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Synthesis and properties of fluoroalkylated end-capped betaine polymers
PERGAMON
European Polymer Journal 35 (1999) 1611±1617
Synthesis and properties of ¯uoroalkylated end-capped betaine polymers Hideo Sawada a, b, *, Michinori Umedo b, Tokuzo Kawase c, Toshio Tomita d, Masanori Baba e a Department of Chemistry, Nara National College of Technology, Yata, Yamatakoriyama, Nara 639-1080, Japan Department of Chemistry, Faculty of Advanced Engineering, Nara National College of Technology, Yata, Yamatokoriyama, Nara 639-1080, Japan c Faculty of Human Life Science, Osaka City University, Sugimoto, Sumiyoshi-ku, Osaka 558-8585, Japan d Faculty of Agriculture, Tohoku University, Tsutsumidori-Amamiya, Aoba-ku, Sendai 981-8555, Japan e Division of Human Retroviruses, Center for Chronic Viral Diseases, Faculty of Medicine, Kagoshima University, Sakuragaoka, Kagoshima 890-8520, Japan
b
Received 25 May 1998; accepted 28 September 1998
Abstract Per¯uoropropylated and some per¯uoro-oxaalkylated end-capped 2-(3-acrylamidopropyldimethylammonio)ethanoate (APDMAE) polymers were prepared by the reactions of ¯uoroalkanoyl peroxides with the corresponding monomer. These ¯uoroalkylated end-capped betaine polymers were soluble in water, methanol and ethanol. However, in these ¯uorinated APDMAE polymers, longer per¯uoro-oxaalkylated end-capped APDMAE polymers were found to form highly viscoelastic ¯uids in water at concentrations above 10 g dm ÿ 3 under non-crosslinked conditions. The series of ¯uoroalkylated end-capped APDMAE polymers, especially longer per¯uoro-oxaalkylated polymers, were able to reduce the surface tension of water eectively with a clear break point resembling a CMC at ca. 0.2 g dm ÿ 3. In addition, some of these ¯uoroalkylated end-capped APDMAE polymers exhibited antibacterial activity against Staphylococcus aureus and Penicillium aeruginosa. Therefore, these ¯uoroalkylated end-capped polymers are suggested to have high potential for new functional materials through not only their unique physical properties, such as surfactant and gelling characteristics, but also antibacterial activity. # 1999 Elsevier Science Ltd. All rights reserved.
1. Introduction Fluorinated polymers, especially partially ¯uorinated polymers, are attractive functional materials because they exhibit various excellent properties, such as a high solubility and biological activities which cannot be achieved by the per¯uorinated polymers [1±6]. From this point of view, we have been actively studying the
* Corresponding author. Fax: +81-743-55-6169; e-mail: [email protected]
synthesis and application of partially ¯uorinated polymers, that is, ¯uoroalkylated end-capped polymers by using ¯uoroalkanoyl peroxides as key intermediates [7]. In these ¯uoroalkylated end-capped polymers, we have recently found that ¯uoroalkylated end-capped 2-acrylamido-2-methylpropanesulfonic acid polymer can cause gelation under non-crosslinked conditions, and that the strong aggregation of the end-capped ¯uoroalkyl segments in water and/or organic media becomes a new driving factor for gelation in addition to the ionic interaction of the betaine segments [3]. Furthermore, these ¯uoroalkylated end-capped poly-
0014-3057/99/$ - see front matter # 1999 Elsevier Science Ltd. All rights reserved. PII: S 0 0 1 4 - 3 0 5 7 ( 9 8 ) 0 0 2 5 0 - X
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H. Sawada et al. / European Polymer Journal 35 (1999) 1611±1617
Table 1 Reactions of ¯uoroalkanoyl peroxides with APDMAE RF-(APDMAE)n-RF RF in Peroxide (mmol)
APDMAE (mmol)
C3F7 3 57 CF(CF3)OC3F7 3 66 CF(CF3)OCF2CF(CF3)OC3F7 2 33 CF(CF3)OCF2CF(CF3) OCF2CF(CF3)OC3F7 1 18 CF(CF3)OCF2CF(CF3) OCF2CF(CF3) OCF2CF(CF3)OC3F7 1 9
Yielda
n M w =M n b M
50
174,700 (3.74)
43
536,800 (1.82)
51
433,100 (1.90)
44
178,700 (4.61)
29
123,800 (5.22)
a
The yields were based on the starting materials (APDMAE) and the decarboxylated peroxide unit (RF±RF). The molecular weights were calculated based on GPC.
b
mers were also shown to be potent and selective inhibitors against HIV-1 replication [8, 9]. Therefore, it is of particular interest to develop the ¯uoroalkylated endcapped polymers, especially novel ¯uorinated betainetype polymers possessing a gelling ability. In this study, we would like to report on the synthesis and properties of novel ¯uoroalkylated end-capped 2-(3 acrylamidopropyldimethylammonio)-ethanoate polymers. 2. Results and discussion The reactions of 2-(3-acrylamidopropyldimethylammonio)ethanoate [APDMAE] with ¯uoroalkanoyl peroxides proceeded under very mild conditions (408C/ 5 h) to give the corresponding ¯uoroalkylated endcapped polymers [RF-(APDMAE)n-RF] as shown in Scheme 1.
The results are shown in Table 1. As shown in Table 1, not only per¯uoropropylated but also per¯uoro-oxaalkylated end-capped APDMAE polymers were obtained in 29±51% isolated yields. Previously, we reported that ¯uoroalkanoyl peroxides react with acrylic acid to give acrylic acid oligomers containing two ¯uoroalkylated end groups [RF-(CH2CHCO2H)n-RF; Mn = 3460±12,800; Mw/ Mn = 1.40±1.82] under similar reaction conditions [10, 11]. The molecular weights and Mw/Mn of these polymers by GPC [gel permeation chromatography calibrated with poly(ethylene glycol) standards by using 0.2 mol dm ÿ 3 Na2HPO4 solution as the eluent] were found to be relatively higher (Mn = 123,800± 536,800) compared with those of ¯uoroalkylated endcapped acrylic acid oligomers, respectively, as in Table 1. These results suggest that our present ¯uoroalkylated end-capped APDMAE polymers can easily form molecular aggregates in aqueous solutions. Thus,
H. Sawada et al. / European Polymer Journal 35 (1999) 1611±1617
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Table 2 Solubility of RF-(APDMAE)n -RF Solvent Run RF in RF-(APDMAE)n-RF
H2O MeOH EtOH THF CHCl3 PhH DMSO DMF
1 2 3 4 5 6
wa w w qc q w
C3F7 CF(CF3)OC3F7 CF(CF3)OCF2CF(CF3)OC3F7 CF(CF3)OCF2CF(CF3) OCF2CF(CF3)OC3F7 CF(CF3)OCF2CF(CF3) OCF2CF(CF3) OCF2CF(CF3)OC3F7 -(APDMAE)n-
w w w w w w
Xb w X w w w
X X X X X X
X X X X X X
X X X X X X
X X X X X X
X X X X X X
a
(w) Soluble. (X) insoluble. c (q) gel. b
the molecular weights by GPC indicate the apparent molecular weights. The series of ¯uoroalkylated end-capped APDMAE polymers thus obtained were tested for solubility, and these results are listed in Table 2. In general, these ¯uoroalkylated end-capped APDMAE polymers were found to be soluble not only in water but also in methanol, and some ¯uorinated polymers (runs 2, 4 and 5) were also soluble in ethanol. However, interestingly, APDMAE polymers with longer per¯uoro-oxaalkyl groups (m = 2, 3) can form highly viscoelastic ¯uids (or can cause gel formation), as shown in Table 2. In contrast, non-¯uorinated APDMAE polymer and ¯uorinated APDMAE polymers with per¯uoropropyl and shorter per¯uoro-
Fig. 1. Viscosity of aqueous solutions of RF-(APDMAE)n-RF at 308C. (w) RF = C3F7; (R) RF = CF(CF3)OCF2CF(CF3)OC3F7; (r) RF = CF(CF3)OCF2CF(CF3)OCF2 CF(CF3)OC3F7; (T) RF = CF(CF3)OCF2CF(CF3)OCF2CF(CF3) OCF2CF(CF3)OC3F; (*) (APDMAE)n-.
