Dendrimers are an important class of polymeric materials for a broad range of applications in which monodispersity and multivalency are of interest. Here we report on a highly efficient synthetic route towards bifunctional polyglycerol dendrons on a multigram scale. Commercially available triglycerol (1), which is highly biocompatible, was used as starting material. By applying Williamson ether synthesis followed by an ozonolysis/reduction procedure, glycerol-based dendrons up to the fourth generation were prepared. The obtained products have a reactive core, which was further functionalized to the corresponding monoazido derivatives. By applying copper(I)-catalyzed 1,3-dipolar cycloaddition, so-called "click" coupling, a library of core-shell architectures was prepared. After removal of the 1,2-diol protecting groups, water-soluble core-shell architectures 24-27 of different generations were obtained in high yields. In the structure-transport relationship with Nile red we observe a clear dependence on core size and generation of the polyglycerol dendrons.

The nonspecific interaction of proteins with surfaces in contact with biofluids leads to adverse problems and is prevented by a biocompatible surface coating. The current benchmark material among such coatings is poly(ethylene glycol) (PEG). Herein, we report on the synthesis of linear polyglycerol derivatives as promising alternatives to PEG. Therefore, gold surfaces as a model system are functionalized with a self-assembled monolayer (SAM) by a two-step anhydride coupling and a direct thiol immobilization of linear poly(methyl glycerol) and polyglycerol. Surface plasmon resonance (SPR) spectroscopy reveals both types of functionalized surfaces to be as resistant as PEG towards the adsorption of the test proteins fibrinogen, pepsin, albumin, and lysozyme. Moreover, linear polyglycerols adsorb even less proteins from human plasma than a PEG-modified surface. Additional cell adhesion experiments on linear poly(methyl glycerol) and polyglycerol-modified surfaces show comparable cell resistance as for a PEG-modified surface. Also, in the case of long-term stability, high cell resistance is observed for all samples in medium. Additional in vitro cell-toxicity tests add to the argument that linear poly(methyl glycerol) and polyglycerol are strong candidates for promising alternatives to PEG, which can easily be modified for biocompatible functionalization of other surfaces.

Nonfouling surface coatings are of great interest for the development of advanced biomaterials used in biomedical and marine applications. Therefore, a lot of effort has been made to design new biocompatible materials and to understand the mechanisms of the protein repulsion. This study examines a series of polyglycerol (PG) dendrons modified by alkanethiols for their interactions with biofouling relevant proteins: fibrinogen (Fib), lysozyme (Lys), albumin (Alb), and pepsin (Pep). All polyglycerol dendrons [G1.0]-[G3.0] self-assembled monolayers with different terminal functionality (-OH, -OCH(3)) were prepared by applying simple Williamson ether formation followed by radical thiol addition to the alkene. Surface modification was performed by chemisorption of the different dendritic PG derivatives onto gold chips from ethanolic solution and then directly used in a screening with the respective proteins applying SPR spectroscopy. The effective and time-dependent SAM formation on gold was also revealed by X-ray photoelectron spectroscopy. It was demonstrated that the all polyglycerol dendrons [G1.0]-[G3.0] possess excellent resistance to the test proteins. Surprisingly, the SAMs of easily accessible [G1.0] dendron (M(w) = 426 g/mol) modified alkanethiol show the same high protein resistance as we could achieved for high molecular weight polymers (e.g., hyperbranched PG with M(n) = 2500 g/mol). However, significant changes in the amount of adsorbed proteins within the studied time frame of 24 h was not observed. Therefore, these oligoglycerol dendrons are a good alternative for the commonly used poly(ethylene glycol) (PEG).

This paper describes a structure-property study of mixed self-assembled monolayers (SAMs) on gold that present methylated or hydroxyl-terminated polyglycerol (PG) structures that vary in size and architecture, and their ability to resist the adsorption of four test proteins from solution. Mixed SAMs were prepared by the reaction of an amine of the polyglycerol structures with a SAM that presents interchain anhydrides (the anhydride method). Surface plasmon resonance spectroscopy was used to measure the adsorption of fibrinogen, lysozyme, albumin, and pepsin to the resulting mixed PG amide/carboxylate-terminated SAMs. In addition, FTIR infrared reflection-absorption spectroscopy (IRRAS) and contact angle goniometry were used to characterize the mixed SAMs. The study showed that even though methylation increases the hydrophobicity of these mixed PG SAMs, it greatly improved their ability to resist the adsorption of the test protein with the best performing surface demonstrating better resistance than a mixed SAM that presented poly(ethylene glycol) (PEG350). It was also shown that increasing the molecular weight of the PG structures (oligomer length or higher dendritic generations) generally resulted in decreased protein adsorption. With respect to the architecture, the linear oligoglycerols showed better resistance than their equal weight branched dendrons, while hyperbranched dendrons were more resistant to protein adsorption than perfect dendrons of equal weight.

A series of novel non-ionic amphiphiles with dendritic oligoglycerol head groups of different generations ([G1]-[G3]) and lipophilic/fluorophilic tail segments, comprising single or double tail alkyl chains, C8F17-perfluoro rod segments as well as flexible spacer groups of different lengths were designed and synthesized. We expected that the differences in the size of the dendritic head groups in combination with perfluorinated segments would have an impact on the supramolecular structures formed in aqueous solution if compared with the hydrogenated analogues. Investigating the self-assembly behavior mainly by cryogenic transmission electron microscopy (cryo-TEM) and cryo-electron tomography (cryo-ET) we found as a new result the formation of perforated bilayer vesicles (stomatosomes) and bicontinuous network structures. Surprisingly, we have observed stomatosome formation by self-assembly of single component fluorinated dendritic amphiphiles. These assembly structures turned out to be extremely robust against harsh conditions, although there are strong indications that they represent non-equilibrium structures, which eventually transform into a bicontinuous cubic network structure of double diamond symmetry. In general, the molecular asymmetry of amphiphiles tuned by chemical design induced the expected trend from spherical micelles through worm-like micelles to perforated bilayers and three-dimensional network structures.