Synthesis of dye/fluorescent functionalized dendrons based on cyclotriphosphazene

Article abstract of DOI:10.3762/bjoc.7.186

Functionalized phenols based on tyramine were synthesized in order to be selectively grafted on to hexachlorocyclotriphosphazene, affording a variety of functionalized dendrons of type AB₅. The B functions comprised fluorescent groups (dansyl)

Full text of DOI:10.3762/bjoc.7.186

Synthesis of dye/fluorescent functionalized dendrons
based on cyclotriphosphazene
Aurélien Hameau1,2, Sabine Fuchs1,2, Régis Laurent1,2,
Jean-Pierre Majoral*1,2 and Anne-Marie Caminade*1,2
Full Research Paper
Open Access
Address:
Beilstein J. Org. Chem. 2011, 7, 1577–1583.
1CNRS, LCC (Laboratoire de Chimie de Coordination), 205, route de
Narbonne, BP 44099, F-31077 Toulouse, France and 2Université de
Toulouse; UPS, INPT, LCC, F-31077 Toulouse, France
doi:10.3762/bjoc.7.186
Received: 29 September 2011
Accepted: 02 November 2011
Published: 28 November 2011
Email:
Jean-Pierre Majoral* - majoral@lcc-toulouse.fr;
Anne-Marie Caminade* - caminade@lcc-toulouse.fr
Dedicated to the memory of our friend and former PhD student Dr Yiqian
Wei who regrettably passed away on February 6th, 2011.
* Corresponding author
Associate Editor: D. O'Hagan
Keywords:
dabsyl; dansyl; dendrimer; dendron; fluorescence
© 2011 Hameau et al; licensee Beilstein-Institut.
License and terms: see end of document.
Abstract
Functionalized phenols based on tyramine were synthesized in order to be selectively grafted on to hexachlorocyclotriphosphazene,
affording a variety of functionalized dendrons of type AB5. The B functions comprised fluorescent groups (dansyl) or dyes
(dabsyl), whereas the A function was provided by either an aldehyde or an amine. The characterization of these dendrons is
reported. An unexpected behaviour of a fluorescent and water-soluble dendron based on dansyl groups in mixtures of dioxane/water
was observed.
Introduction
Dendrimers constitute an important group of hyperbranched fluorescent dendrimers, emphasizing in particular their role as
macromolecules, pertaining both to the field of molecular light-harvesters [4] for organic light-emitting diodes (OLEDs)
chemistry thanks to their perfectly defined structure due to their [5] and as tools in biology [6]. Many different types of fluo-
step-by-step synthesis, and to the field of polymers due to their rophores have been grafted as terminal groups on to dendrimers.
repetitive structure. The numerous terminal groups of In particular the dansyl group has been frequently used to func-
dendrimers are responsible for most of their properties for tionalize poly(propyleneimine) [7,8], poly(lysine) [9],
instance in catalysis, for the elaboration of materials, or in poly(amidoamine) [10], and poly(melamine) [11] dendrimers. It
biology [1,2]. Dendrons are also branched macromolecules, has been shown that no interaction occurs between these
reminiscent of dendrimers, but which possess one functional terminal fluorophores, at least up to generation 5, whereas
group at the level of the core, in addition to the terminal groups protonation induces drastic changes in the absorption and emis-
[3]. Several hundreds of publications have reported the syn- sion bands [12]. The dansyl group has frequently been
thesis, the study of photophysical properties and several uses of employed as the core of dendrons, but very rarely as a terminal
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group. Meanwhile, functionalized dendrons (dendrimeric group of tyramine are able to react with N3P3Cl6, thus the NH2
wedges) are potentially interesting for elaboration of the orig- group has to be protected. The fluorescent N-dansyl tyramine
inal dendrimeric architectures [13,14], or for labelling materials (3) is obtained by reaction of tyramine (1) with dansyl chloride.
or biological entities. In many cases, it is desirable to concen- The dye, dabsylated tyramine 4 is analogously obtained from
trate a maximum number of functional groups in a small com- dabsyl chloride (Scheme 1).
pound (a small size is particularly important so as not to disturb
biological systems); this can be attained if the core of the Having in hand four functionalized phenols (the fourth is
dendron possesses several functions.