oxaalkyl (m = 0, 1) groups were completely soluble not only in water but also in methanol. We have measured the viscosity of aqueous solutions of these ¯uoroalkylated end-capped APDMAE polymers at 308C in order to clarify this unique gelling behavior. The results were shown in Fig. 1. As shown in Fig. 1, the viscosities of non-¯uorinated APDMAE polymers and per¯uoropropylated APDMAE polymer did not increase with increasing concentration. However, APDMAE polymers with per¯uoro-oxaalkyl groups, especially longer per¯uorooxaalkyl groups (m= 2, 3) were found to increase remarkably with increasing concentrations, and we could not measure their viscocities at concentrations above 10 g dm ÿ 3 owing to gelation. We have also measured the minimum concentrations (Cmin) of these polymers necessary for gelation in water (pH 4.1, 6.7 and 9.5) at 308C according to the method reported by Hanabusa et al. [12, 13], and the results are shown in Table 3. As shown in Table 3, per¯uoropropylated and shorter per¯uoro-oxaalkylated (m = 0, 1) APDMAE polymers were soluble in water. However, in the longer per¯uoro-oxaalkylated APDMAE polymers, the amount (Cmin) of a ¯uoroalkylated polymer necessary to gel 1 dm ÿ 3 of water (pH 6.7) was 125±133 g, and polymers with longer per¯uoro-oxaalkyl groups were found to exhibit higher gelling ability. This ®nding was consistent with that of the viscosity of aqueous solutions of ¯uorinated APDMAE polymers. From these results, it is suggested that the main driving forces for gelation are the synergistic interactions between aggregations of ¯uoroalkyl segments in polymers and the ionic interactions of betaine segments, especially that the aggregation of longer per¯uoro-oxaalkyl segments is essential for the gelation. Cmin of longer per¯uoro-oxaalkylated APDMAE polymers necessary to gel one liter of buer solutions of pH 4.1 and pH 9.5 were similar to that of water
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Table 3 Minimum gel concentration Cmin of RF-(APDMAE)n-RF (in g dm ÿ 3 water) necessary for gelation at 308C Cmin (g dm ÿ 3) RF in oligomer
n M w =M n M
pH 4.1
C3F7 CF(CF3)OC3F7 CF(CF3)OCF2CF(CF3)OC3F7 CF(CF3)OCF2CF(CF3) OCF2CF(CF3)OC3F7 CF(CF3)OCF2CF(CF3) OCF2CF(CF3) OCF2CF(CF3)OC3F7 -(APDMAE)nRF-(AMPS)n-RF CF(CF3)OCF2CF(CF3) OCF2CF(CF3)OC3F7
174,700 536,800 433,100 178,700 123,800
Soluble Soluble Soluble 133 118 Soluble
(3.74) (1.82) (1.90) (4.61) (5.22)
24,000 (76)
pH 6.7
pH 9.5
133 125
133 143
33a
a
See Ref. [8, 9].
(pH 6.7), as in Table 3. This result indicates that the ionic interactions between the carboxylate and N + segments in the APDMAE polymers would not strongly participate in the gel, which is constructed from the ¯uoroalkyl units. On the other hand, the gelling ability of the corresponding ¯uoroalkylated endcapped 2-acrylamido-2-methylpropanesulfonic acid polymer {RF-(CH2CHCON + H2CMe2CH2SO3ÿ )n-RF [RF-(AMPS)n-RF]} [9, 10] in Table 3 is quite superior to that of ¯uorolkylated APDMAE polymers, taking into accounting that Cmin are 33 g dm ÿ 3 for RF(AMPS)n-RF and 133 g dm ÿ 3 for RF-(APDMAE)nRF. This result shows that the synergistic interactions of both the aggregations of ¯uoroalkyl segments and the ionic interactions of betaine segments in the AMPS
Fig. 2. Surface tension of aqueous solutions of RF(APDMAE)n-RF at 308C. (*) RF = C3F7; (r) RF = CF(CF3)OC3F7; (Q) RF = CF(CF3)OCF2CF(CF3)OC3F7; (w) RF = CF(CF3)OCF2CF(CF3)OCF2CF(CF3) OC3F7; (r) RF = CF(CF3)OCF2CF(CF3)OCF2CF(CF3) OCF2CF(CF3)OC3 F7; (q) RF-(AMPS)n-RF; RF = CF(CF3)OCF2CF(CF3)OCF2CF(CF3) OC3F7; (t)-(APDMAE)n-.
