New Facile Approach to Novel Water-Soluble Aliphatic Poly(butylene

Hydroxyl functionalized renewable polyesters derived from 10-undecenoic acid: Polymer structure and post-polymerization modification. Carmen Valverde ...
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Biomacromolecules 2005, 6, 3474-3480

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Notes New Facile Approach to Novel Water-Soluble Aliphatic Poly(butylene tartarate)s Bearing Reactive Hydroxyl Pendant Groups Qinghui Hao, Jing Yang, Qiaobo Li, Yang Li, Lin Jia, Qiang Fang, and Amin Cao* Laboratory for Polymer Materials, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Road, Shanghai 200032, China Received May 8, 2005 Revised Manuscript Received June 23, 2005

Introduction In the past decades, functional biodegradable and biocompatible polymers have been extensively investigated for their huge importance in biomedical and pharmaceutical applications.1,2 Up to the present date, aliphatic polyester has already been known as the most promising category of biodegradable polymers and has widely been applied as functional biomaterials and environmentally benign green plastics. On the other hand, most of the aliphatic polyesters in existence are highly hydrophobic, thus practically leading to limitation in their biomedical applications due to the lack of desirable hydrophilicity and reactive pendant functional groups.3 Therefore, new functional biodegradable polyesters bearing hydrophilic reactive pendant groups such as hydroxyl, carboxyl, amino, and so forth become attractive,4-10 and the combination of water solubility, tunable biodegradability, and reactive functional groups made these polyesters possible new biomaterials to be applied in the construction of novel controlled drug delivery systems and functional vectors as well as related biomedical applications.11 Furthermore, these functional polymers bearing reactive pendant groups could be applied to prepare novel comb-type, grafted structural functional polymers through postmodification. So far, there have been a few reports focusing on the preparation of novel functional water-soluble biodegradable polyesters bearing reactive pendant groups. Vert and Lenz et al.12-15 reported the synthesis of water-soluble polyester poly(β-malic acid) via a chemical synthetic strategy, employing ring-opening polymerization of purified benzyl malolactonate and a successive hydrolysis of the benzyl ester protection groups. Because of the multistep carboxylic protection-deprotection synthetic strategy, the instability of intermediate compounds and the process complexity practically limited their potential applications. As an alternative approach to obtain new water-soluble biodegradable polyesters with favorable reactive pendant groups, Gross et al.16,17 successfully prepared a new watersoluble poly(sorbityl adipate) via a biocatalytic route with * Author for correspondence. Phone: +86-21-5492-5303. Fax:+86-216416-7152. E-mail: [email protected].

the aid of lipase CA (Novozyme 435), and sorbitol and adipic acid substrates were selectively catalyzed to produce highmolecular-weight water-soluble polyester products via condensation polymerization. As compared to metal or organic catalysts, the polymerization catalyzed by an enzyme was found to be a simple and facile strategy; however, this approach was actually limited by the high selectivity between the monomer substrates and the as-applied enzyme catalysts, and only a few kinds of monomers could be catalyzed by the lipase to prepare new high-molecular-weight polyesters with enough hydrophilicity and desirable reactive functional groups.16-21 Recently, Emrick et al.22 reported a new synthetic strategy to prepare novel aliphatic copolyesters with reactive hydroxyl side groups via allyl dihydroxylation of the prepared copolyester poly(R-allyl-δ-valerolactone-co--caprolactone)s. However, a homopolymer of poly(R-allyl-δ-valerolactone) could not thereby be attained, and the monomer of R-allylδ-valerolactone indeed needed to be synthesized by complex preparation steps. In a previous study,23 we preliminarily reported a new terpolymer of poly(butylene succinate-cobutylene fumarate-co-butylene tartarate)s via a metalcatalyzed partial dihydroxylation of the aliphatic copolyester poly(butylene succinate-co-butylene fumarate). In this study, we will present a new facile and versatile strategy to prepare novel water-soluble aliphatic polyester poly(butylene tartarate) bearing reactive hydroxyl pendant groups under mild conditions without the tedious functional group protection-deprotection cycle. First, a hydroxylterminated poly(butylene fumarate) (PBF) was synthesized via the condensation polymerization of fumaric acid and 1,4butanediol and was fractionated with chloroform, and then, the chloroform-soluble PBF was further acetyl end-capped. Thereafter, novel water-soluble poly(butylene tartarate) PBT was successfully synthesized in the mixed solvent of chloroform and methanol with the cocatalysts of OsO4 and NMO. Finally, their chemical structures were characterized by NMR, GPC, FTIR, and quantitative titration, and their solubility and physical properties were also examined. Experimental Section Materials. Fumaric acid (AR grade) was purified via recrystallization twice in deionized water. 1,4-Butanediol (AR grade) was dried over calcium oxide for a couple of days and then was distilled under reduced pressure. Dichloromethane (AR grade) was in turn washed with concentrated sulfuric acid and distilled water, and then was dried over CaH2 and distilled. Triethylamine (TEA, AR grade) and pyridine (AR grade) were dried with potassium hydroxide overnight and were further purified via distillation. Acetic anhydride (AR grade) was distilled before use. Osmium tetraoxide (OsO4, AR grade) was dissolved in deionized

