Amphiphilic gradient copolymers of 2‐methyl‐ and 2‐phenyl‐2‐oxazoline: self‐organization in aqueous media and drug encapsulation

Gradient (or pseudo‐diblock) copolymers were synthesized from 2‐methyl‐2‐oxazoline and 2‐phenyl‐2‐oxazoline monomer mixtures via cationic polymerization. The self‐assembling properties of these biocompatible gradient copolymers in aqueous solutions were investigated, in an effort to use the produced nanostructures as nanocarriers for hydrophobic pharmaceutical molecules. Dynamic and static light scattering as well as AFM measurements showed that the copolymers assemble in different supramolecular nanostructures (spherical micelles, vesicles and aggregates) depending on copolymer composition. Fluorescence spectroscopy studies revealed a microenvironment of unusually high polarity inside the nanostructures. This observation is related partly to the gradient structure of the copolymers. The polymeric nanostructures were stable with time. Their structural properties in different aqueous media—PBS buffer, RPMI solution—simulating conditions used in pharmacological/medicinal studies, have been also investigated and a composition dependent behavior was observed. Finally, the hydrophobic drug indomethacin was successfully encapsulated within the gradient copolymer nanostructures and the properties of the mixed aggregates were studied in respect to the initial copolymer assemblies. The produced aggregates encapsulating indomethacin showed a significant increase of their mass and size compared to original purely polymeric ones. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Concentration effects in the cationic ring‐opening polymerization of 2‐ethyl‐2‐oxazoline in N,N‐dimethylacetamide

The monomer concentration for the cationic ring‐opening polymerization of 2‐ethyl‐2‐oxazoline in N,N‐dimethylacetamide was optimized utilizing high‐throughput experimentation methods. Detailed ¹H‐NMR spectroscopic investigations were performed to understand the mechanistic aspects of the observed concentration effects. Finally, the improved polymerization concentration was applied for the synthesis of higher molecular weight (> 10,000 Da) poly(2‐ethyl‐2‐oxazoline)s. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 1487–1497, 2005     

Initiator effect on the cationic ring‐opening copolymerization of 2‐ethyl‐2‐oxazoline and 2‐phenyl‐2‐oxazoline

The aim of this research was to study the effect of the initiator on the resulting monomer distribution for the cationic ring‐opening copolymerization of 2‐ethyl‐2‐oxazoline (EtOx) and 2‐phenyl‐2‐oxazoline (PhOx). At first, kinetic studies were performed for the homopolymerizations of both monomers at 160 °C under microwave irradiation using four initiators. These initiators have the same benzyl‐initiating group but different leaving groups, Cl^?, Br^?, I^?, and OTs^?. The basicity of the leaving group affects the ratio of covalent and cationic propagating species and, thus, the polymerization rate. The observed differences in polymerization rates could be correlated to the concentration of cationic species in the polymerization mixture as determined by ¹H NMR spectroscopy. In a next‐step, polymerization kinetics were determined for the copolymerizations of EtOx and PhOx with these four initiators. The reactivity ratios for these copolymerizations were calculated from the polymerization rates obtained for the copolymerizations. This approach allows more accurate determination of the copolymerization parameters compared to conventional methods using the composition of single polymers. When benzyl chloride (BCl) was used as an initiator, no copolymers could be obtained because its reactivity is too low for the polymerization of PhOx. With decreasing basicity of the used counterions (Br^? > I^? > OTs^?), the reactivity ratios gradually changed from r_EtOx = 10.1 and r_PhOx = 0.30 to r_EtOx = 7.9 and r_PhOx = 0.18. However, the large difference in reactivity ratios will lead to the formation of quasi‐diblock copolymers in all cases. In conclusion, the used initiator does influence the monomer distribution in the copolymers, but for the investigated system the differences were so small that no difference in the resulting polymer properties is expected. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 4804–4816, 2008     

Synthesis of novel hyperbranched polymer through cationic ring‐opening multibranching polymerization of 2‐hydroxymethyloxetane

