Synthesis of Well-Defined Phthalimide Monofunctional Hyperbranched Polyglycerols and Its Transformation to Various Conjugation Relevant Functionalities

Abstract

Phthalimide monofunctional hyperbranched polyglycerols (HbPG) were successfully synthesized, for the first time, by applying a new, highly efficient phthalimide/potassium phthalimide (PhthIm/K-PhthIm) initiating system for the anionic ring-opening multibranching polymerization of glycidol. As the analyses of the resulting polymers by UV and NMR spectroscopies, vapor pressure osmometry, aqueous and organic phase GPCs and ESI-MS proved, well-defined HbPGs with one phthalimide moiety, predetermined average molar masses, and narrow molar mass distributions were formed. The phthaloyl group was quantitatively cleaved by hydrazinolysis to form a monoamine functional HbPG. The amine functionality of the HbPG molecules at the initiating site was transformed into carboxylic, maleimide, and chloroacetamide groups. All functionalization reactions were quantitative as proved by multidimensional NMR spectroscopy. These findings indicate that the PhthIm/K-PhthIm combination can be utilized in the polymerization and subsequent derivatizations of other epoxides as well. In addition, the selectively modifiable reactive headgroup can be applied for obtaining various novel functionalized materials.

Amphiphilic drug–peptide–polymer conjugates based on poly(ethylene glycol) and hyperbranched polyglycerol for epidermal growth factor receptor targeting: the effect of conjugate aggregation on in vitro activity

“…Amino-monofunctional HbPG was produced and characterized in our laboratory, as described earlier. 32 Briefly, phthalimide monofunctional HbPG was synthesized by the ringopening multibranching polymerization of freshly distilled glycidol with a phthalimide/potassium phthalimide initiating system (the monomer/initiator ratio was 15) and by using a slow monomer addition technique (feed rate: 2.5 mL h À1 ) at 95 1C under an inert atmosphere. The phthalimide moiety was transformed to an amine functionality through a reaction with hydrazine monohydrate in ethanol at room temperature.…”

“…29 Moreover, procedures to produce HbPGs by conjugation of relevant functionalities, such as amine, carboxylic, chloroacetamide and maleimide in well-defined numbers and positions, have already been developed. [30][31][32] Such functionalized HbPGs can be utilized to synthesize novel biomaterials, drug delivery systems and/or enhance the water solubility and biocompatibility of the linked residues. Peptide-HbPG conjugates have already been synthesized by the substitution of the multiple hydroxyl groups through thiol-ene 33 or azide-alkyne reactions 34 or ester linkages.…”

Synthetic Methodologies for Chelating Polymer Ligands: Recent Advances and Future Development

“…Mono‐functional phthalimide hyperbranched polyglycerols (HbPG) have been successfully synthesized using an anionic ring‐opening multibranching polymerization of glycidol (Scheme ) . Well‐defined HbPGs with one phthalimide fragment, specified average molar weights and narrow molar weight distributions were formed.…”

Tumor Noninvasive and Target Embolization Therapy Platform by Intravenous Injection Based on Acidic Microenvironment-Responsive Hyperbranched Poly(amino acid)s

“…Specifically, the pH-responsive hyperbranched poly­(amino acid)­s, poly­[ l -threonine- b -( l -glutamic acid- ran - l -tyrosine)]­s (HPTTG) with a tunable pH-responsive value are prepared via ring-opening polymerization of l -amino acid N -carboxyanhydride (NCA), as is illustrated in Scheme S1. Due to its lower hydrodynamic volume, larger number of modifiable end groups, and better solubility of dendritic or hyperbranched polymers compared to linear analogues, − the hyperbranched copolypeptides were adopted in this study. Various properties, including the sol–gel phase transition, the cytotoxicity, and biodegradability, of the copolymers and its aqueous solution were examined.…”