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Notes

Scheme 1. New Synthetic Pathway for Preparation of Novel Water-Soluble Poly(butylene tartarate) PBT

water at a mass concentration equal to 4.0 wt % prior to use. N-methyl morpholine N-oxide (NMO) (50% in water) from Tokyo Kasei Co. Ltd, Japan, and all other reagents of analytical grade were used as received. Synthesis of Novel Water-Soluble Aliphatic Poly(butylene tartarate) PBT. As shown in Scheme 1, novel water-soluble biodegradable aliphatic poly(butylene tartarate) PBT was prepared via a three-step synthetic strategy. Preparation of Aliphatic Poly(butylene fumarate)s PBF. First, 5.80 g (50 mmol) of fumaric acid, 5.41 g (60 mmol) of 1,4-butanediol, and 40 mL of toluene were placed into a 100-mL three-necked round-bottom flask equipped with a magnetic stirrer and a Dean-Stark trap with a reflux condenser and a nitrogen gas inlet, and the reaction mixture was refluxed at 160 °C for 24 h under flowing nitrogen atmosphere. Subsequently, after evaporation of the solvent, the magnetic stirrer was changed into a mechanical stirrer and the Dean-Stark trap was removed under nitrogen atmosphere. Thereafter, the pressure of the condensation polymerization system was gradually decreased, and the reaction temperature was simultaneously elevated to 180 °C. The condensation polymerization was finally terminated when a real-time digital torque of the mechanical stirrer (210 rpm, Eurostar, IKA Ltd, Germany) approached a stable high value. Furthermore, the crude condensation polymerization product was again dissolved in chloroform under ambient temperature. The chloroform-insoluble part (39.0 wt %) was filtered out, and the chloroform-soluble part (61.0 wt %) was allowed to be concentrated via evaporation and then was precipitated with an excess amount of methanol. The precipitated poly(butylene fumarate) products were collected and dried in a vacuum oven at room temperature for 24 h before use. Acetyl End-Capping of the Synthesized Poly(butylene fumarate) A quantity (2.00 g, 0.20 mmol) of the above