polymers can strongly participate in the gel, because the ¯uoroalkylated AMPS polymers possess highly acidic sulfonate segments (-SO3ÿ ) compared with those of APDMAE polymers. Our present ¯uoroalkylated end-capped APDMAE polymers were shown to be soluble in water. In particular, the viscosities of aqueous solutions of APDMAE polymers possessing longer per¯uorooxaalkyl groups (m = 2, 3) increased remarkably with increasing concentrations; however, we could measure their viscocities at concentrations below 10 g dm ÿ 3. Therefore, it is very interesting to study the surfactant properties of these ¯uoroalkylated end-capped APDMAE polymers. Thus, we have measured the surface tension of their aqueous solutions with Wilhelmy plate method at 308C. These results were shown in Fig. 2. As shown in Fig. 2, a signi®cant decrease in the surface tension of water was found for ¯uoroalkylated end-capped APDMAE oligomers. In particular, the degree of reduction in the surface tension of water depends on the length of ¯uoroalkyl segments in polymers as well as the usual ¯uorinated surfactants [14], and longer per¯uoro-oxaalkylated (m= 1, 2, 3) APDMAE polymers were more eective for reducing the surface tension of water to around 15 mN m ÿ 1 levels than the corresponding shorter ¯uoroalkylated [RF = CF(CF3)OC3F7 and C3F7] polymers or non¯uorinated APDMAE polymer. Interestingly, ¯uoroalkylated APDMAE polymers which can cause gelation in water are likely to reduce the surface tension of water more eectively with a clear break point resembling a CMC (critical micelle concentration), although shorter ¯uoroalkylated and non-¯uorinated APDMAE polymers exhibit neither a CMC nor a break point. In fact, hydrocarbon polysoaps are well known not to exhibit a CMC or a break point resembling a CMC [15]. This depends upon ¯uorinated polymers possessing a gelling characteristic which can form
H. Sawada et al. / European Polymer Journal 35 (1999) 1611±1617
easily the intermolecular aggregates in aqueous solutions even under dilute conditions (below 10 g dm ÿ 3). On the other hand, longer per¯uoro-oxaalkylated (m = 2) end-capped AMPS polymer, which possesses a superior gelling ability to the corresponding APDMAE polymers, was not able to reduce the surface tension of water eectively compared with those of per¯uoropropylated and per¯uoro-oxaalkylated APDMAE polymers, and exhibited no break point resembling a CMC, as shown in Fig. 2. This result depends upon the ¯uoroalkyl segments in the AMPS polymer being unlikely to be arranged regularly above the water surface relative to that of the corresponding APDMAE polymer, because RF-(AMPS)n-RF should have stronger aggregations of ¯uoroalkyl segments in water to form the gel even under the dilute conditions (below 10 g dm ÿ 3). On this basis, our present ¯uoroalkylated end-capped APDMAE polymers seem to be more attractive than the ¯uorinated AMPS polymer because of their high surfactant properties. Previously, we reported that ¯uoroalkylated endcapped acrylic acid oligomers [RF-(CH2-CHCO2H)nRF] act as potent and selective inhibitors against HIV1 replication in vitro [16]. In addition, ¯uoroalkylated end-capped oligomers possessing cationic segments were demonstrated to possess not only the well-known properties imparted by ¯uorine, such as surface activity, but also antibacterial activity [17±19]. Therefore, our present ¯uorinated APDMAE polymers are also possible HIV-1 activity or antibacterial activity, having betaine segments. They have been evaluated for their inhibitory eects on HIV-1 replication in MT-4 cells. Each ¯uorinated APDMAE polymer was found to be inactive against HIV-1; however, per¯uoropropylated end-capped APDMAE polymer was toxic to the host cells. Therefore, these ¯uoroalkylated end-capped APDMAE polymers are expected to show antibacterial activity. These ¯uorinated APDMAE polymers have been evaluated for their antibacterial activity against Staphylococcus aureus and Penicllium aeruginosa by the
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viable cell counting method. About 108 cell/ml of S. aureus or P. aeruginosa were exposed to 1 mg/ml of the polymers in saline, and Table 4 shows the colonyforming units versus exposure of these polymers against S. aureus or P. aeruginosa. As shown in Table 4, non-¯uorinated APDMAE polymer was inactive. However, it was found that each of ¯uoroalkylated end-capped APDMAE polymers exhibits bacterial activity against S. aureus or P. aeruginosa, and in particular, the longer per¯uorooxaalkylated APDMAE polymer, [RF = CF(CF3)OCF2CF(CF3)OC3F7] was more active against both S. aureus and P. aeruginosa (below 103 colony forming units levels). This ®nding clearly suggests that the cationic moieties in the betaine segments of ¯uorinated APDMAE polymers are able to interact tightly with the negatively charged bacterial cell. It is especially suggested that the negatively charged bacterial cell would act as guest molecules for the aggregates of ¯uorinated APDMAE betaine polymers to exhibit antibacterial activity through the adsorption process. In this way, it was veri®ed that ¯uoroalkylated endcapped betaine polymers possessing both carboxy and ammonium segments can be prepared under very mild conditions by using ¯uoroalkanoyl peroxides as key intermediates. These ¯uoroalkylaed end-capped betaine polymers are soluble in water, methanol and ethanol, and were able to reduce the surface tension of water eectively around to 15 mN/m levels. However, interestingly, longer per¯uoro-oxaalkylated polymers were found to cause gelation, where the strong aggregations between end-capped longer ¯uoroalkyl segments are essential for establishing a physical gel network in water under non-crosslinked conditions. Furthermore, these ¯uorinated APDMAE polymers were found to exhibit antibacterial activity against S. aureus or P. aeruginosa. Thus, these new ¯uorinated polymers are expected to be widely applicable as new attractive functional materials possessing not only surfactant and gelation properties but also antibacterial activity.
Table 4 Antibacterial activity of ¯uoroalkylated end-capped APDMAE polymers against Staphylococcus aureus and Penicllium aeruginosa a RF in oligomer
n M
S. aureus (cfu/mlb)
P. aeruginosa (cfu/ml)
none C3F7 CF(CF3)OC3F7 CF(CF3)OCF2CF(CF3)OC3F7 CF(CF3)OCF2CF(CF3) OCF2CF(CF3)OC3F7 -(APDMAE)n-
174,700 536,800 433,100 178,700
2.8108 < 1.0103 4.0105 < 1.0103 < 1.0103 3.2108
6.2108 8.0103 5.3104 < 1.0103 3.3104 4.4108
Concentration of polymer is 1 mg ml ÿ 1. Cfu indicates colony-forming units.
a
b
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H. Sawada et al. / European Polymer Journal 35 (1999) 1611±1617
3. Experimental NMR spectra were measured using a Varian Unityplus 500 (500 MHz) spectrometer, while IR spectra were recorded on a HORIBA FT-300 FT-IR spectrophotometer. Molecular weights were calculated by using a JASCO-PU-980-Shodex-SE-11 gel permeation chromatography calibrated with standard poly(ethylene glycol) by using 0.2 mol dm ÿ 3 Na2HPO4 solution as the eluent. Solution viscosities were measured by using a falling-sphere Haake Viscometer D1-G.
