Novel Trifunctional Building Blocks for Fluorescent Polymers

Article abstract of DOI:10.1021/ol035500m

(Matrix presented) Herein, we describe the synthesis of fluorescent 2-(arylsulfonyl)methacrylates and its polymers. These novel trifunctional monomers, possessing a fluorescent arylsulfonyl (ArSO₂) group, an alkyl group (R), and a polymerizable olefin, serve as useful building blocks for functionalized fluorescent polymers.

Full text of DOI:10.1021/ol035500m

ORGANIC
LETTERS
2
003
Vol. 5, No. 21
895-3898
Novel Trifunctional Building Blocks for
Fluorescent Polymers
3
Dolly Batra and Kenneth J. Shea*
Department of Chemistry, UniVersity of California, IrVine, IrVine, California 92697
kjshea@uci.edu
Received August 7, 2003
ABSTRACT
Herein, we describe the synthesis of fluorescent 2-(arylsulfonyl)methacrylates and its polymers. These novel trifunctional monomers, possessing
a fluorescent arylsulfonyl (ArSO ) group, an alkyl group (R), and a polymerizable olefin, serve as useful building blocks for functionalized
fluorescent polymers.
2
Fluorescent probes have played an important role in the
elucidation of physical properties of polymers.1,2 The intro-
duction of the fluorescent probe can be achieved either by
incorporating the probe in a polymerizable monomer or by
uptake following polymerization, either by physical absorp-
tion or covalent attachment. We are developing general
strategies for the introduction of fluorescent diagnostics in
molecularly imprinted network polymers (MIPs). An im-
portant goal of this strategy is to locate the probe in proximity
to the MIP binding site.
noncovalent interaction between the fluorescent monomer
and the template. This resulted in significant nonspecific
fluorescence not associated with analyte binding. A key
design element to a successful MIP fluorescent sensor is to
locate the fluorescent probe only at the binding site.
To that goal, we have designed a new family of polymer-
izable trifunctional monomers 1 that contain a polymerizable
double bond, a functional group to covalently bind the
imprint molecule (R), and a fluorescent probe (F) fragment.
Covalent linking of probe (F) and template (R) would achieve
proximity of the diagnostic only at the binding site. The
monomers described in this report are compatible with radical
copolymerizations, and the imprint molecule (R) can be
cleaved following incorporation into a suitable polymer.
An application of these MIPs would be as chemical
sensors, where the fluorescent probe would serve as a
3
transducer for the binding event. In two recent examples,
the fluorescent molecule was incorporated into the polymer
4
5
matrix or the binding site by a polymerizable fluorescent
probe. In both of these approaches, however, considerable
background fluorescence was observed as a result of the
(
1) Gillispie, G. D. In Structure-Property Relations in Polymers; Urban,
M. W., Craver, C. D., Eds.; American Chemical Society: Washington, DC,
993; Vol. 236, pp 89-127.
2) Winnik, M. A. Photophysical and Photochemical Tools in Polymer
1
(
Science: Conformation, Dynamics, Morphology; D. Reidel Publishing
Company: Boston, 1985; Vol. 182.
(
(
(
3) Haupt, K.; Mosbach, K. Chem. ReV. 2000, 100, 2495-2504.
4) Ye, L.; Mosbach, K. J. Am. Chem. Soc. 2001, 123, 2901-2902.
5) Turkewitsch, P.; Wandelt, B.; Darling, G. D.; Powell, W. S. Anal.
We chose aryl sulfonyl groups such as 5-(dimethylamino)-
-naphthalenesulfonyl (dansyl), 2-anthracenesulfonyl, and
1-pyrensulfonyl as the fluorescent moieties because of the
1
Chem. 1998, 70, 2025-2030.
1
0.1021/ol035500m CCC: $25.00 © 2003 American Chemical Society
Published on Web 09/25/2003

