Poly(acrylamide‐co‐itaconic acid) and Semi‐IPNS with Poly(ethylene glycol): Preparation and Characterization

Summary: A pH‐responsive poly(acrylamide‐co‐itaconic acid) (PAAm/IA) hydrogel and semi‐interpenetrating networks (semi‐IPNs) with 5, 10 and 15 wt.‐% of poly(ethylene glycol) (PAAm/IA/PEG), were synthesized. Their swelling behavior was studied in the pH range from 1.76 to 7.81, as well as their oscillatory swelling behavior at pH = 7.81 and pH = 1.7. Throughout these studies, the gels maintained their mechanical strengths and shape. The shear storage (G′) and loss (G″) moduli, obtained as a function of frequency, for the gels as formed and at equilibrium swelling were higher for the semi‐IPNs than for the copolymer hydrogel. The shear storage moduli of copolymer hydrogel and semi‐IPNs as formed were independent of frequency over the whole experimental range, whereas the values for the gels at equilibrium swelling decreased with increasing degree of swelling, i.e., the PAAm/IA hydrogel which exhibited the largest swelling had the lowest G′ value. The G′ and G″ values also depended on the content of PEG.

Diffusion exponent vs. pH for PAAm, copolymer hydrogel PAAm/IA and semi‐IPN with PEG.     

Polylactones, 45. Homo‐ and Copolymerizations of 3‐Methylmorpholine‐2,5‐dione Initiated With a Cyclic Tin Alkoxide

Morpholine‐2,5‐dione and D ,L ‐3‐methylmorpholine‐2,5‐dione were polymerized with 2,2‐dibutyl‐2‐stanna‐1,3‐dioxepane (DSDOP) as initiator with variation of time and monomer/initiator (M/I)‐ratio. For comparison a few polymerizations were initiated with Sn(II) 2‐ethylhexanoate. The DSDOP initiated polymerizations gave slightly higher molecular weights, but the molecular weights were rather low in all cases and did not parallel the M/I‐ratio. Furthermore, D ,L ‐3‐methylmorpholine‐2,5‐dione was copolymerized with ε‐caprolactone (ε‐CL) or with L ‐lactide. ¹³C NMR spectra proved the formation of nearly random sequences. Therefore, the 1 : 1 copolymers were amorphous. Higher feed ratios of ε‐CL or L ‐lactide yielded higher molecular weights (at constant M/I‐ratio) and they yielded crystalline copolyesters as evidenced by DSC‐measurements.     

Synthesis and Characterisation of Poly[oligo(ε‐caprolactone)L‐malate‐graft‐poly(L‐lactide)]

Graft copolyesters with a PCL backbone and PLLA side chains were successfully prepared in three steps avoiding transesterification. First ε‐caprolactone was polymerised with 1,6‐hexane diol as initiator to obtain hydroxytelechelic oligo(ε‐caprolactone)s. These diols were then subjected—in the second step—to polycondensation with L ‐malic acid yielding in linear poly[oligo(ε‐caprolactone)L ‐malate] having secondary hydroxyl functions in the side chain. For both reactions scandium triflate Sc(OTf)₃ was used as a catalyst. In the third step various amounts of L ‐lactide were grafted from the polymer backbone using Zn(oct)₂ as catalyst. The successful reaction was confirmed by NMR and SEC (size exclusion chromatography) analysis. Further the thermal properties of the graft copolymers with different graft lengths were determined via differential scanning calorimetry.

     

An Injectable ROS‐Responsive Self‐Healing Hydrogel Based on tetra‐poly(ethylene glycol)‐b‐oligo(l‐methionine)

Abnormal physiological conditions provide an ideal stimulus for the design of responsive hydrogels which function as controlled and site‐specific release of drugs. Here, an injectable reactive oxygen species (ROS) responsive self‐healing hydrogel based on tetra‐poly(ethylene glycol)‐b‐oligo (l ‐methionine) (t‐PEG₅₆‐b‐OMeth_n) synthesized by a novel and facile method is reported. The hydrophobic interactions between the side chains of l ‐methionine make the polymer chains crosslinked and lead to the formation of hydrogels which can be injected and self‐healed, meanwhile, the cross‐linker also provides a hydrophobic domain to encapsulate Dox. In presence of ROS, the side chain of l ‐methionine can be oxidized to methionine sulfoxide. The side chain of l ‐methionine is changed accordingly from hydrophobic to hydrophilic. As a result, both the hydrophobic domain and the hydrogel itself are destroyed. The controlled release of Dox by ROS at site‐specific is realized. The excellent biocompatibility of hydrogel based on t‐PEG₅₆‐b‐OMeth_n indicates the door of the potential application in controlled release of drug in a truly physiological environment.     

