Synthesis of Water-Soluble, Ester-Terminated Dendrons and Dendrimers Containing Internal PEG Linkages George R. Newkome,* ,‡ Kishore K. Kotta, † Amaresh Mishra, § and Charles N. Moorefield ‡ Departments of Polymer Science and Chemistry, Department of Chemisry, Maurice Morton Institute of Polymer Science, The University of Akron, Akron, Ohio 44325-4717, and Department of Chemical Sciences, Tata Institute of Fundamental Research, Mumbai, 400 005, India Received May 18, 2004; Revised Manuscript Received August 5, 2004 ABSTRACT: Dendrimers up to three generations, possessing internal PEG units within the branching framework, were synthesized by a convergent approach via the reaction of amine-based dendrons 6, 9, and 11 with 6,6-bis(4-chlorocarbonyl-2-oxabutyl)-4,8-dioxaundecane-1,11-dicarbonyl chloride. These new constructs were fully characterized, shown to exhibit good solubilities in organic as well as aqueous solvents, and demonstrated to solubilize lithium triflate salts in nonaqueous environments, such as chloroform. Introduction During this past decade, the syntheses, characteriza- tion, and applications of dendrimers have been intro- duced into diverse fields of research. 1,2 These highly branched, 3-dimensional, globular macromolecules have shown promising utility in molecular electronic devices, such as light-emitting diodes, 3,4 molecular antennae, 5,6 light-harvesting systems, 7,8 drug delivery systems, 9,10 chemical sensors, 11 receptors in molecular recognition processes, 12,13 enhanced binding or sensor effects, 14,15 and luminescent materials, 16-19 to mention but a few. Poly(ethylene glycol)s (PEGs) and their derivatives are important biocompatible materials that exhibit a wide range of solubilities 20,21 and are generally non- toxic. 22 Hence, their use as drug carriers, 9,23,24 anchors for biological receptors, 25 and metal ion binding for ion transport 26 is well documented. In tethered, bilayer membrane systems, where they are employed as hy- drophilic linkers, PEG units act as the integral compo- nent of an ion channel switch biosensor. 27 Further, ether-, ester-, and amine-based linear polymers with short PEG units in the presence of inorganic salts have potential applications in high-energy density batteries, electrochemical cells, and electrochromic devices. 28-31 For dendritic architectures incorporating the PEG moiety, the most common attachment of PEG moieties is onto their surface in order to instill aqueous solubility in general, to water-insoluble species. In that dendrim- ers have three structural regions in which a PEG unit can be introduced, namely, the core, 32-42 internal con- nective moieties, 43-47 and surface groups, 9,36,48-82 the former and latter attachments predominate due to the ease of instillation. Also, dendrons have been focally PEGed. 38,83-89 Gitsov et al. 32,36 reported linear-dendritic block copolymers using large PEG components, as the internal core as well as surface unit(s), and studied their properties; a review by Gitsov 90 has recently appeared. Diederich et al. utilized a series of dendroclefts 53,60,64 and heme proteins 50,59,61,68,70,91,92 possessing 1 f 3 C-branched monomers capped with small, surface PEGed subunits and then studied their unique properties such as their selective recognition of monosaccharides. Ph- thalocyanines 65,93 and related benzoporphyrins 77 as well as metalloclusters 94 have also been made readily water- soluble by the attachment of small PEG units. Nieren- garten recently reviewed 79 examples of dendritic encap- sulation, which is, in part, based on related PEGed surfaces. The highly stable PEG-functionalized satu- rated hydrocarbon-type dendrimers act as electrolyte materials and were shown to improve the efficiency 95,96 of a lithium rocking chair battery. More recently, Itoh et al. 44,97 studied the ionic conductivity of hyperbranched PEG derivatives in the presence of lithium metal salts [LiCF 3 SO 3 and Li(CF 3 SO 2 ) 2 N] to determine their ef- fectiveness as polymer electrolytes. Only three examples of PEG units being used as noncore, internal linkages have appeared, to the best of our knowledge: function- alization of tetrathiafulvalene (TTF), 43,46 hyperbranched Fre ´chet-type materials, 47,97,98 and in the solid-phase peptide synthesis of multimeric cyclo-(RGDtE)-pep- tides. 45 Our interest in the design and application of den- drimers led us to synthesize a series of useful PEGed dendrons and dendrimers, which utilize a combination of (1) amide connectivity affording minimal internal hydrolytic cleavage in that most PEGed dendrimers possess the more labile ester connectivity, (2) 1 f 3 C-branching motif, and (3) a noncore, internal PEG linkage, derived from commercially available triethylene glycol. Incorporation of PEG functionality within the dendritic framework is also envisioned to enhance the dendrimers potential to facilitate the transport of alkali metal species such as is required of polymer electrolytes in solid-state batteries. Experimental Section General Remarks. Melting point data were obtained in capillary tubes with an Electrothermal 9100 melting point apparatus and are uncorrected. All of chemicals were pur- chased from Aldrich Co. except for the tetradirectional core, † Department of Chemistry, The University of Akron. ‡ Maurice Morton Institute of Polymer Science, The University of Akron. § Tata Institute of Fundamental Research. * Corresponding author: e-mail newkome@uakron.edu. 8262 Macromolecules 2004, 37, 8262-8268 10.1021/ma049017i CCC: $27.50 © 2004 American Chemical Society Published on Web 10/01/2004