chloroform-soluble poly(butylene fumarate) PBF was charged into a flame-dried flask under nitrogen atmosphere and then was dissolved well in 60 mL of dry dichloromethane. After 0.20 mL (1.49 mmol) of dry TEA was again added, 0.11 mL (1.49 mmol) of acetyl chloride was gradually dropped into the reaction mixture. The reaction system was kept stirring for 24 h at room temperature, and then, the organic phase was separated and rinsed with distilled water. The organic phase was concentrated and then was precipitated via pouring into excess amount of methanol. As a result, a white-colored powder product was finally attained after drying at ambient temperature in a vacuum oven for 24 h. Preparation of Novel Water-Soluble PBT via Dihydroxylation of CdC bond. First, 1.00 g of the acetyl endcapped PBF (5.90 mmol of CdC bond as calculated on 1H NMR) was placed into a glass flask and dissolved well in 50 mL of chloroform under nitrogen atmosphere. Subsequently, 1.66 g (1.20 equivalents) of NMO (50% in water) and 0.72 mL (0.02 equivalents) of OsO4 (4.0 wt % in water) were in turn added under agitation at room temperature. During the reaction, 5 mL of methanol was gradually injected with the aid of a syringe to keep the reaction system transparent. After maximum conversion of CdC bonds of the fumarate building blocks was approached (tracked by1H NMR), the reaction mixture was allowed to stir with Na2SO3 for an appropriate period and then was dried with Na2SO4 overnight. The organic phase of the mixed system was extracted and then concentrated under reduced pressure. Furthermore, the crude product was again dissolved in methanol, and the methanol-insoluble mass was filtered out. As a result, the methanol-soluble (45.0%) poly(butylene tartarate) PBT was precipitated with cold chloroform. The collected PBT precipitates were washed with chloroform and benzene several times and dried in a vacuum oven at ambient temperature for 24 h.

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Analytical Procedures. 1. GPC Characterization. Molecular weights of the synthesized PBF and acetyl end-capped PBF samples were measured at 40 °C on a Perkin-Elmer 200 series gel permeation chromatograph equipped with a refractive index detector (RI) and network chromatography interface NCI 900. Double PLgel 5-µm mixed-D type of 300 × 7.5 mm columns (Polymer Laboratories Ltd., G.B.) were set in series with chloroform as the eluent at 1.0 mL/min. Polystyrene standards received from Showa Denko Ltd, Japan were employed to calibrate the GPC traces. Thus, molecular weights (Mw, Mn) and polydispersity (PDI) were evaluated for the PBF and acetyl-PBF. 2. 1H and 13C NMR. NMR spectra were recorded at ambient temperature on a Bruker AMX300 and Varian VXR300 Fourier Transform nuclear magnetic resonance spectrometer operating at 300.0 and 75.5 MHz for the corresponding 1H and 13C nuclei, respectively. The prepared PBF and acetyl end-capped PBF samples were measured in chloroform solution with tetramethylsilane (TMS) as the internal chemical shift reference, while CD3OD was hereby applied as the solvent for the synthesized water-soluble poly(butylene tartarate) PBT. Fourier Transform Infrared Spectroscopy. FTIR spectra were recorded at ambient temperature for the synthesized aliphatic polyester samples on a Bio-Rad FTS-185 FTIR spectrometer, and the pressed KBr tablets were applied as the FTIR samples. Hydroxyl Titration. For determining the hydroxyl content in the prepared poly(butylene tartarate) PBT, a nonaqueous titration method was employed.24,25 A 100-mg portion of the synthesized PBT was added into 4.0 mL of pyridine/acetic anhydride (3:1 v/v) mixed solution, and then, the oil bath temperature was raised to 100 °C and kept for 1 h. Subsequently, 2.0 mL of distilled water was added into the reaction mixture. After 0.5 h, the methanol solution of KOH (109.6 mM) was employed to titrate the PBT polyester solution in triplicate with thymol blue as the indicator. Similarly, the blank titration was also conducted. Thermal Characterization. Thermal analyses of the synthesized samples were implemented on a Perkin-Elmer Pyris 1 differential scanning calorimeter (DSC) and a thermal gravimetric analyzer (TGA). A quantity (8.0∼10.0 mg) of the synthesized sample was first encapsulated in an aluminum pan and then heated to 170 °C to remove its thermal history, and further maintained at room temperature for more than three weeks to approach the equilibrium crystallization state. Subsequently, the DSC sample was allowed to heat up to 170 °C at 20 °C/min (the first heating run). After keeping at 170 °C for 1 min, the sample was rapidly quenched to -120 °C at a programmed rate of 450 °C/min, and then, a second heating scan was recorded from -120 °C to 170 °C at 20 °C/min. Hence, melting point (Tm) and enthalpy of fusion (∆Hm) were evaluated as the main peak top temperature and integral of the endothermic trace recorded by the first DSC run, respectively. Glass transition temperature (Tg) was evaluated as the midpoint of the heat capacity transition as detected in the second heating run. On the other hand, TGA was conducted from 50 to 500 °C at 10 °C/min under flowing nitrogen atmosphere (45 mL/min). Peak tops (Td) of the