The cationic ring‐opening multibranching polymerization of 2‐hydroxymethyloxetane ( 1 ) as a novel latent AB₂‐type monomer was carried out using trifluoromethane sulfonic acid or trifluoroboron diethyl etherate by a slow‐monomer‐addition (SMA) method. The polymer yield of poly‐1 ranged from ca. 58–88%, which increase with the increasing monomer addition time on the SMA method. The absolute molecular weights (M_w,MALLS) and the polydispersities of poly‐1 were in the range of 8,000–43,500 and 1.45–4.53, respectively, which also increased with the increasing monomer addition time. The Mark‐Houwink‐Sakurada exponents α in 0.2 M NaNO₃ aq. were determined to be 0.02–0.25 for poly‐1 , indicating that poly‐1 has compact forms in the solution because of the highly branched structure. The degree of the branching value of poly‐1 , which was calculated by Frey's equation, ranged from ca. 0.50 to 0.58, which increased with the increasing monomer addition time. The steady shear flow of poly‐1 in aqueous solution exhibited a Newtonian behavior with steady shear viscosities independent of the shear rate. The results of the MALLS, NMR, and viscosity measurements indicated that poly‐1 is composed of a highly branched structure, i.e., the hyperbranched poly (2‐hydroxymethyloxetane). © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Equilibrium polymerization behavior in the cationic single ring‐opening polymerization of bicyclo orthoesters

The synthesis and cationic polymerization of the following bicyclo orthoesters were examined: 4‐ethyl‐2,6,7‐trioxabicyclo[2.2.2]octane, 1,4‐diethyl‐2,6,7‐trioxabicyclo[2.2.2]octane, 4‐ethyl‐1‐phenyl‐2,6,7‐trioxabicyclo[2.2.2]octane, 4‐ethyl‐1‐(4‐methoxyphenyl)‐2,6,7‐trioxabicyclo[2.2.2]octane, and 4‐ethyl‐1‐(4‐nitrophenyl)‐2,6,7‐ trioxabicyclo[2.2.2]octane. All the monomers underwent equilibrium polymerization, which was confirmed by the relationships between the polymerization temperature and monomer conversion. The obtained polymers afforded the original monomers via an acid‐catalyst treatment with a low reagent concentration in CH₂Cl₂ at 20 °C. The equilibrium monomer concentration was constant, regardless of the initial reagent concentration, in both polymerization and depolymerization. The bicyclo orthoesters with a bulky and electron‐withdrawing substituent showed a larger equilibrium monomer concentration. © 2001 John Wiley & Sons, Inc. J Polym Sci Part A: Polym Chem 39: 3159–3167, 2001     

Chemistry of 2‐oxazolines: A crossing of cationic ring‐opening polymerization and enzymatic ring‐opening polyaddition

Chemistry of 2‐oxazolines is involved in the polymer synthesis fields of cationic ring‐opening polymerization (CROP) and enzymatic ring‐opening polyaddition (EROPA), although both polymerizations look like a quite different class of reaction. The key for the polymerization to proceed is combination of the catalyst (initiator) and the design of monomers. This article describes recent developments in polymer synthesis via these two kinds of polymerizations to afford various functional polymers having completely different structures, poly(N‐acylethylenimine)s via CROP and 2‐amino‐2‐deoxy sugar unit‐containing oligo and polysaccharides via EROPA, respectively. From the viewpoint of reaction mode, an acid‐catalyzed ring‐opening polyaddition (ROPA) is considered to be a crossing where CROP and EROPA meet. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 1251–1270, 2010     

Synthesis and properties of the polythiourethanes obtained by the cationic ring‐opening polymerization of cyclic thiourethanes

The cationic ring‐opening polymerization of a five‐membered thiourethane [3‐benzyl‐1,3‐oxazolidine‐2‐thione (BOT)] with boron trifluoride etherate afforded the corresponding polythiourethane with a narrow molecular weight distribution in an excellent yield. The molecular weight of the polymers could be controlled by the feed ratio of the monomer to the initiator. A kinetic study of the polymerization revealed that the polymerization rate of BOT (1.3 × 10^?2 L mol^?1 min^?1) was two times larger than that of the six‐membered thiourethane [3‐benzyltetrahydro‐1,3‐oxazolidine‐2‐thione (BTOT); 6.8 × 10^?3 L mol^?1 min^?1], and the monomer conversion obeyed the first‐order kinetic equation. These observations, along with the successful results in the two‐stage polymerization, supported the idea that this polymerization proceeded in a controlled manner. Block copolymerizations of BOT with BTOT were also carried out to afford the corresponding di‐ and triblock copolymers with narrow molecular weight distributions. The order of the 5% weight loss temperatures was as follows: poly(3‐benzyltetrahydro‐1,3‐oxazolidine‐2‐thione) [poly(BTOT)] > poly(BTOT₅₄‐b‐BOT₄₆) > poly(3‐benzyl‐1,3‐oxazolidine‐2‐thione) [poly(BOT)]. This indicated that an increase in the BTOT unit content raised the decomposition temperature. The order of the refractive indices was poly(BOT) > poly(BTOT₅₄‐b‐BOT₄₆) > poly(BTOT₅₄‐b‐BOT₄₆‐b‐BTOT₅₀) > poly(BTOT); this was in accord with the order of the sulfur content in the polymer chain. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 4795–4803, 2006     

