Aldehyde-appended distyrylbenzenes: Amine recognition in water

Article abstract of DOI:10.1002/chem.201200930

Change in water: Aqueous solutions of aldehyde-substituted, water-soluble distyrylbenzenes reacted with amines to give imines or aminals with dramatically changed fluorescence. This approach allowed the detection and recognition of amines in water (see fi

Full text of DOI:10.1002/chem.201200930

COMMUNICATION
DOI: 10.1002/chem.201200930
Aldehyde-Appended Distyrylbenzenes: Amine Recognition in Water
Jan Kumpf and Uwe H. F. Bunz*[a]
Detection of amines is important, because they are envi-
ronmental, biological, and clinical analytes that can signal
environmental hazard, food poisoning, or monitor disease
states.[1] Recent examples of successful amine sensing in-
clude Suslickꢀs colorimetric arrays, LaACTHNUTRGNEUNGvigneꢀs polythiophene
carboxylic acids, Anslynꢀs receptors, and Kanedaꢀs cyclodex-
trin dye.[2–6]
1,3-Dicarbonyl- and trifluoroacetyl-substituted dyes inves-
tigated by Mertz and Zimmerman, as well as by Glass and
co-workers, display changes in fluorescence intensity and
wavelength upon exposure to amines.[7] Also, phenol and al-
dehyde-functionalized cruciform fluorophores detect and
discern amines.[8–10] However, most of the described sensor
types work better in organic solvents than in water, with the
notable exception of Lavigneꢀs polymers and Glassꢀs 1,3-di-
carbonyl compounds. For bio- and environmental detection
of amines, the dyes should work in an aqueous environment.
A problem is the attachment of solubilizing substituents to
the core, preventing the fluorescence quantum yield to drop
when going from an organic solvent into water. This issue is
circumvented by the attachment of branched oligo-
Scheme 1. Synthesis of 3 by Heck reaction.
ACHTUNGTRENNUNG(ethylene)glycol side chains, which efficiently increase the
quantum yield of fluorescent dyes in water.[11] Herein, we
describe the synthesis and amine-responsive properties of
the simple distyrylbenzenes (DSBs) 3 and 8 in water
(Schemes 1 and 2).
Scheme 1 outlines the synthesis of DSB 3. Starting from
1, a double Heck reaction[12] with 2 led to 3 in 73% yield
after silica-gel chromatography. To prepare a different top-
ology of aldehyde-substituted DSBs, we selected 8 as
a target with only one swallowtail substituent. Herein, we
performed the Heck coupling of 4 with 2 and transformed
the protected aldehyde 5 into the styrylstyrene derivative 6.
A final Heck coupling, now with the iodide 7, gave the de-
sired target 8, but only in modest 29% yield (Scheme 2).
Figure 1 displays the optical spectra (absorption and emis-
sion) of 3 and 8 in water, in which both are soluble—3 more
so than 8, which carries only one swallowtail substituent
Scheme 2. Synthesis of aldehyde 8 by a combination of Heck and Wittig
reactions. p-TsOH=para-toluenesulfonic acid.
(Sw: branched oligoethyleneglycol). The emission of 3 is
centered at l=564 nm, 8 emits at l=538 nm (Figure 1). In
both cases, the fluorescence quantum yield is disappointing-
ly low, <0.01 for 3 and 0.06 for 8. The meager quantum
yield of 3 is probably due to the relaxation of the excited p–
p* state into an n–p* state, which is apparently lower in
energy. Alternatively, other radiationless deactivation path-
ways may also operate. Whereas 3 is infinitely stable in
aqueous solution, 8 gives a blue emissive species upon irra-
diation with a UV lamp (lmax =365 nm) after several hours.
[a] J. Kumpf, Prof. U. H. F. Bunz
Organisch-Chemisches Institut
Ruprecht-Karls-Universitꢁt Heidelberg
Im Neuenheimer Feld 270, 69120 Heidelberg (Germany)
E-mail: uwe.bunz@mail.oci.uni-heidelberg.de
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201200930.
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Figure 3. Non-normalized (top) and normalized (bottom) emission spec-
tra of compound 3 (3 mmolLÀ1) in water in the presence of different
amines. The signal for 1,3-diaminopropane was omitted in the top spec-
trum, because its intensity is approximately ten times higher than that of
the solution to which ethylenediamine was added.
Figure 1. Absorption and emission spectra of 3 (3 mmolLÀ1; top) and 8
(bottom) in water.
