Synthesis of novel bis(perfluorophenyl azides) coupling agents: Evaluation of their performance by crosslinking of poly(ethylene oxide)

Article abstract of DOI:10.1016/j.reactfunctpolym.2011.07.011

Novel bis(perfluorophenyl azides) coupling agents, containing spacer arms from ethylene or ethylene glycol subunits, were successfully synthesized. Nitrenes photogenerated from these novel bis(PFPA) coupling agents were applied successfully to the cross-l

Full text of DOI:10.1016/j.reactfunctpolym.2011.07.011

Reactive & Functional Polymers 71 (2011) 1110–1117
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Reactive & Functional Polymers
journal homepage: www.elsevier.com/locate/react
Synthesis of novel bis(perfluorophenyl azides) coupling agents: Evaluation of
their performance by crosslinking of poly(ethylene oxide)
a
Hakim Mehenni a,b, , Osman M. Bakr
⇑
a Functional Nanomaterials Laboratory, Department of Materials Science, King Abdullah University of Science and Technology, Thuwal 23955, Saudi Arabia
b Unité de Chimie Organique et Médicinale, Université Catholique de Louvain, B-1348 Louvain-la-Neuve, Belgium
a r t i c l e i n f o
a b s t r a c t
Article history:
Novel bis(perfluorophenyl azides) coupling agents, containing spacer arms from ethylene or ethylene
glycol subunits, were successfully synthesized. Nitrenes photogenerated from these novel bis(PFPA) cou-
pling agents were applied successfully to the cross-linking of poly(ethylene oxide) (PEO10,000) in either
aqueous medium or at the solid state, thus, we demonstrated the potential of these bis(PFPA) molecules
as promising coupling agents in surface engineering.
Received 25 November 2010
Received in revised form 21 May 2011
Accepted 27 July 2011
Available online 11 August 2011
Ó 2011 Published by Elsevier Ltd.
Keywords:
Nitrene
Bis(perfluorophenyl azides)
Coupling agents
Crosslinking
Photoactivation, Covalent networks
Spacer arm
Poly(ethylene oxide)
1. Introduction
identical PFPA groups linked together by a spacer arm. They are
often used in one-step reaction procedures to crosslink oligomers
Crosslinking is the process of chemically joining two or more
molecules with a covalent bond [1]. Coupling agents that use the
phenylazide group are among the most popular because of their
high reaction efficiencies, excellent storage stability, and ease of
preparation [2]. Photoactivation of the phenyl azide generates a
highly reactive nitrene intermediate (due to its electron deficiency)
that can potentially react with neighboring CAH, NAH, and C@C
bonds to form a covalent bond, thus give highly stable covalently
modified products [2–11]. Furthermore, it has been determined
that the introduction of fluorine atoms on the phenyl ring increases
the yield of the CH or NH insertion as well as the C@C addition
reaction of the nitrene intermediates [12–14]. Indeed, there is
strong evidence that the presence of a halogen atom on the phenyl
ring increases the lifetime of the corresponding halogenated
phenyl nitrenes significantly and thus offers more opportunities
to react with neighboring molecules [12,15–17]. Therefore, it is
not surprising that many coupling agents that use the perfluor-
ophenyl azide (PFPA) group have been developed over the last
few years. Homobifunctional PFPA coupling agents have two
or polymers. Indeed, bis(PFPA) groups have already been devel-
oped as novel efficient crosslinkers for polystyrene [18], poly(3-
octylthiophene) [19], polyimide [20] and poly(vinyl phenol) [21],
but are much less developed for biological applications because
of their limited solubility in aqueous media. In biology, the PFPA
group has often been used as a heterobifunctional coupling agent
(p-substituted tetrafluorophenyl azide) in the biofunctionalization
of surfaces by linking together biomolecules and surfaces via the
two reactive centers, i.e., a chemoselective functional group in
the para position of the tetrafluorophenyl azide and the light-activ-
able azido group. For example, the activated PFPA N-hydroxysucc-
inimidyl (NHS) ester has been used for the covalent immobilization
of proteins on polymer film surfaces [22,23]. However, most of
these methods are time-consuming, complex, and involve multiple
steps because the biomolecules (proteins) are soluble only in an
aqueous medium where PFPA-NHS esters usually have limited sol-
ubility. Consequently, a first step performed in organic medium is
required in which the polymer films are functionalized with PFPA-
NHS. Proteins are then conjugated to the polymer films via the sur-
face NHS groups. In contrast, the vital advantage of the utilization
of a homobifunctional PFPA coupling agent, which is soluble in
aqueous media, is its use as a one-step reaction procedure to link
the biomolecule (e.g. protein) to the polymer surface, provided that
the biological properties of the biomolecule are not destroyed by
⇑
Corresponding author at: Functional Nanomaterials Laboratory, Department of
Materials Science, King Abdullah University of Science and Technology, Thuwal
23955, Saudi Arabia.