Notes

Figure 1. 1H NMR spectrum for the synthesized hydroxyl-terminated poly(butylene fumarate) PBF.

thermal decomposition rate trace were employed to characterize thermal degradation behavior and stabilities of the synthesized samples. Wide-Angle X-ray Diffraction (WAXD). WAXD patterns were measured for the prepared PBT under ambient temperature on a Rigaku 200 X-ray diffractometer (18 kW, 60 KV/450 mA, Rigaku Instrument Co. Ltd., Japan). The sample was scanned from 8° to 40° at 10°/min, and the nickel-filtered copper KR X-ray beams with a pinhole graphite monochromator were applied as the incident source (λ ) 0.154 nm). Results and Discussion Synthesis of Aliphatic Poly(butylene fumarate)PBF and Acetyl End-Eapped PBF. To synthesize acetyl end-capped aliphatic PBF, hydroxyl-terminated PBF was first prepared. In published literature,26 it has been reported that a functional polyester bearing an unsaturated moiety could hardly be efficiently prepared through a routine melt polycondensation due to the occurrence of gelation at the initial stage. Therefore, solution polycondensation was thus employed as an alternative strategy to synthesize the functional polyester prepolymer.27-30 In this study, the reactants of fumaric acid and 1,4-butanediol were allowed to reflux at 160 °C in toluene for 24 h under inert nitrogen atmosphere for preparation of the PBF prepolymers, and the initial diol to diacid molar ratio was optimized to be 1.20. Then, the toluene solvent was completely evaporated, and polycondensation of the PBF prepolymer continued by gradually increasing the reaction temperature and the degree of vacuum. With regard to the polycondensation temperature, an optimum temperature of 180 °C was used to achieve a faster reaction rate and less cross-linking in the range 150∼200 °C. Furthermore, the prepared crude product was dissolved in chloroform at ambient temperature and then was fractionated. Finally, the chloroform-soluble fraction was attained with 61.0 wt % of the raw polyester product. Figure 1 depicts the 1H NMR spectrum for the chloroformsoluble fraction, and the proton resonance signals were accordingly assigned. The 1H resonance signals occurring

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Notes

Table 1. Synthetic Results for the PBF, Acetyl-PBF, and PBT molecular weight sample

yield (%)

PBF 45.0 acetyl-PBF 99.3 PBT 41.4

conversiona (%) 100 100

Mn,NMR Mn,GPCc Mn,theo (KDa)b (KDa) Mw/Mnc (KDa) 10.8 7.2 10.2

8.6 6.8

2.38 2.79

10.8d 8.6e

a Conversion was evaluated by 1H NMR. b Molecular weights were evaluated by 1H NMR. c Molecular weights were evaluated by GPC with PS standards. d Mn,theo ) Mn,NMR, PBF + 84. e Mn,theo ) (Mn,NMR acetyl-PBF 174) × 204/170 + 174.

