acetic anhydride
and tetrafluoroboric acid with a yield of 27%.
ionized trans-chalcone Ct2ꢁ, as observed for similar flavyli-
um compounds.[17] This species can be titrated back to acidic
pH, forming Ctꢁ and Ct with pKa values of 9.4 and 7.9, as
shown in Figure 1C. If the titration continues to more acidic
pH values (not shown) formation of flavylium takes place
because it is the stable species in acidic medium, as seen in
Figure 1B.
The kinetics of the formation of the equilibrium species
from direct pH jumps is pH-dependent corresponding to the
disappearance of the flavylium cation to form Ct, see for ex-
ample, the spectral variations that follow a pH jump from
an equilibrated solution at pH 1 to 3.2 (Figure 2A).
Representation of the rates of the direct pH jumps as a
function of pH leads to the previously described[18] bell-
shaped curve characteristic of the compounds lacking a high
thermal cis/trans isomerization barrier (Figure 2B). These ki-
netics can be accounted for by Equation (7).[18]
Model compound: 7-hydroxy-4’-methylflavylium tetrafluoro-
borate (4): The network of chemical reactions of model
compound 4 was characterized by following an experimental
strategy that consists of the study of the pH-dependent ther-
modynamic equilibria and the kinetics that result from a
perturbation of the system by pH jumps and by light.
The changes in absorption spectra upon direct pH jumps
from stock solutions of model compound 4 at pH 1.0 (AH+)
to higher pH values are shown in Figure 1A and B.
In Figure 1A the absorption spectra were taken circa 30
seconds after the pH jump. The shape and position of the
bands clearly indicate the for-
mation of the quinoidal base al-
lowing us to calculate pKa =4.1
[Eq. (1)]. Figure 1B shows the
pH-dependent absorption of
the equilibrated solutions after
one day in the dark, leading to
pK’a =2.85. These values com-
pare with pKa =3.55 and pK’a =
2.70 for 7-hydroxyflavylium.[6]
The slightly lower acidity and
higher pK’a of 4 relatively to 7-
hydroxyflavylium are conse-
quences of the electron-donor
properties of the methyl sub-
stituent at the 4’-position rela-
tive to the proton.
On the other hand, pH jumps
to high pH values (pH>12)
Figure 2. Time evolution of UV/Vis spectra upon a pH jump from a stock solution of compound 4 at pH 1
(6.4ꢂ10ꢁ5 m) to pH 3.2 (A); inset: fitting of the absorbance at 439 nm with a single exponential allows us to
calculate kobs at pH 3.2. Similar measurements at several pH values leads to kobs rate constants that plotted
*
*
lead to the formation of the against pH lead to bell-shaped curves for both model compound 4 ( ) and bis(flavylium) 3 ( ).
Chem. Eur. J. 2011, 17, 6359 – 6368
ꢁ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
6361

F. Pina et al.
½Hþꢀ
KhKtki þ kꢁi½Hþꢀ
½HþꢀþKa
ð7Þ
kobs
¼
kiKt
þ ½Hþꢀ
k
ꢁh
*
Fitting of the data in Figure 2 (see ) with Equation (7)
was achieved for KhKtki =8.1ꢂ10ꢁ7 msꢁ1, kꢁi =5.0ꢂ10ꢁ4 sꢁ1,
and kiKt/kꢁh =3.7ꢂ10ꢁ5 m.
Photochemistry
Continuous irradiation: Continuous irradiation of aqueous
solutions of Ct at different pH values with 365 nm light
causes spectral changes as shown in Figure 3A (pH 4.3) and
B (pH 5.39). In both cases, the disappearance of the Ct to
give a mixture of AH+ and A in Figure 3A and practically
only A in Figure 3B is clear. This is easily explained by
means of Equation (1) and the data reported in Figure 1A,
(pKa =4.1).
The quantum yield is pH-dependent and can be approxi-
mately given by Equation (8).[18]
k
½Hþꢀ
ꢁh
½Hþꢀ
1þKt
ð8Þ
F ¼ Fint
¼ Fint
kiKt
k
½Hþꢀ
kiKt
ꢁh
½Hþꢀ þ
þ
k
ꢁh
1þKt
1þKt
In Equation (8) it is assumed that hemiketal B2 and cis-
chalcone Cc are in fast equilibrium. Formation of the col-
ored species (AH+ or A) upon irradiation of Ct to give Cc
is the product of the intrinsic quantum yield of the photoiso-
merization reaction, Fint, by the efficiency of formation of
AH+ from Cc (ratio between the rate at which AH+ or A is
formed from Cc and the rates of all processes contributing
for the disappearance of Cc). Fitting was achieved for Fint
=
0.45 and kiKt/kꢁh =4.1ꢂ10ꢁ5 m, this last value is in good
agreement with the fitting obtained with Equation (7).