Poly(hydroxyethyl methacrylate)‐Based Macroporous Hydrogels with Disulfide Cross‐Linker

Biodegradable supermacroporous PHEMA cryogels were produced by combining two crosslinkers, poly(ethylene glycol) diacrylate and a newly developed disulfide water soluble crosslinker, N,N′‐bis(methacryloyl)‐L ‐cystine. The biodegradable PHEMA cryogels were prepared with gel fraction yields up to 70% and were characterized by highly interconnected pores of micrometer size and good mechanical stability. When subjected to reductive agents like DTT, the biodegradable PHEMA cryogels disintegrated into small pieces. The rate of disintegration was controlled by the crosslinking density in the cryogels and the DTT concentration.

     

Studies on Poly[acrylamide‐co‐(ε‐caprolactone)]: Synthesis,Characterization and Biodegradability

The synthesis, characterization, hydrolysis and biodegradation of a copoly(ester amide), poly[acrylamide‐co‐(ε‐caprolactone)], are described. The hydrogen transfer copolymerization of acrylamide (AA) with ε‐caprolactone (CLN) in the presence of butyllithium or calcium hydride as initiators has been investigated. The calcium hydride was effective for the synthesis of the copoly(ester amide) in a wide range of polymer composition (AA/CLN =  10 : 90 to 90 : 10). The copoly(ester amide) was readily hydrolyzed in the presence of hydrochloric acid (0.1 n) at 125°C in an autoclave (e. g. AA/CLN =  59 : 41, degradation 93%). Furthermore, the copoly(ester amide) was hydrolyzed enzymatically by lipase from Rhizopus arrhizus. The behavior of the enzymatic hydrolysis differed to the non‐enzymatic hydrolysis. The enzymatic hydrolyzability was remarkable in the range of the AA repeating unit (β‐alanine unit) from 10 to 40 mol‐% (e. g. AA/CLN =  27 : 73, degradation 44%), while, the degradability for the non‐enzymatic hydrolysis rose with increasing AA repeating unit content. The biodegradation of the copoly(ester amide) was evaluated using a standard activated sludge (e. g. AA/CLN =  27 : 73 biodegradation 45%). The relationship between the biodegradation and the polymer composition was similar for the standard activated sludge and the enzymatic hydrolysis.     

Interpenetrating Networks of Poly(N‐isopropyl‐acrylamide) with Anionic and Cationic Polymers

A series of interpenetrating polymer networks (IPNs) of poly(N‐isopropylacrylamide) (PNIPA) with anionic poly(acrylic acid) (PAA) and cationic poly[[3‐(methacryloylamino)propyl]trimethylammonium chloride] (PMAPTAC) have been synthesized. The swelling behavior of the IPNs is monitored as a function of both pH and temperature. The swelling ratios of IPNs are significantly larger than those reported for pure PNIPA gels. [PNIPA‐PAA] IPNs show a continuous volume phase transition (VPT) at pHs below the pK_a of PAA and at pH > pK_a the IPNs show a temperature independent swelling. [PNIPA‐PMAPTAC] IPNs do not exhibit VPT at any given pH and over the range of temperatures studied.     

Hydroxy‐telechelic copolyesters with well defined sequence structure through ring‐opening polymerization

New well‐defined macrodiols were prepared by ring‐opening copolymerization of lactones and cyclic diesters with a low molecular weight diol. Suitable monomers are diglycolide, L,L ‐dilactide, ε‐caprolactone, and rac‐β‐butyrolactone. With exception of rac‐β‐butyrolactone, the reaction can be performed with or without a catalyst. The use of a catalyst influences the sequence structure of the telechelics. Copolyesterdiols from ε‐caprolactone, diglycolide, and ethylene glycol with random, blocky, and intermediate structure were synthesized and characterized. The analogous copolyesterdiols from L,L ‐dilactide, ε‐caprolactone, and ethylene glycol were also prepared. The sequence structure of the random chains with diglycolide corresponds to a random distribution of glycolate units, that of the corresponding chains with L,L ‐dilactide exhibit a random distribution of L,L ‐dilactate units.     

