Cooperative effects on functionalised vesicles

were examined and successfully applied to enhance the aqueous hydrolysis of active esters and the upconversion of light. In addition, a fast screening technique for visible light photocatalysis reactions was developed. Chapter 1 briefly introduces into the topic of functionalised vesicles and explains the design of the projects in this thesis spanning from cooperative effects on functionalised vesicles to the development of a screening technique. Chapter 2 presents the concept of cooperative hydrolysis on the surface of membranes. Hydrolytic activity is provided by vesicles functionalised with an amphiphilic zinc complex, which acts as a Lewis acid and is able to hydrolyse aryl esters. We showed that co-embedding of different membrane additives into the surface of the vesicles increases the hydrolytic rate up to 16-fold. We examined different lipids and observed the highest cooperative enhancement of hydrolysis in fluid DOPC membranes. Mechanistic studies suggested that in such fluid membranes the reactions follow a Michaelis-Menten saturation kinetic, while in rigid DSPC vesicles second order kinetics are observed. Chapter 3 shows that, not only catalytic activity of functionalised vesicles can be enhanced using membrane additives, but also the selectivity. By co-embedding of an amphiphilic nonchiral hydrolysis catalyst with amphiphilic chiral additives into the membrane of a phospholipid vesicle we were able to introduce enantioselectivity to a non-chiral catalyst. This was shown for enantiomerically pure amino acid esters, which in the presence of an appropriate chiral additive show a twofold enhancement of the hydrolysis rate of one enantiomer. In Chapter 4 we tried to simplify the concept of functionalised vesicles for hydrolysis and instead of using custom made amphiphilic metal complexes we examined the direct adsorption of lanthanide ions onto the surface of the vesicles. We show that their interaction with vesicles prepared from zwitterionic phosphatidylcholine lipids provides soft particles with surface functionalised with lanthanide ions. This was confirmed via sensitisation of europium ions by pyrene that was co-embedded inside the phospholipid bilayer. Such assembly provides a high density of Lewis-acidic metal centres, which hydrolyse phosphodiesters 17 times faster compared to homogeneous aqueous lanthanide solutions. Chapter 5 is a study on triplet-triplet annihilation upconversion process in vesicles. We show that such light upconverting soft particles can be made on the basis of fluid DOPC vesicles in aqueous media. This process consists of the interaction between two sets of dyes (sensitizer and annihilator). We studied the effect of their position in the membrane on the upconversion efficiency: High local concentration of the dyes in the membrane increases the intensity of the detected delayed fluorescence. This was observed whether the dyes were on the surface of the bilayer or inside. Crucial for the upconversion to take place in vesicles is the fluidity of the membrane. In rigid membranes no upconversion is observed. In Chapter 6 we developed a high throughput screening technique for photocatalytic transformations using known indicators and microtiter plate instrumentation. Photocatalytic reactions often produce beside the desired products a stoichiometric by-product, such as reactive oxygen species or acids. These can be easily detected by an indicator allowing to perform 96 reactions at once and evaluate the reaction conversion by addition of the indicator measuring its absorbance. The concept is able to reproduce reported reaction results and correlates well with GC analysis. We used this system for identifying two new catalysts for the hydroxylation of boronic acids. We successfully employed the technique for photochemical reductions, monitoring the formation of aryl radicals from aryl halides. To confirm the robustness of the method for different substrates we screened various drugs bearing an aryl halide moiety and identified two new dehalogenation reactions

Fast colorimetric screening for visible light photocatalytic oxidation and reduction reactions

Fast screening accelerates the discovery and optimization of chemical reactions. Here, we present the parallel irradiation and evaluation of 96 visible light photocatalytic reactions in a microtiter plate. After completion, a chemical indicator is added, allowing the spectroscopic determination of the formed stoichiometric by-products. Their quantity correlates in many cases with the conversion of starting materials and yield of photochemical reaction products. We demonstrate the concept with known photooxidations of organic compounds by riboflavin tetraacetate (RFTA) and reproduce published results and gas chromatographic analyses by a colorimetric assay. Two new photocatalysts for the hydroxylation of boronic acids and new substrates for the photocatalytic generation of aryl radicals from aryl halides were identified. By screening a series of drug molecules containing aryl halides, new photochemical dehalogenation reactions were found. The presented methods enable laboratories lacking sophisticated high-throughput analytical instrumentation to perform parallel optimization and scope determination of photocatalytic oxidation and reduction reactions

Enantioselective ester hydrolysis by an achiral catalyst co-embedded with chiral amphiphiles into a vesicle membrane

Co-embedding of an amphiphilic non-chiral hydrolysis catalyst with amphiphilic chiral additives into the membrane of a phospholipid vesicle induces different rates of ester hydrolysis for enantiomeric amino acid esters

The interface makes a difference: lanthanide ion coated vesicles hydrolyze phosphodiesters

Lanthanide ions are strong Lewis acids. Their complexation to a variety of ligands can further enhance their Lewis acidity allowing the hydrolysis of phosphoesters and even DNA. We show that the interaction of lanthanide ions with vesicles from zwitterionic phosphatidylcholine lipids gives supramolecular structures in which the metal ion is loosely coordinated to the surface. This assembly provides a high density of Lewis-acidic metal centres, which hydrolyze phosphodiesters with enhanced rates

Light Upconverting soft particles: Triplet-triplet annihilation in the phospholipid bilayer of self-assembled vesicles

Large unilamellar vesicles (100 nm) were functionalised to obtain supramolecular particles capable of light upconversion in pure aqueous media. Triplet-triplet annihilation of diphenylanthracene (DPA) leading to delayed fluorescence at 420 nm was used to up-convert the light absorbed by embedded metal complex sensitisers. The lipid type and the chromophore position in the membrane affect the TTA intensity, which remains constant over a large concentration range

Transition-Metal-Free Radical C(sp³)–C(sp²) and C(sp³)–C(sp³) Coupling Enabled by 2‑Azaallyls as Super-Electron-Donors and Coupling-Partners

The past decade has witnessed the rapid development of radical generation strategies and their applications in C–C bond-forming reactions. Most of these processes require initiators, transition metal catalysts, or organometallic reagents. Herein, we report the discovery of a simple organic system (2-azaallyl anions) that enables radical coupling reactions under transition-metal-free conditions. Deprotonation of <i>N</i>-benzyl ketimines generates semistabilized 2-azaallyl anions that behave as “super-electron-donors” (SEDs) and reduce aryl iodides and alkyl halides to aryl and alkyl radicals. The SET process converts the 2-azaallyl anions into persistent 2-azaallyl radicals, which capture the aryl and alkyl radicals to form C–C bonds. The radical coupling of aryl and alkyl radicals with 2-azaallyl radicals makes possible the synthesis of functionalized amine derivatives without the use of exogenous radical initiators or transition metal catalysts. Radical clock studies and 2-azaallyl anion coupling studies provide mechanistic insight for this unique reactivity