Pulsed irradiation: Pulsed radiation is a powerful comple-
mentary technique to study the flavylium reaction network
since it does not need any pH modification and is a source
of kinetic information as shown in Figure 4, in which equili-
brated solutions containing Ct were irradiated. After the
flash, the system can be monitored at a wavelength at which
Ct absorbs (Figure 4A) and at the flavylium or quinoidal
base absorptions depending on pH (Figure 4B). In Fig-
ure 4A, a bleaching is observed immediately after the flash
that corresponds to the disappearance of Ct to give Cc,
which is known to possess a lower absorption coefficient
compared to Ct. The second process corresponds to the re-
covery of some Ct absorption as a result of the thermal
back reaction from Cc to Ct in competition with flavylium/
quinoidal base formation observed in Figure 4B. These two
processes are parallel reactions and the observed rate con-
stant, kobs, is the sum of both. In other words, the rate con-
stant measured at 365 (Ct) and 436 nm (AH+/A) is the
same, within experimental error, as expected. The [H+] de-
pendence of this process is represented in Figure 4C. At
high proton concentrations, the hydration/dehydration reac-
Figure 3. Spectral variations observed upon continuous irradiation
(365 nm) of dark equilibrated solutions of Ct (4.17ꢂ10ꢁ5 m) as a function
of time at pH 4.3 (A) and 5.3 (B). The quantum yields of formation of
quinoidal base A and flavylium cation AH+ were calculated on the basis
of the total light absorbed by the system and plotted as a function of the
pH of the irradiated solution (C).
tion [Eq. (2)] is faster than the tautomerization [Eq. (3)] due
to its direct dependence on [H+] and the rate-determining
step of the process is the tautomerization. As soon as B2 is
formed from Cc it immediately dehydrates to give AH+,
and the rate is controlled by the value of kꢁt [Eq. (9)]. At
lower proton concentrations, the rate-determining step is
6362
www.chemeurj.org
ꢁ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2011, 17, 6359 – 6368

Symmetric Bis(7-hydroxyflavylium) Containing a Methyl Viologen Bridge
FULL PAPER
The slower process reported in Figure 4A and B is the
complete recovery of Ct and disappearance of AH+ to
reach the initial equilibrium condition. It is the same kinetic
process of the pH jumps and both follow Equation (7).
A global fitting of the data including time-resolved acid–
base titrations in Figure 1 [Eqs. (11) and (12)], pH jump ex-
periments yielding the bell-shaped curve in Figure 2B
[Eq. (7)], quantum yields in Figure 3C [Eq. (8)], and flash
photolysis experiments in Figure 4C [Eqs. (9) and (10)]
allows us to calculate all the equilibrium and rate constants
of the system, shown in Tables 1 and 2.
Table 1. Equilibrium constants for model compound 4 (water) and bis-
AHCTUNGTREG(NNUN flavylium) 3 (water/acetonitrile 80:20 v/v) at 295 K.
Kh (m)
model compound 4 1.7ꢂ10ꢁ6 4.8
bis(flavylium) 3
Kt
Ki
pKa
pK’a
200
4.1 (4.1)[a] 2.78 (2.85)[a]
1.4ꢂ10ꢁ5 0.86 8.2ꢂ103 3.2 (3.2)[a] 1.0 (1.01)[a]
[a] Experimentally observed.
Table 2. Rate constants for model compound 4 (water) and bis(flavyli-
um) 3 (water/acetonitrile 80:20 v/v) at 295 K.
kh
[sꢁ1
kꢁh
[mꢁ1 sꢁ1
kt
[sꢁ1
kꢁt
[sꢁ1
ki
[sꢁ1
kꢁi
[sꢁ1
G
]
E
]
R
]
G
]
N
]
N
]
model compound 4 0.02
1.3ꢂ104 12
1.9ꢂ104 1.25
2.5
1.45
0.11
1.0
5ꢂ10ꢁ4
bis(flavylium) 3
0.26
1.2ꢂ10ꢁ4
Ka ¼ 10ꢁ4:1
ð11Þ
ð12Þ
K0a ¼ Ka þ Kh þ KhKt þ KhKtKi ¼ 10ꢁ2:85
Bis(flavylium) 3
The network of chemical reactions: According to the model
compound and following the behavior of other 7-hydroxyfla-
vylium compounds[6] it is expected that each flavylium is in-
volved in a fast equilibrium with its quinoidal base counter-
part on one hand and that each hemiketal is in fast equilibri-
um with its cis-chalcone counterpart on the other. In other
words, both hemiketal/cis-chalcone pairs are transient spe-
1
cies not detected by H NMR spectroscopy, as verified ex-
perimentally (see below). Each flavylium network can thus
be viewed as an equilibrium involving AH+/A, a transient
intermediate X (B2 in fast equilibrium with Cc), and Ct
(AH+/AQXQCt; Scheme 3).