Sequence‐controlled cationic ring‐opening copolymerization of spiroorthocarbonate and oxetane

Pseudo block and triblock copolymers were synthesized by the cationic ring‐opening copolymerization of 1,5,7,11‐tetraoxaspiro[5.5]undecane (SOC1) with trimethylene oxide (OX) via one‐shot and two‐shot procedures, respectively. When SOC1 and OX were copolymerized cationically with boron trifluoride etherate (BF₃OEt₂) as an initiator in CH₂Cl₂ at 25 °C, OX was consumed faster than SOC1. SOC1 was polymerized from the OX‐rich gradient copolymer produced in the initial stage of the copolymerization to afford the corresponding pseudo block copolymer, poly [(OX‐grad‐SOC1)‐b‐SOC1]. We also succeeded in the synthesis of a pseudo triblock copolymer by the addition of OX during the course of the polymerization of SOC1 before its complete consumption, which provided the corresponding pseudo triblock copolymer, poly[SOC1‐b‐(OX‐grad‐SOC1)‐b‐SOC1]. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 3233–3241, 2006     

Controlled cationic ring‐opening polymerization of cyclic thiocarbonates with ester groups

This work deals with the cationic ring‐opening polymerization of the cyclic thiocarbonates 5‐benzoyloxymethyl‐5‐methyl‐1,3‐dioxane‐2‐thione ( 1 ), 5,5‐dimethyl‐1,3‐dioxane‐2‐thione ( 2 ), and 4‐benzoyloxymethyl‐1,3‐dioxane‐2‐thione ( 3 ). The polymerization was carried out with 2 mol % trifluoromethanesulfonic acid, methyl trifluoromethanesulfonate, boron trifluoride etherate, or triethyloxonium tetrafluoroborate as the initiator to afford the polythiocarbonate with a narrow molecular weight distribution accompanying isomerization of the thiocarbonate group. The molecular weight of the obtained polymer could be controlled by the feed ratio of the monomer to the initiator and increased when the second monomer was added to the polymerization mixture after the quantitative consumption of the monomer in the first stage. The block copolymerization of 2 and 3 was also achieved, and this supported the idea that the cationic ring‐opening polymerization of these monomers proceeded via a living process. The order of the polymerization rate was 3 > 2 > 1 . The cationic ring‐opening polymerization of 1 and 3 involved the neighboring group participation of ester groups according to the polymerization rate and molecular orbital calculations with the ab initio method. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 185–195, 2003     

Combining cationic ring‐opening polymerization and click chemistry for the design of functionalized polyurethanes

A straightforward strategy for the synthesis and functionalization of polyurethanes (PUs) via the use of alkyne‐functionalized polytetrahydrofuran (PTHF) diols is described. The alkyne groups have been introduced into the PTHF chains by the cationic ring‐opening copolymerization of tetrahydrofuran and glycidyl propargyl ether. These PTHF prepolymers were combined with 1,4‐butanediol and hexamethylene diisocyanate for the synthesis of linear PUs with latent functionalization sites. The polyether segments of the PUs have then been coupled with several types of functionalized azides by the copper‐catalyzed azide‐alkyne “click” chemistry, for example with phosphonium containing azides for their antibacterial properties. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Cationic ring‐opening polymerization (CROP) major mechanistic phenomena

A number of today's accepted basic viewpoints related to cationic ring‐opening polymerizations (CROP) were a matter of vivid disagreements between various research groups in the past. These controversies are described in this article and reasons of some differencies in opinions are explained. It is shown in which way we learned that polyacetals are not exclusively cyclic (as it was assumed), why CROP ions and ion pairs have similar reactivities, and why it was necessary to propose that CROP proceeds at certain conditions by Activated Monomer Mechanism. Among other subtle kinetic problems, application of the dynamic NMR and “temperature jump” techniques in determining rate constants of active species interconversions are discussed. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 38: 1919–1933, 2000     

Photoinduced cationic ring‐opening frontal polymerizations of oxetanes and oxiranes

The photoinitiated cationic ring‐opening polymerizations of certain epoxides and 3,3‐disubstituted oxetanes display the characteristics of frontal polymerizations. When irradiated with UV light, these monomers display a marked induction period, during which little conversion of the monomer to the polymer takes place. The local application of heat to an irradiated monomer sample results in polymerization that occurs as a front propagating rapidly throughout the entire reaction mass. For the characterization of these frontal polymerizations, the use of a new monitoring technique, employing optical pyrometry, has been instituted. This method provides a simple, rapid means of following these fast polymerizations and quantitatively determining their frontal velocities. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 1630–1646, 2004     