4. Materials A series of ¯uoroalkanoyl peroxides [(RFCOO)2] were prepared by the method described in the literature [20, 21]. 2-(3-Acrylamidopropyldimethylammonio)-ethanoate (APDMAE) was used as received from Kohjin Co. Ltd. 4.1. General procedure for the synthesis of ¯uoroalkylated end-capped APDMAE polymers Per¯uorbutyrtyl peroxide (3 mmol) in 1:1 mixed solvents (AK-225) of 1,1-dichloro-2,2,3,3,3-penta¯uoropropane and 1,3-dichloro-1,2,2,3,3-penta¯uoropropane (100 g) was added to an aqueous solution (50%, w/w) of APDMAE (57 mmol). The heterogeneous solution was stirred vigorously at 408C for 5 h under nitrogen. After evaporating the solvent, the crude product obtained was reprecipitated from water-tetrahydrofuran to give a a, o-bis(per¯uoropropylated) APDMAE polymer (12.60 g). This polymer exhibited the following spectral characteristics: IR(cm ÿ 1) 3470 (NH), 1641[C(1O)], 1390 (CF3), 1254(CF2); 1H NMR(D2O) d 1.70±2.01 (CH, CH2), 2.92±3.29 (CH2, 19 CH3), 3.36±3.68(CH2), 3.71±3.84 (CH2); F NMR(D2O, ext. CF3CO2H) d ÿ5.48 (6F), ÿ42.97 (4F), ÿ52.09(4F). The other products obtained exhibited the following spectral characteristics: C3F7OCF(CF3)-(APDMAE)n-CF(CF3)OC3F7: IR(cm ÿ 1) 3470 (NH), 1641[C(1O)], 1320 (CF3), 1241 (CF2); 1H NMR(D2O) d 1.14±2.15 (CH, CH2), 2.78±3.30 (CH2, CH3), 3.39±3.68 (CH2), 3.71±3.89 (CH2); 19F NMR(D2O, ext. CF3CO2H) d ÿ5.63 to ÿ7.61(16F), ÿ53.92 (6F). C3F7OCF(CF3)CF2OCF(CF3)-(APDMAE)n-CF(CF3)OCF2CF(CF3)OC3F7: IR(cm ÿ 1) 3435 (NH), 1641[C(1O)], 1320 (CF3), 1242 (CF2); 1H NMR(D2O) d 1.13±2.16 (CH, CH2), 2.79±3.28 (CH2, CH3), 3.36± 3.59 (CH2), 3.69±3.84 (CH2); 19F NMR(D2O, ext. CF3CO2H) d ÿ5.63 to ÿ11.53 (26F), ÿ53.97 to ÿ56.70 (6F), ÿ68.64 (2F).
C3F7OCF(CF3)CF2OCF(CF3)CF2OCF(CF3)-(APDMAE)n-CF(CF3)OCF2CF(CF3)OCF2CF(CF3)OC3F7: IR(cm ÿ 1) 3505 (NH), 1639[C(1O)], 1304 (CF3), 1242 (CF2); 1H NMR(D2O) d 1.13±2.16 (CH, CH2), 2.79± 3.28 (CH2, CH3), 3.36± 3.59(CH2), 3.69±3.84 (CH2); 19 F NMR(D2O, ext. CF3CO2H) d ÿ4.52 to ÿ8.46 (36F), ÿ51.98 to ÿ54.98 (6F), ÿ69.48 to ÿ72.48 (4F). C3F7OCF(CF3)CF2OCF(CF3)CF2OCF(CF3)CF2OCF(CF3)-(APDMAE)n-CF(CF3)OCF2CF(CF3)OCF2CF(CF3)OCF2CF(CF3)OC3F7: IR(cm ÿ 1) 3475 (NH), 1635[C(1O)], 1330 (CF3), 1244 (CF2); 1H NMR(D2O) d 1.13±2.12 (CH, CH2), 2.79±3.27 (CH2, CH3), 3.33± 3.65(CH2), 3.70±3.93 (CH2); 19F NMR(D2O, ext. CF3CO2H) d ÿ4.47 to ÿ8.98 (46F), ÿ54.20 to ÿ56.55 (6F), ÿ70.54 to ÿ71.42 (6F). 5. Viscosity measurements The viscosities of aqueous solutions of ¯uoroalkylated end-capped APDMAE polymers were measured at 308C using a falling-sphere viscometer (Haake Viscometer D1-G). 6. A typical procedure for gelation test A procedure for studying the gel-formation ability was based on a method reported by Hanabusa et al. [12, 13], and the aqueous solutions used for this gelation test were as follows: 0.2 mol dm ÿ 3 acetic acid±0.2 mol dm ÿ 3 sodium acetate buer (pH 4.1), distilled water which was passed through ion-exchange resin (pH 6.7), and 0.2 mol dm ÿ 3 tris(hydroxymethyl)aminomethane±0.1 mol dm ÿ 3 HCl (pH 9.5). 7. Antiviral assays Antiviral activity of the compounds against HIV-1 (HTLV-IIIB starin) replication was based on the inhibition of the virus-induced cytopathic eect in MT-4 cells as described previously [16]. 8. Antibacterial assessment The antibacterial activity of the oligomers was evaluated against Staphylococcus aureus by viable cell counting method as described previously [17±19]. Acknowledgements This work was partially supported by a Grant-inAid for Scienti®c Research no. 09650945 from the
H. Sawada et al. / European Polymer Journal 35 (1999) 1611±1617
Ministry of Education, Science, Sports and Culture, Japan, for which the authors are grateful. Thanks are due to Kohjin Co. Ltd for supply of APDMAE. References [1] Yang Z-Y, Feiring AE, Smart BE. J Am Chem Soc 1994;116:4135. [2] Hunt MO, Jr, Belu AM, Linton RW, Desimone JM. Macromolecules 1993;26:4854. [3] Wang J, Mao G, Ober CK, Kramer EJ. Polym Prepr (Am Chem Soc, Div Polym Chem) 1997;38:953. [4] Su Z, Wu D, Hsu SL, McCarthy TJ. Polym Prepr (Am Chem Soc, Div Polym Chem) 1997;38:951. [5] Cooper AI, Londono JD, Wignall G, McClain JN, Samuiski ET, Lin JS, Dobrynin A, Rubinstein M, Burke ALC, Frechet JMJ, DeSimone JM. Nature 1997;389:368. [6] Sawada H, Ohashi A, Baba M, Kawase T, Hayakawa Y. J Fluorine Chem 1996;79:149. [7] Sawada H. Chem Rev 1996;96:1779. [8] Sawada H, Katayama S, Nakamura Y, Kawase T, Hayakawa Y, Baba M. Polymer 1998;39:743. [9] Sawada H, Katayama S, Ariyoshi Y, Kawase T, Hayakawa Y, Nakamura Y, Kawase T, Hayakawa Y, Tomita T, Baba M. J Mater Chem 1998;8:1517.