Porous Semi‐Interpenetrating Hydrogel Networks Based on Dextran and Polyacrylamide With Superfast Responsiveness

AAm was free‐radical polymerized at various temperatures in the presence of N,N'‐methylenebisacrylamide as a cross‐linker and dextran resulting in novel Dx/PAAm semi‐IPNs. The structure and morphology of networks were investigated by means of FTIR, DSC, and ESEM. In comparison to the PAAm network, the interior network structures of the novel semi‐IPNs prepared at ?18 °C exhibit a heterogeneous morphology consisting of pores of sizes about 80 µm, while those formed at +5 and +25 °C have pores with sizes about 3 µm. The Dx/PAAm semi‐IPNs exhibited higher swelling ratios, than those without Dx, irrespective of the gel preparation temperature. Moreover, Dx/PAAm semi‐IPN hydrogels formed at ?18 °C attain the equilibrium state in water within 15 s.

     

Controlled Synthesis and Characterization of Poly[ethylene‐block‐(L,L‐lactide)]s by Combining Catalytic Ethylene Oligomerization with “Coordination‐Insertion” Ring‐Opening Polymerization

Model poly[ethylene‐block‐(L ,L ‐lactide)] (PE‐block‐PLA) block copolymers were successfully synthesized by combining metallocene catalyzed ethylene oligomerization with ring‐opening polymerization (ROP) of L ,L ‐lactide (LA). Hydroxy‐terminated polyethylene (PE‐OH) macroinitiator was prepared by means of ethylene oligomerization on rac‐dimethyl‐silylen‐bis(2‐methyl‐benz[e]indenyl)‐zirconium(IV)‐dichloride/methylaluminoxane (rac‐MBI/MAO) in presence of diethyl zinc as a chain transfer agent, and subsequent in situ oxidation with synthetic air. Poly[ethylene‐block‐(L ,L ‐lactide)] block copolymers were obtained via ring‐opening polymerization of LA initiated by PE‐OH in toluene at 100 °C mediated by tin octoate. The formation of block copolymers was confirmed by ¹H NMR spectroscopy, fractionation experiments, thermal behavior, and morphological characterization using AFM and light microscopy techniques.

     

Poly(N,N‐dimethylacrylamide)‐block‐Poly(L‐lysine) Hybrid Block Copolymers: Synthesis and Aqueous Solution Characterization

Four poly(N,N‐dimethylacrylamide)‐block‐poly(L ‐lysine) (PDMAM‐block‐PLL) hybrid diblock copolymers and two PLL homo‐polypeptides are prepared via ROP of ε‐trifluoroacetyl‐L ‐lysine N‐carboxyanhydride initiated by primary amino‐terminated PDMAM and n‐hexylamine respectively. The PLL blocks render the copolymers a multi‐responsive behavior in aqueous solution due to their conformational transitions from random coil to α‐helix with increasing pH, and from α‐helix to β‐sheet upon heating. The random coil‐to‐α‐helix transition is found to depend on the PLL length: the longer the peptide segment, the more readily the transition occurred. The same trend was observed for the α‐helix‐to‐β‐sheet transition, which was found to be inhibited for short polypeptides unless conjugated with the PDMAM block.

     

Separate Crystallization and Cocrystallization of Poly(L‐lactide) in the Presence of L‐Lactide‐Based Copolymers With Low Crystallizability,Poly(L‐lactide‐co‐glycolide) and Poly(L‐lactide‐co‐D‐lactide)

Poly(L ‐lactide) (PLLA) and poly(L ‐lactide‐co‐glycolide) (78/22)0 [P(LLA‐GA)] were phase‐separated in PLLA/P(LLA‐GA) blends, forming independent domains and thence crystallizing separately. The crystallization of PLLA was not disturbed or delayed by the presence of P(LLA‐GA) and vice versa. PLLA and poly(L‐lactide‐co‐D ‐lactide) (77/23) [P(LLA‐DLA)] were miscible in the PLLA/P(LLA‐DLA) blends, overall crystallization was delayed, and the growth of crystallites was disturbed in the presence of P(LLA‐DLA). In isothermal crystallization, the originally noncrystallizable P(LLA‐DLA) became crystallizable in the presence of PLLA, with which it cocrystallized. The disturbance effect on periodical lamella twisting of PLLA was larger for P(LLA‐GA) than for P(LLA‐DLA).     