Synthesis and properties of gradient copolymers based on 2‐phenyl‐2‐oxazoline and 2‐nonyl‐2‐oxazoline

In this study, the structure–property relationships for a series of statistical 2‐nonyl‐2‐oxazoline (NonOx) and 2‐phenyl‐2‐oxazoline (PhOx) copolymers were investigated for the first time. The copolymerization kinetics were studied and the reactivity ratios were calculated to be r_NonOx = 7.1 ± 1.4 and r_PhOx = 0.02 ± 0.1 revealing the formation of gradient copolymers. The synthesis of a systematical series of NonOx–PhOx copolymers is described, whereby the amount of NonOx was increased in steps of 10 mol %. The thermal and surface properties were investigated for this series of well‐defined copolymers. The thermal properties revealed a linear decrease in glass transition temperature for copolymers containing up to 39 wt % NonOx. Furthermore, the melting temperature of the copolymers containing 0 to 55 wt % PhOx linearly decreased most likely due to disturbance of the NonOx crystalline domains by incorporation of PhOx in the NonOx part of the copolymer. The surface energies of spincoated polymer films revealed a strong decrease in surface energy upon incorporation of NonOx in the copolymers due to strong phase separation between NonOx and PhOx allowing the NonOx chains to orient to the surface. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 6433–6440, 2009     

Cationic ring‐opening polymerization of monothiocarbonate with a norbornene group

This work deals with the cationic ring‐opening polymerization of cyclic thiocarbonates with a norbornene or norbornane moiety, that is, 5,5‐(bicyclo[2.2.1]hept‐2‐ene‐5,5‐ylidene)‐1,3‐dioxane‐2‐thione ( TC1 ) or 5,5‐(bicyclo[2.2.1]heptane‐5,5‐ylidene)‐1,3‐dioxane‐2‐thione ( TC2 ), respectively. The reaction of TC1 initiated by trifluoromethanesulfonic acid (TfOH), methyl trifluoromethanesulfonate (TfOMe), boron trifluoride etherate (BF₃OEt₂), or triethyloxonium tetrafluoroborate (Et₃OBF₄) afforded unidentified products; however, TC1 underwent cationic ring‐opening polymerization with methyl iodide as an initiator to afford polythiocarbonate because the propagating end was stabilized by the covalent‐bonding property. The polymerization of TC2 initiated by TfOH, TfOMe, BF₃OEt₂, or Et₃OBF₄ afforded polythiocarbonate with good solubility in common organic solvents and a narrow molecular weight distribution because of the absence of a double‐bond moiety. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 1698–1705, 2002     

Synthesis and ring‐opening polymerization of new monoalkyl‐substituted lactides

New monoalkyl‐substituted lactides were synthesized by reaction of α‐hydroxy acids with 2‐bromopropionyl bromide, and polymerized with various catalysts in the presence of benzyl alcohol by ring‐opening polymerization (ROP). The classic tin(II) 2‐ethylhexanoate (Sn(Oct)₂) catalyst was leading to polymers with narrow distribution and predictable molecular weights, in polymerizations in bulk or toluene at 100 °C. The polymerization rate was corresponding to the steric hindrance of the alkyl substituents, such as butyl, hexyl, benzyl, isopropyl, and dimethyl groups. A yield of 83% was obtained with the hexyl‐substituted lactide after 1 h of polymerization. Excellent conversions (97%) could be achieved by using the alternative catalyst 4‐(dimethylamino)pyridine (DMAP). This latter organic catalyst was most efficient in polymerizing the more steric‐hindered lactides with good molecular weight and polydispersity control, in comparison to the tin(II) 2‐ethylhexanoate and tin(II) trifluoromethane sulfonate [Sn(OTf)₂] catalysts. The efficiency of the DMAP catalyst and the variability of the monomer synthesis route for new alkyl‐substituted lactides allow to prepare and to envision a wide range of new functionalized polylactides for the elaboration of tailored materials. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 4379–4391, 2004     

Study on the cationic ring‐opening polymerization of 1,3‐dioxepane in the presence of organic acids

1,3‐Dioxepane was polymerized with triflic acid as an initiator in the presence of acetic acid (AA) and hexane diacid. The structure of the poly(1,3‐dioxepane) (polyDOP) obtained was characterized by ¹H NMR spectra and gel permeation chromatography. The molecular weights (MWs) were determined by vapor pressure osmometry. The results obtained in both systems were completely different from those in which low‐MW polyols were used as chain‐transfer agents. When the molar ratio of carboxylic acid to triflic acid was low, high‐MW polyDOP with a controlled MW and narrow MW distribution was obtained. The content of the ester group in the final product depended greatly on the molar ratio of AA to triflic acid. The polymerization mechanism is discussed. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 38: 1232–1240, 2000     

