Chiral and enantiopure perfluorinated sulfonimidamides act as low-molecular weight gelators at low critical gelation concentration (<1 mg mL-1) via supramolecular polymerization in nonpolar organic solvents and more heterogenic mixtures, such as biodiesel and oil. Freeze-drying of the organogel leads to ultralight aerogel with extremely low density (1 mg mL-1). The gelation is driven by hydrogen bonding resulting in a helical molecular ordering and unique fibre assemblies as confirmed by scanning electron microscopy, CD spectroscopy, and computational modeling of the supramolecular structure.

Nickel boride catalyst prepared in situ from NiCl2 and sodium borohydride allowed, in the presence of an aqueous solution of TEMPO-oxidized nanocellulose (0.01 wt%), the reduction of a wide range of nitroarenes and aliphatic nitro compounds. Here we describe how the modified nanocellulose has a stabilizing effect on the catalyst that enables low loading of the nickel salt pre-catalyst. Ni-B prepared in situ from a methanolic solution was also used to develop a greener and facile reduction of azides, offering a substantially lowered catalyst loading with respect to reported methods in the literature. Both aromatic and aliphatic azides were reduced and the protocol is compatible with a one-pot Boc-protection of the obtained amine yielding the corresponding carbamates. Finally, bacterial crystalline nanocellulose was chosen as a support for the Ni-B catalyst to allow an easy recovery step of the catalyst and its recyclability for new reduction cycles.

Sulfonimidamides (SIAs) and sulfoximines (SOIs) have attracted attention due to their potential in agriculture and in medicinal chemistry as bioisosteres of biologically active compounds, and new synthetic methods are needed to access and explore these compounds. Herein, we present a light-promoted generation of perfluorinated aromatic nitrenes, from perfluorinated azides, that subsequently are allowed to react with sulfinamides and sulfoxides, generating achiral and chiral SIAs and SOIs. One of the enantiopure SIAs was evaluated as a novel chiral auxiliary in Grignard additions to the imines yielding the product in up to 96:4 diastereomeric ratio.

The work presented in this thesis stems from the chemistry of the azido group, and more specifically from the unique reactivity of perfluorinated aromatic azides and how to use this reactivity to access new types of molecules to enable new applications in asymmetric synthesis and materials.

In the first section of this thesis, a photoactivatable fluorescence probe is presented, where the non-luminescent azide was activated via a UV-light-promoted intramolecular N–H insertion reaction forming a fluorescence emitter. Furthermore, ciprofloxacin was reacted with perfluorinated aromatic azide (PFAA) and phenylacetaldehyde, to form a drug derivative with a propeller-shaped architecture. The drug derivatization enabled the self-aggregation of the molecules into nanoparticles and the consequent aggregation-induced fluorescence emission (AIE). 

The second section of the thesis focuses on the development of a reaction between the photogenerated perfluorinated phenylnitrene and sulfoxides or sulfinamides to obtain sulfoximines and sulfonimidamides. One of these compounds, an enantiopure sulfonimidamide with an unprotected amino group, was employed as a novel chiral auxiliary for the synthesis of an enantioenriched amine via addition of Grignard reagents to the formed imines. In addition to the use as chiral auxiliary, the same sulfonimidamide containing a pyridine group was studied as an organogelator. The supramolecular aggregation led to the formation of the gel, which showed a microscopic chirality controlled by the stereocenter of the sulfur atom in the low-molecular weight gelator molecule. 

The last section illustrates a general method for the reduction of aromatic and aliphatic azides. The reduction is catalyzed by a nickel boride (Ni-B) catalyst that is prepared in situ from a Ni(II) salt and sodium borohydride in methanol allowing catalyst loading as low as 0.5 mol%. Moreover, bacterial nanocellulose (BNC) was used as solid support for the Ni-B catalyst enabling easy recovery of the catalyst and recyclability.

Arbetet som presenteras i denna avhandling härrör från reaktiviteten hos azidogruppen, som uppvisar en unik reaktivitet som inte återfinns i naturen vilket gör att azidgruppen kan användas i bioortogonala reaktioner. I det första avsnittet av denna avhandling presenteras en molekyl som innehålleren azid-grupp som kan aktiveras med ljus för att avge fluorescens. Aziden är ej luminescerande, men vid belysning med UV-ljus initieras en intramolekylärreaktion och omvandlades följaktligen till en fluorescerande molekyl. I ett annat projekt, reagerades ciprofloxacin med perfluorerad aromatisk azid (PFAA) och fenylacetaldehyd för att bilda ett läkemedelsderivat med en propellerformad arkitektur. Derivatiseringen möjliggjorde en självaggregation av molekylerna i nanopartiklar vilket ledde till en så kallad aggregeringsinducerad fluorescensemission (AIE).

