Synthesis of poly(ethylene glycol methyl ether)-b-poly(ethylenimine) and its derivatives containing thymine and amino acids as pendants

Poly(ethylene glycol methyl ether)tosylate was prepared and used to initiate the polymerization of 2-methyl-2-oxazoline. The resulting poly(ethylene glycol methyl ether)-b-poly(N-acetyl ethylenimine) was hydrolyzed and neutralized to give poly(ethylene glycol methyl ether)-b-poly(ethyl-enimine) (PEO–PEI). 2-(thymin-1-yl)propionic acid, N-Cbz-alanine, N-Cbz-proline, N-Cbz-O-t-Bu-serine. and N-FMOC-proline were grafted onto the PEO–PEI copolymer; attempts were then made to remove the Cbz and FMOC protecting groups.     

Janus-type dendrimer-like poly(ethylene oxide)s

A straightforward and original methodology allowing the synthesis of Janus-type dendrimer-like poly(ethylene oxide)s (PEOs) carrying orthogonal functional groups on their surface is described. The use of 3-allyloxy-1,2-propanediol (1) as a latent AB2-type heterofunctional initiator of anionic ring-opening polymerization (AROP) of ethylene oxide (EO) and of selective branching agents of PEO chain ends served to construct the two dendrons of these dendrimer-like PEOs, following a divergent pathway. Thus, the first PEO generation of the first dendron was grown by AROP from 1 followed by the reaction of the corresponding alpha-allyl,omega,omega'-bishydroxy- heterofunctional PEO derivative with 2-(3'-chloromethybenzyloxymethyl)-2-methyl-5,5-dimethyl-1,3-dioxane (2) used as a branching agent. This afforded the dendron A with four latent peripheral hydroxyls protected in the form of two ketal rings. The remaining alpha-allylic double bond of the PEO thus prepared was transformed into two hydroxyl groups using OsO4 in order to create the first PEO generation of the dendron B by AROP of EO. Allyl chloride (3) was then used as another (latent) branching agent to react with the terminal hydroxyl of the corresponding PEO chains. Deprotection under acidic conditions of the ketal groups of dendron A, followed by AROP of EO, afforded the second PEO generation on this face. This alternate and divergent procedure, combining AROP of EO and selective branching of PEO branches, could be readily iterated, one dendron after the other up to the generation six, leading to a Janus-type dendrimer-like PEO exhibiting a total mass of around 300 kg/mol and possessing 64 peripheral groups on each face. The possibility of orthogonal functionalization of the surfaces of such Janus-type dendritic PEOs was exploited. Indeed, a dendron of generation 4 was functionalized with hydroxyl functions at its periphery, whereas the other was end-capped with either tertiary amino or disulfide groups. In a variant of this strategy, azido groups and acetylene could also be orthogonally introduced at the periphery of the fourth generation Janus-type dendrimer-like PEO and subjected to polycondensation by a 1,3-dipolar cycloaddition reaction. This afforded a necklace-like covalent assembly of dendrimer-like PEOs through the formation of stable [1,2,3]-triazole linkages.     