Hyperbranched polyethers by ring‐opening polymerization: Contribution of activated monomer mechanism

Propagation in the cationic ring‐opening polymerization of cyclic ethers involves nucleophilic attack of oxygen atoms from the monomer molecules on the cationic growing species (oxonium ions). Such a mechanism is known as the active chain‐end mechanism. If hydroxyl groups containing compounds are present in the system, oxygen atoms of HO? groups may compete with cyclic ether oxygen atoms of monomer molecules in reaction with oxonium ions. At the proper conditions, this reaction may dominate, and propagation may proceed by the activated monomer mechanism, that is, by subsequent addition of protonated monomer molecules to HO? terminated macromolecules. Both mechanisms may contribute to the propagation in the cationic polymerization of monomers containing both functions (i.e., cyclic ether group and hydroxyl groups) within the same molecule. In this article, the mechanism of polymerization of three‐ and four‐membered cyclic ethers containing hydroxymethyl substituents is discussed in terms of competition between two possible mechanisms of propagation that governs the structure of the products—branched polyethers containing multiple terminal hydroxymethyl groups. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 457–468, 2003     

Synthesis of poly(tetrahydrofuran)‐b‐polystyrene block copolymers from dual initiators for cationic ring‐opening polymerization and atom transfer radical polymerization

A dual initiator (4‐hydroxy‐butyl‐2‐bromoisobutyrate), that is, a molecule containing two functional groups capable of initiating two polymerizations occurring by different mechanisms, has been prepared. It has been used for the sequential two‐step synthesis of well‐defined block copolymers of polystyrene (PS) and poly(tetrahydrofuran) (PTHF) by atom transfer radical polymerization (ATRP) and cationic ring‐opening polymerization (CROP). This dual initiator contains a bromoisobutyrate group, which is an efficient initiator for the ATRP of styrene in combination with the Cu(0)/Cu(II)/N,N,N′,N″,N″‐pentamethyldiethylenetriamine catalyst system. In this way, PS with hydroxyl groups (PS‐OH) is formed. The in situ reaction of the hydroxyl groups originating from the dual initiator with trifluoromethane sulfonic anhydride gives a triflate ester initiating group for the CROP of tetrahydrofuran (THF), leading to PTHF with a tertiary bromide end group (PTHF‐Br). PS‐OH and PTHF‐Br homopolymers have been applied as macroinitiators for the CROP of THF and the ATRP of styrene, respectively. PS‐OH, used as a macroinitiator, results in a mixture of the block copolymer and remaining macroinitiator. With PTHF‐Br as a macroinitiator for the ATRP of styrene, well‐defined PTHF‐b‐PS block copolymers can be prepared. The efficiency of PS‐OH or PTHF‐Br as a macroinitiator has been investigated with matrix‐assisted laser desorption/ionization time‐of‐flight spectroscopy, gel permeation chromatography, and NMR. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 3206–3217, 2003     

Synthesis and application as polymer electrolyte of hyperbranched polyether made by cationic ring‐opening polymerization of 3‐{2‐[2‐(2‐hydroxyethoxy)ethoxy]ethoxymethyl}‐3′‐methyl‐oxetane

A novel cyclic ether monomer 3‐{2‐[2‐(2‐hydroxyethoxy)ethoxy]ethoxy‐methyl}‐3′‐methyloxetane (HEMO) was prepared from the reaction of 3‐hydroxymethyl‐3′‐methyloxetane tosylate with triethylene glycol. The corresponding hyperbranched polyether (PHEMO) was synthesized using BF₃·Et₂O as initiator through cationic ring‐opening polymerization. The evidence from ¹H and ¹³C NMR analyses revealed that the hyperbranched structure is constructed by the competition between two chain propagation mechanisms, i.e. active chain end and activated monomer mechanism. The terminal structure of PHEMO with a cyclic fragment was definitely detected by MALDI‐TOF measurement. A DSC test implied that the resulting polyether has excellent segment motion performance potentially beneficial for the ion transport of polymer electrolytes. Moreover, a TGA assay showed that this hyperbranched polymer possesses high thermostability as compared to its liquid counterpart. The ion conductivity was measured to reach 5.6 × 10^?5 S/cm at room temperature and 6.3 × 10^?4 S/cm at 80 °C after doped with LiTFSI at a ratio of Li:O = 0.05, presenting the promise to meet the practical requirement of lithium ion batteries for polymer electrolytes. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 3650–3665, 2006