Marie V. Walter

Simplifying the synthesis of dendrimers: accelerated approaches

Dendrimers are highly branched and monodisperse macromolecules that display an exact and large number of functional groups distributed with unprecedented control on the dendritic framework. Based on their globular structure, compared to linear polymers of the same molecular weight, dendrimers are foreseen to deliver extraordinary features for applications in areas such as cancer therapy, biosensors for diagnostics and light harvesting scaffolds. Of the large number of reports on dendrimer synthesis only a few have reached commercial availability. This limitation can be traced back to challenges in the synthetic paths including a large number of reaction steps required to obtain dendritic structures with desired features. Along with an increased number of reaction steps come not only increased waste of chemical and valuable starting materials but also an increased probability to introduce structural defects in the dendritic framework. This tutorial review briefly covers traditional growth approaches to dendrimers and mainly highlights accelerated approaches to dendrimers. A special focus capitalizes on the impact of the click chemistry concept on dendrimer synthesis and the promise it has to successfully accomplish highly sophisticated dendrimers, both traditional as well as heterofunctional, in a minimum number of chemical steps. It is clear that accelerated synthetic approaches are of greatest importance as these will encourage the scientific community to synthesize and access dendrimers for specific applications. The final goal of accelerated synthesis is to deliver economically justified dendritic materials for future applications without compromising the environmental perspective.

Stability and biocompatibility of a library of polyester dendrimers in comparison to polyamidoamine dendrimers

Dendrimers can be designed for several biomedical applications due to their well-defined structure, functionality and dimensions. The present study focused on the in vitro biocompatibility evaluation of a library of aliphatic polyester dendrimers based on 2,2-bis(methylol)propionic acid (bis-MPA) with an overall diameter of 0.5-2 nm. In addition, dendrimers with two different chemical surfaces (neutral with hydroxyl end group and anionic with carboxylic end group) and dendrons corresponding to the structural fragments of the dendrimers were evaluated. Commercial polyamidoamine dendrimers (PAMAM) with cationic (amine) or neutral (hydroxyl) end group were also included for comparison. Cell viability studies were conducted in human cervical cancer (HeLa) and acute monocytic leukemia cells (THP.1) differentiated into macrophage-like cells as well as in primary human monocyte-derived macrophages. Excellent biocompatibility was observed for the entire hydroxyl functional bis-MPA dendrimer library, whereas the cationic, but not the neutral PAMAM exerted dose-dependent cytotoxicity in cell lines and primary macrophages. Studies to evaluate material stability as a function of pH, temperature, and time, demonstrated that the stability of the 4th generation hydroxyl functional bis-MPA dendrimer increased at acidic pH. Taken together, bis-MPA dendrimers are degradable and non-cytotoxic to human cell lines and primary cells.

Linear dendritic polymeric amphiphiles with intrinsic biocompatibility: synthesis and characterization to fabrication of micelles and honeycomb membranes

Linear dendritic hybrid materials enable a range of architectural variations which offers novel possibilities in the tailoring of polymeric materials. In this study dendrons based on the 2,2-bis(methylol)propionic acid (bis-MPA) building block, bearing click chemistry moieties in the core and peripheral hydroxyl functionalities, have been used as macroinitiators for ring opening polymerization of e-caprolactone. A library of star branched polymers with poly(e-caprolactone) chains was initially constructed using dendrons up to 4th generation. In a second step, the popular CuAAC or thiol–ene click reaction was efficiently used to attach poly(ethylene glycol) chains of different lengths to the core. Potential applications of the resulted amphiphilic linear dendritic hybrids were investigated. Both self-assembled micelles loaded with doxorubicin anticancer drug and ordered honeycomb membranes with enhanced surface area were successfully fabricated and characterized.

A one component methodology for the fabrication of honeycomb films from biocompatible amphiphilic block copolymer hybrids: a linear–dendritic–linear twist

The development of a facile method for the fabrication of breath figure (BF) films from hydrophobic polymers is gaining significant importance for their accessibility as templates in fields ranging from electronics and cell culturing to sensing and catalysis. By introducing polyester-based dendritic linkers, a library of micrometre sized honeycomb structures was successfully fabricated from amphiphilic linear–dendritic–linear hybrids comprising hydrophobic PCL or PLA and hydrophilic PEG blocks. From the array of produced films, the incorporation of a third generation dendritic linker was found to generate well-ordered honeycomb films in the several hundreds of micrometre range. This one component approach minimizes the number of unknown parameters and represents a fully reliable methodology for the fabrication of functional BFs from challenging and biocompatible polymers.

Hybrid one-dimensional nanostructures: one-pot preparation of nanoparticle chains via directed self-assembly of in situ synthesized discrete Au nanoparticles.

The fabrication of well-defined one-dimensional (1D) arrays is becoming a challenge for the development of the next generation of advanced nanodevices. Herein, a simple concept is proposed for the in situ synthesis and self-assembly of gold nanoparticles (AuNPs) into 1D arrays via a one-step process. The results demonstrated the formation of nanoparticle chains (NPC) with high aspect ratio based on discrete Au nanoparticles stabilized by short thiol ligands. A model was proposed to explain the self-assembly based on the investigation of several parameters such as pH, solvent, temperature, and nature of the ligand on the 1D assembly formation. Hydrogen bonding was identified as a key factor to direct the self-assembly of the hybrid organic–inorganic nanomaterials into the well-defined 1D nanostructures. This simple and cost-effective concept could potentially be extended to the fabrication of a variety of hybrid 1D nanostructures possessing unique physical properties leading to a wide range of applications including catalysis, bionanotechnology, nanoelectronics, and photonics.

Functional porous membranes from amorphous linear dendritic polyester hybrids

By combining ATRP, dendrimer chemistry and ‘click’ reactions, a library of novel linear dendritic block copolymers (hybrids) was successfully synthesized. The isolated polymers displayed hydrophilic alkyne groups and Tgs ranging from 14 °C to 67 °C. A Tg threshold of 39 °C was found necessary for straightforward porous membrane fabrication via the breath figure method. Exploiting the copper(I)-catalyzed azide–alkyne cycloaddition (CuAAC) reaction, a robust and benign protocol was identified enabling surface functionalization under aqueous conditions. Such manipulations included the introduction of fluorescent rhodamine for thorough assessment by confocal fluorescence microscopy as well as polyethylene glycol chains or perfluorinated groups for tuning the membrane wettability. Finally, with the initial indication of being nontoxic to human dermal fibroblasts (hDF) and osteoblast-like MG63, the porous membranes can potentially find use in the field of controlled cell culture such as patterning of cell growth.