Both aqueous solutions of 3 and 8 were exposed to
a series of different amines, and vibrant color changes oc-
Figure 3 displays the normalized and the non-normalized
emission spectra of 3 in water in presence of the different
amines. Compared with the reference, all spectra are blue-
shifted. There are four distinct groups. Benzylamine only eli-
cited a slight blueshift, whereas all of the other primary
amines caused signals centered at l=470 nm with a signifi-
cant vibronic shoulder that changes in height and therefore
allows the discernment of the amines. Cadaverine, even
though a diamine, is also in this group. Morpholine as a sec-
ondary amine showed yet a different spectral trace, and
then ethylene diamine and 1,3-diaminopropane form the
last group with the most blueshifted spectral features. The
question is, how the differences in spectroscopic properties
can be explained. The primary amines, ethanolamine and ca-
daverine, will form imines, which will maintain conjugation
to the DSB unit, and therefore the emission features are
only somewhat blueshifted. Ethylene diamine and 1,3-diami-
nopropane will form cyclic aminals with 3 or 8, in which the
conjugation to the carbonyl group is interrupted. Morpho-
line as a secondary amine will form a hemiaminal.
curred. Particularly, the dully yellowish fluorescent
3
(Figure 2) turned vibrantly green upon addition of primary
Figure 2. Amine-sensing panels of
3
(10 mmolLÀ1
;
top) and
8
(10 mmolLÀ1; bottom) in water: 1) reference; 2) butylamine; 3) tert-butyl-
amine; 4) benzylamine; 5) cyclohexylamine; 6) ethylene diamine; 7) 1,3-
diaminopropane; 8) cadaverine; 9) morpholine; 10) ephedrine; 11) 4-ami-
nopyridine; 12) ethanolamine.
amines and blue upon addition of primary diamines
(Figure 2). The monoaldehyde 8 also showed color changes,
however, much less distinct than those observed for 3. Pri-
mary amines seem to induce quenching in 8, and only 1,3-di-
aminopropane led to a significant blueshift in the emission.
These observations are surprising and the performance of 8
is quite disappointing compared with that of 3. From
Figure 2, we can directly discern most amines just with the
naked eye.
To test the structural hypotheses, 1H NMR spectra of 3
with 1,3-diaminopropane and ethanolamine in D2O/
CD3OD-mixtures were recorded (Figure 4). Ethanolamine
gave the imine, whereas the addition of 1,3-diaminopropane
to 3 gave mainly the aminal, as expected from the emission
spectra and photographical results (Figure 5).
Imine formation of 3 is fast. Figure 5 shows the time de-
pendence of the fluorescence-intensity signal. Addition of
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Amine Recognition in Water
COMMUNICATION
Therefore, both the imine and the aminal formation must be
favored under these conditions. For benzylamine, solutions
of 3 containing 196 ppm (1.83 mm) of amine already dis-
played a significant emission color change, whereas for 1,3-
diaminopropane, a concentration about 22 ppm (0.30 mm)
was sufficient for signal generation (Figure 5).
Aldehydes reacted with amines in water. One might
expect the resulting imines or aminals to hydrolyze. Scout-
ing the older literature, both Sprung and Layer noted that
the formation of aldimines from aromatic aldehydes with
aliphatic primary amines proceeded in water.[13]
Aqueous solutions of 3 and 8 were exposed to biogenic
amines (dopamine, histamine, tryptamine, tyramine, 4-ami-
nobutyrate (GABA), acetaminophene, epinephrine, and di-
clofenac). Tryptamine and diclofenac showed color changes
for both aldehydes. In a second set of experiments, aqueous
solutions of 3 or 8 were exposed to the 20 natural amino
acids. Herein, only a few amino acids reacted, and 3 gave
consistently more vibrant responses than 8 (Figure 6).
Figure 4. 1H NMR spectra of 3 (5 mg in 0.5 mL D2O/CD3OD) in the pres-
ence of 1,3-diaminopropane (20 mL) and ethanolamine (20 mL). The
upper trace displays the spectrum of dialdehyde 3.
Figure 5. Time-dependent evolution of the emission wavelength and
emission intensity for the reaction of 3 (3 mmolLÀ1) with benzylamine
(0.3 vol%, 30 mm; top) and with 1,3-diaminopropane (0.03 vol%, 4 mm;
bottom). The photographic panels show solutions of 3 with an increasing
amount of benzylamine (top) and 1,3-diaminopropane (bottom) after 3 h
of reaction.