E-mail address: hakim.mehenni@kaust.edu.sa (H. Mehenni).
1381-5148/$ - see front matter Ó 2011 Published by Elsevier Ltd.
doi:10.1016/j.reactfunctpolym.2011.07.011

H. Mehenni, O.M. Bakr / Reactive & Functional Polymers 71 (2011) 1110–1117
1111
UV irradiation. The polymer surface could then be simply rinsed
thoroughly with the same aqueous solvent, to remove the non-
immobilized proteins. Moreover, homobifunctional PFPA coupling
agents containing a long spacer arm have not been developed be-
fore, despite the need for coupling agents that can be tailored with
spacers that can span the distances between potential reaction
sites for crosslinking in various organic systems of interest [24].
Generally, short spacer arms are often used for intramolecular
crosslinking while long spacer arms promote intermolecular cross-
linking [24].
with reference to tetramethylsilane. Signals are described in terms
of chemical shifts, multiplicity and assignment. The following
abbreviations were used: s (singlet), d (doublet), dd (doublet of
doublets), m (multiplet) and b (broad). Mass measurements were
performed on a LCQ instrument from ThermoFinnigan (San-José,
California) in ESI and APCI ionization modes. Either protonated
molecular ions (M+H)+ or sodium adducts (M+Na)+ were used for
peak assignment. The Infra-Red spectra were recorded on a Shima-
dzu Infrared spectrophotometer (FTIR – 8400S) over the range of
600–4000 cmꢀ1. The melting points were measured using a Fish-
er–Johns Melting Point Apparatus. UV–vis spectra were recorded
on a Varian spectrophotometer (Cary, 50 Conc). Photolysis was
performed under UV lamps of k = 254 nm. Molar masses and poly-
dispersity indices of the polymers were measured on a Waters SEC
system equipped with a Waters 510 pump and a 410 differential
refractometer (40 °C; eluent: DMF; flow rate of 0.5 mL/min) and
on a PSS SEC system equipped with an Agilent 1200 series differen-
tial refractometer (35 °C; eluent: DMF; flow rate of 1 mL/min). The
calibration was performed using polyethylene oxide (PEO)
standards.
Consequently, we have developed novel bisPFPA coupling
agents containing different spacer arm lengths to increase their
solubility in aqueous medium and their efficiency at crosslinking
sites of varying distances in macromolecules.
We have synthesized the N,N0-heptyl-1,7-bis (4-azido-20,30,50,
60-tetrafluorobenzamide) (3a) and the N,N0-dodecyl-1,12-bis (4-azi-
do-20,30,50,60-tetrafluorobenzamide) (3b) which contain spacer arms
of ethylene subunits, resulting in a polyethylene chain. We have
also synthesized the N,N0-(3,6,9-trioxaundecyl)-1,11-bis (4-azido-
20,30,50,60-tetrafluorobenzamide) (3c) and the N,N0-(3,6,9,12,15-pen-
taoxaheptadecyl)-1,17-bis (4-azido-20,30,50,60-tetrafluorobenzamide)
(3d) compunds, which contain spacer arms of ethylene glycol
subunits, resulting in a polyethylene oxide chain with abundant
oxygen atoms to provide water solubility. Herein, we report the
synthesis and the characterization of these novel bisPFPA coupling
agents, and illustrate their potential utilization: oligomers of poly-
2.3. Synthesis of the bis(perfluorophenyl azides) crosslinking agents
2.3.1. With hydrophobic spacer arm (3a and 3b)
The N-hydroxysuccinimidyl 2,3,5,6-tetrafluorobenzoate (NHS
PFPA ester) (1) was synthesized following a previously reported
procedure [13].
ethylene oxide with a molecular mass of 10,000 g/mol (PEO10,000
were crosslinked in both solid state and aqueous media.