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[10] Sawada H, Gong Y-F, Minoshima Y, Matsumoto T, Nakayama M, Kosugi M, Migita T. J Chem Soc Chem Commun 1992;537. [11] Sawada H, Minoshima Y, Nakajima H. J Fluorine Chem 1992;65:169. [12] Hanabusa K, Tanaka R, Suzuki M, Kimura M, Shirai H. Adv Mater 1997;9:1095. [13] Hanabusa K, Okui K, Karaki K, Kimura M, Shirai H. J Colloid Interface Sci 1997;195:86. [14] Abe M, Morikawa K, Ogino K, Sawada H, Matsumoto T, Nakayama M. Langmuir 1992;8:763. [15] Anton P, Koberle P, Laschewsky A. Makromol Chem 1993;194:1. [16] Baba M, Kira T, Shigeta S, Matsumoto T, Sawada H. J Aquir Immun De®c Syndr 1994;7:24. [17] Sawada H, Katayama S, Oue M, Kawase T, Hayakawa Y, Baba M, Tomita T, Mitani M. J Jpn Oil Chem Soc 1996;45:161. [18] Sawada H, Wake A, Maekawa T, Kawase T, Hayakawa Y, Tomita T, Baba M. J Fluorine Chem 1997;83:125. [19] Sawada H, Tanba K, Tomita T, Kawase, Baba M, Ide T. J Fluorine Chem 1997;84:141. [20] Sawada H, Nakayama M. J Fluorine Chem 1990;51:117. [21] Sawada H, Yoshida M, Hagii H, Aoshima K, Kobayashi M. Bull Chem Soc Jpn 1986;59:215.
European Polymer Journal 35 (1999) 1611±1617
Synthesis and properties of ¯uoroalkylated end-capped betaine polymers Hideo Sawada a, b, *, Michinori Umedo b, Tokuzo Kawase c, Toshio Tomita d, Masanori Baba e a Department of Chemistry, Nara National College of Technology, Yata, Yamatakoriyama, Nara 639-1080, Japan Department of Chemistry, Faculty of Advanced Engineering, Nara National College of Technology, Yata, Yamatokoriyama, Nara 639-1080, Japan c Faculty of Human Life Science, Osaka City University, Sugimoto, Sumiyoshi-ku, Osaka 558-8585, Japan d Faculty of Agriculture, Tohoku University, Tsutsumidori-Amamiya, Aoba-ku, Sendai 981-8555, Japan e Division of Human Retroviruses, Center for Chronic Viral Diseases, Faculty of Medicine, Kagoshima University, Sakuragaoka, Kagoshima 890-8520, Japan
b
Received 25 May 1998; accepted 28 September 1998
Abstract Per¯uoropropylated and some per¯uoro-oxaalkylated end-capped 2-(3-acrylamidopropyldimethylammonio)ethanoate (APDMAE) polymers were prepared by the reactions of ¯uoroalkanoyl peroxides with the corresponding monomer. These ¯uoroalkylated end-capped betaine polymers were soluble in water, methanol and ethanol. However, in these ¯uorinated APDMAE polymers, longer per¯uoro-oxaalkylated end-capped APDMAE polymers were found to form highly viscoelastic ¯uids in water at concentrations above 10 g dm ÿ 3 under non-crosslinked conditions. The series of ¯uoroalkylated end-capped APDMAE polymers, especially longer per¯uoro-oxaalkylated polymers, were able to reduce the surface tension of water eectively with a clear break point resembling a CMC at ca. 0.2 g dm ÿ 3. In addition, some of these ¯uoroalkylated end-capped APDMAE polymers exhibited antibacterial activity against Staphylococcus aureus and Penicillium aeruginosa. Therefore, these ¯uoroalkylated end-capped polymers are suggested to have high potential for new functional materials through not only their unique physical properties, such as surfactant and gelling characteristics, but also antibacterial activity. # 1999 Elsevier Science Ltd. All rights reserved.
1. Introduction Fluorinated polymers, especially partially ¯uorinated polymers, are attractive functional materials because they exhibit various excellent properties, such as a high solubility and biological activities which cannot be achieved by the per¯uorinated polymers [1±6]. From this point of view, we have been actively studying the
* Corresponding author. Fax: +81-743-55-6169; e-mail: [email protected]
synthesis and application of partially ¯uorinated polymers, that is, ¯uoroalkylated end-capped polymers by using ¯uoroalkanoyl peroxides as key intermediates [7]. In these ¯uoroalkylated end-capped polymers, we have recently found that ¯uoroalkylated end-capped 2-acrylamido-2-methylpropanesulfonic acid polymer can cause gelation under non-crosslinked conditions, and that the strong aggregation of the end-capped ¯uoroalkyl segments in water and/or organic media becomes a new driving factor for gelation in addition to the ionic interaction of the betaine segments [3]. Furthermore, these ¯uoroalkylated end-capped poly-
0014-3057/99/$ - see front matter # 1999 Elsevier Science Ltd. All rights reserved. PII: S 0 0 1 4 - 3 0 5 7 ( 9 8 ) 0 0 2 5 0 - X
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Table 1 Reactions of ¯uoroalkanoyl peroxides with APDMAE RF-(APDMAE)n-RF RF in Peroxide (mmol)
APDMAE (mmol)
C3F7 3 57 CF(CF3)OC3F7 3 66 CF(CF3)OCF2CF(CF3)OC3F7 2 33 CF(CF3)OCF2CF(CF3) OCF2CF(CF3)OC3F7 1 18 CF(CF3)OCF2CF(CF3) OCF2CF(CF3) OCF2CF(CF3)OC3F7 1 9
Yielda
n M w =M n b M
50
174,700 (3.74)
43
536,800 (1.82)
51
433,100 (1.90)
44
178,700 (4.61)
29
123,800 (5.22)
a
The yields were based on the starting materials (APDMAE) and the decarboxylated peroxide unit (RF±RF). The molecular weights were calculated based on GPC.
b
mers were also shown to be potent and selective inhibitors against HIV-1 replication [8, 9]. Therefore, it is of particular interest to develop the ¯uoroalkylated endcapped polymers, especially novel ¯uorinated betainetype polymers possessing a gelling ability. In this study, we would like to report on the synthesis and properties of novel ¯uoroalkylated end-capped 2-(3 acrylamidopropyldimethylammonio)-ethanoate polymers. 2. Results and discussion The reactions of 2-(3-acrylamidopropyldimethylammonio)ethanoate [APDMAE] with ¯uoroalkanoyl peroxides proceeded under very mild conditions (408C/ 5 h) to give the corresponding ¯uoroalkylated endcapped polymers [RF-(APDMAE)n-RF] as shown in Scheme 1.
