Biomacromolecules 2005, 6, 1345-1352
1345
Copolymerizations of E-Caprolactone and GlycolidesA Comparison of Tin(II)Octanoate and Bismuth(III)Subsalicylate as Initiators† Hans R. Kricheldorf* and Simon Rost Institut fu¨r Technische und Makromolekulare Chemie, Bundesstr. 45, D-20146 Hamburg, Germany Received September 30, 2004; Revised Manuscript Received December 22, 2004
Copolymerizations of -caprolactone (CL) and glycolide (GL) were conducted in bulk at 120 °C with variation of the reaction time. Either Sn(II) 2-ethylhexanoate (SnOct2) or bismuth(III)subsalicylate (BiSS) were used as initiators combined with tetra(ethylene glycol) as co-initiator. The resulting copolyesters were analyzed by 1H and 13C NMR spectroscopy with regard to the total molar composition and to the sequence of the comonomers. Furthermore, two series of copolymerizations (either Sn- or Bi-initiated) were performed at constant time with variation of the temperature. It was found that BiSS favors alternating sequences more than SnOct2. Time-conversion curves and MALDI-TOF mass spectrometry of homopolymerization suggest that SnOct2 is the more efficient transesterification catalyst. A hypothetical reaction mechanism is discussed. Introduction In addition to polylactides, poly(-caprolactone), polyglycolide and copolymers of -caprolactone (CL), glycolide (GL) and L-lactide (LLA) belong to the most intensively studied and most widely used biodegradable polyesters. The properties and potential applications depend very much on the molar composition and on the sequence of the comonomers. Block copolymers are crystalline with melting temperatures (Tm’s) between 60 and 65 °C (poly(CL)), 170-175 °C (poly(LLA)), and 220-225 °C (poly(GL)). The glass-transition temperatures may be as low as -65/-60 °C typical for poly(CL) or as high as 50/55 °C typical for polylactides. Random copolyesters of these monomers are amorphous with glass-transition temperatures between the extremes of the homopolyesters. Copolyesters of CL and GL are particularly interesting, because they combine rapidly hydrolyzing ester bonds (GL-GL) with slowly hydrolyzing ones (CL-CL). Copolymerizations of CL and GL were studied by several research groups.1-7 As first demonstrated by Kricheldorf,2,3 1 H NMR and 13C NMR spectroscopies are useful for the determination of the molar composition and for a characterization of the sequences. The most widely used initiators for both academic research and technical production of biodegradable polyesters are tin compounds, in particular, Sn(II) 2-ethylhexanoate (SnOct2). However, all tin-based initiators are highly cytotoxic and should be replaced by less toxic ones. Bismuth salts are components of several ointments and drugs and belong to the least toxic heavy-metal compounds.8 Particularly interesting are bismuth subsalicylate (BiSS) and bismuth subcitrate, because they have been †
“Polylactones”, Part 80. * To whom correspondence should be addressed. Tel.: +49-40-42838-3168; fax: +49-40-42838-6008; e-mail: kricheld@ chemie.uni-hamburg.de.