)
N3
N3
F
F
F
F
F
F
F
F
N3
N3
(3c)
F
F
F
F
F
F
F
F
(3a)
(3b)
O
O
N
N
O
O
O
H
H
N
O
N
O
H
H
N3
N3
N3
F
F
F
F
F
F
F
N3
F
F
F
F
F
F
F
(3d)
F
F
HN
O
HN
O HN
O
O
O
N
O
O
O
O
H
Bis(perfluorophenylazides) coupling agents
2. Experimental section
2.3.1.1. N,N0-heptyl-1,7-bis (4-azido-20,30,50,60-tetrafluorobenzamide)
2.1. Materials
The following reagents were purchased from the Aldrich Chem-
ical Company (Germany) and used as received: PEO10,000, 1,7-dia-
minoheptane,
1,12-diaminododecane,
1,11-diamino-3,6,9-
trioxaundecane, magnesium sulfate (MgSO4), anhydrous acetoni-
trile (ACN). Dichloromethane (DCM, HPLC grade), chloroform
(CHCl3, HPLC grade) and hexane were purchased from Fischer Sci-
entific. All experimental solutions were prepared using doubly dis-
tilled water obtained from a Milli-Q water system (18 M
X cm).
2.2. Characterization
(3a).
A solution of 1,7-diaminoheptane (23.12 mg, 0.1775 mmol) dis-
solved in 10 ml anhydrous ACN was added dropwise to the NHS
PFPA ester (118 mg, 0.355 mmol) in 10 ml anhydrous ACN. The
solution was stirred under argon at room temperature for 4 h.
The precipitated white solid was collected by filtration and washed
Nuclear Magnetic Resonance (NMR) spectra were measured at
300, 282 and 125 MHz for 1H , 19F, and 13C spectra, respectively
on Bruker instruments. All NMR spectra were recorded in chloro-
form deuterium (CDCl3) or deuteroacetone (acetone-d6) solutions

1112
H. Mehenni, O.M. Bakr / Reactive & Functional Polymers 71 (2011) 1110–1117
successively with ACN. A 50-ml aliquot of H2O was added and the
product was extracted with 3 ꢁ 50 ml CHCl3. The resulting organic
extracts were assembled, washed three times with 50 ml H2O and
dried over MgSO4. The solvent was then evaporated to give a white
solid. The product was purified by recrystallization overnight in
the fridge (6 °C) from CHCl3/Hexane.
MS (APCI) m/z: 635 (MH+, 100%)
UV (DCM): kmax nm: 260
2.3.2. With hydrophilic spacer arm (3c and 3d)
The 1,17-diamino-3,6,9,12,15-pentaoxaheptadecane was syn-
thesized following a previously reported procedure [25].
Color: white solid
yield: 70% (70 mg)
N3
N3
mp: 128 °C
1
F
F
F
F
F
F
6 F
F
1H NMR (CDCl3, 300 MHz) d: 6.13 (2H, s, NHCO), 3.46
2
000—7000
000—6000
000—4000—5000
(4H; q; H1
), 1.62 (4H; m; H2
), 1.40 (6H; m; H3
)
3
5
13C NMR (CDCl3, 125 MHz) d: 158.1 (CO, amide), 145.4 (m, aryl-
CAF), 143.4 (m, aryl-CAF), 141.8 (d, aryl-CAF), 139.8 (d, aryl-
O
O
1'
N
H
N
H
O
O
O
6'
0
CAF), 122.1 (m, aryl-CACO), 112 (t, aryl-CAN3), 40.2 (C1 ),
0
0
0
29.3 (C2 ), 28.3 (C4 ), 26.5 (C3 ).