Homo and Block Copolymers of Poly(β‐benzyl‐L‐aspartate)s and Poly(γ‐benzyl‐L‐glutamate)s of Different Architectures

Homopolypeptides of linear and star‐like architectures were prepared by polymerizing benzylic‐protected L ‐glutamic acid and L ‐aspartic acid N‐carboxyanhydrides (Glu NCA, Asp NCA) in DMF. The polymerization rate of the Glu NCA is faster than that of Asp NCA. Using a simple monoamino initiator, its hydrochloride, di‐, tri‐, and tetraamino functional initiators, homopolypeptides with well‐defined structures and molar masses were obtained. The molar‐mass averages of the poly(γ‐benzyl‐L ‐glutamate)s lie very close to calculated values, according to the initial [M]:[I] ratios, while those of the linear poly(β‐benzyl‐L ‐aspartate)s were lower than the predicted ones. PBAs had somewhat broader molar‐mass distributions than PBGs.

     

Star‐shaped poly[(trimethylene carbonate)‐co‐(ε‐capro‐lactone)] and its block copolymers with lactide/glycolide: synthesis,characterization and properties

Linear and star‐shaped copolymers of trimethylene carbonate/ε‐caprolactone were synthesized using different polyol initiators and catalysts. Unexpectedly, when dipentaerythritol was used as an initiator cross‐linked rubbers were obtained, that swell in chloroform. This network formation can be understood by ‘in situ’ generation of cross‐linker molecules from trimethylene carbonate and initiator. SEC analysis showed that with D‐sorbitol star‐shaped copolymers are synthesized with an average functionality between 4 and 6. These low molecular weight rubbers were used as a macro‐initiator for the subsequent lactide/glycolide polymerization. Star‐shaped lactide/glycolide block copolymers with a poly[(trimethylene carbonate)‐co‐(ε‐caprolactone)] rubber core based on D ‐sorbitol show good mechanical properties. At relatively low rubber content ductile tensile behavior was observed indicating extensive toughening.     

Stereocomplex Crystallization Behavior and Physical Properties of Linear 1‐Arm, 2‐Arm,and Branched 4‐Arm Poly(L‐lactide)/Poly(D‐lactide) Blends: Effects of Chain Directional Change and Branching

For number‐average molecular weight (M _n) below 1 × 10⁴ g mol^?1, the comparison of cold crystallization temperature and spherulite growth rate and crystallinity of linear 1‐arm, 2‐arm, and branched 4‐arm poly(L ‐lactide)/poly(D ‐lactide) blends exhibits that the effects of chain directional change and branching significantly disturb stereocomplex crystallization. In contrast, the comparison of glass transition and melting temperatures of linear 1‐arm, 2‐arm, and branched 4‐arm poly(L ‐lactide)/poly(D ‐lactide) blends indicates that the effects of chain directional change and branching insignificantly alter and largely increase the segmental mobility of the blends, respectively, and the crystalline thickness of the blends is determined by M _n per one arm not by M _n and is not affected by the molecular architecture.

     

Effect of Arrangement of L‐Lactide and D‐Lactide in Poly[(L‐lactide)‐co‐(D‐lactide)] on its Resistance to Hydrolysis Studied by Molecular Modeling

Molecular modeling is used to explain how the resistance of poly[(L ‐lactide)‐co‐(D ‐lactide)] to hydrolysis is affected by the percentages of L ‐ and D ‐lactide and their arrangements in blocks or random arrangements in the polymer. Previous studies on improving the hydrolysis resistance of PLA have involved forming either poly(L ‐lactide)/poly(D ‐lactide) (PLLA/PDLA) polyblends or copolymers of L ‐ and D ‐lactide. In this study, molecular modeling was used to study the hydrolysis resistance of PLA containing various arrangements of L ‐ and D ‐lactide in the polymers. PLA copolymers are found to have less resistance to hydrolysis than a PLLA/PDLA polyblend having the same percentages of L ‐ and D ‐lactide because a polyblend can form more stereocomplexes, which is the most stable structure PLA can form.

     

On the Phase B of Comb‐Like Poly(α‐alkyl‐β‐L‐aspartate)s: A Simulation of the Solubility of Small Penetrants

The structure and thermal properties of the phase B of poly(α‐alkyl‐β‐L ‐aspartate)s, abbreviated PAALA‐n (n being the number of carbon atoms in the linear alkyl side chain), with n = 14 and 16 were determined using X‐ray diffraction and DSC methods, respectively. These data together with those previously reported by us for the dodecyl derivative were used to perform Monte Carlo simulations of these comb‐like polymers. The results allowed to predict the solubility of different gases in the phase B of PAALA‐n. The variation of both the unoccupied space and the excess chemical potential with the size of the penetrant were computed. An attractive interaction between the polymer matrix and the penetrants was found when small gases were considered. The results have been compared with those recently obtained for crystalline poly(α‐alkyl‐β‐L ‐aspartate)s bearing short linear alkyl side chains.     