Figure 2. 13C NMR spectrum for the synthesized hydroxyl-terminated poly(butylene fumarate) PBF.

at 3.69 and 4.26 ppm originated from the methylene proton nuclei of the -OCH2CH2CH2CH2OH and -OCH2CH2CH2CH2O- moieties, respectively. Meanwhile, the resonance signal at 6.86 ppm could be assigned to the unsaturated -CHdCH- with the E-configuration, and it was noted that there was not any detectable resonance signal for those -CHdCH- proton nuclei with the Z-configuration as reported to occur at 6.31 ppm;26 this demonstrated no appreciable isomerization of the CdC configuration during the melt polymerization. Moreover, Figure 2 shows the 13C NMR spectrum for the chloroform-soluble fraction, and the 13 C resonance signals at δ ) 165.4, 134.2, 65.2, and 62.7 ppm were assignable to the CdO of the fumarate moieties, -CHdCH-, -OCH2CH2CH2CH2O-, and the terminal -OCH2CH2CH2CH2OH, respectively. On the basis of this NMR evidence, the chloroform-soluble fraction of the raw polyester product was therefore demonstrated to be the hydroxyl-terminated poly(butylene fumarate) PBF. On the other hand, in the polyesterification reaction, the primary hydroxyl functional group has been known to exhibit higher reactivity than the secondary hydroxyl; thus, hydroxyl end groups of the synthesized PBF were hereby protected to avoid possible side reactions before further hydroxylation of the unsaturated CdC bonds. The acetyl protection reaction was done at room temperature in dichloromethane for 24 h, and the methylene proton and carbon resonance signals of the terminal -OCH2CH2CH2CH2OH of the prepared PBF as detected at 3.69 and 62.7 ppm were thoroughly eliminated, and new resonance signals at 2.06, 21.6, and 178.9 ppm concurrently occurred and could be assigned to the corresponding methyl proton, methyl carbon, and carbonyl carbon of the acetyl groups, indicating successful end-capping of hydroxyl functional groups of the chloroform-soluble PBF. Table 1 summarizes the synthetic results for the chloroformsoluble poly(butylene fumarate) and acetyl end-capped PBF product. The number average molecular weights (Mn,NMR) were evaluated on the basis of the 1H NMR spectrum in accordance with Mn,NMR (chloroform-soluble PBF) ) 170 × n + 90 and Mn,NMR (acetyl end-capped PBF) ) 170 × n + 174, respectively, where n expresses the degree of polymerization. It was seen that Mn,NMR of the acetyl-PBF is equal to 7.2 KDa was a little lower than that of the

fractionated chloroform-soluble PBF (10.8 KDa), and the detectable decrease in molecular weight after acetyl endcapping might be accounted for by possible ester bond cleavage under the alkaline experimental conditions. Alternatively, molecular weights were also evaluated by GPC in chloroform, and the calculated number average molecular weights (Mn,GPC) were obviously lower than those evaluated on the basis of NMR resonance intensities. The difference in molecular weights could reasonably be interpreted by the GPC calibration using polystyrene standards. In view of the acetyl end-capped PBF, 1H and 13C NMR spectra indicated efficient protection of the hydroxyl end groups for the prepared chloroform-soluble PBF. Preparation of Novel Water-Soluble Poly(butylene tartarate) PBT. For the sake of synthesizing new aliphatic poly(butylene tartarate) from the PBF precursor, catalytic systems such as H2O2/HCOOH, m-CPBA/chloroform, cold and diluted KMnO4 aqueous solution, K2OsO2(OH)4/K3Fe(CN)3/CH3SO2NH2, and OsO4/NMO were employed to oxidize the unsaturated CdC bonds of fumarate moieties. It has always been reported that in the presence of OsO4 cisdihydroxylation of unsaturated CdC bonds with NMO was a reliable synthetic strategy for some small-molecular-weight olefin compounds.31 In this study, the OsO4/NMO catalytic system was finally selected on the basis of PBF dihydroxylation efficiency, and an excess amount of NMO was applied as the cocatalyst. Meanwhile, the initial amount of OsO4 catalyst was optimized as 0.02 equiv to the unsaturated Cd C bonds of PBF, and the cocatalyst of NMO was also optimized as 1.20 equiv to the unsaturated CdC bonds to increase the conversion rate. In practice, because of the limited solubility of the PBF synthetic precursor in methanol, a mixed solvent of chloroform and methanol was applied to keep the reaction mixture homogeneous and enhance the dihydroxylation efficiency . As a result, a methanol-soluble fraction (45.0%) of the acetyl PBF dihydroxylation product was achieved. Figures 3 and 4 show NMR spectra for methanol-soluble fraction of the prepared PBF hydroxylation product. As compared to the NMR resonance signals for the PBF precursor, the proton resonance signal of -OCCHdCHCOentirely disappeared, and a new 1H resonance peak obviously detected at 4.57 ppm could be assignable to those proton nuclei of new -OCCH(OH)sCH(OH)CO-. On the other hand, the 13C resonance signals for the fumarate moieties as seen at δ ) 134.2 and 165.4 ppm disappeared, accompanied by the occurrence of new 13C resonance signals at δ ) 73.6 and 173.1 ppm, and these new resonance signals were