pH responsiveness of dendrimer-like poly(ethylene oxide)s

Poly(ethylene oxide) (PEO) and poly(acrylic acid) (PAA), two polymers known to form pH-sensitive aggregates through noncovalent interactions, were assembled in purposely designed architecture -a dendrimer-like PEO scaffold carrying short inner PAA chains-to produce unimolecular systems that exhibit pH responsiveness. Because of the particular placement of the PAA chains within the dendrimer-like structure, intermolecular complexation between acrylic acid (AA) and ethylene oxide (EO) units-and thus macroscopic aggregation or even mesoscopic micellization-could be avoided in favor of the sole intramolecular complexation. The sensitivity of such interactions to pH was exploited to generate dendrimer-like PEOs that reversibly shrink and expand with the pH. Such PAA-carrying dendrimer-like PEOs were synthesized in two main steps. First, a fifth-generation dendrimer-like PEO was obtained by combining anionic ring-opening polymerization (AROP) of ethylene oxide from a tris-hydroxylated core and selective branching reactions of PEO chain ends. To this end, an AB(2)C-type branching agent was designed: the latter includes a chloromethyl (A) group for its covalent attachment to the arm ends, two geminal hydroxyls (B(2)) protected in the form of a ketal ring for the growth of subsequent PEO generations by AROP, and a vinylic (C) double bonds for further functionalization of the interior of dendrimer-like PEOs. Reiteration of AROP and derivatization of PEO branches allowed us to prepare a dendrimer-like PEO of fourth generation with a total molar mass of 52,000 g x mol(-1), containing 24 external hydroxyl functions and 21 inner vinylic groups in the interior. A fifth generation of PEO chains was generated from this parent dendrimer-like PEO of fourth generation using a "conventional" AB(2)-type branching agent, and 48 PEO branches could be grown by AROP. The 48 outer hydroxy-end groups of the fifth-generation dendrimer-like PEO obtained were subsequently quantitatively converted into inert benzylic groups using benzyl bromide. The 21 internal vinylic groups carried by the PEO scaffold were then chemically modified in a two-step sequence into bromoester groups. The latter which are atom transfer radical polymerization (ATRP) initiating sites thus served to grow poly(tert-butylacrylate) chains. After a final step of hydrolysis of the tert-butyl ester groups, double, hydrophilic, dendrimer-like PEOs comprising 21 internal junction-attached poly(acrylic acid) (PAA) blocks could be obtained. Dynamic light scattering was used to determine the size of these dendrimer-like species in water and to investigate their response to pH variation: in particular, how the pH-sensitive complexation of EO and AA units affects their overall behavior.     

Functionalizable branched poly(ethylene oxide)s grafted from poly(1,3‐diisopropenylbenzene) backbones

A new method to synthesize functionalizable branched poly(ethylene oxide) (PEO) is presented. Soluble linear poly(1,3‐diisopropenylbenzene) (1,3‐DIB) samples exhibiting one unsaturation per DIB unit in the chain were obtained through anionic polymerization. These unsaturations served, after reaction with a stoichiometric amount of cumyl‐potassium, as efficient initiators for the anionic polymerization of oxirane. Accurate characterization of these samples demonstrated that a far better control of the functionality is reached as compared to the case of poly(DVB) cores.     

Study of the Crystallization Kinetics. Poly(ethylene oxide) and a blend of poly(ethylene oxide) and poly(bisphenol A-co-epichlorohydrin)

A kinetic study of the crystallization of poly(ethylene oxide) (PEO) and of a blend of PEO+poly(bisphenol A-co-epichlorohydrin) (PBE) was performed by using DSC in a non-isothermal program at constant cooling rates. The curves obtained were analyzed by the Kissinger, Ozawa and Friedman methods, with determination of the kinetic parameters in each case. As a consequence of the presence of PBE, the kinetic parameters were altered, leading to the conclusion that PBE has some influence on the crystallization of PEO, modifying its mechanism. This revised version was published online in July 2006 with corrections to the Cover Date.     

First aldehyde-functionalized poly(2-oxazoline)s for chemoselective ligation

A protected aldehyde-functionalized 2-oxazoline, 2-[3-(1,3)-dioxolan-2-ylpropyl]-2-oxazoline (DPOx), was synthesized from commercially available compounds in high yields. The polymerization of DPOx with different initiators proceeds via a living ionic mechanism; thus, the polymers were of low polydispersity and the degree of polymerization could be precisely adjusted. Copolymerization with 2-methyl-2-oxazoline gave water-soluble statistical copolymers. Hydrolysis of the homo- and copolymers resulted in well-defined, aldehyde-bearing poly(2-oxazoline)s. The aldehyde side functions reacted quantitatively with an amino-oxy compound to form the corresponding oxime.     

Interpolymer complex between poly(ethylene oxide) and poly(carboxylic acid)

An interpolymer complex was prepared by mixing aqueous solutions of poly(ethylene oxide) (PEO) and of a poly(carboxylic acid), i.e., poly(acrylic acid)(PAA), poly(methacrylic acid)(PMAA), or styrene-maleic acid copolymer(PSMA). The complexation mechanism was discussed on the basis of results of such experimental methods as viscosity, potentiometric titration, and turbidimetry. The hydrogen bond is primarily involved in these complexations, but the influence of hydrophobic interaction on complexation can not be ignored. If the degree of dissociation α of carboxylic acid or the degree of polymerization P_n of PEO was perceptibly changed, a stable complex was obtained at about α 0.1 or P_n (PEO) = 40 for PMAA, 200 for PAA. This fact indicates that more than a definite number of binding sites are necessary for a stable interpolymer complex to be formed and that cooperative interaction among active sites plays an important role in complex formation.     