known for several decades as successful commercial drugs against intestinal complaints.9-11 In previous publications,12,13 it has been demonstrated that bismuth acetate or hexanoate are useful initiators for homopolymerizations of CL and LA. In this context, the present work has the purpose to study the usefulness of BiSS as initiator for copolymerizations of CL and GL. Experimental Section Materials. -Caprolactone was purchased from Aldrich Co. (Milwaukee, WI) and distilled over freshly powdered calcium hydride in vacuo. Glycolide (S-grade) was kindly supplied by Boehringer KG (Ingelheim-Rhein, Germany). It was recrystallized twice from ethyl acetate and it was dried over P4O10 in vacuo. Tetra(ethylene glycol), TEG, was also purchased from Aldrich Co. It was azeotropically dried with toluene and distilled over a short-path apparatus in vacuo. SnOct2 (Aldrich Co.) was purified as described previously.14 Bismuth subsalicylate (Aldrich Co.) was used as received. Time-Conversion Curves. CL (50 mmol) and TEG (1 mmol) were weighed into a 50-mL Erlenmeyer flask with silanized glass walls. The reaction vessel was closed with a glass stopper and steel spring and immersed into an oil bath preheated to 120 °C. After 5 min, 0.1 mL of a 0.5 M solution of SnOct2 in chlorobenzene or 18 mg of BiSS was added. The polymerization was allowed to continue at 120 °C for 14 h, and small samples were removed from time to time (under an atmosphere of dry nitrogen) to monitor the conversion by 1H NMR spectroscopy up to 99% (the reaction products were dissolved in CDCl3). Polymerizations for MALDI-TOF Mass Spectroscopy (Table 5). Four homopolymerizations of CL were conducted as described above. In two cases, SnOct2 was used as initiator, and in two cases BiSS was used. No samples were removed for NMR spectroscopy before the polymerizations
10.1021/bm040070o CCC: $30.25 © 2005 American Chemical Society Published on Web 03/26/2005
1346
Biomacromolecules, Vol. 6, No. 3, 2005
Kricheldorf and Rost
Table 1. Copolymerizations of -Caprolactone and Glycolide in Bulk Initiated by SnOct2a and BiSSa: Variation of the Temperature
LCLc
LGLd
copol. no.
initiator
temp (°C)
time (h)
CL/GL/TEGb (1H NMR)
1H
13C
altern. dyads (%) GL-CL
1H
13C
altern. dyads (%) CL-G L
1 2 3 4 5 6 7 8
SnOct2 SnOct2 SnOct2 SnOct2 BiSS BiSS BiSS BiSS
100 120 140 160 100 120 140 160
24 8 2 0.5 48 24 5 2
27/13/1 26/12/1 27/13/1 26/12/1 25/13/1 26/12/1 27/13/1 25/12/1
3.70 2.00 1.60 1.55 2.25 1.60 1.50 1.47
3.10 1.90 1.50 1.50 2.05 1.65 1.50 1.45
27 48 62 63 44 63 67 69
3.20 2.20 1.60 1.55 2.30 1.55 1.50 1.45
2.90 1.95 1.50 1.45 2.10 1.50 1.40 1.40
31 45 61 63 44 65 70 72
a Monomer initiator ratio (M/I ) 1000/1). b Molar feed ratio: 26/13/1. c Average lengths of the homogeneous blocks calculated according to eq 1 from the O-CH2 1H NMR signals and from the CO-signals, respectively. d Average lengths of the homogeneous blocks calculated according to eq 2 from the O-CH2 1H NMR signals and from the CO-signals, respectively.
were stopped. The reaction products were dissolved in CH2Cl2 and precipitated into diethyl ether. The polyesters were characterized after drying at 40 °C in vacuo (see Table 4 and Figure 6). Copolymerizations with Variation of the Temperature (Table 1). CL (13 mmol), GL (7 mmol), and TEG (0.5 mmol) were weighed into a 50-mL Erlenmeyer flask having silanized glass walls. The reaction vessel was closed with a glass stopper and steel spring and immersed into an oil bath preheated to 100 °C (or higher, see Table 1). When (after hot stirring with a magnetic bar) a homogeneous melt was obtained, either BiSS (0.02 mmol) was added as a powder or SnOct2 (0.04 mL) of a 0.5 M solution in dry chlorobenzene was added. The reaction mixture was again homogenized by magnetic stirring, and the copolymerization was continued until the conversion of CL reached g97%. After cooling, the virgin reaction product was characterized by NMR spectroscopy after dissolution of small samples in hot DMSO-d6. Copolymerization with Variation of the Time (Tables 3 and 4). CL (13 mmol), GL (7 mmol), and TEG (0.5 mmol) were polymerized at 120 °C as described above. From time to time, a