4-hydroxybenzaldehyde, (5)), the synthesis of AB5-type com-
pounds starting from N3P3Cl6 could be accomplished either by
We report here the use of hexachlorocyclotriphosphazene reacting first one A then five B functions, or by reacting first
(N3P3Cl6) for such a purpose, which allows the gathering of five B, then one A function. The products from attempts made
five fluorescent dansyl groups in a small dendron, thanks to the with phenol 5 were found to be easier to purify when the first
specific functionalization of N3P3Cl6 [15]. The method elabo- method was used. A slight substoichiometric amount of phenol
rated is also useful for the grafting of dyes, as will be illustrated was used, in order to avoid disubstitution with phenols 5 or 2
with the dabsyl dye. We also paid particular attention to the (the A function). The monosubstituted products 6 and 7 were
nature of the remaining function (usable for the grafting of the isolated in moderate yield after work-up (51.7 and 48.3%, res-
dendron). We choose an aldehyde and a primary amine, both pectively) (Scheme 2). Both compounds were characterized by
being well-known for their broad and versatile reactivities.
multinuclear NMR, in particular by 31P NMR, which displayed
in both cases the presence of one triplet and one doublet
(2J (P,P) = 60 Hz), showing the unsymmetrical nature of these
compounds.
Results and Discussion
Synthesis of functionalized dendrons
The first step of the strategy entails the non-symmetrical func-
tionalization of hexachlorocyclotriphosphazene (N3P3Cl6) in
order to synthesize AB5-type compounds, where A is the func-
tion usable, for instance, for the coupling with another dendron,
and the B functions are either the dyes or the fluorescent
groups. Due to the known, relatively easy functionalization of
N3P3Cl6 by phenols, and the stability of the resulting com-
pounds, we chose functionalized phenols as the A and B func-
tions. Functionalized phenols 2, 3 and 4 are synthesized from
tyramine (1). The N-Boc protected tyramine 2 is synthesized by
using Boc2O. Tyramine cannot be used directly to introduce the
amine functionality, because both the phenol and the amine
Scheme 2: Single substitution of hexachlorocyclotriphosphazene.
Reagents and conditions: a) Cs2CO3, 1.67 equiv, THF, rt, 16 h.
Scheme 1: Synthesis of functionalized phenols. Reagents and conditions: a) Boc2O, 1.0 equiv, THF, 0 °C → rt, 4 h. b) Dansyl chloride, 1.1 equiv,
MeOH, rt, 6 h. c) Dabsyl chloride, 1.0 equiv, CH2Cl2 and MeOH, rt, 16 h.
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The next step involves the grafting of five equivalents of the The same procedure was applied to afford the dabsylated
dansyl phenol 3 on compounds 6 or 7, to afford dendrons 8 or 9, dendron 11 in 43.3% yield from the dabsyl phenol 4 and the
respectively. These were isolated in good yields after work-up Boc-protected cyclotriphosphazene derivative 7. The deprotec-
(69.2 and 56.6%), and characterized by mass spectrometry and tion was carried out as described above to afford the dendron 12
multinuclear NMR. The 31P NMR spectra generally consisted (Scheme 4).
of multiplets, due to the non-symmetrical nature of these com-
pounds. The aldehyde group is directly usable for grafting, as
we have already demonstrated for the elaboration of Janus
dendrimers [12], but the Boc protection of compound 9 must be
removed in order to afford the amine group. The Boc protec-
tion of tyramine was cleaved by using trifluoroacetic acid. The
reaction was monitored by 1H NMR, which showed the total
disappearance of the signal corresponding to Boc (δ = 1.41
ppm) after the repetition of the cleavage step. The dendron 10
was isolated as a salt in 98.1% yield after work-up (Scheme 3).
Scheme 4: Synthesis of dabsylated dendrons. Reagents and condi-
tions: a) Cs2CO3, 11 equiv, THF, rt, 48 h. b) TFA (10% v:v), CH2Cl2, rt,
1 h, evaporation, repeated once.
UV–vis absorption spectra and fluorescence
properties
Having in hand five different dendrons, we recorded the
UV–vis spectra in 1,4-dioxane. As expected, each family
affords a coherent series of spectra. In the case of the dansyl
Scheme 3: Synthesis of dansylated dendrons. Reagents and condi-
tions: a) Cs2CO3, 11 equiv, THF, rt, 48 h. b) Cs2CO3, 11 equiv, THF,
rt, 48 h. c) TFA (25% v:v), CH2Cl2, rt, 1 h, evaporation, repeated once.
Table 1: UV–vis characteristics and fluorescence characteristics of dendrons 8–10 in 1,4-dioxane.
Dendron
λmax (1) (nm)
ε (1) (L·mol−1·cm−1)
λmax (2) (nm)
ε (2) (L·mol−1·cm−1)
λem,maxa (nm) Quantum yield Φ (%)
8
9
253
253
255
103 × 103
71 × 103
69 × 103
338
336
336
21 × 103
21 × 103
21 × 103
493
491
492
47
55
51
10
aExcitation wavelength 347 nm.