Grafting of poly(ethylene oxide) on poly(methyl methacrylate) by transesterification

The grafting of the potassium alkoxide derivative of poly(ethylene oxide) on poly(methyl methacrylate) in homogeneous solution in toluene was studied. The alkoxide was prepared by reaction with potassium metal with methanolic potassium methoxide, or with potassium naphthalene. The last was the most suitable for the systematic investigation of the grafting process. Soluble graft polymers were formed, and essentially the initial poly(ethylene oxide) (PEO) and poly(methyl methacrylate) (PMMA) participated in the production of graft polymer. The composition of the graft polymers and the frequency of grafting of the side chains were determined by NMR. The solubility of the graft polymers in methanol and water increased with increasing PEO contents, while the melting ranges decreased. Fractionation of the crude graft polymers showed that the grafting reaction was random, and graft polymers containing one PEO side chain per about 10–170 MMA units were obtained.     

Novel amphiphilic linear polymer/dendrimer block copolymer: Synthesis of poly(2-methyl-2-oxazoline)-block-poly(amido amine) dendrimer

Novel linear polymer/dendrimer block copolymers, poly(2-methyl-2-oxazoline)-block-poly(amido amine) dendrimers (water-soluble full-generation type 4 (G = 4.0 and 5.0) and amphiphilic half-generation type 5 (G = 3.5, 4.5, and 5.5)), were synthesized by divergent-growth dendrimer construction with ω-ethylenediamine-terminated poly(2-methyl-2-oxazoline), which was prepared by living ring-opening polymerization of 2-methyl-2-oxazoline. Assembly of the amphiphilic dendrimer-based block copolymer (G = 5.5) was investigated by surface tension measurements (critical micelle concentration, 0.49 wt.-%) and by small-angle neutron scattering analysis (spherical particles; assembled number, ca. 10³).     

Synthesis of amphiphilic poly(methyl methacrylate‐ b‐ethylene oxide) copolymers from monohydroxy telechelic poly(methyl methacrylate) as macroinitiator

The synthesis of well‐defined poly(methyl methacrylate)‐block‐poly(ethylene oxide) (PMMA‐b‐PEO) dibock copolymer through anionic polymerization using monohydroxy telechelic PMMA as macroinitiator is described. Living anionic polymerization of methyl methacrylate was performed using initiators derived from the adduct of diphenylethylene and a suitable alkyllithium, either of which contains a hydroxyl group protected with tert‐butyldimethylsilyl moiety in tetrahydrofuran (THF) at ?78 °C in the presence of LiClO₄. The synthesized telechelic PMMAs had good control of molecular weight with narrow molecular weight distribution (MWD). The ¹H NMR and MALDI‐TOF MS analysis confirmed quantitative functionalization of chain‐ends. Block copolymerization of ethylene oxide was carried out using the terminal hydroxyl group of PMMA as initiator in the presence of potassium counter ion in THF at 35 °C. The PMMA‐b‐PEO diblock copolymers had moderate control of molecular weight with narrow MWD. The ¹H NMR results confirm the absence of trans‐esterification reaction of propagating PEO anions onto the ester pendants of PMMA. The micellation behavior of PMMA‐b‐PEO diblock copolymer was examined in water using ¹H NMR and dynamic light scattering. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 2132–2144, 2008     

Grafting of poly(ethylene oxide) with Schiff's base end group onto chloromethylated polystyrene via Decker-Forster reaction

Amphiphilic graft copolymer of polystyrene (PS) as backbone and poly(ethylene oxide) (PEO) as branch chain was prepared by Decker-Forster reaction. PEO with Schiff's base end group (PEO_s) was obtained by ring-opening polymerization of ethylene oxide (EO) initiated with protected potassium aminoethoxide, and then alkylated with chloromethylated polystyrene (c-PS). A graft copolymer with high grafting efficiency was derived by hydrolysis of the above-mentioned product.     

Synthesis and morphology of BAB type poly(styrene-b-2-methyl-2-oxazoline) block copolymers

Well defined BAB-type poly[styrene(ST)-b-2-methyl-2-oxazoline(MeOz)] was prepared by the cationic polymerization of α,ω-p-toluenesulfonic acid ester-terminated PST (PST-BTs) as an initiator. Alkaline hydrolysis of this block copolymer was carried out under various reaction conditions to obtain BAB-type poly[ST-b-ethylene imine(EI)]. Morphologies of these block copolymer specimens cast from several solvents were observed by electron microscope. The results are discussed in some detail.     