The results are shown in Table 1. As shown in Table 1, not only per¯uoropropylated but also per¯uoro-oxaalkylated end-capped APDMAE polymers were obtained in 29±51% isolated yields. Previously, we reported that ¯uoroalkanoyl peroxides react with acrylic acid to give acrylic acid oligomers containing two ¯uoroalkylated end groups [RF-(CH2CHCO2H)n-RF; Mn = 3460±12,800; Mw/ Mn = 1.40±1.82] under similar reaction conditions [10, 11]. The molecular weights and Mw/Mn of these polymers by GPC [gel permeation chromatography calibrated with poly(ethylene glycol) standards by using 0.2 mol dm ÿ 3 Na2HPO4 solution as the eluent] were found to be relatively higher (Mn = 123,800± 536,800) compared with those of ¯uoroalkylated endcapped acrylic acid oligomers, respectively, as in Table 1. These results suggest that our present ¯uoroalkylated end-capped APDMAE polymers can easily form molecular aggregates in aqueous solutions. Thus,
H. Sawada et al. / European Polymer Journal 35 (1999) 1611±1617
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Table 2 Solubility of RF-(APDMAE)n -RF Solvent Run RF in RF-(APDMAE)n-RF
H2O MeOH EtOH THF CHCl3 PhH DMSO DMF
1 2 3 4 5 6
wa w w qc q w
C3F7 CF(CF3)OC3F7 CF(CF3)OCF2CF(CF3)OC3F7 CF(CF3)OCF2CF(CF3) OCF2CF(CF3)OC3F7 CF(CF3)OCF2CF(CF3) OCF2CF(CF3) OCF2CF(CF3)OC3F7 -(APDMAE)n-
w w w w w w
Xb w X w w w
X X X X X X
X X X X X X
X X X X X X
X X X X X X
X X X X X X
a
(w) Soluble. (X) insoluble. c (q) gel. b
the molecular weights by GPC indicate the apparent molecular weights. The series of ¯uoroalkylated end-capped APDMAE polymers thus obtained were tested for solubility, and these results are listed in Table 2. In general, these ¯uoroalkylated end-capped APDMAE polymers were found to be soluble not only in water but also in methanol, and some ¯uorinated polymers (runs 2, 4 and 5) were also soluble in ethanol. However, interestingly, APDMAE polymers with longer per¯uoro-oxaalkyl groups (m = 2, 3) can form highly viscoelastic ¯uids (or can cause gel formation), as shown in Table 2. In contrast, non-¯uorinated APDMAE polymer and ¯uorinated APDMAE polymers with per¯uoropropyl and shorter per¯uoro-
Fig. 1. Viscosity of aqueous solutions of RF-(APDMAE)n-RF at 308C. (w) RF = C3F7; (R) RF = CF(CF3)OCF2CF(CF3)OC3F7; (r) RF = CF(CF3)OCF2CF(CF3)OCF2 CF(CF3)OC3F7; (T) RF = CF(CF3)OCF2CF(CF3)OCF2CF(CF3) OCF2CF(CF3)OC3F; (*) (APDMAE)n-.
oxaalkyl (m = 0, 1) groups were completely soluble not only in water but also in methanol. We have measured the viscosity of aqueous solutions of these ¯uoroalkylated end-capped APDMAE polymers at 308C in order to clarify this unique gelling behavior. The results were shown in Fig. 1. As shown in Fig. 1, the viscosities of non-¯uorinated APDMAE polymers and per¯uoropropylated APDMAE polymer did not increase with increasing concentration. However, APDMAE polymers with per¯uoro-oxaalkyl groups, especially longer per¯uorooxaalkyl groups (m= 2, 3) were found to increase remarkably with increasing concentrations, and we could not measure their viscocities at concentrations above 10 g dm ÿ 3 owing to gelation. We have also measured the minimum concentrations (Cmin) of these polymers necessary for gelation in water (pH 4.1, 6.7 and 9.5) at 308C according to the method reported by Hanabusa et al. [12, 13], and the results are shown in Table 3. As shown in Table 3, per¯uoropropylated and shorter per¯uoro-oxaalkylated (m = 0, 1) APDMAE polymers were soluble in water. However, in the longer per¯uoro-oxaalkylated APDMAE polymers, the amount (Cmin) of a ¯uoroalkylated polymer necessary to gel 1 dm ÿ 3 of water (pH 6.7) was 125±133 g, and polymers with longer per¯uoro-oxaalkyl groups were found to exhibit higher gelling ability. This ®nding was consistent with that of the viscosity of aqueous solutions of ¯uorinated APDMAE polymers. From these results, it is suggested that the main driving forces for gelation are the synergistic interactions between aggregations of ¯uoroalkyl segments in polymers and the ionic interactions of betaine segments, especially that the aggregation of longer per¯uoro-oxaalkyl segments is essential for the gelation. Cmin of longer per¯uoro-oxaalkylated APDMAE polymers necessary to gel one liter of buer solutions of pH 4.1 and pH 9.5 were similar to that of water
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Table 3 Minimum gel concentration Cmin of RF-(APDMAE)n-RF (in g dm ÿ 3 water) necessary for gelation at 308C Cmin (g dm ÿ 3) RF in oligomer
n M w =M n M
pH 4.1
C3F7 CF(CF3)OC3F7 CF(CF3)OCF2CF(CF3)OC3F7 CF(CF3)OCF2CF(CF3) OCF2CF(CF3)OC3F7 CF(CF3)OCF2CF(CF3) OCF2CF(CF3) OCF2CF(CF3)OC3F7 -(APDMAE)nRF-(AMPS)n-RF CF(CF3)OCF2CF(CF3) OCF2CF(CF3)OC3F7
174,700 536,800 433,100 178,700 123,800
Soluble Soluble Soluble 133 118 Soluble
(3.74) (1.82) (1.90) (4.61) (5.22)
24,000 (76)
pH 6.7
pH 9.5
133 125
133 143
33a
a
See Ref. [8, 9].
(pH 6.7), as in Table 3. This result indicates that the ionic interactions between the carboxylate and N + segments in the APDMAE polymers would not strongly participate in the gel, which is constructed from the ¯uoroalkyl units. On the other hand, the gelling ability of the corresponding ¯uoroalkylated endcapped 2-acrylamido-2-methylpropanesulfonic acid polymer {RF-(CH2CHCON + H2CMe2CH2SO3ÿ )n-RF [RF-(AMPS)n-RF]} [9, 10] in Table 3 is quite superior to that of ¯uorolkylated APDMAE polymers, taking into accounting that Cmin are 33 g dm ÿ 3 for RF(AMPS)n-RF and 133 g dm ÿ 3 for RF-(APDMAE)nRF. This result shows that the synergistic interactions of both the aggregations of ¯uoroalkyl segments and the ionic interactions of betaine segments in the AMPS
Fig. 2. Surface tension of aqueous solutions of RF(APDMAE)n-RF at 308C. (*) RF = C3F7; (r) RF = CF(CF3)OC3F7; (Q) RF = CF(CF3)OCF2CF(CF3)OC3F7; (w) RF = CF(CF3)OCF2CF(CF3)OCF2CF(CF3) OC3F7; (r) RF = CF(CF3)OCF2CF(CF3)OCF2CF(CF3) OCF2CF(CF3)OC3 F7; (q) RF-(AMPS)n-RF; RF = CF(CF3)OCF2CF(CF3)OCF2CF(CF3) OC3F7; (t)-(APDMAE)n-.