The question is if the two flavylium reaction networks
have a stochastic behavior, that is, are they independent
from each other or in spite of the methyleneviologen bridge
separating them, the chemical changes taking place in one
branch influence the other?
Figure 4. Time evolution of the absorbances at 365 nm (Ct absorption, A)
and 436 nm (AH+/A absorption, B) upon flash irradiation of a solution
of model compound 4 at pH 4.37. The rate constant for the fast process,
kfast, as a function of proton concentration is plotted in (C).
the hydration/dehydration and the proton dependence
should be given by Equation (10).
The study of the network of bis(flavylium) 3 was carried
out by using an approach identical to the one used to study
model compound 4. Direct pH jumps from stock acidic solu-
tions of the bis(flavylium) in a mixture of water and acetoni-
trile (80:20, v/v) to higher pH values were monitored imme-
diately after the jump by UV/Vis spectrophotometry.
kobs,fast ðplateauÞ ¼ kꢁt ¼ 2:5 sꢁ1
ð9Þ
Ktki
kꢁh½Hþꢀ
kobs,fast ¼ kh þ
þ
¼ 0:25 þ 2:2 ꢂ 103½Hþꢀ
ð10Þ
1 þ Kt
1 þ Kt
Chem. Eur. J. 2011, 17, 6359 – 6368
ꢁ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
6363

F. Pina et al.
Scheme 3. Simplified network of chemical reactions arising from bis(fla-
vylium) 3.
The spectral characterization of the solutions immediately
after the pH jumps was best carried out by stopped-flow
since the high rate of the hydration reaction leads to the
presence of already some B and Cc when the spectra are
run in a common UV/Vis spectrophotometer instead of the
dyode array spectrophotometer used in the stopped-flow
equipment. Regarding the formation of the quinoidal base
monitored at lmaxACHTUNGTRENNUNG
(AH+)=430 and lmax(A)=480 nm (Fig-
ure 5A), it was not possible to distinguish two separated pKa
values. This does not mean that they are equal since it is dif-
ficult to distinguish by spectrophotometry two pKa values
when they differ by less than one pH unit.[19] However, the
experimental data of Figure 5A indicate that if the two pKa
values are not equal they are at least very close and thus the
influence of the deprotonation in one branch of the com-
pound has only a small effect on the other. Comparison of
the pKa of bis(flavylium) 3 (pKa =3.2) with that of the
model compound 4 (pKa =4.1) reflects the effect of the posi-
tive charge of the viologen bridge on the 7-OH group
making it more acidic. The same was observed for the
global pK’a. The global acidity constant defined by Equa-
tion (5) is higher for bis(flavylium) 3 (pK’a =1.0) than for
the model compound 4 (pK’a =2.85). The fact that DpK’a =
1.85 is larger than DpKa =0.9 probably reflects the closer
proximity of the hydration point (C2) to the viologen when
compared with the acidity point (OH in C7). The acidity
constants of the chalcones in bis(flavylium) 3, pKCt =8.4 and
10.0, compared with the values of 7.9 and 9.4, respectively,
in the model compound 4. This is only explained if the
acidic form is relatively more stabilized than the basic one,
and we do not have any reliable explanation unless to con-
sider that the ionized chalcones are less stable in the solvent
mixture used due to its zwitterionic character.
Figure 5. A) Absorbance data and/or absorption spectra of bis(flavylium)
3 immediately after a pH jump from a stock solution of 7.1ꢂ10ꢁ5 m at
pH 0 to higher pH values; B) the same at the equilibrium. C) Spectral
variations upon pH jumps of a solution at pH 12 (Ct2ꢁ) to less basic pH
values, leading to the protonation of the trans-chalcones; fittings at 384
and 505 nm, with pKa values of 8.4 and 10.0. Solutions in water contain-
ing 20% acetonitrile.
Solutions thermally equilibrated of bis(flavylium) 3 were
made less acidic by addition of base and the respective ki-
netic processes followed by 1H NMR spectroscopy. In
1
Figure 6, a H NMR spectrum run 32 min upon a pH jump
cone). In particular, the methylene peaks of the MV spacer
can be decomposed into the contributions from AH+–MV–
AH+ (taken at low pH values or at the initial time of the
pH jump), Ct–MV–Ct (at higher pH values after complete
conversion of both AH+ moieties into Ct), and from the in-
to pH 1.6 is shown (see the Supporting Information for a
complete set of data). This NMR spectroscopic data allows
us to discriminate between the species AH+–MV–AH+ (all-
flavylium), AH+–MV–Ct, and Ct–MV–Ct (all trans-chal-
6364
www.chemeurj.org
ꢁ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2011, 17, 6359 – 6368

Symmetric Bis(7-hydroxyflavylium) Containing a Methyl Viologen Bridge
FULL PAPER
suggests some influence of the
first isomerization into the
second. This is also in accord-
ance with the fact that the
1H NMR spectra show small de-
viations that permitted us to
characterize the three species.