I avhandlingens andra avsnitt beskrivs reaktionen mellan ljusgenererade perfluorerade fenylnitrener och sulfoxider eller sulfinamider för att syntetisera sulfoximiner och sulfonimidamider. En av de enantiomert rena sulfonimidamiderna med en oskyddad aminogrupp användes som en ny kiral hjälpgrupp för syntesen av en enantiomert ren amin. Vidare användes en av de kirala sulfonimidamiderna som en organogelator. Den supramolekylära aggregeringen som ledde till bildandet av gelen, visade en mikroskopisk kiralitet styrd av stereorienteringen av det kirala centret på svavelatomen i gelatormolekylen.

I det sista avsnittet presenteras en metod för reduktion av aromatiska och alifatiska azider. Reduktionen katalyseras av nickelborid framställd från ettNi(II)-salt och natriumborhydrid i metanol och fungerade låg mängd katalysator(0,5 mol%). Dessutom användes bakteriell nanocellulosa (BNC) som fast stödför Ni-B-katalysatorn vilket möjliggjorde enkel återvinning av katalysatorn och dess återvinningsbarhet.

Molecules, capable of fluorescence turn-on by light, are highly sought-after in spatio-temporal labeling, surface patterning, monitoring cellular and molecular events, and high-resolution fluorescence imaging. In this work, we report a fluorescence turn-on system based on photoinitiated intramolecular C-H insertion of azide into the neighboring aromatic ring. The azide-masked fluorogens were efficiently synthesized via a cascade nucleophilic aromatic substitution of perfluoroaryl azides with carbazoles. The scaffold also allows for derivatization with biological ligands, as exemplified with D-mannose in this study. This photoinitiated intramolecular transformation led to high yields, high photo-conversion efficiency, and well-separated wavelengths for photoactivation and fluorescence excitation. The mannose-derivatized structure enabled spatio-temporal activation and showed high contrast and signal amplification. Live cell imaging suggested that the mannose-tagged fluorogen was transported to the lysosomes.

We report the modular formulation of ciprofloxacin-based pure theranostic nanodrugs that display enhanced antibacterial activities, as well as aggregation-induced emission (AIE) enhancement that was successfully used to image bacteria. The drug derivatives, consisting of ciprofloxacin, a perfluoroaryl ring, and a phenyl ring linked by an amidine bond, were efficiently synthesized by a straightforward protocol from a perfluoroaryl azide, ciprofloxacin, and an aldehyde in acetone at room temperature. These compounds are propeller-shaped, and upon precipitation into water, readily assembled into stable nanoaggregates that transformed ciprofloxacin derivatives into AIE-active luminogens. The nanoaggregates displayed increased luminescence and were successfully used to image bacteria. In addition, these nanodrugs showed enhanced antibacterial activities, lowering the minimum inhibitory concentration (MIC) by more than one order of magnitude against both sensitive and resistant Escherichia coli. The study represents a strategy in the design and development of pure theranostic nanodrugs for combating drug-resistant bacterial infections.

A new conjugation method for the immobilization of carbohydrates on nanomaterials was demonstrated simply by mixing perfluorophenyl azide-functionalized silica nanoparticles (SNPs), an amine-derivatized carbohydrate, and phenylacetaldehyde under ambient conditions without any catalyst. The density of carbohydrates on the glyconanoparticles was determined using the quantitative F-19 NMR (F-19 qNMR) technique; for example, the density of D-mannose (Man) on Man-SNPs was 2.5 +/- 0.2 x 10(-16) nmol/nm(2). The glyconanoparticles retained their binding affinity and selectivity toward cognate lectins. The apparent dissociation constant of the glyconanoparticles was measured by a fluorescence competition assay, where the binding affinity of Man-SNPs was almost 4 orders of magnitude higher than that of Man with concanavalin A. Moreover, even with a ligand density of 2.6 times lower than Man-SNPs synthesized by the copper catalyzed azide-alkyne cycloaddition, the binding affinity of Man-SNPs prepared by the current method was more than 4 times higher.

We report on a supramolecular polymerization by a novelorganogelators, (S)-SIA and (R)-SIA, based on a chiral,perfluorinated sulfonimidamide that gelates in nonpolar organicsolvents. The gelating ability is driven by the supramolecularordering of fibres as confirmed by SEM-microscopy and CDspectroscopy