RMN 19F (CDCl3, 282 MHz) d: ꢀ141.12 (4F, q, F2–6), ꢀ150.61 (4F,
q, F3–5).
Infra Red: 3294 (
1554, 1485,
m
NH), 2923, 2854, 2125 (
m
N3), 1654 (
m
CO),
2.3.2.1. N,N0-(3,6,9-trioxaundecyl)-1,11-bis (4-azido-20,30,50,60-tetra-
fluorobenzamide) (3c).
995 (
m
CF), 724.
A solution of 1,11-diamino-3,6,9-trioxaundecane (34.7 mg,
MS (ESI) m/z: 587 (MNa+, 100%)
UV (DCM): kmax nm: 260
0.181 mmol) dissolved in 10 ml anhydrous ACN was added drop-
wise to the NHS PFPA ester (120 mg, 0.361 mmol) in 10 ml anhy-
drous ACN. The solution was stirred under argon at room
temperature for 4 h. A 20-ml aliquot of H2O was then added, and
the product was extracted with 3 ꢁ 50 ml CHCl3. The resulting or-
ganic extracts were assembled, washed three times with 50 ml
H2O and dried over MgSO4. The solvent was then evaporated to
give a white solid.
N3
N3
F
F
F
1
F
F
6 F
2
F
Color: white solid
yield: 74% (84 mg)
3
5
F
HN
6'
O
1'
N
H
O
mp: 96.7 °C
1H NMR (CDCl3, 300 MHz) d: 6.74 (2H, s, NHCO), 3.64–3.62
0
0
0
0
(16H, m, H1 –2 –4 –5 ).
13C NMR (CDCl3, 125 MHz) d: 158.1 (CO, amide), 145.4 (m, aryl-
CAF), 143.4 (m, aryl-CAF), 141.7 (d, aryl-CAF), 139.7 (d, aryl-
2.3.1.2. N,N0-dodecyl-1,12-bis (4-azido-20,30,50,60-tetrafluorobenza-
mide) (3b).
0
CAF), 122.1 (m, aryl-CACO), 111.9 (t, aryl-CAN3), 70.8 (C5 ),
0
0
0
70.6 (C2 ), 69.7 (C4 ), 40.3 (C1 ).
A solution of 1,12-diaminododecane (36.3 mg, 0.181 mmol)
dissolved in 10 ml anhydrous ACN was added dropwise to the
NHS PFPA ester (120 mg, 0.361 mmol) in 10 ml anhydrous ACN.
The solution was stirred under argon at room temperature for
4 h. The precipitated white solid was collected by filtration and
washed successively with ACN. 50-ml aliquot of H2O was then
added, and the product was extracted with 3 ꢁ 50 ml CHCl3.
The resulting organic extracts were assembled, washed three
times with 50 ml H2O and dried over MgSO4. The solvent was
then evaporated to give a white solid. The product was purified
by recrystallization from CHCl3/hexane overnight in the fridge
(6 °C).
RMN 19F (CDCl3, 282 MHz) d: ꢀ141.08 (4F, q, F2–6), ꢀ150.73 (4F,
q, F3–5).
Infra Red: 3292 (
m
NH, amide), 2923, 2854, 2125 (
m
N3), 1652 (m
CO, amide), 1558, 1488, 1101, 993 (
MS (APCI) m/z: 627 (MH+, 100%)
UV (DCM): kmax nm: 260
m
CF).
N3
1
N3
F
F
F
F
F
F
6
2
Color: white solid
yield: 57% (66 mg)
3
5
F
F
1'
9'
O
HN
O
O
O
HN
mp: 140.2 °C
O
O
O
1H NMR (CDCl3, 300 MHz) d: 5.95 (2H, s, NHCO), 3.45 (4H, q,
0
H1 ), 1.61 (5H, m, aliphatic), 1.39–1.28 (15H, m, aliphatic).
