Synthesis and Properties of Carborane-Functionalized Aliphatic Polyester Dendrimers

Abstract

The incorporation of multiple p-carborane cages within an aliphatic polyester dendrimer was accomplished through the preparation of a bifunctional carborane synthon. A p-carborane derivative having an acid and a protected alcohol functionality was found to efficiently couple to peripheral hydroxyl groups of low-generation dendrimers under standard esterification conditions. Deprotection of carborane hydroxyl groups allowed for further dendronization through a divergent approach using the highly reactive anhydride of benzylidene-protected 2,2-bis(hydroxymethyl)propanoic acid. This approach was used to prepare fourth- and fifth-generation dendrimers that contain 4, 8, and 16 carborane cages within their interior. Upon peripheral deprotection to liberate a polyhydroxylated dendrimer exterior, these structures exhibited aqueous solubility as long as a minimum of eight hydroxyl groups per carborane were present. Several of the water-soluble structures were found to exhibit a lower critical solution temperature. Additionally, irradiation of these materials with thermal neutrons resulted in emission of gamma radiation that is indicative of boron neutron capture events occurring within the carborane-containing dendrimers.

Polyester Dendrimers: Smart Carriers for Drug Delivery

“…To address this problem, high boron content species such as polyhedral borane clusters, closo-[B 10 [158]. With this in mind, Adronov and coworkers prepared aliphatic polyester dendrimers based on bis-HMPA that incorporate an easily controllable number of carboranes within the interior of the dendritic structure [163]. Newkome and coworkers had previously reported the production of water-soluble carborane-functionalized dendrimers, involving the reaction of alkyne moieties with decaborane to form ortho-carborane cages within the interior of cascade macromolecules [164].…”

“…Newkome and coworkers had previously reported the production of water-soluble carborane-functionalized dendrimers, involving the reaction of alkyne moieties with decaborane to form ortho-carborane cages within the interior of cascade macromolecules [164]. Here [163], It was critical to develop a bifunctional carborane synthon that matches the dual functionality of the bis-HMPA monomer, allowing it to be inserted within the dendrimer synthesis at any generation using traditional esterification reactions. This flexibility in the position of carborane insertion provided control over the boron concentration within a specific dendrimer target compound.…”

Polyester Dendrimers

“…Dendritic species based on bis-HMPA containing carboranes were reported by both Adronov [153] and Zharov [169]. These compounds are of interest because of their potential use for boron neutron capture therapy in the treatment of diseases such as cancer.…”

“…Polyester dendrimers were prepared up to the fourth generation using even sterically congested cores like pentaerythritol in good yields using DMAP and DCC to promote ester formation. Since then, a number of research groups have utilized the benzylidene-protected bis-HMPA as a convenient building block [127,129,130,146,[150][151][152][153]. Synthesis of a dendritic macro-initiator for atom transfer radical polymerization [146].…”

Dendrimer-based bionanomaterials produced by surface modification, assembly and hybrid formation

“…These include hydrophobic aminoacid residues, such as L-phenylalanine and L-leucine residues 47 and carborane. 48 In addition, surface modification has been applied to provide temperature-sensitive properties to hyperbranched polymers of various backbone structures including polyamidoamines, 49 poly(ethyleneimine) 50,51 and poly(glycidol). [52][53][54][55] As another type of thermosensitive polymers, dendrimers and hyperbranched polymers consisting of thermosensitive polyether backbones have also been developed.…”