small sample was removed under an atmosphere of dry nitrogen. This sample was dissolved in hot DMSO-d6 and a 1H NMR spectrum was recorded immediately afterward. The copolymerizations were terminated when the conversions of both monomers had reached 99%. Measurements. The inherent viscosities were measured in CH2Cl2 using an automated Ubbelohde viscometer thermostated at 20 °C. The 400 MHz 1H NMR spectra were recorded on a Bruker Avance 400 FT NMR spectrometer in 5-mm o.d. sample tubes at 100 °C. The 100.4 MHz 13C NMR spectra were also recorded on a Bruker “Avance 400” spectrometer at 100 °C, but 10-mm o.d. sample tubes were used. DMSO-d6 containing TMS served as solvent for all measurements. In the 13C NMR spectra, 2500 scans were accumulated with a pulse width of 25.1 kHz, a pulse length of 12.4 µs, an acquisition time of 0.65 s, and a relaxation delay of 5 s using the pulse sequence “waltz 16”. The MALDI-TOF mass spectra were measured with a Bruker Biflex III spectrometer equipped with a nitrogen laser (λ ) 337 nm). All mass spectra were recorded in the reflection mode with an acceleration voltage of 20 kV. The
irradiation targets were prepared from CHCl3 solutions with dithranol as matrix and K-trifluoroacetate as dopant. The SEC measurements were performed with an apparatus of Polymer Laboratories containing a RI detector “Shodex RI 101”. A combination of three PL mixed bed columns was used with chloroform as eluent (flow rate 1.0 mL/min). Commercial polystyrene standards served for calibration, but the original molar mass data were corrected by multiplication with the factor 0.68 according to the results published in refs 15-18. Results and Discussion All copolymerizations were conducted in such a way that tetra(ethylene glycol) served as co-initiator. This diol was selected first because its 1H NMR signals do not overlap with those of the monomeric units, so that its incorporation can easily be detected and quantified. Second, a diol as coinitiator yields telechelic oligo- and polyesters having two OH- endgroups. Third, TEG is a useful model for higher polydisperse poly(ethylene glycol)s which are of interest as hydrophilic, biocompatible blocks. The relatively low monomer/co-initiator ratio was selected to prepare difunctional copolyesters which may serve as amorphous soft segments in A-B-A triblock and in multiblock copolymers (described in a future publication). Copolymerizations with Variation of the Temperature. Two series of copolymerizations were performed with variation of the temperature between 100 and 160 °C. The first series, the reaction conditions and results of which are summarized in Table 1, is based on SnOct2 as initiator, whereas BiSS was used for the second series (also compiled in Table 1). In both series of copolymerizations, TEG served as co-initiator. All copolymerizations were conducted in bulk with an CL/GL feed ratio of 2:1. The conversions were monitored by 1H NMR spectroscopy. The copolymerizations were stopped when the conversions of CL reached g97%. Since the polymerization of GL was faster, a nearly quantitative conversion of CL automatically included quantitative conversion of GL. Yet, as will be discussed below, BiSS proved to be less reactive than SnOct2 and required longer reaction times. Therefore, it was a satisfactory consequence that the molar compositions determined by 1H NMR spectroscopy of the virgin reaction products agreed well with
Biomacromolecules, Vol. 6, No. 3, 2005 1347
Copolymerizations of -Caprolactone and Glycolide Table 2. SEC and DSC Measurement of CL-GL Copolyesters Listed in Table 1 no. of Table 1
catalyst
1 2 3 4 5 6 7 8
SnOct2 SnOct2 SnOct2 SnOct2 BiSS BiSS BiSS BiSS
temp (°C)
Mn calcda (1H NMR)
Mn corr.b with 0.68
Mnc (SEC)
PD
Tgd (°C)
120 140 160
4600 4800 4400
4800 4900 4700
7100 7200 6900
1.75 1.67 1.74
120 140 160
4600 4800 4600
5000 4800 4800
7400 7100 7000
1.67 1.69 1.75
-41 -41 -40 -40 -40 -40 -39
Tmd (°C) 47/170
a Calculated from NMR spectroscopic TEG/CL and GL ratios. b SEC values multiplied with the factor 0.68. c Original SEC data obtained by calibration with polystyrene. d DSC measurements with a heating rate of 10 °C/min.
