Scott M. Grayson

Synthetic approaches for the preparation of cyclic polymers

Despite decades of studies devoted to the unique physical properties and potential applications of cyclic polymer topologies, their exploration has remained limited because of synthetic inefficiencies and acyclic impurities. Many recently developed synthetic techniques offer efficient routes to well-defined cyclic macromolecules to answer this need. This tutorial review aims to provide a concise overview of the most significant synthetic contributions in this field, and highlight the relative advantages and disadvantages of each approach.

Approaches for the preparation of non-linear amphiphilic polymers and their applications to drug delivery.

Amphiphilic polymers are particularly useful for drug delivery because of their ability to self-assemble into discrete aggregates. While this behavior has been studied in depth for simple linear block copolymer amphiphiles, recent advances in synthetic methodologies have provided efficient routes to amphiphilic polymers with more complex architecture, including dendrimers, hyperbranched polymers, star polymers, and cyclic polymers. These architectures can impart unique advantages, such as increased stability, on their micellar aggregates. Herein the different strategies for preparing these complex amphiphiles are described, and the application of their assemblies towards drug delivery are summarized.

Cyclic polyesters: synthetic approaches and potential applications

The synthetic strategies that have been developed for the preparation of cyclic polyesters are reviewed. While linear and branched polyesters are used extensively for biomedical and materials applications, the synthetic difficulty of preparing cyclic polyesters has limited their exploration. Recently synthetic methodologies have been developed which compliment previous techniques, and promise to increase the availability of cyclic polyesters for future studies. The relative advantages and disadvantages of each approach are discussed, as well as some of the unique physical properties demonstrated by cyclic polymers.

The role of macromolecular architecture in passively targeted polymeric carriers for drug and gene delivery

The use of polymeric carriers for drug delivery has become increasingly popular because of the ability to easily tune the physical and biological properties of macromolecules. With the growing commercial accessibility of branched and dendritic polymers, their incorporation into polymeric carriers is being explored with increased frequency. However, while a handful of systematic studies have explored the use of branched macromolecules for drug delivery, the role of polymer architecture in optimizing the polymeric carriers is not yet fully understood. Herein, the authors summarize the effect that architecture has on the basic physical properties of polymers, and review our preliminary understanding of the architectural effects on polymer-assisted drug delivery.

Dendronized supramolecular nanocapsules: pH independent, water-soluble, deep-cavity cavitands assemble via the hydrophobic effect.

At neutral pH, dendronized deep-cavity cavitands were shown to form supramolecular nanocapsules via assembly around a range of guest molecules.

Synthesis of cyclic amphiphilic homopolymers and their potential application as polymeric micelles

Although amphiphilic copolymers have been widely studied due to their ability to phase segregate in bulk and form micelle-like nanostructures in solution, previous research has focused primarily on block copolymers. Amphiphilic homopolymers, in which each monomer along the backbone contains an amphiphilic unit, have seen only limited exploration, while non-linear amphiphilic homopolymers remain largely unexplored. Building from methods established in our laboratories for the synthesis of cyclic polymers, bifurcated amphiphiles were attached via a highly efficient “click” coupling to access analogous sets of linear and cyclic amphiphilic homopolymers (the first reported example of cyclic amphiphilic homopolymers). These amphiphilic homopolymers showed solubility in a wide range of solvents with varying polarities and also have demonstrated the ability to encapsulate guests in incompatible solvents. For the mass range examined, the cyclic polymers showed only a negligible difference in guest encapsulation when compared to linear analogs.

Differentiation of Linear and Cyclic Polymer Architectures by MALDI Tandem Mass Spectrometry (MALDI-MS2)

Abstract[M + Ag]+ ions from cyclic and linear polystyrenes and polybutadienes, formed by matrix-assisted laser desorption ionization (MALDI), give rise to significantly different fragmentation patterns in tandem mass spectrometry (MS2) experiments. In both cases, fragmentation starts with homolytic cleavage at the weakest bond, usually a C–C bond, to generate two radicals. From linear structures, the separated radicals depolymerize extensively by monomer losses and backbiting rearrangements, leading to low-mass radical ions and much less abundant medium- and high-mass closed-shell fragments that contain one of the original end groups, along with internal fragments. With cyclic structures, depolymerization is less efficient, as it can readily be terminated by intramolecular H-atom transfer between the still interconnected radical sites (disproportionation). These differences in fragmentation reactivity result in substantially different fragment ion distributions in the MS2 spectra. Simple inspection of the relative intensities of low- versus high-mass fragments permits conclusive determination of the macromolecular architecture, while full spectral interpretation reveals the individual end groups of linear polymers or the identity of the linker used to form the cyclic polymer. FigureMacrocyclic and linear polystyrene and polydiene architectures are conclusively distinguished by the MS2 fragmentation patterns of Ag+-cationized oligomers.

The identification of synthetic homopolymer end groups and verification of their transformations using MALDI-TOF mass spectrometry.

Recent advances in the resolving power of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) enable the detailed characterization of linear homopolymers, and in particular provide invaluable data for the determination of their end-group functionalities. With the growing importance of macromolecular coupling reactions in building complex polymer architectures, the ability to accurately monitor end-group transformations is becoming increasingly important for synthetic polymer chemists. This tutorial demonstrates the application of MALDI-TOF MS in determining both end-group functionalities and their transformations for linear homopolymers. Examples of both polycaprolactone and polystyrene are examined, and the strengths and weaknesses of various approaches to data analysis are given.

Efficient Synthesis of High Purity Homo-arm and Mikto-arm Poly(ethylene glycol) Stars Using Epoxide and Azide–Alkyne Coupling Chemistry

High purity homo-arm and mikto-arm poly(ethylene glycol) (PEG) stars are successfully prepared by the combination of epoxide ring-openings and azide-alkyne click reactions. First, monohydroxy-PEG was modified via epoxide chemistry to bear one hydroxyl and one azide functionality at the same end. An alkyne-functionalized PEG chain was then coupled to the azide. Subsequently, the remaining hydroxyl could be reactivated to an azide again and again to enable stepwise addition of alkyne-functionalized polymer arms. The use of efficient reactions for this iterative route provides star polymers with an exact number of arms, and a tailorable degree of polymerization for each arm. Detailed characterization confirms the high purity of multi-arm polyethylene glycol products.

Surface-initiated atom transfer radical polymerization of glycidyl methacrylate and styrene from boron nitride nanotubes

Boron nitride nanotubes (BNNTs) grafted with polyglycidyl methacrylate (PGMA) and polystyrene (PSt) brushes are described. This surface modification of BNNTs with polymer brushes is efficiently achieved involving only two steps: the introduction of benzyl bromide ATRP initiating sites on the BNNTs’ surface by a one-step radical addition method and the surface-initiated atom transfer radical polymerization (SI-ATRP) of GMA or St from the initiator immobilized BNNTs surface. The structure and properties of the resultant hybrid materials are characterized by Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis, scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The FTIR analysis of hybrid materials shows infrared signals characteristic of the grafted polymers (PGMA and PSt) while SEM and TEM images clearly show the formation of polymer grafts on the BNNT surface.