polymers can strongly participate in the gel, because the ¯uoroalkylated AMPS polymers possess highly acidic sulfonate segments (-SO3ÿ ) compared with those of APDMAE polymers. Our present ¯uoroalkylated end-capped APDMAE polymers were shown to be soluble in water. In particular, the viscosities of aqueous solutions of APDMAE polymers possessing longer per¯uorooxaalkyl groups (m = 2, 3) increased remarkably with increasing concentrations; however, we could measure their viscocities at concentrations below 10 g dm ÿ 3. Therefore, it is very interesting to study the surfactant properties of these ¯uoroalkylated end-capped APDMAE polymers. Thus, we have measured the surface tension of their aqueous solutions with Wilhelmy plate method at 308C. These results were shown in Fig. 2. As shown in Fig. 2, a signi®cant decrease in the surface tension of water was found for ¯uoroalkylated end-capped APDMAE oligomers. In particular, the degree of reduction in the surface tension of water depends on the length of ¯uoroalkyl segments in polymers as well as the usual ¯uorinated surfactants [14], and longer per¯uoro-oxaalkylated (m= 1, 2, 3) APDMAE polymers were more eective for reducing the surface tension of water to around 15 mN m ÿ 1 levels than the corresponding shorter ¯uoroalkylated [RF = CF(CF3)OC3F7 and C3F7] polymers or non¯uorinated APDMAE polymer. Interestingly, ¯uoroalkylated APDMAE polymers which can cause gelation in water are likely to reduce the surface tension of water more eectively with a clear break point resembling a CMC (critical micelle concentration), although shorter ¯uoroalkylated and non-¯uorinated APDMAE polymers exhibit neither a CMC nor a break point. In fact, hydrocarbon polysoaps are well known not to exhibit a CMC or a break point resembling a CMC [15]. This depends upon ¯uorinated polymers possessing a gelling characteristic which can form
H. Sawada et al. / European Polymer Journal 35 (1999) 1611±1617
easily the intermolecular aggregates in aqueous solutions even under dilute conditions (below 10 g dm ÿ 3). On the other hand, longer per¯uoro-oxaalkylated (m = 2) end-capped AMPS polymer, which possesses a superior gelling ability to the corresponding APDMAE polymers, was not able to reduce the surface tension of water eectively compared with those of per¯uoropropylated and per¯uoro-oxaalkylated APDMAE polymers, and exhibited no break point resembling a CMC, as shown in Fig. 2. This result depends upon the ¯uoroalkyl segments in the AMPS polymer being unlikely to be arranged regularly above the water surface relative to that of the corresponding APDMAE polymer, because RF-(AMPS)n-RF should have stronger aggregations of ¯uoroalkyl segments in water to form the gel even under the dilute conditions (below 10 g dm ÿ 3). On this basis, our present ¯uoroalkylated end-capped APDMAE polymers seem to be more attractive than the ¯uorinated AMPS polymer because of their high surfactant properties. Previously, we reported that ¯uoroalkylated endcapped acrylic acid oligomers [RF-(CH2-CHCO2H)nRF] act as potent and selective inhibitors against HIV1 replication in vitro [16]. In addition, ¯uoroalkylated end-capped oligomers possessing cationic segments were demonstrated to possess not only the well-known properties imparted by ¯uorine, such as surface activity, but also antibacterial activity [17±19]. Therefore, our present ¯uorinated APDMAE polymers are also possible HIV-1 activity or antibacterial activity, having betaine segments. They have been evaluated for their inhibitory eects on HIV-1 replication in MT-4 cells. Each ¯uorinated APDMAE polymer was found to be inactive against HIV-1; however, per¯uoropropylated end-capped APDMAE polymer was toxic to the host cells. Therefore, these ¯uoroalkylated end-capped APDMAE polymers are expected to show antibacterial activity. These ¯uorinated APDMAE polymers have been evaluated for their antibacterial activity against Staphylococcus aureus and Penicllium aeruginosa by the
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viable cell counting method. About 108 cell/ml of S. aureus or P. aeruginosa were exposed to 1 mg/ml of the polymers in saline, and Table 4 shows the colonyforming units versus exposure of these polymers against S. aureus or P. aeruginosa. As shown in Table 4, non-¯uorinated APDMAE polymer was inactive. However, it was found that each of ¯uoroalkylated end-capped APDMAE polymers exhibits bacterial activity against S. aureus or P. aeruginosa, and in particular, the longer per¯uorooxaalkylated APDMAE polymer, [RF = CF(CF3)OCF2CF(CF3)OC3F7] was more active against both S. aureus and P. aeruginosa (below 103 colony forming units levels). This ®nding clearly suggests that the cationic moieties in the betaine segments of ¯uorinated APDMAE polymers are able to interact tightly with the negatively charged bacterial cell. It is especially suggested that the negatively charged bacterial cell would act as guest molecules for the aggregates of ¯uorinated APDMAE betaine polymers to exhibit antibacterial activity through the adsorption process. In this way, it was veri®ed that ¯uoroalkylated endcapped betaine polymers possessing both carboxy and ammonium segments can be prepared under very mild conditions by using ¯uoroalkanoyl peroxides as key intermediates. These ¯uoroalkylaed end-capped betaine polymers are soluble in water, methanol and ethanol, and were able to reduce the surface tension of water eectively around to 15 mN/m levels. However, interestingly, longer per¯uoro-oxaalkylated polymers were found to cause gelation, where the strong aggregations between end-capped longer ¯uoroalkyl segments are essential for establishing a physical gel network in water under non-crosslinked conditions. Furthermore, these ¯uorinated APDMAE polymers were found to exhibit antibacterial activity against S. aureus or P. aeruginosa. Thus, these new ¯uorinated polymers are expected to be widely applicable as new attractive functional materials possessing not only surfactant and gelation properties but also antibacterial activity.
Table 4 Antibacterial activity of ¯uoroalkylated end-capped APDMAE polymers against Staphylococcus aureus and Penicllium aeruginosa a RF in oligomer
n M
S. aureus (cfu/mlb)
P. aeruginosa (cfu/ml)
none C3F7 CF(CF3)OC3F7 CF(CF3)OCF2CF(CF3)OC3F7 CF(CF3)OCF2CF(CF3) OCF2CF(CF3)OC3F7 -(APDMAE)n-
174,700 536,800 433,100 178,700
2.8108 < 1.0103 4.0105 < 1.0103 < 1.0103 3.2108
6.2108 8.0103 5.3104 < 1.0103 3.3104 4.4108
Concentration of polymer is 1 mg ml ÿ 1. Cfu indicates colony-forming units.
a
b
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H. Sawada et al. / European Polymer Journal 35 (1999) 1611±1617
3. Experimental NMR spectra were measured using a Varian Unityplus 500 (500 MHz) spectrometer, while IR spectra were recorded on a HORIBA FT-300 FT-IR spectrophotometer. Molecular weights were calculated by using a JASCO-PU-980-Shodex-SE-11 gel permeation chromatography calibrated with standard poly(ethylene glycol) by using 0.2 mol dm ÿ 3 Na2HPO4 solution as the eluent. Solution viscosities were measured by using a falling-sphere Haake Viscometer D1-G.