Polylactones, 53. Formation of Cyclic Polyesters in the Combined Ring‐Expansion Polymerization/Ring‐Opening Polycondensation of Lactones

Ring‐expansion polymerizations of β‐D ,L ‐butyrolactone (β‐BL) or ε‐caprolactone (ε‐CL) were initiated with 2,2‐dibutyl‐2‐stanna‐1,3‐dioxepane (DSDOP) and the monomer‐initiator ratio (M/I) was varied. The resulting tin‐containing polylactones were polycondensed in situ either with succinyl chloride (in the case of β‐BL) or with suberoyl chlorid (for ε‐CL). The reaction conditions were optimized towards high molecular weights by the addition of bipyridine. The isolated tin‐free polylactones were characterized by MALDI‐TOF mass spectrometry. In the best spectra cyclic poly(ε‐caprolactone)s were detected up to masses around 10 600 Da and cyclic poly(β‐butyrolactone)s up to masses around 17 000 Da. In addition to the cyclic polyesters linear chains having alcoholic OH and/or CO₂H group were found. These results suggest that the chain growth is limited by cyclization and by incomplete conversion of the functional groups.     

Immiscible Poly(L‐lactide)/Poly(ε‐caprolactone) Blends: Influence of the Addition of a Poly(L‐lactide)‐Poly(oxyethylene) Block Copolymer on Thermal Behavior and Morphology

Summary: A binary blend of poly (L ‐lactide) (PLLA) and poly(ε‐caprolactone) (PCL) of composition 70:30 by weight was prepared using a twin screw miniextruder and investigated by differential scanning calorimetry (DSC), optical microscopy and scanning electron microscopy (SEM). Ternary 70:30:2 blends were also obtained by adding either a diblock copolymer of PLLA and poly(oxyethylene) (PEO) or a triblock PLLA‐PCL‐PLLA copolymer as a third component. Optical microscopy revealed that the domain size of dispersed PCL domains is reduced by one order of magnitude in the presence of both copolymers. SEM confirmed the strong reduction in particle size upon the addition of the copolymers, with an indication of an enhanced emulsifying effect in the case of the PLLA‐PEO copolymer. These results are analyzed on the basis of solubility parameters of the blend components.

Optical micrograph of M3EG2 blend melt quenched at 125 °C.     

Heterostereocomplex‐ and Homocrystallization and Thermal Properties and Degradation of Substituted Poly(lactic acid)s,Poly(l‐2‐hydroxybutanoic acid) and Poly(d‐2‐hydroxy‐3‐methylbutanoic acid)

Heterostereocomplex‐ and homocrystallization behavior, thermal properties and degradation of neat poly(l ‐2‐hydroxybutanoic acid) [P(l ‐2HB)], poly(d ‐2‐hydroxy‐3‐methylbutanoic acid) [P(d ‐2H3MB)], and their equimolar blend are first investigated. Regime I and II kinetics are observed for neat P(l ‐2HB), whereas regime II and III kinetics are seen for the blend. The growth geometry of the neat P(l ‐2HB) is linear and circular while that of the blend is spherical, whereas that of the neat P(d ‐2H3MB) changes from linear to spherical, depending on crystallization temperature (T _c). The main crystalline species is heterostereocomplex (HTSC) in the blend for a wide T _c range of 0–180 °C and a very small amount of P(d ‐2H3MB) homocrystallites form for melt‐crystallization at T _c below 70 °C and solution‐crystallization. The equilibrium melting temperature of P(l ‐2HB)/P(d ‐2H3MB) HTSC crystallites (234.5 °C) is higher than those of P(l ‐2HB) and P(d ‐2H3MB) homocrystallites (114.9 and 208.6 °C, respectively). The activation energy values for thermal degradation of the P(l ‐2HB)/P(d ‐2H3MB) blend (190–219 kJ mol^?1) are between those of neat P(l ‐2HB) and P(d ‐2H3MB) (164–180 and 210–380 kJ mol^?1, respectively), reflecting that the interaction between the polymers with opposite configurations is similar to or lower than that between the polymers with the same configurations at a high temperature in the melt.