ready availability of their sulfonyl chloride derivatives and
their application as microenvironment diagnostics in polymer
Table 1. Synthesis of Monomers 7
6,7
systems.
Monomers bearing the dansyl group8,9 were synthesized
by a modified procedure based on the work of Najera et
1
0,11
al.
(
Dansyl iodide (4) was synthesized from the chloride
12
2) by a Na SO /NaHCO reduction, followed by an iodine
oxidation in 70% overall yield (Scheme 1). This conversion
2 3 3
13
Scheme 1
probe could also be incorporated into the cross-linking
monomer, ethylene glycol dimethacrylate (EGDMA), and
bulky functional monomer, tert-butyl methacrylate, albeit in
modest yield (30-32%).
Fluorescent monomers bearing a 2-anthracenesulfonyl or
1-pyrenesulfonyl group were targeted next. However, the
conversion of commercially available anthracenesulfonyl
chloride (8) and pyrenesulfonyl chloride (9) to the corre-
sponding iodides was not successful because of the insolubil-
ity of the arylsodium sulfinate intermediates. To overcome
this difficulty, 2-anthracenesulfonyl chloride (8) and 1-py-
renesulfonyl chloride (9) were reduced to the corresponding
aryl thiols under anhydrous conditions using dichlordimeth-
ylsilane, zinc, and dimethylacetamide (Scheme 3).14 In situ
to the iodide was necessary because the subsequent halo-
sulfonylation of methacrylates does not proceed with sulfonyl
chlorides.
Condensation of dansyl iodide (4) with methacrylate 5 was
achieved in a one-pot procedure by the addition of triethyl-
amine. The reaction involves a tandem iodosulfonylation-
dehydroiodination to afford the vinylic sulfone 6, which is
equilibrated to the thermodynamically more stable allylic
sulfone 7 under reflux in the presence of base (Scheme 2).
Scheme 3
Scheme 2
This methodology was applicable for the conversion of
methacrylates 5a-e to the corresponding (2-dansyl)-
methacrylates 7a-e (Table 1). The reaction proceeded in
moderate 60-78% yields for most R groups. The fluorescent
addition of 2-bromomethacrylate 10 to the reaction mixture
gave the aryl sulfides 11 and 12 in 25-36% overall yield.
(9) Morawetz, H. In Photophysical and Photchemical Tools in Polymer
Science: Conformation, Dynamics, Morphology; Winnik, M. A., Ed.; D.
Reidel Publishing Company: Boston, 1985; Vol. 182, pp 85-96.
(10) Najera, C.; Baldo, B.; Yus, M. J. Chem. Soc., Perkin Trans. 1 1988,
1029-1032.
(
6) (a) Shea, K. J.; Sasaki, D. Y.; Stoddard, G. J. Macromolecules 1989,
2, 1722-1730. (b) Shea, K. J.; Stoddard, G. J.; Sasaki, D. Y. Macromol-
ecules 1989, 22, 4303-4308.
7) (a) Carlier, E.; Revillon, A.; Chauvet, J. P. Eur. Polym. J. 1993, 29,
25-830. (b) Carlier, E.; Revillon, A.; Guyot, A.; Chauvet, J. P. Eur. Polym.
J. 1993, 29, 819-823.
8) Li, Y. H.; Chan, L. M.; Tyer, L.; Moody, R. T.; Himel, C. M.;
Hercules, D. M. J. Am. Chem. Soc. 1975, 97, 3118-3126.
2
(
(11) Najera, C.; Mancheno, B.; Yus, M. Tetrahedron Lett. 1989, 30,
3837-3840.
8
(12) Field, L.; Clark, R. D. Org. Synth. 1958, 38, 62-65.
(13) Harvey, I. W.; Phillips, E. D.; Whitham, G. H. Tetrahedron 1997,
53, 6493-6508.
(
3896
Org. Lett., Vol. 5, No. 21, 2003