Another confirmation of this
interpretation was obtained by
fitting the mole fractions of the
three components as a function
of time, considering AH+–MV–
AH+QAH+–MV–CtQCt–MV–
Ct (Figure 7B).[21,22] The rate
constant of the first isomeriza-
tion is approximately three
times faster than the second
one (6.3ꢂ10ꢁ4 vs. 2.3ꢂ10ꢁ4 sꢁ1,
Figure 7B). In conclusion, the
viologen bridge and the methyl-
ene spacers do not isolate both
flavylium moieties from each
other allowing their communi-
cation to some extent.
Finally, by using the data
from Table 1 it is possible to
construct an energy-level dia-
gram (Figure 8) in which the
relative position of the different
species of the network are rep-
resented as previously reported
from other flavylium networks.
Comparison between the two
compounds indicates that in
bis(flavylium) it is not only
easier to remove the proton
from the phenol, but also the
hydration to give the hemiketal
is more efficient. This can be
explained by the effect of the
Figure 6. 1H NMR spectrum of bis(flavylium) 3, 32 min after of a pH jump from pHꢃ0 to 1.6. Decomposition
of the signal of the methylene groups in Lorentzian curves is shown in the inset.
termediate AH+–MV–Ct species. The decomposition was
achieved by a global fitting of Lorentzian curves for differ-
ent conversion times, as exemplified in Figure 6 (see also
the Supporting Information) for t=32 min. The normalized
areas of the Lorentzian curves allow calculation of the mole
fraction of each species over time from which a kinetic anal-
ysis can be carried out.
In Figure 7A, the mole fraction distribution of the three
species, AH+–MV–AH+, AH+–MV–Ct, and Ct–MV–Ct
were represented as a function of the fraction of the total
Cc!Ct isomerization according to a stochastic behavior
(c).[20] In the same figure, a indicate another limit sit-
uation in which all-flavylium AH+–MV–AH+ species was
completely converted into AH+–MV–Ct species before the
isomerization of the other branch to give all-trans-chalcone
Ct–MV–Ct species. The experimental data indicate that the
present system deviates from the stochastic situation, which
positive charge of the bridge. On the other hand, the ring-
opening implies a tautomerization reaction, that is, the
transfer of a proton from the hydroxyl in the 2-position to
the oxygen atom at the 1-position. This process is not fa-
vored by the positive charge of the bridge and by conse-
quence Cc is less stable than B2. Finally the cis/trans isomer-
ization is easier in the bis(flavylium), a result that is expect-
ed if the inductive effect of the bridge is considered.
Photochemistry: The photochemistry of the bis(trans-chal-
cone) of bis(flavylium) 3 is much less efficient than the one
of the model compound 4 (Figure 9). Inspection of Table 1
gives some clues since the back reaction to restore trans-
chalcone (ki) is almost one order of magnitude faster in the
former.
Chem. Eur. J. 2011, 17, 6359 – 6368
ꢁ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
6365

F. Pina et al.
tassium
peroxodisulphate,
which recovers the absorption
of the reduced form. However,
the system is not completely re-
versible and some decomposi-
tion takes place, approximately
12% in one cycle.
Cyclic voltammetry was also
performed. All cyclic voltam-
mograms were run in aqueous
solutions at pH 5.5 (acetate
buffer 0.1m; Figure 11, see the
Supporting Information for in-
dividual voltammograms).
The trans-chalcone of the
model compound shows two re-
duction peaks and an oxidation
peak all corresponding to
poorly reversible processes.[23,24]
Regarding the Ct–MV–Ct spe-
cies, the shape of the reduction
peaks (see the Supporting In-
+
Figure 7. Mole fraction distribution of species AH+–MV–AH+
( ), Ct–MV–AH ( ), and Ct–MV–Ct ( ) as
~
&
*
a function of the total fraction of trans-chalcone moieties converted (A) and as a function of time (B). The fit-
ting of the kinetic data was achieved by taking into account the reverse reaction in both isomerizations: 6.3ꢂ
10ꢁ4 and 7.2ꢂ10ꢁ5 sꢁ1, respectively, for the direct and reverse reactions for the conversion of AH+–MV–AH+
into Ct–MV–AH+; 2.3ꢂ10ꢁ4 and 6.5ꢂ10ꢁ5 sꢁ1 for the analogous processes during the conversion of Ct–MV–
AH+ into Ct–MV–Ct.
formation) is identical to the one of the methyl viologen, al-
though shifted to lower reduction potentials. Similarly, an
analogous shift for the reduction peaks of the trans-chalcone
moiety is expected. This means that the observed peaks for
the Ct–MV–Ct species are superpositions of the reduction
of the methyl viologen and the two Ct moieties. This also
explains the lack of complete reversibility of the system.