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Figure 3. 1H NMR spectrum for the synthesized novel poly(butylene tartarate) PBT in CD3OD.

Notes

Figure 5. FTIR spectra for the synthesized acetyl-PBF and PBT. Table 2. Solubility of Novel Poly(butylene tartarate) in Various Solvents solvent

HEX

Et2O

EA

acetone

toluene

CH2Cl2

solubilitya

-

-

-

-

-

-

CHCl3 -

THF -

C2H5OH -

CH3OH +

H2O +

DMF +

DMSO +

a

- means insoluble; + means soluble.

Table 3. Thermal Characteristics of the Synthesized Acetyl-PBF and PBT sample

Tma (°C)

∆Hma (J/g)

Tgb (°C)

Tdc (°C)

acetyl- PBF PBT

137.4

63.9

-19.2 2.5

389.3 256.4

a T and ∆H were measured by the first DSC scan at heating rate of m m 20 °C/min. b Tg was estimated from the second DSC scan at heating rate of 20 °C/min after a rapid quenching. c Td was evaluated from the dTGA traces recorded at a scanning rate of 10 °C/min.

Figure 4. 13C NMR spectrum for the synthesized novel poly(butylene tartarate) PBT in CD3OD.

assigned to new methylene and carbonyl carbon nuclei of -OCsCH(OH)sCH(OH)CO- for the newly formed tartarate moieties. Therefore, this evidence of the methanolsoluble fraction substantiated complete dihydroxylation of the BF CdC bonds and formation of the novel aliphatic poly(butylene tartarate) bearing pendant hydroxyl groups. Figure 5 depicts the FTIR spectra of the acetyl PBF precursor and the methanol-soluble fraction of the dihydroxylation product. Two FTIR absorption bands (upper in Figure 5) were observed at 1708 and 1664 cm-1, reflecting the stretching vibration modes of the carbonyl and CdC double bonds in the fumarate building block. In contrast, the carbonyl stretching vibration of the methanol-soluble fraction (bottom in Figure 5) was observed to shift to 1736 cm-1, and the absorption band at 1664 cm-1 disappeared. Meanwhile, an additional strong and broad absorption band could be observed at 3426 cm-1, implying the presence of hydroxyl structure. A further quantitative titration of the hydroxyl content was conducted via hydroxyl titration and indicated a hydroxyl content equal to 9.53 mmol/g, which was in close agreement with a value of 9.64 mmol/g as calculated on 1H NMR. As a result, a novel aliphatic