Table 2: Synthesis and Analysis of Polymers Derived from Fluorescent Monomers 7d, 13, and 14
a
Determined by GPC analysis (THF, 35 °C, polystyrene standard). b Calculated from residual fluorescence of the MeOH extraction of the polymers.
c
Molecular weight could not be determined because of the insolubility of the polymer. d Determined for the soluble portion of the polymer (∼5%). Remaining
portion of the polymer was insoluble and its molecular weight could not be determined.
Although low yielding, this methodology offers a rapid one-
pot procedure for attaching the pyrene and anthracene
moieties to methacrylates. The sulfides can subsequently be
oxidized to the desired sulfones 13 and 14 using oxone in
good yield.
Although the fluorescence spectra of the swollen polymers
showed the presence of the anthracene moiety, the peaks
were significantly shifted compared to the monomer 13. This
change could have been caused by the polymer microenvi-
8
ronment but could also show evidence of the anthracene
2
-Substituted methacrylates have been successfully homo-
group reacting under the thermal, radical polymerization
conditions and resulting in a cross-linked polymer. The
mechanism for this cross-linking is currently under investiga-
tion.
The labeled polymers were analyzed for fluorescent
monomer incorporation by measuring the residual fluores-
cence of the MeOH extracts from the polymer precipitations.
This was done from Beer’s law plots of the fluorescence
emission maxima of monomers 7d, 13, and 14 at various
concentrations. The plots were then used to determine the
residual fluorescence in the MeOH extracts.
15-18
polymerized.
Template loading in molecularly imprinted
polymers, however, is typically 1-2%. For diagnostic
applications, loadings can be substantially less. Therefore,
to demonstrate the efficacy of these fluorescent molecules
as reactive polymerizable monomers, one monomer from
each fluorescent derivative, dansyl (7d), 2-anthracenesulfonyl
13) and 1-pyrenesulfonyl (14) was copolymerized with an
excess of styrene or methyl acrylate (Table 2).
The resulting polymers were precipitated with MeOH and
analyzed by GPC (THF, 35 °C, polystyrene standard, Table
(
19
2
). The polymers were high molecular weight (30-168 k),
All three fluorescent monomers were incorporated quan-
titatively (>99%) into the polystyrenes (P1-P3, Table 2).
These results agreed with the comparable reactivity ratios
and the PDI ranged from 1.9-3.8. These materials compared
well with the molecular weight and PDI of polymers
synthesized in the absence of fluorescent monomer, i.e.,
polystyrene P7 and polyacrylate P8. Two polymers, P2 and
P5, which incorporated the 2-anthracenesulfonyl monomer
found for styrene (r
1
) 0.52) with methacrylate (r
) 0.46).20
2
As for the polyacrylates, the dansyl and 1-pyrenesulfonyl
derivatives were found to be incorporated at 80% and 77%
within the polymers P4 and P6, respectively. This lower
13, gave insoluble polymers that swelled in organic solvents.
incorporation agrees with the mismatched reactivity ratios
(
(
14) Uchiro, H.; Kobayashi, S. Tetrahedron Lett. 1999, 40, 3179-3182.
15) Smith, T. J.; Mathias, L. J. Biomacromolecules 2002, 3, 1392-
20
of methacrylates (r
1
) 1.91) with acrylates (r ) 0.50).
2
The anthracenesulfonyl monomer 13 seemed to be an
exception, proving to be very reactive with methyl acrylate
and giving more than 99% incorporation in polymer P5. This
higher reactivity may be due to the reactivity of the
anthracene group under the free radical polymerization
conditions, giving a cross-linked polymer (vide supra).
1
3
4
399.
(16) Avci, D.; Mathias, L. J. J. Polym. Sci., Part A: Polym. Chem. 1999,
7, 901-907.
(17) Avci, D.; Mathias, L. J. J. Polym. Sci., Part A: Polym. Chem. 2002,
0, 3221-3231.
18) Avci, D.; Kusefoglu, S. H.; Thompson, R. D.; Mathias, L. J.
Macromolecules 1994, 27, 1981-1982.
19) The monomers 7d, 13, and 14 were copolymerized at 1 mol %.
(
(
The polymers were initiated thermally (65 °C) by AIBN (1 mol %). Styrene
polymerizations were carried out neat. Acrylate polymerizations required
solvent (1:1, CH3CN/CHCl3) for solubility of the fluorescent monomers in
the reaction mixture.
(20) Reactivity ratios calculated from Alfrey-Price Q-e values at 60 °C.
See Allcock, H. R.; Lampe, F. W. In Contemporary Polymer Chemistry;
Prentice Hall: Englewood Cliffs, 1990; pp 309-311.
Org. Lett., Vol. 5, No. 21, 2003
3897

Finally, the use of these labeled functional monomers in
imprinted polymers requires the template molecule to be
selectively cleaved after polymerization without loss of
fluorescence. This can be performed in the styrene polymers,
as the ester moiety is only present at the functional site. The
ester group can be cleaved from the polymer under a variety
incorporation of a fluorescent diagnostic at a MIP binding
site is necessary. We are currently incorporating these
monomers in cross-linked imprinted polymers and analyzing
their ability to behave as chemosensors for steroids and
marine toxins. In addition to various MIPs, these monomers
can also be incorporated into other functionalized polymers
where a fluorescent probe (F) and an amenable functional
group (R) are required in a polymerizable monomer. For
styrene-based polymers, the R group can be successfully
cleaved under reducing conditions.
21
of conditions. We chose to reductively cleave the template
22
with LiAlH
4
,
which removed the cholesterol group from
the polymer P1, leaving the fluorescent dansyl group in tact.
The resulting polymer P9 showed the same fluorescent
properties as P1, and 69% of the theoretical amount of
cholesterol present in polymer P1 was recovered (Scheme
Acknowledgment. This work was supported by grants
from the NIH and the FDA administered by the Florida
Marine Research Institute. Special thanks to Dr. Robert
Dickey of Gulf Coast Seafood Laboratory, Dauphin Island,
AL. We also thank Allergan for a research fellowship for
D.B.
4).
Scheme 4
Supporting Information Available: Experimental pro-
cedures and characterization data for all compounds; ex-
perimental procedures for the synthesis and analysis of all
fluorescent polymers is also available. This material is
available free of charge via the Internet at http://pubs.acs.org.
OL035500M
(
21) Shea, K. J.; Thompson, E. A.; Pandey, S. D.; Beauchamp, P. S. J.
Am. Chem. Soc. 1980, 102, 3149-3155.
22) Bystrom, S. E.; Borje, A.; Akermark, B. J. Am. Chem. Soc. 1993,
115, 2081-2083.
In conclusion, the methodologies described above offer
convenient syntheses of trifunctional monomers where the
(
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Org. Lett., Vol. 5, No. 21, 2003