13C NMR (CDCl3, 125 MHz) d: 157.3 (CO, amide), 144.9 (m, aryl-
CAF), 142.9 (m, aryl-CAF), 141.8 (d, aryl-CAF), 139.8 (d, aryl-
2.3.2.2. N,N0-(3,6,9,12,15-pentaoxaheptadecyl)-1,17-bis (4-azido-
20,30,50,60-tetrafluorobenzamide) (3d).
0
CAF), 121.4 (t, aryl-CACO), 115.5 (t, aryl-CAN3), 40 (C1 ),
0
0
0
0
0
29.76 (C5 –6 ), 29.74 (C2 ), 29.4 (C4 ), 26.9 (C3 ).
RMN 19F (CDCl3, 282 MHz) d: ꢀ141 (4F, q, F2–6), ꢀ150.53 (4F, q,
A solution of 1,17-diamino-3,6,9,12,15-pentaoxaheptadecane
(50.6 mg, 0.181 mmol) dissolved in 5 ml anhydrous ACN was
added dropwise to the NHS PFPA ester (120 mg, 0.361 mmol) in
10 ml ACN. The solution was stirred under argon at room temper-
ature for 4 h. A 15-ml of H2O was then added and the product was
extracted with 3 ꢁ 50 ml CHCl3. The resulting organic extracts
F3–5).
Infra Red: 3315 (
1544, 1475,
m NH), 2921, 2852, 2123 (m N3), 1652 (m CO),
991 (m CF).

H. Mehenni, O.M. Bakr / Reactive & Functional Polymers 71 (2011) 1110–1117
1113
were assembled, washed three times with 50 ml H2O and dried
2.4. General procedure for crosslinking of PEO10,000
over MgSO4. The solvent was then evaporated to give a white
(lightly yellow) liquid.
Our coupling agents (3a and 3b) were used to perform cross-
linking reactions of PEO10,000 in the solid state. While in the aque-
ous liquid state, only the coupling agents 3c and 3d have been used
because of their hydrophilic spacers, which facilitate their solubili-
zation. The irradiation wavelength for photochemical crosslinking
was set to correspond to the absorption peak of the bis(perfluor-
ophenyl azides) coupling agents, for example, Fig. 1 shows the
changes in the UV absorption spectra for the coupling agent 3a
in ACN with increasing irradiation time. The peak was observed
at 260 nm for all of the coupling agents. The intensities of the
absorptions decreased with increasing irradiation time. After 60 s
of irradiation, the absorption peak decreased by 90%, relative to
its original height, suggesting a that UV lamp of 254 nm is efficient
at initiating a photochemical reaction in the PFPA group responsi-
ble for the crosslinking of PEO10,000. The UV–vis spectra of the cou-
pling agent 3b, 3c and 3d are reported in Figs. S9–S11, respectively,
in the Supporting Information.
Color: white liquid
yield: 72% (98 mg)
1H NMR (CDCl3, 300 MHz) d: 7.1 (2H, s, NHCO), 3.62–3.53 (24H,
0
0
0
0
0
0
m, H1 –2 –4 –5 –7 –8 ).
13C NMR (CDCl3, 125 MHz) d: 158.1 (CO, amide), 145.4 (m, aryl-
CAF), 143.4 (m, aryl-CAF), 141.7 (d, aryl-CAF), 139.7 (d, aryl-
0
CAF), 121.8 (t, aryl-CACO), 112.4 (t, aryl-CAN3), 70.8 (C8 ),
0
0
0
0
0
70.75 (C7 ), 70.74 (C5 ), 70.5 (C2 ), 69.8 (C4 ), 40.4 (C1 ).
RMN 19F (CDCl3, 282 MHz) d: ꢀ141.06 (4F, q, F2–6), ꢀ150.9 (4F,
q, F3–5).
Infra Red: 3299 (m NH, amide), 2931, 2871, 2125 (m N3), 1652 (m
CO, amide), 1550, 1488, 1107, 993 (
MS (APCI) m/z: 715 (MH+, 50%)
UV (DCM): kmax nm: 260
m CF).