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derivatives (8–10), two absorption peaks are observed at 253 All the dansyl dendrons (8–10) are fluorescent; their excitation
and ca. 338 nm (Table 1). Compound 10 is also soluble in and fluorescence spectra were recorded in dioxane. The excita-
water; its UV–vis spectrum in this solvent is analogous to that tion and emission spectra are given in Figure 3. It appears that
in dioxane. It is important to note that there is no peak at the fluorescence quantum yield is slightly sensitive to the nature
280 nm [12], meaning that no protonation of dansyl occurred, of the A functionality (Table 1).
even in the case of derivative 10 in water (Figure 1). In the case
of the dabsyl derivatives, there is a large signal at 434 nm, the
high intensity of which corresponds to its dye properties, and a
smaller one at 271 nm. The wavelength of the signal in the
visible part remains constant, indicating here also that there is
no protonation of dabsyl, even for dendron 12 (Figure 2) [16].
Figure 3: Excitation (left) and emission (right) spectra of compounds
8–10 in 1,4-dioxane (the excitation spectra of the 3 compounds are
entirely superimposed).
Dendrons 8 and 9 are soluble in organic solvents, as is dendron
10, but in the case of 10 it is also soluble in water in contrast to
the others, thus we also studied its fluorescence in water. We
observed a notable decrease of its fluorescence quantum yield
(Φ) in water upon going from pure dioxane (Φ = 51) to pure
Figure 1: UV–vis spectra of compounds 8–10.
water (Φ = 17), which cannot be related to protonation, as indi-
cated from the UV–vis spectrum [10]. An analogous phenom-
enon was already described for a dansyl derivative of adeno-
sine in solution in water or in pyridine, and was ascribed to the
solvent polarity, which modifies the interactions between both
parts of the molecule [17]. In our case, we may consider that the
structure of dendron 10 in solution in dioxane is more expanded
than in water, which should bring the hydrophobic moieties (the
dansyl groups) closer, favoring the quenching. A slight red-shift
of the maxima of emission (from 492 to 501 nm) was also
observed (Table 2 and solid lines in Figure 4), which might be
related to changes in the polarity of the solvent [18]. Given that
dioxane and water are miscible, we decided to measure the fluo-
rescence spectra of compound 10 in mixtures of both solvents in
various proportions. Even a small quantity of water in dioxane
(molar fraction 0.1) is sufficient to induce a large drop in the
fluorescence intensity. To our surprise, increasing the quantity
of water induces an increased red-shift of the fluorescence
wavelength up to a molar fraction of 0.8 in water (from 492 to
524 nm), then a dramatic blue-shift is observed as the quantity
Figure 2: UV–vis spectra of compounds 4, 11 and 12 in dioxane.
was increased up to pure water (501 nm) (Figure 4).
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Table 2: Viscosity (η) [17], maximum of absorption (λmax), fluorescence emission (excitation wavelength 347 nm) (λem), and quantum yield (Φ) (refer-
ence: quinine sulfate) of compound 10 in mixtures of water/dioxane with different molar fractions (x) of water in 1,4-dioxane.
xwater
water/dioxane (% v/v)
η (mPa·s)
λmax (1) (nm)
λmax (2) (nm)
λem,max (nm)
quantum yield, Φ (%)
0
0/100
2/98
1.31
1.35
1.45
1.53
1.66
1.86
1.98
2.2
255
248
250
252
250
254
249
252
253
250
249
251
253
252
253
256
336
336
336
338
339
339
337
338
338
336
339
338
341
339
341
340
492
499
505
507
510
514
516
520
524
524
521
514
506
501
501
501
51
47
46
31
28
29
29
29
26
18
18
18
16
17
16
17
0.10
0.20
0.25
0.34
0.47
0.54
0.63
0.75
0.83
0.87
0.89
0.9
5/95
7/93
10/90
15/85
20/80
26/74
39/61
50/50
59/41
62/38
65/35
77/23
83/17
100/0
2.3
2.2
2.01
1.92
1.86
1.50
1.31
1.01
0.94
0.96
1
This unexpected behavior must be related to the variation of the with the viscosity of the mixture dioxane/water. A good correla-
viscosity of the mixtures dioxane/water, which is maximal at tion between both curves is observed, showing that the viscosity
the molar fraction 0.8 [19]. Figure 5 displays the comparison is indeed the most important criterion that needs to be taken into
between the maxima wavelength of emission of dendron 10 account to explain the phenomenon observed.
Figure 4: Emission spectra (λexc = 347 nm) of compound 10 in mixtures water/dioxane with different molar fractions of water (x) in 1,4-dioxane.
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Supporting Information File 1
Experimental details.
19.Omota, L.-M.; Iulian, O.; Ciocîrlan, O.; Niţă, I. Rev. Roum. Chim. 2008,
53, 977–988.
[http://www.beilstein-journals.org/bjoc/content/
supplementary/1860-5397-7-186-S1.pdf]
Supporting Information File 2
Spectral details.
[http://www.beilstein-journals.org/bjoc/content/
supplementary/1860-5397-7-186-S2.pdf]
Acknowledgements
Thanks are due to the CNRS for financial support and to the
COST program CM0802 (PhoSciNet).
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