ChemInform Abstract: Multifunctional Poly(ethylene glycol)s

In the rapidly evolving multidisciplinary field of polymer therapeutics, tailored polymer structures represent the key constituent to explore and harvest the potential of bioactive macromolecular hybrid structures. In light of the recent developments for anticancer drug conjugates, multifunctional polymers are becoming ever more relevant as drug carriers. However, the potentially best suited polymer, poly(ethylene glycol) (PEG), is unfavorable owing to its limited functionality. Therefore, multifunctional linear copolymers (mf-PEGs) based on ethylene oxide (EO) and appropriate epoxide comonomers are attracting increased attention. Precisely engineered via living anionic polymerization and d…

N,N-Diallylglycidylamine: A Key Monomer for Amino-Functional Poly(ethylene glycol) Architectures

The first application of N,N-diallylglycidylamine (DAGA) as a monomer for anionic ring-opening polymerization is presented. The monomer is obtained in a one-step procedure using epichlorohydrin and N,N-diallylamine. Both random and block copolymers consisting of poly(ethylene glycol) and poly(N,N-diallylglycidylamine) with adjusted DAGA ratios from 2.5 to 24% have been prepared, yielding well-defined materials with low polydispersities (Mw/Mn) in the range 1.04–1.19. Molecular weights ranged between 2600 and 10 300 g mol–1. Isomerization of allylamine to enamine structures during polymerization depending on time, temperature, and counterion has been realized. The kinetics of the formation o…

PEG-based Multifunctional Polyethers with Highly Reactive Vinyl-Ether Side Chains for Click-Type Functionalization

Introduction of highly reactive vinyl ether moieties along a poly(ethylene-glycol) (PEG) backbone has been realized by copolymerization of the novel epoxide monomer ethoxy vinyl glycidyl ether (EVGE) with ethylene oxide (EO). A series of copolymers with varying structure (block and random) as well as EVGE comonomer content (5-100%) with molecular weights in the range of 3,900-13,200 g/mol and narrow molecular weight distributions (M-w/M-n = 1.06-1.20) has been synthesized and characterized with respect to their microstructure and thermal properties. The facile transformation of the vinyl ether side chains in click type reactions was verified by two different post polymerization modification…

Poly(ethylene glycol-co-allyl glycidyl ether)s: a PEG-based modular synthetic platform for multiple bioconjugation.

A series of random copolymers comprising ethylene oxide (EO) and 0-100% allyl glycidyl ether (AGE) has been prepared by anionic ring-opening polymerization with molecular weights between 5000 and 13,600 g/mol and polydispersity indices in the range of 1.04-1.19. As key for the homogeneity of the PEG conjugates, real-time ¹H NMR polymerization kinetics, ¹³C NMR analysis of triad sequence distribution, and analysis of the thermal behavior by differential scanning calorimetry (DSC) revealed a distinctive random copolymer structure. Via thiol-ene coupling (TEC), showing mainly "click" characteristics and nearly quantitative yields, PEG derivatives with multiple amino, carboxy, or hydroxy functi…

Multifunctional Poly(ethylene glycol)s

In the rapidly evolving multidisciplinary field of polymer therapeutics, tailored polymer structures represent the key constituent to explore and harvest the potential of bioactive macromolecular hybrid structures. In light of the recent developments for anticancer drug conjugates, multifunctional polymers are becoming ever more relevant as drug carriers. However, the potentially best suited polymer, poly(ethylene glycol) (PEG), is unfavorable owing to its limited functionality. Therefore, multifunctional linear copolymers (mf-PEGs) based on ethylene oxide (EO) and appropriate epoxide comonomers are attracting increased attention. Precisely engineered via living anionic polymerization and d…

Macromol. Rapid Commun. 3/2010

Introducing an amine functionality at the block junction of amphiphilic block copolymers by anionic polymerization strategies

A series of block copolymers bearing a single amino in-chain functionality was synthesized via anionic polymerization of styrene and ethylene oxide. By means of both a conventional and a continuous setup, living polystyrene was quantitatively end functionalized with an oxirane (DBAG) prior to the polymerization of the poly(ethylene oxide) segment. The in-chain amine was conjugated with a fluorescent dye.