Figure 6. Exposure of aqueous solutions of 3 (10 mmolLÀ1) and 8 to dif-
ferent biogenic amines (0.5 vol%): 1) reference; 2) dopamine; 3) hista-
mine; 4) tryptamine; 5) tyramine; 6) g-aminobutanoic acid; 7) acetamino-
phene; 8) epinephrine; 9) diclofenac (top). Exposure (bottom) to differ-
ent amino acids: 10) arginine; 11) aspartic acid; 12) cysteine; 13) glutamic
acid; 14) lysine.
benzylamine (0.3%) resulted in 40-fold increased emission
When the experiments were repeated in different buf-
fered solutions, no reaction was observed in acidic buffers,
and basic buffers (>pH 7) gave identical results to the ex-
periments performed with 3 in distilled water. Amino acids
after 10 min. When
3 reacts with 1,3-diaminopropane
(0.03%), even a 300-fold increased fluorescence intensity
accompanied by a wavelength shift is complete in 2.5 min.
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U. H. F. Bunz and J. Kumpf
did not react well with aldehydes to give the corresponding
aldimines.[14] Only amino acids (Figure 6), which have an ad-
ditional SH or NH2 group, such as cysteine, arginine, or
lysine, reacted with 3, whereas 8 also displayed a weak inter-
action with some other amino acids. The presence of the
electronegative carboxylate might reduce the reactivity of
the amino group towards the aldehyde, and the formation of
the aldimine is therefore not competitive anymore.
In conclusion, we have synthesized two aldehyde-substi-
tuted DSBs, 3 and 8, and investigated their reaction with
amines in water. Both 3 and 8 formed imines or cyclic ami-
nals depending on the structure of the employed amine.
Turn on and blueshift of the fluorescence resulted. The dia-
ldehyde 3 discerned and identified different amines as could
be demonstrated by photography. Both 3 and 8 gave fairly
unique color responses towards biogenic amines and amino
acids that can undergo aminal or thioacetal formation. One
does not need highly electronegative, trifluoromethyl-substi-
tuted keto groups, or reactive 1,3-dicarbonyl compounds to
obtain working sensor-type dyes. Aromatic aldehyde groups
alone are powerful sensory appendages that react with
amines accompanied by a change of the emission color and
intensity in concentration ranges useful for biological appli-
cations.
Keywords: aldehydes · aldimines · amines · fluorescence ·
sensors
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Under
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a nitrogen atmosphere, the di-iodide 1 (500 mg, 457 mmol,
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
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compound as a viscous yellow oil (369 mg, 334 mmol, 73%). 1H NMR
3
(300 MHz, CDCl3): d=9.99 (s, 2H), 7.87 (d, J
N
7.64 (m, 6H), 7.38 (s, 2H), 7.15 (d, 3J
ACHTUNGTRNE(NUNG H,H)=16.5 Hz, 2H), 4.54 (quint,
3J
ACHTUNGTRENNUNG
(m, 8H), 3.33 ppm (s, 12H); 13C NMR (75 MHz, CDCl3): d=191.71 (2C),
151.47 (2C) 144.06 (2C), 135.39 (2C), 130.37 (4C), 128.98 (2C), 128.14
(2C), 127.15 (4C), 126.87 (2C), 114.64 (2C), 79.90 (2C), 72.02 (4C), 71.19
(4C), 70.8770.62 (m, 20C), 59.12 ppm (4C); HRMS (ESI): m/z calcd for
C58H86O20 +H+: 1103.5791 [M+H+], found: 1103.5780; m/z calcd for
C58H86O20 +Na+: 1125.5610 [M+Na+]; found: 1025.5593; m/z calcd for
C58H86O20 +K+: 1141.5350 [M+K+]; found: 1141.5337; elemental analysis
calcd (%) for C58H86O20: C 63.14, H 7.86; found: C 62.77, H 8.01.
[14] S. Dayagi in The Chemistry of the Carbon–Nitrogen Double Bond
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Acknowledgements
We thank the Struktur- und Innovationfond des Landes Baden-Wꢄrttem-
berg for generous support.
Received: March 19, 2012
Published online: && &&, 0000
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Amine Recognition in Water
COMMUNICATION
Sensors
J. Kumpf, U. H. F. Bunz* . . . &&&& — &&&&
Aldehyde-Appended Distyrylben-
zenes: Amine Recognition in Water
Change in water: Aqueous solutions of
aldehyde-substituted, water-soluble
distyrylbenzenes reacted with amines
to give imines or aminals with dramati-
cally changed fluorescence. This
approach allowed the detection and
recognition of amines in water (see
figure).
Chem. Eur. J. 2012, 00, 0 – 0
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These are not the final page numbers!