polyester PBT was successfully attained with a molecular weight Mn,NMR equal to 10.2 KDa. Solubility in Diverse Solvents. With respect to solubility of the new aliphatic poly(butylene tartarate) PBT at ambient temperature in diverse solvents, the testing results are generalized in Table 2. It was found that the new PBT could not be dissolved well in a solvent with low polarity, and only a solvent like methanol, water, N,N-dimethylformamide (DMF), or dimethylsulfoxide (DMSO) with high polarity could thoroughly dissolve the new PBT polyester bearing abundant pendant polar hydroxyl groups, and this unique nature of the new water-soluble PBT seems much different from most of the currently known aliphatic polyesters. Thermal and Crystallization Characterization. Thermal and crystallization behavior of the chloroform-soluble acetylPBF and new water-soluble PBT were examined by means of DSC, TGA, and WAXD, and the results are summarized in Table 3. In view of DSC traces measured by the first heating run in Figure 6, a sharp endothermic trace of PBF crystal melting could be observed around 137 °C, implying a high crystallinity of the linear PBF bearing CdC bonds with E-configuration. Regarding the new water-soluble poly(butylene tartarate), only a broad endothermic trace with a peak near 100 °C could be detected, and this might be due

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water with enhanced affinity through hydrogen bonding between the water and the pendant hydroxyl groups of the resultant PBT. Conclusions

Figure 6. DSC traces for the acetyl-PBF and PBT by the first heating scan.

Figure 7. dTGA traces for the synthesized PBF and new watersoluble PBT.

to the presence of a trace amount of water absorbed by the new highly hydrophilic PBT polyester. Furthermore, the WAXD pattern of the synthesized PBT (not shown here) indicated the typical diffraction pattern of an amorphous polymer. On the basis of the evidence of DSC and WAXD, the new water-soluble poly(butylene tartarate) could therefore be concluded to form an amorphous solid structure. On the other hand, as shown in Table 3, the glass transition temperature of the PBT equal to 2.5 °C was higher than that of the acetyl end-capped PBF, and the higher glass transition temperature (Tg) of PBT might suggest the possible formation of an interesting hydrogen bond network for the abundant hydroxyl pendant functional groups. Figure 7 shows the thermal degradation rate traces (dTGA) for the acetyl PBF precursor and the synthesized new poly(butylene tartarate). After dihydroxylation of the CdC bonds, thermal degradation of the PBT under nitrogen atmosphere obviously shifted toward the lower-temperature side when it was compared with the acetyl-PBF synthetic precursor, demonstrating a lower thermal stability for the new watersoluble PBT. In the meantime, the weight loss at 108 °C in the PBT dTGA trace might stem from the loss of absorbed

