A pyridinium-barbiturate-betaine dye with pronounced negative solvatochromism: A new approach for molecular recognition

Full text of DOI:10.1002/anie.200902860

Communications
DOI: 10.1002/anie.200902860
Molecular Recognition
A Pyridinium–Barbiturate–Betaine Dye with Pronounced Negative
Solvatochromism: A New Approach for Molecular Recognition**
Ina Bolz, Dieter Schaarschmidt, Tobias Rꢀffer, Heinrich Lang, and Stefan Spange*
Dedicated to Professor Christian Reichardt
The perfection of the complementary hydrogen-bonding
sequence of DNA base pairs fascinates many chemists and
inspires them to use similar coupling motifs for the con-
struction of supramolecular structures.[1] Often low-molec-
ular-weight model systems are used, because the complexity
of the tautomeric equilibria makes the simultaneous detection
of structurally different bases difficult at the molecular
level.[2,4] The adaptation of each tautomer of a DNA base to
its complementary partner, however, does not appear to be an
intrinsic property of the base, but rather is evidently also
determined by the molecular environment of the molecule.[5]
By using chromophoric probe molecules capable of adapta-
tion, different hydrogen-bonding sequences can be distin-
guished. The capacity of adaptation is related to the
controlled formation of defined tautomers, which are stabi-
lized only upon complex formation.[6] Our underlying idea is
that the electronic structure of the chromophore can be
effectively modified by the formation of a supramolecular
complex and can thus result in a change in its optical
properties. On route to this challenging target, we have
Scheme 1. Synthesis of chromophore 3.
developed a new class of pyridinium–barbiturate–betaine
dyes with exceptional solvatochromic properties and adapt-
able hydrogen-bonding sequences, which we are reporting
here for the first time.
this, a favorable conjugation between the electron-donating
barbiturate unit and the electron-accepting pyridinium sub-
stituent is achieved.
A further indication of the presence of a pronounced
push–pull system is given by the remarkably high negative
solvatochromism, which leads to absorptions extending over
practically the whole visible region from l = 380 nm (in 2,2,2-
trifluoroethanol) to l = 639 nm (in 1,4-dioxane) (Figure 2).
The pyridinium–barbiturate–betaine dye 3 was obtained
from 1-methyl-5-phenylbarbituric acid (1) via 2 (Scheme 1).
X-ray structure analysis shows that 3 is present in the crystal
as a centrosymmetric dimer, which is held together by two
moderately strong intermolecular hydrogen bonds between
the partially negatively charged O1 atom and the N2 atom on
the barbituric acid ring (Figure 1, Table 1).[7,8] Because of
~
packing effects, there are two additional weak hydrogen
Since the absorption maxima cover an energy range of Dn =
[9]
À
À
bonds across O2···H C28 and O1···H C26. As a result of
À10683 cmÀ1, barbiturate 3 setsa new record for negative
solvatochromic compounds. Because of this, barbiturate 3
exhibits a greater sensitivity towards changes in the solvent
polarity than other known, structurally similar, betaine dyes
(see the Supporting Information).[10,11]
[*] I. Bolz, Prof. Dr. S. Spange
Institut fꢀr Chemie, Professur Polymerchemie
Technische Universitꢁt Chemnitz
Strasse der Nationen 62, 09107 Chemnitz (Germany)
Fax: (+49)371-531-21239
The individual interactions of chromophore 3 with the
solvent environment were investigated by means of linear
solvation energy (LSE) relationships, using the empirical
solvent parameters according to Kamlet and Taft[12] and
Catalꢀn.[13] The solvatochromism of 3 is thus determined
principally by the hydrogen-bond-donor capacity and the
dipolarity of the solvent, which bring about a hypsochromic
E-mail: stefan.spange@chemie.tu-chemnitz.de
D. Schaarschmidt,[+] Dr. T. Rꢀffer,[+] Prof. Dr. H. Lang[+]
Institut fꢀr Chemie, Professur Anorganische Chemie
Technische Universitꢁt Chemnitz (Germany)
[+] Single-crystal X-ray structure analysis
~
shift of nmax. In addition, the high electron density of the
[**] We thank the Deutsche Forschungsgemeinschaft and the Fonds der
Chemischen Industrie (FCI) for financial support.
enolate substituent enhances the basic character of the
barbiturate acid unit, and consequently 3 is sensitive to
acids and hydrogen-bonding donor sequences.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.200902860.
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Chemie
donor–acceptor recognition system
complementary to 3. Besides, complex
formation with BuCy is electronically
limited, as 3 and BuCy mainly act as
hydrogen-bond acceptors. The very
weak complex formation expected
therefore leads to no measurable shift
in the UV/Vis absorption band.
Complete protonation of 3 is ach-
ieved by the addition of trifluoroacetic
acid (TFA, pKA = 0.23 in H2O). This
lowers the charge density in the barbi-
turate and a downfield shift of the
1H NMR signal (Figure 4). In contrast,
the signals of the H atoms on C26 and
C28 show a marked upfield shift (black
arrows, Dd = 0.76 ppm). This is
Figure 1. ORTEP drawing of the molecular structure of the centrosymmetric dimer of 3. Complete
numbering of the atoms can be found in the Supporting Information.
Table 1: Bond lengths d and bond angles q of the hydrogen bonds in
dimeric 3 (D=donor, A=acceptor).
Hydrogen bond
d [ꢂ]
q [8]
À
À
D H
À
À
D H···A
H···A
D H···A
D H···A
À
intra
intra
inter
C26 H···O1
0.93
0.93
0.97(5)
2.24
2.31
1.83(5)
2.819(4)
2.833(4)
2.796(4)
120
115
173(4)
À
C28 H···O2
À
N2 H···O1
Scheme 2. The synthetic receptors employed.