2.4.1. Crosslinking of PEO10,000 in solid state
10 mg of PEO 10,000 and 1 mg of coupling agent (3a or 3b) were
solubilized and mixed together in 10 ml of DCM (weight ratio of
10%). The solvent was then evaporated to give 11 mg a white solid,
which was intensely crushed to give a fine white powder. Thereaf-
ter, the white powder was transferred to a 10 ml quartz round-bot-
tom flask subsequently exposed to a UV lamp (k = 254 nm), placed
at a distance of 10 cm, for a duration of 15 min.
2.4.2. Crosslinking of PEO10,000 in aqueous phase
0.6 mg of coupling agent (3c or 3d) was solubilized in 30 ll of
ACN. The coupling agent solution was then added and mixed into
a 3-ml Millipore water (or D2O when the photochemical reacting
was monitored by NMR spectroscopy) solution containing 6 mg
of dissolved PEO10,000. Thereafter, the mixture was transferred to
a 4-ml quartz cuvette which was subsequently exposed to a UV
Fig. 1. Evolution of the UV/vis spectra of 3a in ACN (0.17 mM) after irradiation at
254 nm for 60 s at ambient temperature. The curves were measured at 0, 5, 10, 20,
30, 40, 50 and 60 seconds after irradiation.
(2a)
H2N
NH2
(3a)
(3b)
(3c)
(3d)
ACN
(2b)
NH2
H2N
N3
ACN
F
F
F
F
(2c)
2 x
O
O
O
O
NH2
O
H2N
N
O
O
ACN
(1)
(2d)
H2N
O
O
NH2
O
O
O
ACN
Scheme 1. Synthesis of bis(perfluorophenyl azides) coupling agents.

1114
H. Mehenni, O.M. Bakr / Reactive & Functional Polymers 71 (2011) 1110–1117
N3
N3
F
F
F
F
F
F
F
F
Crosslinker 3c
O
O
N
N
H
O
O
O
H
Irradiation
at 254 nm
2 x N2
N
N
F
F
F
F
F
F
F
F
O
O
N
N
O
O
O
H
H
Insertion into C-H bonds
H2
C
H2
C
O
O
O
O
C
O
C
H2
H2
O
CH
C
H
HN
NH
O
F
F
F
F
F
O
F
F
F
O
O
N
N
H
O
O
O
H
Scheme 2. Illustration of crosslinking reaction of PEO10,000
.
lamp (k = 254 nm), placed at a distance of 10 cm for a duration of
15 min. The resultant product (yellow/orange solid) was obtained
by evaporation in vacuum, followed by removing the water azeo-
tropically with ACN.
insert into carbon-hydrogen bonds in PEO10,000 to form substituted
amines. One crosslink forms when these two groups bond to two
different polymer chains. The two chains become joined together
by the crosslink to give a larger molecular weight (Mw) that is
the sum of the two chains. Thus, many different chains of polymer
could be joined to form a crosslinked network of chains.
3. Results and discussion
The crosslinking reaction was monitored by FTIR spectroscopy.
Fig. 2 shows the FTIR spectra of a mixture of PEO10,000 and coupling
agent 3c (weight ratio of 10%) before and after irradiation in the so-
lid state. Before irradiation, the FTIR spectra shows strong absor-
bance bands at 1681 and 2125 cmꢀ1 for the C@O stretch and the
N3 stretch, respectively. After irradiation, the FTIR spectra shows
the disappearance of almost the entire N3 band and a shift of the
C@O band, indicating that the coupling agent had reacted to form
nitrenes and therefore that the crosslinking reaction had gone to
completion. The FTIR spectra of the mixtures of PEO10,000 and the
coupling agents 3a, 3b, 3d and pure PEO10,000 before and after irra-
diation, are shown in Figs. S3, S4, S5 and S6, respectively, in the
Supporting Information. The crosslinking reaction was also moni-
tored by 19F NMR. For example, before irradiation, the 19F NMR
shows the characteristic fluorine signal from the coupling agent
3c (in CDCl3: quadruplet peaks at d/ppm (ref: TFA): ꢀ67.33 and
ꢀ76.15). After irradiation, the 19F NMR spectroscopy shows a shift
in the fluorine peaks from ꢀ67.33 to ꢀ69.82 and from ꢀ76.15 to
ꢀ86.53, indicating a complete conversion of the bis(PFPA) into
bis(perfluorophenyl nitrene).