Effect of end group polarity upon the lower critical solution temperature of poly(2-isopropyl-2-oxazoline)

Thermo-sensitive poly(2-isopropyl-2-oxazoline)s (PiPrOx) were functionalized with end groups of different polarity by living cationic ring-opening polymerization using the initiator and/or termination method as well as sequential block copolymerization with 2-methyl-2-oxazoline. As end groups, methyl, n-nonyl, piperidine, piperazine as well as oligo(ethylenglygol) and oligo(2-methyl-2-oxazoline) were introduced quantitatively. The lower critical solution temperature (LCST) of the aqueous solutions was investigated. The introduction of hydrophobic end groups decreases the LCST, while hydrophilic polymer tails raise the cloud point. In comparison to poly(N-isopropyl acrylamide), the impact of the end group polarity upon the modulation of the LCST was found to be significantly stronger. Surprisingly, terminal oligoethylenegycol units also decrease the LCST of PiPrOx, thus acting as moieties of higher hydrophobicity as compared to the poly(2-oxazoline) main chain. Together with the possible variation of the side group polarity, this allows a broad modulation of the LCST of poly(2-oxazoline)s.     

Hydrophilic–hydrophobic AB diblock copolymers containing poly(trimethylene carbonate) and poly(ethylene oxide) blocks

AB‐type block copolymers with poly(trimethylene carbonate) [poly(TMC); A] and poly(ethylene oxide) [PEO; B; number‐average molecular weight (M_n) = 5000] blocks [poly(TMC)‐b‐PEO] were synthesized via the ring‐opening polymerization of trimethylene carbonate (TMC) in the presence of monohydroxy PEO with stannous octoate as a catalyst. M_n of the resulting copolymers increased with increasing TMC content in the feed at a constant molar ratio of the monomer to the catalyst (monomer/catalyst = 125). The thermal properties of the AB diblock copolymers were investigated with differential scanning calorimetry. The melting temperature of the PEO blocks was lower than that of the homopolymer, and the crystallinity of the PEO block decreased as the length of the poly(TMC) blocks increased. The glass‐transition temperature of the poly(TMC) blocks was dependent on the diblock copolymer composition upon first heating. The static contact angle decreased sharply with increasing PEO content in the diblock copolymers. Compared with poly(TMC), poly(TMC)‐b‐PEO had a higher Young's modulus and lower elongation at break. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 4819–4827, 2005     

Syntheses of poly[N-(1-pyrenyl)acetyl ethylenimine] [pyrene-substituted linear poly(ethylenimine)] and poly[methyl 2-(1-pyrenyl)acetamidopropenoate] [pyrene-substituted poly(dehydroalanine methyl ester)]

The syntheses of two new pyrene-containing monomers—2-(1-pyrenyl)methyl-2-oxazoline ( 6 ) and methyl 2-(1-pyrenyl)acetamidopropenoate ( 12 )—and their polymerization are described. Cationic isomerization polymerization of 6 with ethylene glycol ditosylate initiator gave poly[N-(1-pyrenyl)acetyl ethylenimine] ( 7 ) and free-radical polymerization of 12 with AIBN initiator gave poly[methyl 2-(1-pyrenyl)acetamidopropenoate] ( 15 ). The monomer model compounds of the two polymers, namely, N,N-diethyl(1-pyrenyl)acetamide ( 9 ) and methyl 2-methyl-2-(1-pyrenyl)acetamidopropanoate ( 14 ), were also synthesized. The polymers were characterized by elemental analysis, IR spectroscopy, and a comparison of their ¹H-NMR spectra with those of the respective monomer model compounds.     

Preparation of poly(ethylene oxide)‐block‐poly(isoprene) by nitroxide‐mediated free radical polymerization from PEO macroinitiators

Amphiphilic poly(ethylene oxide)‐block‐poly(isoprene) (PEO‐b‐PI) diblock copolymers were prepared by nitroxide‐mediated polymerization of isoprene from alkoxyamine‐terminal poly(ethylene oxide) (PEO). PEO monomethyl ether (M_n ≈ 5200 g/mol) was functionalized by esterification with 2‐bromopropionyl bromide with subsequent copper‐mediated replacement of the terminal bromine with 2,2,5‐trimethyl‐4‐phenyl‐3‐azahexane‐3‐nitroxide. The resulting PEO‐alkoxyamine macroinitiator was used to initiate polymerization of isoprene in bulk and in solution at 125 °C to yield PEO‐b‐PI block copolymers with narrow molecular weight distributions (M_w/M_n ≤ 1.1). Polymerizations were first order in isoprene through 35% conversion. Micellar aggregates of PEO‐b‐PI in aqueous solution were crosslinked by treatment with a water‐soluble redox initiating system, and persistent micellar structures were observed in the dry state by AFM. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 2977–2984, 2005     