In this work, a new facile and versatile synthetic approach to novel water-soluble aliphatic PBT has been studied. Through condensation polymerization of fumaric acid and 1,4-butanediol and successive fractionation in chloroform, hydroxyl-terminated poly(butylene fumarate) was synthesized in good yield. After further acetyl end-capping of the PBF, this synthetic precursor was allowed to be hydroxylated in a mixed solvent of chloroform and methanol under an optimized cocatalyst system of OsO4 and NMO, and the fractionated methanol-soluble dihydroxylation product with Mn,NMR equal to 10.2 KDa was characterized to be novel aliphatic poly(butylene tartarate) PBT. Furthermore, this new aliphatic polyester was found to be soluble in diverse solvents with high polarity like water, methanol, DMF, and DMSO. DSC and X-ray diffraction demonstrated that the PBT had an organized amorphous solid structure with a higher glass transition temperature and lower thermal stability than its PBF synthetic precursor. This new water-soluble aliphatic polyester bearing abundant reactive side groups will thus possibly be used as a novel biodegradable polymer toward potential applications as a drug carrier and new functional biomaterials. Further studies concerning its biodegradability and its possible application as a lipophilic steroid-type antiinflammation drug carrier are now under investigation in this lab. Acknowledgment. The authors are grateful to the fund supports partially from the hundreds of talents project, Chinese Academy of Sciences (CAS), national science foundation of China (contract 20204019) and rising star project 04QMX1445 of the science and technology committee of Shanghai municipality. References and Notes (1) Pitt, C. G.; Marks, T. A.; Schindler, A. Biodegradable Drug Delivery Systems based on Aliphatic Polyester: Application of Contraceptives and Narcotic Antagonists In Controlled Release of BioactiVe Materials; Baker, R., Ed. Academic Press: New York, 1980. (2) Lenz, R. W.; Guerin, P. Polymers in Medicine; Plenum: New York, 1983; Vol. 23, p 219. (3) Tian, D.; Dubois, P.; Grandfils, C.; Je´roˆme, R. Macromolecules 1997, 30, 406. (4) Vert, M.; Lenz, R. W. Polym. Prepr. 1979, 20, 608. (5) Kimura, Y.; Shirotani, K.; Yamane, H.; Kitao, T. Macromolecules 1988, 21, 3338. (6) Zhou, Q. X.; Kohn, J. Macromolecules 1990, 23, 3399. (7) Gelbin, M. E.; Kohn, J. J. Am. Chem. Soc. 1992, 114, 3962. (8) Kimura, Y.; Shirotani, K.; Yamane, H.; Kitao, T. Polymer 1993, 34, 1741. (9) Barrera, D. A.; Zylstra, E.; Lansbury, P. T.; Langer, R. J. Am. Chem. Soc. 1993, 115, 11010. (10) Vert, M.; Fournier, P.; Boustta, M.; Domurado, D.; Guerin, P.; Braud, C.; Holler, H. Macromol. Rep. 1994, A31, 723. (11) Kopecek, J.; Ulbrich, K. Prog. Polym. Sci. 1983, 9, 1. (12) Guerin, P.; Vert, M.; Braud, C.; Lenz, R. W. Polym. Bull. 1985, 14, 187. (13) Gross, R. A.; Zhang, Y.; Konrad, G.; Lenz, R. W. Macromolecules 1988, 21, 2657. (14) Benvenuti, M.; Lenz, R. W. J. Polym. Sci., Polym. Chem. 1991, 29, 793. (15) Vert, M. Polym. Degrad. Stab. 1998, 59, 169.

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(16) Kumar, A.; Kulshrestha, A. S.; Gao, W.; Gross, R. A. Macromolecules 2003, 36, 8219. (17) Fu, H.; Kulshrestha, A. S.; Gao, W.; Gross, R. A. Macromolecules 2003, 36, 9804. (18) Kline, B. J.; Beckman, E. J.; Russell, A. J. Am. Chem. Soc. 1998, 120, 9475. (19) Uyama, H.; Inada, K.; Kobayashi, S. Macromol. Biosci. 2001, 1, 40. (20) Uyama, H.; Inada, K.; Kobayashi, S. Macromol. Rapid Commun. 1999, 20, 171. (21) Uyama, H.; Klegraf, E.; Wada, S.; Kobayashi, S. Chem. Lett. 2000, 29, 800. (22) Parrish, B.; Emrick, T. Macromolecules 2004, 37, 5863. (23) Zhang, S.; Yang, J.; Liu, X.; Chang, J.; Cao, A. Chin. J. Org. Chem. 2003, 23, 1008.

Notes (24) Deng, X.; Hao, J. Eur. Polym. J. 2001, 37, 211. (25) Zhang, S.; Yang, J.; Liu, X.; Chang, J.; Cao, A. Biomacromolecules 2003, 4, 437. (26) Takenouchi, S.; Takasu, A.; Inai, Y.; Hirabayashi, T. Polym. J. 2001, 33, 746. (27) Batzer, H.; Holtschmidt, H.; Wiloth, F.; Mohr, B. Makromol. Chem. 1951, 7, 82. (28) Batzer, H.; Mohr, B. Makromol. Chem. 1952, 8, 217. (29) Won, C.; Chu, C.; Lee, J. D. Polymer 1998, 39, 6677. (30) Won, C.; Chu, C.; Lee, J. D. J. Polym. Sci., Polym. Chem. 1998, 36, 2949. (31) VanRheenen, V.; Kelly, R. C.; Cha, D. Y. Tetrahedron Lett. 1976, 23, 1973.

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