Crystalline and Soft Materials Based on Dative Boron-Nitrogen Bonds

The thesis describes the utilization of dative boron-nitrogen bond is used for the construction of new materials. In chapter 2.1, the synthesis of new organogels based on bisimidazolyl ligands and diboronate esters is described. Gels with a critical gel concentration as low as 0.02 wt% were obtained. The high tunability of the system allowed the development of a light-responsive gel by means of an azobenzene spacer. Structural characterization was performed by electron microscopy, rheology and X-ray analysis to better understand the aggregation of the polymer components. The association of imidazole and arylboronate esters is investigated with isothermal titration calorimetry and NMR titrations. It is shown that the association constant of imidazole is on average two orders of magnitude higher than the one of pyridyl analogues. In the second part of this chapter, the simultaneous utilization of boronate esters, imine bonds and dative boron-nitrogen bonds was exploited for the fabrication of a four-component organogel in one step. It is demonstrated that each reversible interaction can be addressed selectively by using an appropriate stimulus. In one case, the mechanical resistance of the gel could be significantly increased by a transesterification reaction between two catechols. The synthesis of self-complementary monomers for the formation of supramolecular polymers in solution is described in chapter 2.2. Analysis by DOSY NMR revealed the formation of large assemblies from monomers composed of two imidazolyl end groups and one boronate ester. In the last chapter, the directionality of the boron-nitrogen bond is explored through the de-sign and synthesis of two new tripyridyl ligands and their coordination to diboronate esters. The formation of crystalline polymers is studied by X-ray crystallography. For the first time, polymers composed of chains of macrocycles based on boron-nitrogen bond are observed.

Boron-Nitrogen Dative Bonds in Structural Supramolecular Chemistry

Erin Sheepwash

This work describes the use of boron-nitrogen dative bonds in supramolecular chemistry. Molecular tectons have been synthesized for crystal engineering. These tectons are linked via B-N dative bonds to form 1-dimensional polymers and macrocycles. B-N dative bonds were further used for the formation of crystalline organic networks by assembly of a tritopic boronate ester with ditopic N-donor ligands. These networks could be structurally characterized by single crystal X-ray diffraction to reveal 2-dimensional polymers. These structures were observed by PXRD to collapse upon removal of solvent. The reaction of a larger triboronate ester with 4,4'-bipyridine resulted in an organogel which formed with as little as 0.5 wt% of the network in toluene. The orange gel exhibited thermochromic properties, with a Tgel of 60 °C. Association constants for the formation of B-N dative bonds between dioxaborole and pyridyl ligands were examined by 1H NMR and ITC titrations. Ka values in excess of 106 M-1 can be obtained by varying the electronics of the reaction partners. The adducts have been characterized comprehensively by single crystal X-ray diffraction. Finally, the dative B-N bond was used for the synthesis of main-chain supramolecular polymers. Self-complementary monomers were synthesized containing a dialkylaminopyridine and a dioxaborole. These monomers assembled in chloroform to form polymers which were characterized by viscosity and DOSY NMR experiments.

EPFL2012

Multicomponent Assembly of Boronic Acid-Based Macrocycles, Cages, and Polymers

Burçak Içli

This work describes the synthesis and characterization of boronic acid-based supramolecular structures. Different reversible interactions such as boronate ester formation, imine condensation and dative B–N bond formation are used to assemble macrocycles, cages and polymers. Multicomponent condensation reactions of different diamines with tetraols and formylphenylboronic acids give macrocycles via formation of imine bonds and boronate esters. The [4+2+2] condensation products are generally preferred but larger macrocycles are observed for some combinations of staring materials. The larger macrocycles are in dynamic equilibrium with the smaller [4+2+2] products. Utilization of a triamine instead of the diamine results in the formation of molecular cages. The syntheses of these cages require the formation of 18 covalent bonds between 11 building blocks, and, interestingly, can be performed in a ball mill. Multicomponent reactions of diboronic acids, catechol derivatives, and different pyridyl ligands are described. The condensation of diboronic acids with catechols gives dioxaboroles. Upon crystallization, the ester aggregates with the N-donor ligands via dative B−N bonds. Depending on the nature of the pyridyl ligand, molecularly defined macrocycles, cages or polymeric structures are obtained. One-dimensional polymers are formed with 4,4-bipyridine and 1,2-di(4-pyridyl)ethylene, whereas a two-dimensional network is obtained with the tetradentate ligand tetra(4-pyridylphenyl)ethylene. A tripyridyl linker results in the formation trigonal prismatic cages. The size of the cages can be varied by changing the diboronic acid building block. The cages are able to encapsulate polyaromatic molecules such as triphenylene or coronene. The results highlight the potential of dative B−N bonds in structural supramolecular chemistry and crystal engineering.