3.1. Synthesis of the bis(perfluorophenyl azides) coupling agents (3a,
3b, 3c and 3d)
Scheme 1 shows the synthetic routes for bis(perfluorophenyl
azides) coupling agents (3a–3d). The starting materials, NHS PFPA
ester (1) and the 1,17-diamino-3,6,9,12,15-pentaoxaheptadecane
(2c), were synthesized following previously reported procedures
according to refs. [13] and [25], respectively. The compounds 2a,
2b and 2c are commercially available. The NHS is used to activate
carboxylic acid groups and the resulting active esters react readily
with primary amines [26]. Thus, treatment of 2 equivalents of 1
with 1 equivalent of the compounds 2a, 2b, 2c and 2d in ACN at
room temperature for 4 h afforded the bis(perfluorophenyl azides)
coupling agents 3a, 3b, 3c and 3d in 70%, 57%, 74% and 72% yields,
respectively.
3.2. Evaluation of the bis(PFPA) coupling agents as crosslinking agents
for PEO10,000
The crosslinking efficiency of PEO10,000 by our bis(PFPA) cou-
pling agents was also examined by GPC in DMF. The GPC analysis
results in Table 1 clearly demonstrate that the crosslinking capabil-
ity of the bisPFPA coupling agents in the solid state (for 3a and 3b)
and in aqueous medium (for 3c and 3d). Indeed, the comparison of
the GPC elugrams of the PEO10,000 alone with that of PEO10,000
mixed with the corresponding bis(PFPA) coupling agent after UV
irradiation, shows that the crosslinking process leads mainly to
After mixing the corresponding coupling agent with PEO10,000 in
the solid state or in aqueous phase, the coupling agent was photo-
activated by irradiation under a UV lamp at 254 nm for 15 min. A
plausible mechanism for the crosslinking reactions is shown in
Scheme 2 in which a bis(PFPA) coupling agent is used as a cross-
linker. Under photochemical irradiation, the bis(PFPA) decomposes
to nitrogen gas and reactives nitrenes. The resulting nitrenes can

H. Mehenni, O.M. Bakr / Reactive & Functional Polymers 71 (2011) 1110–1117
1115
Fig. 2. FTIR spectrum of a mixture in the solid state of PEO10,000/coupling agent 3c before and after irradiation. The azide peak disappears almost completely after irradiation
which confirming the formation of the product.
the formation of 2 or 3 products corresponding to covalent net-
works of PEO10,000 of very high molecular weights.
The molecular weights of the resulting covalent networks, listed
in Table 1, were determined by GPC using PEO standards. Hence,
the molecular weight values of the produced networks are relative
and not absolute values.
The molecular weights of the resulting covalent networks reach
to approximately, to 42–149 times the PEO10,000 molecular weight,
for the crosslinking in solid state, and up to 57–90 times for the
crosslinking process in aqueous medium. For example, as shown
in Fig. 3, the GPC elugram B exhibits one peak and two major
shoulders, due to the formation of three covalent networks, P1,
P2 and P3, corresponding to molecular weights of 420,970,
686,860 and 1,490,200 g/mol, respectively. The formation of these
peaks and corresponding molecular weights was caused by the UV
irradiation of PEO10,000 mixed with the coupling agent 3a (weight
ratio 10%) in the solid state. The GPC elugram C (using coupling
agent 3c in water) shows only one peak and one shoulder, due to
the formation of 2 major networks, P1 and P2, corresponding to
molecular weights of 572,090 and 941,780 g/mol, respectively.
The GPC elugrams of the resulting products of the crosslinking of

1116
H. Mehenni, O.M. Bakr / Reactive & Functional Polymers 71 (2011) 1110–1117
Table 1
Table 2
Resulting products of the cross-linking of PEO10,000 using 2a, 2b, 2c and 2d in solid
Resulting products of the cross-linking of PEO10,000 using 2c and 2d in aqueous phase.
state.