the feed ratios. Another satisfactory result was the molecular weight data obtained by polystyrene calibrated SEC measurements (Table 2). Four different research groups have demonstrated15-18 that calibration with polystyrene overestimates the real molecular weights of poly(CL) and other aliphatic polyesters by approximately 50%. When the original number average molecular weights (Mn’s) were corrected with the factor 0.68,18 they were in good agreement with the Mn values determined by 1H NMR spectroscopy from the CL and GL/TEG ratios. The sequences were analyzed by 1H NMR and 13C NMR spectroscopy, an analytical approach at first elaborated by Kricheldorf et al.2,3 and later refined by Bero et al. and Kasperczyk.4,5 The sequences were characterized by two types of values, namely, by average block lengths (L) and by the percentage of alternating dyads (signals representing the crossover steps from CL to GL or GL to CL units). The signal assignments used in this work are presented in Figures 1-4. The block lengths were calculated from the signal intensities of homo and alternating dyads according to eqs 1 and 2. LCL )
ICL-CL +1 ICL-GL
(1)
LGL )
IGL-GL +1 IGL-CL
(2)
ICL-GL or IGL-CL ) intensities of signals representing a homo dyad ICL-GL or IGL-CL ) intensities of signals representing alternating dyads For a random sequence of block lengths, around 2.0 and 50% of alternating dyads is expected. Therefore, the values obtained with SnOct2 at 100 °C clearly indicate a significant blockiness of the sequence. Since the homopolymerizations discussed below demonstrated that the polymerization of GL is much faster than that of CL, the blocky sequence is obviously the result of a faster incorporation of GL in the early stage of the copolymerization. From higher temperatures, a tendency toward random sequences is expected, and the sequence data obtained with SnOct2 at 120 °C satisfy this expectation. Therefore, it was surprising that at even higher temperatures (140 and 160 °C), not a perfection of the randomization was found, but a predominant formation of alternating dyads. This tendency was even more pro-
Figure 1. 13C NMR spectra (CO-signals) of CL/GL copolyesters initiated with SnOct2 and TEG: variation of the temperature (nos. 1-4, Table 1).
nounced when BiSS was used as initiator (nos. 5-8, Table 1). At 100 °C, a nearly random sequence was formed, but at all higher temperatures the alternating dyads were favored.
1348
Biomacromolecules, Vol. 6, No. 3, 2005
Kricheldorf and Rost
Figure 2. 13C NMR spectra (CO-signals) of CL/GL copolyesters initiated with BiSS and TEG: variation of the temperature (nos. 5-8, Table 1).
The 13C NMR spectra presented in Figures 1 and 2 illustrate the temperature effect and the difference between SnOct2 and BiSS. In this connection, the DSC measurements (compiled in Table 2) should be mentioned. Melting endotherms (Tm’s) of both CL blocks and GL-blocks were only observed in the heating trace of the copolyester initiated with SnOct2 at 100 °C (no. 1). In this case, the NMR spectra indicated that the average block lengths were distinctly higher than expected for a random sequence. For all other samples, an amorphous morphology was found in agreement with average block lengths around or below 2. The glass-transition temperatures (Tg’s) were almost uniform. They were closer to the value of poly(CL) (around -60 °C) than to the Tg of
Figure 3. 1H NMR spectra (O-CH2 signals) of CL/GL copolyesters initiated with SnOct2 and TEG at 120 °C: variation of the reaction time (Table 3).
poly GL (around 30 °C). Therefore, these copolyesters may serve as flexible soft segments in block-copolymers over a broad temperature range. Copolymerizations with Variation of the Time. Two series of copolymerizations were conducted in bulk at 120 °C either initiated with SnOct2 (Table 3) or with BiSS (Table 4). Both feed ratio and co-initiator were identical with
Copolymerizations of -Caprolactone and Glycolide
Figure 4. 1H NMR spectra (O-CH2 signals) of CL/GL copolyesters initiated with BiSS and TEG at 120 °C: variation of the reaction time (Table 4).