EPFL2012

Chemistry and Analysis of Nanoparticle-Modified Living Cells

Tanja Thomsen

Conventional therapeutics are often limited by their targeting ability, resulting in harmful and potential fatal side-effects for the patients. Recently, new strategies have been developed to improve target specificity of drugs in order to generate more efficient therapeutics. An innovative concept, examined in this thesis, is the use of cells as therapeutic carriers. This concept termed cell-mediated drug delivery, relies on the intrinsic targeting properties of cells to transport the therapeutic drug to the target location. The conjugation of nanoparticles, loaded with drugs or adjuvants, to the surface of cells enables the transport to the desired location and increases the local drug concentration, reducing the required therapeutic leading to further attenuation of side effects. Chapter 1 introduces the concept of cell-mediated drug delivery. It highlights the advantages of using cells decorated with nanoparticles as carriers for therapeutics as opposed to free (polymer) nanoparticles. Examples of various covalent and non-covalent nanoparticle conjugations strategies are discussed and an overview of all approaches, which have been used previously to attach nanoparticles to the cell surface, is presented. The importance of a thorough in vitro characterization of nanoparticle-modified cells is emphasized. The use of common characterization techniques such as flow cytometry, UV-Vis and fluorescence spectroscopy, fluorescence and electron microscopy, and radiolabeling is discussed in detail and examples of qualitative and quantitative in vitro analysis of nanoparticle- modified cells are reviewed. Chapter 2 contains an extensive in vitro analysis of cell-nanoparticle conjugates using fluorescent- and fluorescent label-free methods. The stability of nanoparticles loaded with cargo attached to cells was investigated by encapsulating three different green fluorescent dyes into nanoparticles and tracking the fluorescence signal over 24 h. Two of the dyes revealed a complete loss of fluorescence of a time period of 24 h, whereas a third entrapped dye and a covalently attached dye did not have a decrease in fluorescence over 24 h. Finally, we developed a fluorescent label-free method as an alternative to characterize nanoparticle-decorated cells without the need for any fluorescent label. Chapter 3 systematically explores conjugation chemistries to immobilize two platforms of functional biodegradable polymer nanoparticles (PEG-PLA (poly(ethylene glycol) - poly(lactide)) nanoparticles and carboxylic PLA nanoparticles) on T cells as potential carrier across the blood-brain barrier (BBB). We compared a series of covalent and non-covalent immobilization strategies by flow cytometry (FACS), confocal microscopy, and impact on cell proliferation and cellular viability. We found that T-cell surface coupling of nanoparticles is dependent on the ratio of nanoparticles to cells and that higher ratios led to more particles attached to cells. Furthermore, the most efficient strategy to attach nanoparticles was via ligand-receptor interactions (lectin - sialic acid and biotin - NeutrAvidin). In addition, nanoparticle-decorated T cells were investigated for their ability to cross an in vitro mouse BBB model under static conditions in a two-chamber assay. Decorating the cells with nanoparticles does not affect their ability to bind ICAM-1 (a protein involved in the transmigration process) or to cross the model biological barrier.

EPFL2020

Chemistry and Analysis of Nanoparticle-Modified Living Cells

Tanja Thomsen

EPFL2020