From an epoxide monomer toolkit to functional PEG copolymers with adjustable LCST behavior.

The lower critical solution temperature (LCST) behavior of novel poly(ethylene glycol) (PEG)-based copolymers bearing multiple functional groups, obtained by anionic ring-opening (co)polymerization (AROP), has been investigated. Variable comonomer ratios of ethylene oxide (EO) and the corresponding oxiranes isopropylidene glyceryl glycidyl ether (IGG), ethoxyl vinyl glycidyl ether (EVGE), allyl glycidyl ether (AGE), or N,N-dibenzyl amino glycidyl (DBAG), particularly designed to implement functional groups at the PEG backbone, were found to influence the LCST behavior. Sharp transitions from translucent to opaque solutions, comparable to other well-established stimuli-responsive polymers, w…

“Functional Poly(ethylene glycol)”: PEG-Based Random Copolymers with 1,2-Diol Side Chains and Terminal Amino Functionality

A series of poly(ethylene glycol-co-isopropylidene glyceryl glycidyl ether) (P(EO-co-IGG)) random copolymers with different fractions of 1,2-isopropylidene glyceryl glycidyl ether (IGG) units was synthesized. After acidic hydrolysis a new type of "functional PEGs", namely poly(ethylene glycol-co-glyceryl glycerol) (P(EO-co-GG)) was obtained. Using an initiator that releases a terminal amino moiety after deprotection, functional end groups with orthogonal reactivity to the in-chain groups were obtained. All polymers showed narrow molecular weight distributions (1.07-1.19), and control of the molecular weights was achieved in the range 5000-30 000 g/mol. Random incorporation of both comonomer…

Amino Functional Poly(ethylene glycol) Copolymers via Protected Amino Glycidol

The synthesis of poly(ethylene glycol) (PEG) copolymers with multiple amino functionalities within the chain is described, relying on an epoxide comonomer bearing a protected amino group. N,N-dibenzyl amino glycidol (DBAG) and ethylene oxide (EO) were copolymerized via anionic polymerization, leading to well-defined polymers with varied comonomer content and low polydispersities (Mw/Mn in the range of 1.1 to 1.2). Subsequent hydrogenolysis with Pearlman’s catalyst afforded poly(ethylene glycol-co-amino glycerol)s (PEG-co-PAG) with a precisely adjusted number of randomly incorporated amino groups in the range of 2−15%. For the first time, the kinetics of an EO copolymerizations have has been…

Multifunktionelle Poly(ethylenglycole)

Hetero-Multifunctional Poly(ethylene glycol) Copolymers with Multiple Hydroxyl Groups and a Single Terminal Functionality

Hetero-multifunctional poly(ethylene glycol-co-glycerol) random copolymers with multiple hydroxyl functionalities and a single terminal functionality have been prepared by copolymerization of ethylene oxide (EO) and ethoxy ethyl glycidyl ether (EEGE) with the use of a suitable initiator, introducing a protected amino group or a double bond, respectively. Acidic deprotection was used for removal of the acetal protecting groups in the chain, and the terminal amino group was regenerated by catalytic hydrogenation. A series of copolymers with narrow polydispersity was obtained, varying comonomer fractions from 3 to 67% and molecular weights in the range of 5 000-32 000 g · mol(-1) (1.05 < $\ove…

Partially Quarternized Amino Functional Poly(methacrylate) Terpolymers: Versatile Drug Permeability Modifiers

Partially quarternized poly(methacrylate) terpolymers (Q-BBMCs) have been synthesized, based on the basic butylated methacrylate copolymer (BBMC/EUDRAGIT E), an excipient approved by the Food and Drug Administration (FDA) and to date mainly applied for tablet coatings. Via straightforward polymer modification reactions, a series of Q-BBMCs with quarternization degrees of 22%, 42%, and 65% has been prepared. Apical to basolateral transport across Caco-2 cell monolayers was investigated, employing the paracellular transported compounds trospium and mannitol. At pH 6.5 quarternization resulted in increased permeation enhancement up to 2.8-fold compared to BBMC, that is, up to 7.3-fold compared…