the conditions used for the copolymerizations compiled in Table 1. As evidenced by 1H NMR spectroscopy, the molar compositions of the virgin copolyesters show a clear trend. The polymerization of GL was extremely fast, and a nearly quantitative incorporation of GL was achieved at the shortest reaction time (0.5 h). In contrast, the complete incorporation of CL required 24 h. In perfect agreement with this trend,
Biomacromolecules, Vol. 6, No. 3, 2005 1349
long blocks of GL units were formed at the beginning, but the average lengths decrease with time. Correspondingly, the percentage of alternating (GL∠CL) dyads increased from the low value of 11 to 42, that is, to a value rather close to randomness. The sequences of the CL units display the complementary trend. They change from a predominance of alternating dyads to random nature. When BiSS was used as initiator (Table 4), similar trends were observed. In the beginning, the rapid polymerization of GL produces copolyesters containing long blocks of GL units. In contrast, the full incorporation of CL requires 24 h. In the very beginning, the blocks of CL units are short. Correspondingly, the percentage of alternating dyads is high. With increasing time, the sequence characteristics of both GL and CL units approach the same values, block lengths around 1.5 and alternating dyads around 65%. Therefore, the final sequence structure of the BiSS-initiated copolyesters is quite different from that of the SnOct2-initiated one. Alternating dyads clearly dominate in BiSS as illustrated in Figure 4, whereas SnOct2 favors randomization (Figure 3). An analogous trend was observed in a parallel study comparing initiation by SnOct2 and bismuth(III)n-hexanoate. Mechanistic Discussion. For a better understanding of the reaction mechanisms, a couple of homopolymerizations were conducted with both initiators (Table 5). At first, attempts were made to elaborate time-conversion curves under the reaction conditions used for most copolymerizations (120 °C in bulk). However, it turned out that the homopolymerizations of GL with both initiators and TEG (M/C ) 50/1) were so fast that it was not feasible to monitor the polymerization by 1H NMR spectroscopy. An analogous study with CL as monomer was successful and yielded the curves displayed in Figure 5. These results indicated that the homopolymerization of GL is much faster than that of CL regardless of the initiator, and it demonstrated that the polymerization initiated with BiSS is by a factor of 17-18 slower than that initiated with SnOct2. This factor was extracted from the times required for 50% conversion of CL. Analogous time-conversion measurements were conducted in a parallel study for the pair SnOct2 and bismuth(III)hexanoate under identical conditions. In that case, the bismuth initiator was slower by a factor of 11-12. The lower reactivity of BiSS relative to bismuth(III)hexanoate is certainly a consequence of the low solubility of BiSS in the reaction mixture, whereas the hexanoate is completely soluble. Regardless of this difference, all these kinetic studies proved that the bismuth(III) salts are less efficient initiators than SnOct2. Furthermore, the homopolymerizations of CL at 120 °C were repeated and the resulting homopolyesters were isolated after a relatively short time (Table 5) or after 16 h (i.e., after nearly complete conversion). The isolated polyesters were subjected to MALDI-TOF mass spectrometry and small amounts of cyclic oligolactones were detected (Figure 6). After 3 or 6 h, the cyclic lactones were barely detectable, but their content was slightly higher after 16 h. No significant difference was detectable between SnOct2- or BiSS-initiated polymerizations. This finding evidenced that both initiators
Biomacromolecules, Vol. 6, No. 3, 2005
1350
Kricheldorf and Rost
Table 3. Copolymerizations of -Caprolactone and Glycolide in Bulk at 120 °C Initiated by TEG and SnOct2 (M/I ) 1000/1): Variation of the Time copol. no.
time (h)
conversion CL (%)
1 2 3 4 5 6
0.5 1.0 2.0 4.0 8.0 24.0
34 42 60 83 96 99
conversion GL (%)
CL/GL/TEGa (1H NMR)
Lh CL
98 99 99 99 99 99
9/13/1 11/13/1 15/13/1 21/13/1 24/13/1 26/13/1
1.65 1.70 1.85 2.05 2.15 2.10
b
alternc dyads (%) GL-CL
Lh GL
61 59 54 48 46 46
8.90 7.15 4.80 3.35 2.70 2.35
d
altern.c dyads (%) CL-GL 11 14 21 30 37 42
a Molar feed ratio 27/13/1. b Determined from the O-CH 1H NMR signals using eq 1. c Calculated from the O-CH 1H NMR signals (relative to the 2 2 sum of all dyads). d Calculated from the O-CH2 1HNMR signals using eq 2.