Crosslinker
Resulting products
Mn GPC (g/mol)
Mw/Mn GPC (PDI)
Crosslinker
Resulting products
Mn GPC (g/mol)
Mw/Mn GPC (PDI)
3c
P1
P2
572,090
941,780
1.02
1.02
3a
P1
P2
P3
420,970
686,860
1490,200
1.01
1.02
1.05
3d
P1
P2
578,240
904,800
1.02
1.02
3b
3c
3d
P1
P2
467,580
735,910
1.01
1.01
P1
P2
421,440
767,650
1.01
1.05
nitrenes photogenerated upon the spacer arms of other coupling
agents. Concerning the UV irradiation effects upon the PEO10,000
,
P1
P2
530,370
826,130
1.02
1.02
we discarded the possibility that the UV irradiation could degrade
the PEO10,000 because the GPC elugrams of irradiation tests of
PEO10,000, in the same experimental conditions but in absence of
bis(PFPA) coupling agents, have not shown any other peak than
that of the PEO10,000. Even though that the crosslinking process is
non-specific and partial, due to the remaining presence of
PEO10,000 after the crosslinking process, these results are promising
and clearly illustrate the crosslinking potential of our bis(PFPA)
coupling agents in the solid state (for 3a and 3b) and in aqueous
medium (for 3c and 3d).
PEO10,000 using 3b and 3d are respectively reported in Figs. S1 and
S2 in the supporting information (see Table 2).
In the case of the crosslinking reaction of PEO10,000 in the solid
state, the 3a coupling agent was shown to be more efficient than
the 3b, with molar yields of 0.167 and 0.157, respectively. Due to
the difficulty of predicting the molecular weight of the PEO net-
work products, the molar yield corresponds to the number of
PEO10,000 moles crosslinked by one mole of coupling agent after
the UV irradiation (see Table S1 in Supporting information for
more details). In the case of aqueous solutions, the 3c coupling
agent is more efficient than the 3d with molar yields of 0.125
and 0.105, respectively.’’
4. Conclusion
Novel bis(PFPA) coupling agents, containing different spacer
arm lengths were successfully synthesized. We synthesized four
new coupling agents: N,N0-heptyl-1,7-bis (4-azido-20,30,50,60-tetraflu-
orobenzamide) (3a), N,N0-dodecyl-1,12-bis (4-azido-20,30,50,60-tetra-
fluorobenzamide) (3b), N,N0-(3,6,9-trioxaundecyl)-1,11-bis (4-azido-
20,30,50,60-tetrafluorobenzamide) (3c) and N,N0-(3,6,9,12,15-pentaoxa-
heptadecyl)-1,17-bis (4-azido-20,30,50,60-tetrafluorobenzamide) (3d).
We also noticed the emergence of peaks situated at larger elu-
tion volumes, hence at lower molecular weights, in comparison to
the PEO10,000 elution volume. One possible explanation is that
these products could be the result of chemical interactions of the
Fig. 3. (A) GPC elugram of the PEO10,000 alone, GPC elugrams of the resulting products of the crosslinking of PEO10,000 using 3a (B) in solid state and 3c (C) in water.

H. Mehenni, O.M. Bakr / Reactive & Functional Polymers 71 (2011) 1110–1117
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1117
Crosslinking tests of PEO10,000, in the solid state or in aqueous
medium, by photochemical activation under UV light, showed that
our bis(PFPA) coupling agents are highly efficient due to the forma-
tion of the resulting PEO10,000 covalent networks having very high
molecular weights. Thus, these new bis(PFPA) coupling agents are
very promising, especially the coupling agents 3c and 3d, because
of their ability to crosslink under aqueous conditions.
Consequently, they could become versatile tools for covalent link-
ing in biology (biofunctionalization of surfaces).
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This work was supported by a grant from the Wallonia region
(Belgium) and King Abdullah University of Science and Technology
(Saudi Arabia).
Appendix A. Supplementary material
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.reactfunctpolym.2011.07.011.
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Publication Date (Web): August 6, 2010.