Conclusions
The viologen unit has been shown to be a peculiar bridge
linking two symmetric flavylium systems. The positive
charge of the bridge has a significant effect on the proper-
ties of the flavylium moieties relative to the model com-
pound 7-hydroxy-4ꢃ-methylflavylium: it favors the deproto-
nation and the hydration reactions, retards the tautomeriza-
Figure 8. Combined energy-level diagram for bis(flavylium) 3 (water/ace-
tonitrile 80:20 v/v) and model compound 4 (water); T=295 K.
Electrochemical studies: The flavylium cation is easily irre-
versibly reduced and by consequence the all trans-chalcone
Ct–Ct species was used to carry
out the electrochemical experi-
ments. On the other hand, the
methyl viologen (MV2+) can be
reversibly reduced to the blue
radical cation (MV+ ), which
C
suggests the possibility of intro-
ducing a redox stimulus in the
network. The formation of the
methyl viologen radical was
achieved by reducing a solution
of Ct–Ct with dithionite, see
Figure 10 (a and blue–gray
photo). The absorption spec-
trum is characteristic of the
methyl viologen radical cation.
The reversibility of the system
Figure 9. Spectral modifications upon irradiation at 365 nm of the bis(trans-chalcone) of bis(flavylium) 3,
was checked by addition of po- 2.46ꢂ10ꢁ5m in water/acetonitrile 80:20 v/v, at pH 1.83 (A) and 2.37 (B).
6366
www.chemeurj.org
ꢁ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2011, 17, 6359 – 6368

Symmetric Bis(7-hydroxyflavylium) Containing a Methyl Viologen Bridge
FULL PAPER
Experimental Section
Measurements: Solutions were prepared by using Millipore water and ab-
solute ethanol (when needed). The pH of solutions was adjusted by addi-
tion of HCl, NaOH, or universal buffer of Theorell and Stenhagen[25] and
pH was measured in a Radiometer Copenhagen PHM240 pH/ion meter.
UV/Vis absorption spectra were recorded in a Varian-Cary 100 Bio spec-
trophotometer or in a Shimadzu VC2501-PC. Quantum yields were de-
termined by irradiation at 365 nm, by using a medium pressure mercury
arc lamp and the excitation bands were isolated with interference filters
(Oriel). Actinometry was made by using the ferrioxalate system.[26]
General methods for synthesis: All reagents and solvents used were of
analytical grade. NMR spectra were run on a Bruker AMX 400 instru-
ment operating at 400.13 (1H) and 100.00 MHz (13C). COSY, HMQC,
HMBC, and eventually NOESY spectra were run on each sample to
allow full assignment of the NMR spectroscopic peaks. Mass spectra
were run on an Applied Biosystems Voyager-DE PRO. Elemental analy-
ses were obtained on a Thermofinnigan Flash EA 1112 Series instru-
ment.
Figure 10. Reduction of bisACHTNUTRGNE(NUG chalcone), Ct–MV–Ct, of 3 at pH 4.4 in 0.1m
acetate buffer (c, yellow color) with sodium dithionite (g, blue–
gray color); the system is partially reversible upon oxidation with potassi-
um peroxodisulphate (a).
4’-Bromomethylacetophenone (1): 4’-Bromomethylacetophenone was
prepared according to the method described by Leventis et al.[27] 4’-Meth-
ylacetophenone (14.9 mmol; 1.99 mL) was dissolved in CCl4 (40 mL,
carbon tetrachloride). NBS (16.37 mmol; 2.91 g) and AIBN (2.96 mmol;
0.486 g) were added. The resulting mixture was stirred and left in reflux
for 4 days. The succinimide was filtered off, and the solvent removed
under reduced pressure. The residue was purified by flash chromatogra-
phy in hexane/ethyl ether (8:2) to yield 4’-bromomethylacetophenone
tion, and enhances the isomerization. The methylene violo-
gen bridge does not isolate both flavylium moieties from
each other allowing their communication to some extent, as
(2.632 g, 12.35 mmol, 82.9%) as a yellow stable oil. 1H NMR (CD3OD,
3
400.13 MHz):[28] d=7.93 (d, 2H, JH2’ H6’– H3’
,
,
H5’ =8.1 Hz; H2’, H6’), 7.48 (d,
1
shown by the methylene H NMR spectroscopic signals that
3
2H, JH3’
,
,H6’ =7.9 Hz; H3’, H5’), 4.50 (s, 2H; CH2), 2.60 ppm (s, 3H;
H5’–H2’
allow us to distinguish between bis(flavylium), mixed flavyli-
um-trans-chalcone, and all-trans-chalcone species. The
bridge can also be electrochemically reduced permitting us
to introduce a redox stimuli on the multistate network of
the bisACHTUNGTRENNUNG(flavylium) system, although it was not possible to
carry out the reduction reversibly, a decomposition of 12%
taking place in one cycle.