4. Materials A series of ¯uoroalkanoyl peroxides [(RFCOO)2] were prepared by the method described in the literature [20, 21]. 2-(3-Acrylamidopropyldimethylammonio)-ethanoate (APDMAE) was used as received from Kohjin Co. Ltd. 4.1. General procedure for the synthesis of ¯uoroalkylated end-capped APDMAE polymers Per¯uorbutyrtyl peroxide (3 mmol) in 1:1 mixed solvents (AK-225) of 1,1-dichloro-2,2,3,3,3-penta¯uoropropane and 1,3-dichloro-1,2,2,3,3-penta¯uoropropane (100 g) was added to an aqueous solution (50%, w/w) of APDMAE (57 mmol). The heterogeneous solution was stirred vigorously at 408C for 5 h under nitrogen. After evaporating the solvent, the crude product obtained was reprecipitated from water-tetrahydrofuran to give a a, o-bis(per¯uoropropylated) APDMAE polymer (12.60 g). This polymer exhibited the following spectral characteristics: IR(cm ÿ 1) 3470 (NH), 1641[C(1O)], 1390 (CF3), 1254(CF2); 1H NMR(D2O) d 1.70±2.01 (CH, CH2), 2.92±3.29 (CH2, 19 CH3), 3.36±3.68(CH2), 3.71±3.84 (CH2); F NMR(D2O, ext. CF3CO2H) d ÿ5.48 (6F), ÿ42.97 (4F), ÿ52.09(4F). The other products obtained exhibited the following spectral characteristics: C3F7OCF(CF3)-(APDMAE)n-CF(CF3)OC3F7: IR(cm ÿ 1) 3470 (NH), 1641[C(1O)], 1320 (CF3), 1241 (CF2); 1H NMR(D2O) d 1.14±2.15 (CH, CH2), 2.78±3.30 (CH2, CH3), 3.39±3.68 (CH2), 3.71±3.89 (CH2); 19F NMR(D2O, ext. CF3CO2H) d ÿ5.63 to ÿ7.61(16F), ÿ53.92 (6F). C3F7OCF(CF3)CF2OCF(CF3)-(APDMAE)n-CF(CF3)OCF2CF(CF3)OC3F7: IR(cm ÿ 1) 3435 (NH), 1641[C(1O)], 1320 (CF3), 1242 (CF2); 1H NMR(D2O) d 1.13±2.16 (CH, CH2), 2.79±3.28 (CH2, CH3), 3.36± 3.59 (CH2), 3.69±3.84 (CH2); 19F NMR(D2O, ext. CF3CO2H) d ÿ5.63 to ÿ11.53 (26F), ÿ53.97 to ÿ56.70 (6F), ÿ68.64 (2F).
C3F7OCF(CF3)CF2OCF(CF3)CF2OCF(CF3)-(APDMAE)n-CF(CF3)OCF2CF(CF3)OCF2CF(CF3)OC3F7: IR(cm ÿ 1) 3505 (NH), 1639[C(1O)], 1304 (CF3), 1242 (CF2); 1H NMR(D2O) d 1.13±2.16 (CH, CH2), 2.79± 3.28 (CH2, CH3), 3.36± 3.59(CH2), 3.69±3.84 (CH2); 19 F NMR(D2O, ext. CF3CO2H) d ÿ4.52 to ÿ8.46 (36F), ÿ51.98 to ÿ54.98 (6F), ÿ69.48 to ÿ72.48 (4F). C3F7OCF(CF3)CF2OCF(CF3)CF2OCF(CF3)CF2OCF(CF3)-(APDMAE)n-CF(CF3)OCF2CF(CF3)OCF2CF(CF3)OCF2CF(CF3)OC3F7: IR(cm ÿ 1) 3475 (NH), 1635[C(1O)], 1330 (CF3), 1244 (CF2); 1H NMR(D2O) d 1.13±2.12 (CH, CH2), 2.79±3.27 (CH2, CH3), 3.33± 3.65(CH2), 3.70±3.93 (CH2); 19F NMR(D2O, ext. CF3CO2H) d ÿ4.47 to ÿ8.98 (46F), ÿ54.20 to ÿ56.55 (6F), ÿ70.54 to ÿ71.42 (6F). 5. Viscosity measurements The viscosities of aqueous solutions of ¯uoroalkylated end-capped APDMAE polymers were measured at 308C using a falling-sphere viscometer (Haake Viscometer D1-G). 6. A typical procedure for gelation test A procedure for studying the gel-formation ability was based on a method reported by Hanabusa et al. [12, 13], and the aqueous solutions used for this gelation test were as follows: 0.2 mol dm ÿ 3 acetic acid±0.2 mol dm ÿ 3 sodium acetate buer (pH 4.1), distilled water which was passed through ion-exchange resin (pH 6.7), and 0.2 mol dm ÿ 3 tris(hydroxymethyl)aminomethane±0.1 mol dm ÿ 3 HCl (pH 9.5). 7. Antiviral assays Antiviral activity of the compounds against HIV-1 (HTLV-IIIB starin) replication was based on the inhibition of the virus-induced cytopathic eect in MT-4 cells as described previously [16]. 8. Antibacterial assessment The antibacterial activity of the oligomers was evaluated against Staphylococcus aureus by viable cell counting method as described previously [17±19]. Acknowledgements This work was partially supported by a Grant-inAid for Scienti®c Research no. 09650945 from the
H. Sawada et al. / European Polymer Journal 35 (1999) 1611±1617
Ministry of Education, Science, Sports and Culture, Japan, for which the authors are grateful. Thanks are due to Kohjin Co. Ltd for supply of APDMAE. References [1] Yang Z-Y, Feiring AE, Smart BE. J Am Chem Soc 1994;116:4135. [2] Hunt MO, Jr, Belu AM, Linton RW, Desimone JM. Macromolecules 1993;26:4854. [3] Wang J, Mao G, Ober CK, Kramer EJ. Polym Prepr (Am Chem Soc, Div Polym Chem) 1997;38:953. [4] Su Z, Wu D, Hsu SL, McCarthy TJ. Polym Prepr (Am Chem Soc, Div Polym Chem) 1997;38:951. [5] Cooper AI, Londono JD, Wignall G, McClain JN, Samuiski ET, Lin JS, Dobrynin A, Rubinstein M, Burke ALC, Frechet JMJ, DeSimone JM. Nature 1997;389:368. [6] Sawada H, Ohashi A, Baba M, Kawase T, Hayakawa Y. J Fluorine Chem 1996;79:149. [7] Sawada H. Chem Rev 1996;96:1779. [8] Sawada H, Katayama S, Nakamura Y, Kawase T, Hayakawa Y, Baba M. Polymer 1998;39:743. [9] Sawada H, Katayama S, Ariyoshi Y, Kawase T, Hayakawa Y, Nakamura Y, Kawase T, Hayakawa Y, Tomita T, Baba M. J Mater Chem 1998;8:1517.
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