Table 4. Copolymerizations of -Caprolactone and Glycolide in Bulk at 120 °C Initiated by TEG and BiSS (M/I ) 1000/1): Variation of the Time copol. no.
time (h)
conversion CL (%)
conversion GL (%)
CL/GL/TEGa (1H NMR)
1 2 3 4 5
1.0 2.0 4.0 8.0 24.0
34 51 70 89 99
98 99 99 99 99
9/13/1 13/13/1 18/13/1 24/13/1 26/13/1
Lh CLb 1.25 1.35 1.45 1.50 1.55
altern.c dyads (%) GL-CL 80 76 71 67 65
Lh GLd 11.00 4.30 2.50 1.80 1.55
altern.c dyads (%) GL-CL 9 23 40 56 65
a Molar feed ratio 27/13/1. b Determined from the O-CH 1H NMR signals via eq 1. c Calculated from the O-CH 1H NMR signals relative to the sum 2 2 of all dyads. d Calculated from the O-CH2 1H NMR signals via eq 2.
Table 5. Homopolymerizations of CL in Bulk at 120 °C. TEG Was Used as Co-Initiator (M/C ) 50:1) polym. no.
initiator
time (h)
conversion (%)
yield (%)
DPa (1H NMR)
ηinhb (dL/g)
1 2 3 4
SnOct2 BiSS SnOct2 BiSS
3 6 16 16
99 59 99 99
89 50 89 88
40 25 41 41
0.20 0.13 0.22 0.22
b
a Determined by 1H NMR spectroscopy from the TEG endgroup signals. Measured at 20 °C with c ) 2 g/L in CH2Cl2.
Figure 5. Time-conversion curves of CL polymerized in bulk at 120 °C and initiated (A) with TEG/50:1 ) and SnOct2 or (B) with BiSS (M/I ) 1000/1).
catalyze “back-biting equilibration” of poly(CL) as formulated in eq 3, but this special transesterification mechanism
Figure 6. MALDI-TOF mass spectra of poly(CL) initiated with SnOct2 and TEG at 120 °C: (A) after 2 h and (B) after 16 h.
proved to be quite slow. It is clearly not efficient enough to produce a total randomization of the sequences within the time allotted to the copolymerizations. The polymerization mechanism itself was recently established for SnOct2 by two research groups,14,19 and all results and theoretical considerations suggest that bismuth(III)carboxylates involve the same mechanism. This mechanism consists of an activation of the initiator by a reversible
Copolymerizations of -Caprolactone and Glycolide
Biomacromolecules, Vol. 6, No. 3, 2005 1351
exchange reaction with the co-initiator (eqs 4 and 5). The
resulting alkoxide groups are the active species. The chain growth steps formulated in eqs 6 and 7 represent the normal
coordination-insertion mechanism. As demonstrated for several metal alkoxides,20 more than one chain can grow from one initiator molecule, provided that the initiator contained more than one alkoxide group. The back-biting equilibration and intermolecular transesterifications necessarily obey the same coordinationinsertion mechanism, but the energy of activation is higher than that of a propagation step, because the transoid ester bond in a polyester backbone is less reactive than the cisoid ester group of a cyclic monomer. Therefore, temperatures higher than the minimum temperature required for polymerization favor randomization of sequences. Therefore, it is a surprising result that BiSS favors alternating and not random sequences when the temperature is raised from 100 to 160 °C or when longer reaction times are applied. The following hypothesis offers a preliminary explanation. Higher temperatures favor an extensive transformation of BiSS into cyclic or noncyclic Bi-alkoxides having two (e.g., structure 1) or three alkoxide bonds (e.g., structure 2). These active species can initiate two or three chains (not necessarily at the same time). When at least two chains grow from one Bi atom, an intramolecular transesterification can occur which has a relatively low energy of activation for two reasons. First, it involves a five-membered transition state, and second, the most electrophilic ester group reacts with the most nucleophilic alkoxide group (eq 8). In combination with two growing steps (eq 9), the consequence is a predominant formation of CL-OCH2-CO-CL triads, which is confirmed by the NMR spectra (Figures 1-4).