COCH3); MS-MALDI/TOF+: m/z: calcd (%) for C9H9BrO+: 211.98
(100); found: 211.1 [MꢁH]+ (33.5), 212.1 [M]+ (5).
1,1’-Di[(acetophenone-4-il)methyl]-4,4’-bipyridinium bromide (2): 1,1’-
Di[(acetophenone-4-il)methyl]-4,4’-bipyridinium bromide was prepared
according to the method described by Porter et al.[16] 4,4’-Bipiridil
(2 mmol; 0.312 g) was dissolved in DMF (20 mL) in a round-bottomed
flash containing a magnetic stir bar and a reflux condenser. The solution
was degassed and placed under N2. To the stirred solution, 4’-bromome-
thylacetophenone (6 mmol; 1.278 g) previously dissolved in DMF (6 mL)
was added via syringe. The resulting mixture was stirred under N2 and
Figure 11. Reduction and oxidation potentials for the Ct–MV–Ct species of 3 and for model compounds MV and 4 (aqueous 0.1m acetate buffer at
pH 5.5) obtained from cyclic voltammetry carried out in a three-electrode cell with SCE as reference electrode, platinum wire as counter-electrode, and
glassy carbon as the working electrode with a scan rate of 100 mVsꢁ1
.
Chem. Eur. J. 2011, 17, 6359 – 6368
ꢁ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
6367

F. Pina et al.
was allowed to reflux for 10 h and then concentrated by distillation. The
crude was dissolved in methanol and an orange precipitate was obtained
by adding ethyl ether. The solid was filtered off, washed with diethyl
ether and dried, yielding 1,1’-di[(acetophenone-4-il)methyl]-4,4’-bipyridi-
nium bromide (1.114 g, 1.91 mmol, 95.7%). 1H NMR (CD3OD,
PTDC/QUI/67786/2006 and PTDC/QUI-QUI/104129/2008 and grants
SFRH/BD/48226/2008 (A.D.) and SFRH/BPD/18214/2004 (V.P.).
3
[1] T. Swain in The Flavonoids (Eds.: J. B. Harborne, T. J. Mabry, H.
Mabry), Chapman and Hall, London, 1975, p. 1129.
[2] Anthocyanins as Food Colors (Ed.: P. Markakis), Academic Press,
New York, 1982.
[3] R. Brouillard, J.-E. Dubois, J. Am. Chem. Soc. 1977, 99, 1359–1364.
[4] R. McClelland, S. Gedge, J. Am. Chem. Soc. 1980, 102, 5838–5848.
[5] F. Pina, M. Maestri, V. Balzani in Handbook of Photochemistry and
Photobiology, Vol. 3, American Scientific Publishers, Stevenson,
2003, Chapter 9, pp. 411–449.
400.13 MHz): d=9.36 (d, 4H, JH2’,H6’,H2,H6–H3’,H5’,H3,H5 =6.6 Hz; H2’, H6’, H2,
H6), 8.70 (d, 4H, 3JH3’,H5’,H2,H5–H2’,H6’,H2,H6 =6.5 Hz; H3’, H5’, H3, H5), 8.09 (d,
4H, 3JH9’,H13’,H9,H13–H10’,H12’,H10,H12 =8.2 Hz; H9’, H13’, H9, H13), 7.67 (d, 4H,
3JH10’,H12’,H10,H12–H9’,H13’,H9,H13 =6.6 Hz; H10’, H12’, H10, H12), 6.05 (s, 4H; N-
CH2), 2.60 ppm (s, 6H; COCH3); 13C NMR (CD3OD; 400.13 MHz): d=
151.86 (C4, C4’), 147.37 (C2, C6, C2’, C6’), 139.56 (C8, C8’), 139.04 (C11, C11’),
130.58 (C9, C13, C9’, C13’), 130.45 (C10, C12, C10’, C12’), 128.73 (C3, C5, C3’,
C5’), 65.26 (CNꢁCH2), 26.79 ppm (CCH3); MS-MALDI/TOF+: m/z: calcd
(%) for C28H26N2O2+: 422.20 (100); found: 289.5 [MꢁC9H9O]+ (100);
421.6 [MꢁH]+ (73); 423.5 [M+H]+ (13); elemental analysis calcd (%)
[6] F. Pina, M. J. Melo, A. J. Parola, M. Maestri, V. Balzani, Chem. Eur.