Photo-initiated post-polymerization in micellar system of amphiphilic poly(ethylene oxide) macromonomers

Aqueous micellar polymerization of amphiphilic poly(ethylene oxide) macromonomers carrying p-vinylphenylheptyl end-group has been found to persist to proceed after turning-off of the UV-irradiation. Simulation of the kinetics revealed a high propagation rate constant coupled with a low termination constant, supporting a living-like polymerization at the initial stage. Micellar copolymerization with equimolar styrene also proceeded after UV-irradiation. Polymer molecular weights in MALLS-SEC were also found to evolve with time after irradiation.     

New aspects in chemistry and characterization of poly(ethylene oxide) hydrogels

To extend the variability of poly(ethylene oxide) (PEO) hydrogels in their swelling behaviour, ability to bind various subjects, and possible applications, some new synthetic approaches have been elaborated recently: (i) PEO networks with ionic and reactive groups were prepared by the reaction of P-OH groups of poly(oligoethylene glycol phosphate)s with diepoxide. The swelling degree of these hydrogels is strongly affected by salts, what is typical of polyelectrolyte networks. The structure parameters of the network evaluated from the swelling data are discussed. (ii) A series of hydrogels with controlled structure was obtained by radical polymerization of methacrylate PEO macromonomers of various molecular weights and average functionality (0.99–1.85) in aqueous media. The networks prepared are characterized by means of elastic modulus and swelling pressure measurements as well as with the help of microparticles of liquid-crystalline dispersion of DNA as probes highly sensitive to the network structure and state.     

Toward an easy access to dendrimer-like poly(ethylene oxide)s

Dendrimer-like poly(ethylene oxide)s (PEOs) were synthesized by an iterative divergent approach combining anionic polymerization of ethylene oxide from multi-hydroxylated precursors and branching reactions of PEO chain ends. Partial deprotonation of the hydroxyls (< 30%) and use of dimethyl sulfoxide as solvent proved crucial for a "controlled/living" polymerization of ethylene oxide at room temperature. These sequences of reactions allowed us to prepare a dendrimer-like PEO up to the eighth generation with a molar mass of 900 000 g mol(-1) and 384 external hydroxyl functions. All samples from generation 1 to 8 were characterized by 1H NMR spectroscopy, light scattering, and viscometry. The evolution of the intrinsic viscosity versus the generation number of these dendrimer-like PEO is similar to that of regular dendrimers.     

Poly(ethylene oxide)/poly(methyl methacrylate) (semi-)interpenetrating polymer networks: Synthesis and phase diagrams

Interpenetrating polymer networks (IPNs) of poly(ethylene oxide) (PEO) and poly(methyl methacrylate) (PMMA) were prepared by simultaneous network formation. The PEO network was produced by acid-catlayzed self-condensation of α,ω-bis(triethoxysilane)-terminated PEO in the presence of small amounts of water. The PMMA network was formed by free radical polymerization of MAA in the presence of divinylbenzene as crosslinker. The reaction conditions were adjusted to obtain similar crosslinking kinetics for both reactions. An attempt was made to construct a phase diagram of the IPNs by measuring the composition of the IPNs at the moment of the appearance of the phase separation, as indicated by the onset of turbidity. This composition could be determined because the siloxane crosslinks of the PEO network could be hydrolyzed in aqueous NaOH with the formation of linear, soluble PEO chains. The phase diagram was compared with phase diagrams of blends of linear polymers and of semi-IPNs (crosslinked PMMA and linear PEO), obtained under similar conditions, i.e. polymerization of MMA in the presence of varying amounts of PEO. It was observed that the form of the phase diagrams of the linear polymers is similar to that of the IPNs, but is quite different from that of the semi-IPNs. Thus, homogeneous transparent materials containing up to 60% of PEO could be prepared in the blends and the IPNs, but in the semi-IPNs, phase separation occurred with PEO contents as low as 10%.