Figure 2. UV/Vis absorption spectra of 3 in six selected solvents of
varying polarity. In the region shown, lmax is independent of the dye
concentration.
The influence of the chromophoric system of the betaine
dye 3 through supramolecular binding is demonstrated by
means of complexation experiments with five artificial
receptors.[14] Because of their different amide substituents,
the pyridine derivatives 2,6-diacetamidopyridine (DAC) and
2,6-bis(trifluoroacetamido)pyridine (BTF) are suitable for a
systematic investigation of acid–base and noncovalent inter-
actions. The nucleic acid bases 9-ethyladenine (EtAd), 1-n-
butylcytosine (BuCy), and 1-n-butylthymine (BuTy) can
mimic the base pairing found in nature (Scheme 2).
Figure 3. Shift of the UV/Vis absorption maximum of 3
(0.098 mmolLÀ1, lmax =533 nm) in dichloromethane by acid–base
interactions with TFA and by the formation of supramolecular com-
plexes with the receptors BTF, DAC, and EtAd.
explained by the cleavage of both of the intramolecular
À
nonclassical hydrogen bonds O···H C. The repulsive inter-
actions between the enol hydrogen atom and the H atoms on
C26 and C28 cause a twist between the barbiturate unit and
the phenylene ring, which makes the charge transfer more
difficult. For the protonated chromophore 3-H+, a hypso-
chromic shift to lmax = 409 nm is observed (Figure 3). An
excess of TFA leads to multiple protonation of the barbitu-
rate, which is detected both by a further hypsochromic shift of
The formation of supramolecular complexes of betaine
dye 3 with these five receptors can be followed by UV/Vis
spectroscopy (Figure 3). Almost no change is observed on
addition of BuTy or BuCy, as these compounds have only a
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Communications
three hydrogen bonds is observed. 1H NMR titration in
CD2Cl2 was used to determine the association constant KA
from the downfield shift of the barbiturate NH hydrogen
signal as a function of the receptor concentration (KA =
(2718 Æ 38)mÀ1). Furthermore, the UV/Vis absorption max-
imum of 3 in dichloromethane undergoes a hyperchromic and
a hypsochromic shift on addition of DAC (Dl = 21 nm, KA =
(2479 Æ 448)mÀ1). Both values for KA are on the same order of
magnitude and are typical for threefold hydrogen-bonding
ADA–DAD systems.[15]
Formation of a supramolecular complex between 3 and
EtAd in dichloromethane causes a small hyperchromic and a
bathochromic shift of the UV/vis absorption maximum of 3
(Dl = 3 nm, Table 2, Figure 3). In spite of this minimal
change, the association constant of the 3 + EtAd complex
Figure 4. Sections of the 1H NMR (400 MHz) spectra from the titra-
tions of 3 (0.372 mmolLÀ1) with TFA and the receptor BTF in CD2Cl2
(signals of the receptors are marked with asterisks).
Table 2: Complexation properties of the pyridinium–barbiturate–betaine
3 in dichloromethane.
Receptor
Type of H bonds
Number of
H bonds
KA
lmax
[nm][b]
formed by 3[a]
[mÀ1
]
lmax with signal hypochromism, and by a broadening of the
1H NMR signal with increasing TFA concentration.
DAC
BTF
BuTy
EtAd[g]
BuCy
DAD
DDA
AD
DAD
AD
enolate
enol
enolate
enolate
enolate
3
3
2
3
2
2718Æ38[c]
512
412[e]
[f]
536
[f]
[d]
The receptor BTF is acidic because of the two highly
electron-withdrawing trifluoroacetyl substituents, and as a
result consecutive association via acid–base and noncovalent
interactions is observed with 3. Here also protonation of the
barbiturate unit hinders the charge transfer in 3-H+, which is
evident in the UV/Vis experiment by a hypsochromic shift of
Dl = 121 nm to lmax = 412 nm. The conjugated acid–base pair
3-H+/BTFÀ (Scheme 3) forms a very stable threefold hydro-
gen-bonded complex as a result of its favorable electrostatic
interactions and its complementary AAD–DDA recognition
sequences.[15]
[f]
1309Æ179 [h]
[f]
[a] D: H-bond donor, A: H-bond acceptor. [b] Complexed enolate form.
[c] Determined by H NMR titration. [d] Not measurable. [e] Complexed
enol form. [f] No interaction. [g] Hoogsteen geometry. [h] Obtained by
UV/Vis titration.
1
can be determined as KA = (1309 Æ 179)mÀ1. On the basis of
the work of Quinn et al.[16] a threefold hydrogen-bonded
complex with Hoogsteen geometry is assumed for 3 + EtAd
(Scheme 3). In this structure EtAd shows a complementary
DAD recognition sequence and thus acts as an H-bond donor.
The new pyridinium–barbiturate–betaine dye 3 presented
here permits the simultaneous spectroscopic monitoring of
polarity changes, acid–base reactions, and the formation of
supramolecular complexes with complementary H-bonding
sequences, on the basis of its pronounced negative solvato-
chromism. It should be emphasized that each interaction
between the chemical sensor 3 and the hydrogen-bond-
donating receptors leads to a specific UV/Vis signal, which
can be followed with the naked eye. We expect that this new
class of UV/Vis probe molecules should find new applications.
As the receptor DAC is less acidic than BTF and has a
complementary DAD recognition sequence, upon titration of
3 with DAC formation of a supramolecular complex through
Received: May 28, 2009
Published online: September 8, 2009
Keywords: barbiturates · donor–acceptor systems ·
.
molecular recognition · solvatochromism ·
supramolecular chemistry
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Scheme 3. Formation of supramolecular complexes of the pyridinium–
barbiturate–betaine dye 3 with artificial receptors.
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À
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