J. 1998, 4, 2001–2007.
.
for C28H26Br2N2O2 H2O: C 56.02, H 4.70, N 4.67; found: C 56.60, H 4.64,
[7] M. J. Melo, F. Pina, C. Andary, Anthocyanins, Natureꢀs Glamorous
Palette in Handbook of Natural Colorants (Eds.: T. Bechtold, R.
Mussak), Wiley, 2009, pp. 135–150.
[8] M. J. Melo, A. J. Parola, J. C. Lima, F. Pina, Chromogenic Materials
Based on 2-Phenyl-1-benzopyrylium: From Anthocyanins to Synthet-
ic Flavylium Compounds in Chromic Materials, Phenomena and
their Technological Applications (Ed.: P. R. Somani), RSC, London,
2010, Chapter 16, pp. 537–576.
[9] F. Pina, J. C. Lima, A. J. Parola, C. A. M. Afonso, Angew. Chem.
2004, 116, 1551–1553; Angew. Chem. Int. Ed. 2004, 43, 1525–1527.
[10] L. Giestas, F. Folgosa, JC Lima, A. J. Parola, F. Pina, Eur. J. Org.
Chem. 2005, 4187–4200.
[11] M. C. Moncada, D. Fernandꢄz, J. C. Lima, A. J. Parola, C. Lodeiro,
F. Folgosa, Org. Biomol. Chem. 2004, 2, 2802–2808.
[12] A. Roque, C. Lodeiro, F. Pina, M. Maestri, S. Dumas, P. Passaniti, J.
Am. Chem. Soc. 2003, 125, 987–994.
[13] A. Roque, C. Lodeiro, F. Pina, M. Maestri, R. Ballardini, V. Balzani,
Eur. J. Org. Chem. 2002, 2699–2709.
[14] R. Robinson, D. D. Pratt, J. Chem. Soc. 1922, 1577–1585.
[15] A. R. Katritzky, P. Czerney, J. R. Levell, W. Du, Eur. J. Org. Chem.
1998, 2623–2629.
[16] W. W. Porter, T. P. Vaid, A. L. Rheingold, J. Am. Chem. Soc. 2005,
127, 16559.
[17] F. Galindo, J. C. Lima, S. V. Luis, A. J. Parola, F. Pina, Adv. Funct.
Mater. 2005, 15, 541–545.
[18] R. Gomes, A. J. Parola, C. A. T. Laia, F. Pina, Photochem. Photo-
biol. Sci. 2007, 6, 1003–1009.
[19] J. T. Edsall, J. Wyman, Biophysical Chemistry, Vol. 1, Academic
Press, New York, 1958.
[20] A. Bencini, M. A. Bernardo, A. Bianchi, M. Ciampolini, V. Fusi,
A. J. Parola, F. Pina, B. Valtancoli, J. Chem. Soc. Perkin Trans. 2
1998, 413–418.
[21] K. A. Conners, Chemical Kinetics The Study of Reaction Rates in So-
lution, VCH, Weinheim, Chapter III, 1990.
[22] V. Petrov, F. Pina, J. Math. Chem. 2010, 47, 1005–1026.
[23] L. D. Hicks, A. J. Fry, V. C. Kurzweil, Electrochim. Acta 2004, 50,
1039–1047.
[24] N. Cotelle, P. Hapiot, J. Pinson, C. Rolando, H. Vꢄzin, J. Phys.
Chem. B 2005, 109, 23720–23729.
[25] F. W. Kꢅster, A. Thiel, Tabelle per le Analisi Chimiche e Chimico-Fi-
siche, 12nd ed., Hoepli, Milano, 1982, pp. 157–160.
[26] C. G. Hatchard, C. A. Parker, Proc. R. Soc. London Ser. A 1956,
235, 518–536.
N 4.82.
1,1’-Di[(7-hydroxyflavylium-4’-il)methyl]-4,4’-bipyridinium
(3): 1,1’-Di[(acetophenone-4-il)methyl]-4,4’-bipyridinium
perchlorate
bromide
(0.2 mmol; 0.116 g) and 2,4-dihydroxybenzaldehyde (0.2 mmol; 0.027 g)
were dissolved in glacial acetic acid (4 mL). Sulfuric acid (1.2 mL) was
added and the resulting mixture was allow to stir overnight. A reddish
solid was obtained by treating the solution with H2O and perchloric acid.