conditions, three chains grow from one Al atom, and neither back-biting nor intermolecular transesterification takes place. A special intramolecular transesterification such as that formulated in eq 8 is thus a reasonable explanation for the preferential formation of CL-OCH2-CO-CL triads. In summary, the Al(OiPr)3-initiated copolymerizations definitely support the above hypothesis about the BiSS-initiated copolymerization mechanism. Conclusion The results obtained in this work demonstrate that a commercial drug, BiSS, is a useful initiator for copolymerizations of CL and GL. Compared to SnOct2, the most widely used standard initiator, it is somewhat less reactive so that longer reaction times or higher temperatures are needed to achieve quantitative conversions. However, it has two important advantages. First, the sequences are less blocky and depending on time and temperature may contain an excess of alternating dyads. Such sequences are favorable for an amorphous homogeneous morphology and for rather uniform rates of hydrolytic degradations. Second, BiSS is far less toxic than SnOct2 or other tin compounds, and in this respect, few efficient initiators can rival with BiSS or other bismuth carboxylates. References and Notes
As published previously,2 a predominant formation of these alternating triads was also observed for Al(OiPr)3-initiated copolymerizations of CL and GL at 100 °C. Under these
(1) Gilding, D. K.; Reed, A. M. Polymer 1979, 20, 1489. (2) Kricheldorf, H. R.; Mang, T.; Jonte´, J. M. Macromolecules 1984, 17, 2173. (3) Kricheldorf, H. R.; Jonte´, J. M.; Berl, M. Makromol. Chem. 1985, Suppl. 12, 25. (4) Bero, M.; Czaplo, B.; Dobrzynski, P.; Jenerczek, H.; Kasperczyk, J. Makromol. Chem. Phys. 1999, 911, 200. (5) Kasperczyk, J. Macromol. Chem. Phys. 1999, 903, 2000. (6) Dobrzynski, P. J. Polym. Sci., Part A: Polym. Chem. 2002, 40, 1379. (7) Pack, J. W.; Kim, S. H.; Cho, I. W.; Park, S. Y.; Kim, Y. H. J. Polym. Sci., Part A: Polym. Chem. 2002, 40, 544. (8) Rodilla, V.; Miles, A. T.; Jenner, W.; Harcksworth, G. M. Chem. Biol. Interact. 1998, 115, 71. (9) Gordon, M. F.; Abrams, R. I.; Rubin, D. R.; Barr, W. B.; Correa, D. D. MoV. Disord. 1995, 10, 220.
1352
Biomacromolecules, Vol. 6, No. 3, 2005
(10) Gill, H. H.; Desai, H. G.; Mehta, P. R.; Ranganathan, S.; Kalro, R. H.; Musti, P. K.; Prabhu, S. R. J. Assoc. Physicians India 1991, 39, 743. (11) Suarez, M. S.; Gonzales-Cansino, J.; Velasco-Izalde, C.; Sabatier, C. A.; Castillo-Hernandez, J. Arch. Med. Res. 1999, 30, 55. (12) Kricheldorf, H. R.; Hachmann-Thiessen, H. Biomacromolecules 2004, 5, 492. (13) Kricheldorf, H. R.; Hachmann-Thiessen, H. Macromolecules, in press. (14) Kricheldorf, H. R.; Kreiser-Saunders: I.; Stricker, A. Macromolecules 2000, 33, 702. (15) McLain, S. J.; Drysdale, N. E. Polym. Prepr. (Am. Chem. Soc., DiV. Polym. 1992, 33, 174.
Kricheldorf and Rost (16) Pasch, H.; Rode, K. J. Chromatogr., A 1995, 699, 24. (17) Kricheldorf, H. R.; Eggerstedt, S. Macromol. Chem. Phys. 1998, 199, 283. (18) Kowalski, A.; Libiszowski, J.; Duda, A.; Penczek, S. Macromolecules 2000, 33, 1964. (19) Kowalski, A.; Duda, A.; Penczek, S. Macromolecules 2000, 33, 7359. (20) Kricheldorf, H. R.; Berl, M.; Scharnagel, N. Macromolecules 1988, 21, 286.
BM040070O
