Monika Wyszogrodzka

Synthesis and Characterization of Glycerol Dendrons, Self-Assembled Monolayers on Gold: A Detailed Study of Their Protein Resistance

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).

Linear Poly(methyl glycerol) and Linear Polyglycerol as Potent Protein and Cell Resistant Alternatives to Poly(ethylene glycol)

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.

Study of Single Protein Adsorption onto Monoamino Oligoglycerol Derivatives: A Structure−Activity Relationship

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.

Supramolecular behavior of fluorous polyglycerol dendrons and polyglycerol dendrimers with perfluorinated shells in water

In this article, we describe the synthesis of a perfluoro-tagged polyglycerol dendron and its aggregation behavior in the presence of polyglycerol dendrimers with perfluorinated shells in water. The perfluoro-alkyl–perfluoro-alkyl interactions between the perfluorinated shells of the dendrimers and the perfluorinated tags of the dendrons lead to highly stable supramolecular architectures, due to self-assembly of the perfluorinated moieties. Furthermore, we show that the size of the resulting supramolecular complexes can be tuned by simple variation of the dendrimer–dendron ratio. Complexes at various ratios are characterized by optical microscopy, DLS, and TEM. In general, the results presented herein demonstrate that perfluoro-alkyl–perfluoro-alkyl interactions are applicable for the formation of stable supramolecular structures in water and thus provide a new tool for the design of supramolecular architectures in addition to traditional non-covalent interactions.

pH-triggered self-assembly of zwitterionic polyglycerol dendrons into discrete and highly stable supramolecular dendrimers in water.

The objective of this work is to show how the pH-dependent dimerization of a polyglycerol dendron modified with a self-complementary zwitterionic binding site can be used to form well-defined and highly stable discrete supramolecular dendrimers in water. Dendrimers are monodisperse macromolecules built from iteratively repeated subunits. They are an interesting class of new nanomaterials that are currently explored for various applications in chemistry, material sciences, biology, or even medicine (e.g. as drug carriers). However, the chemical synthesis of larger dendrimers is difficult and often hampered by defects in the structure and problems with the analysis and/or purification. An alternative is the self-assembly of smaller dendrons into larger supramolecular dendritic nanostructures. However, most often polymeric aggregates such as columnar stacks, fibers, or hollow spheres result from the assembly of a large (often unpredictable) number of dendrons. To control the exact size and sometimes even shape of these polymeric aggregates is difficult. Discrete self-assembled dendrimers of specific size and shape have been obtained with the help of structurally well-defined templates that organize and assemble a given number of dendrons with complementary binding sites around themselves thus forming well-defined supramolecular aggregates. However, this templated assembly requires the synthesis of at least two different molecules, the dendron and the template, and the aggregation mode critically depends on their ratio. Direct and untemplated self-assembly of dendrons into well-defined, specific aggregates is much less explored. For example, the groups of Zimmermann or Reinhoudt reported different hexameric dendritic rosettes based on various types of H-bond mediated assembly, whereas supramolecular dendritic bow-ties were obtained by Frechet and Gillies from the assembly of two different dendrons using complementary charge interactions in combination with hydrogen bonds. However, these types of H-bonded supramolecular dendrimers are only stable in organic solvents such as chloroform but dissociate into monomers in more polar or protic solvents. In water, hydrophobic interactions can be used to self-assemble amphiphilic dendrons into micelles of defined size and shape as reported for example by Hirsch and co-workers. Another important advantage of self-assembled dendrimers in contrast to covalent ones is the possibility to trigger aggregate formation using external stimuli (e.g. solvent, pH, presence of metal ions). Self-assembly is based on reversible, noncovalent interactions that allow one to control under which circumstances the nanostructures are formed (or not formed). However, it is still a challenge to develop discrete, well-defined supramolecular dendrimers, which can be deliberately switched back and forth between monomer and self-assembled aggregate. In the last few years we have used the pH-dependent dimerization of a self-complementary guanidiniocarbonyl pyrrole carboxylate zwitterion to obtain different types of nanostructures such as vesicles or supramolecular polymers in aqueous solution. The stability of the aggregates is primarily based on the formation of H-bond induced ion pairs between two zwitterions and thus limited to a pH of about 5–8, respectively. In more acidic or basic solution the zwitterion is either protonated or deprotonated and accordingly the binding motif is not self-complementary anymore. Based on this dimerization behavior of the guanidiniocarbonyl pyrrole carboxylate zwitterion we now present here the first example of an untemplated self-assembly of two biocompatible polyglycerol dendrons into discrete well-defined supra[a] Dipl.-Chem. M. Merschky, Prof. Dr. C. Schmuck Lehrstuhl f r Organische Chemie 2, Fakult t f r Chemie Universit t Duisburg-Essen Universit tsstrasse 7, 45141 Essen (Germany) Fax: (+49) 201-183-4259 E-mail : carsten.schmuck@uni-due.de [b] Prof. Dr. R. Haag Institut f r Chemie und Biochemie Organische Chemie Freie Universit t Berlin Takustrasse 3, 14195 Berlin (Germany) [c] Dr. M. Wyszogrodzka Organische Chemie, Technische Universit t Dortmund Otto-Hahn-Strasse 6, 44225 Dortmund (Germany) Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.201002658.

Film formation of nonionic dendritic amphiphiles at the water surface.

This study focuses on the modular synthesis of a new class of nonionic dendritic amphiphiles and their behavior at the water-air interface. Our approach is based on a modular architecture consisting of two different generations of hydrophilic polyol dendrons connected to a two-chain hydrophobic block. Caused by different polarities of polyol and aliphatic groups, the molecules are surface-active and, by analogy to phospholipids, can form well-organized Langmuir monolayers at the water surface. The self-association process and phase behavior of these molecules with two different headgroup sizes were investigated by means of surface pressure and surface potential area isotherms by surface shear rheology and Brewster angle microscopy. With these techniques, we were able to observe marked differences in the phase behavior of the two molecular generations.