The solid was filtered off, washed with ethyl acetate, and dried, yielding
1,1’-di[(7-hydroxyflavylium-4’-il)methyl]-4,4’-bipyridinium
perclorate
(0.123 g, 0.12 mmol, 59.8%). 1H NMR (DCl/CD3OD, pDꢃ1.0,
3
400.13 MHz): d=9.47 (d, 4H, JH2’,H6’,H2,H6–H3’,H5’,H3,H5 =6.6 Hz; H2’, H6’, H2,
H6), 9.39 (d, 2H, 3JH4f–H3f =8.3 Hz; H4f), 8.78 (d, 4H, JH3’,H5’,H3,H5–
3
H2’,H6’,H2,H6 =6.6 Hz; H3’, H5’, H3, H5), 8.59 (d, 4H, 3JH3’f,H5f’–H2’f,H6’f =8.6 Hz;
H3’f, H5’f), 8.58 (d, 2H, 3JH3f–H4f =8.6 Hz; H3f), 8.33 (d, 2H, JH5f–H6f
=
3
9.0 Hz; H5f), 7.96 (d, 4H, 3JH2’f,H6f’–H3’f,H5’f =8.2 Hz; H2’f, H6’f), 7.67 (s, 2H;
H8f), 7.55 (d, 2H, 3JH6f–H5f =9.0, 4JH6f–H8f =2.2 Hz; H6f), 6.23 ppm (s, 4H;
N CH2); MS-MALDI/TOF+: m/z: calcd (%) for C42H32N2O4+: 628.24
ꢁ
(100); found: 627.7 [MꢁH]+ (32.8); 391.7 [MꢁC16H13O2
]
(25); 235.6
+
+
3+
+
[MꢁC26H20N2O2
]
(100); elemental analysis calcd (%) for
C42H32Cl4N2O20·3H2O: C 46.68, H 3.54, N 2.59; found: C 46.48, H 3.13, N
2.70.
7-Hydroxy-4’-methylflavylium tetrafluorborate (4): 7-Hydroxy-4’methyl-
flavylium tetrafluorborate was prepared according to a procedure adapt-
ed from Katritzky. 2,4-Dihydroxybenzaldehyde (10 mmol, 1.38 g) and 4-
methylacetophenone (10 mmol, 1.34 g) were dissolved in acetic acid
(10 mL) and HBF4 (2 mL). Acetic anhydride (10 mL) was then added
dropwise and the temperature of the reaction raised. The reaction mix-
ture was stirred overnight. By the following day diethyl ether and ethyl
acetate were added and the orange solid precipitated was filtered off and
carefully washed with diethyl ether and dried yielding 7-hydroxy-4’meth-
ylflavylium tetrafluorborate (0.57 g, 1.78 mmol, 18%). 1H NMR
3
(CD3OD, 400.13 MHz): d=9.27 (d, 1H, JH4,H3 =8.5 Hz; H4), 8.48 (d, 1H,
3JH3,H4 =8.5 Hz; H4), 8.39 (d, 2H, JH2’,H6’–H3’,H5’ =8.3 Hz; H2’6’), 8.25 (d, 1H,
3
3JH5,H6 =9.0 Hz; H5), 7.62 (d, 1H, 4JH8,H6 =1.6 Hz; H8), 7.56 (d, 2H,
3JH3’,H5’– H2’,H6’ =8.2 Hz; H3’5), 7.49 ppm (d, 1H, JH6,H5 =9.0, JH6,H8 =2.0 Hz;
H6); 13C NMR (CD3OD; 400.13 MHz): d=173.55 (C2), 171.36 (C7),
161.15 (C8a), 156.21 (C4), 149.75 (C4’), 134.44 (C5), 132.05 (C3’, C5’),
3
3
130.61
ACHTUNGTRENNUNG(C2’, C6’), 127.81 (C1), 123.46 (C6), 121.29 (C4a), 114.07 (C3), 103.74
(C8), 22.13 ppm (CCH3).
Acknowledgements
[27] N. Leventis, C. Sotiriou-Leventis, A. M. M. Rawashdeh, G. Zhang,
Electrochim. Acta 2003, 48, 2799.
We thank J. C. Lima and C. A. T. Laia for fruitful discussions and
LabRMN at FCT-UNL and Rede Nacional de RMN (supported with
funds from FCT-MCTES, Portugal) for access to the facilities. FCT-
MCTES is also acknowledged for financial support through projects
[28] See the Supporting Information for numeration of hydrogen and
carbon atoms.
Received: December 24, 2010
Published online: April 19, 2011
6368
www.chemeurj.org
ꢁ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2011, 17, 6359 – 6368