Rigid Multidimensional Alkoxyamines: A Versatile Building Block Library

Since the discovery of the “living” free‐radical polymerization, alkoxyamines were widely used in nitroxide‐mediated polymerization (NMP). Most of the known alkoxyamines bear just one functionality with only a few exceptions bearing two or more alkoxyamine units. Herein, we present a library of novel multidimensional alkoxyamines based on commercially available, rigid, aromatic core structures. A versatile approach allows the introduction of different sidechains which have an impact on the steric hindrance and dissociation behavior of the alkoxyamines. The reaction to the alkoxyamines was optimized by implementing a mild and reliable procedure to give all target compounds in high yields. Utilization of biphenyl, p‐terphenyl, 1,3,5‐triphenylbenzene, tetraphenylethylene, and tetraphenyl‐methane results in linear, trigonal, square planar, and tetrahedral shaped alkoxyamines. These building blocks are useful initiators for multifold NMP leading to star‐shaped polymers or as a linker for the nitroxide exchange reaction (NER), to obtain dynamic frameworks with a tunable crosslinking degree and self‐healing abilities

Dynamic porous organic polymers with tuneable crosslinking degree and porosity

Porous organic polymers (POPs) show enormous potential for applications in separation, organic electronics, and biomedicine due to the combination of high porosity, high stability, and ease of functionalisation. However, POPs are usually insoluble and amorphous materials making it very challenging to obtain structural information. Additionally, important parameters such as the exact molecular structure or the crosslinking degree are largely unknown, despite their importance for the final properties of the system. In this work, we introduced the reversible multi-fold nitroxide exchange reaction to the synthesis of POPs to tune and at the same time follow the crosslinking degree in porous polymer materials. We synthesised three different POPs based on the combination of linear, trigonal, and tetrahedral alkoxyamines with a tetrahedral nitroxide. We could show that modulating the equilibrium in the nitroxide exchange reaction, by adding or removing one nitroxide species, leads to changes in the crosslinking degree. Being able to modulate the crosslinking degree in POPs allowed us to investigate both the influence of the crosslinking degree and the structure of the molecular components on the porosity. The crosslinking degree of the frameworks was characterised using EPR spectroscopy and the porosity was determined using argon gas adsorption measurements. To guide the design of POPs for desired applications, our study reveals that multiple factors need to be considered such as the structure of the molecular building blocks, the synthetic conditions, and the crosslinking degree

Transcriptomic analysis identifies lactoferrin-induced quiescent circuits in neonatal macrophages

IntroductionUpon birth, a hitherto naïve immune system is confronted with a plethora of microbial antigens due to intestinal bacterial colonization. To prevent excessive inflammation and disruption of the epithelial barrier, physiological mechanisms must promote immune-anergy within the neonatal gut. As high concentrations of human lactoferrin (hLF), a transferrin glycoprotein shown to modulate macrophage function, are frequently encountered in colostrum, its direct interaction with intestinal macrophages may satisfy this physiological need. Thus, the primary objective of this study was to investigate transcriptional changes induced by human lactoferrin in neonatal monocyte-derived macrophages.MethodsCord blood-derived monocytes were differentiated with M-CSF in presence or absence of 500 µg/mL hLF for 7 days and afterwards stimulated with 1 ng/mL LPS or left untreated. RNA was then isolated and subjected to microarray analysis.ResultsDifferentiation of cord blood-derived monocytes in presence of hLF induced a distinct transcriptional program defined by cell cycle arrest in the G2/M phase, induction of IL-4/IL-13-like signaling, altered extracellular matrix interaction, and enhanced propensity for cell-cell interaction. Moreover, near-complete abrogation of transcriptional changes induced by TLR4 engagement with LPS was observed in hLF-treated samples.DiscussionThe global transition towards an M2-like homeostatic phenotype and the acquisition of quiescence elegantly demonstrate the ontogenetical relevance of hLF in attenuating pro-inflammatory signaling within the developing neonatal intestine. The marked anergy towards proinflammatory stimuli such as LPS further underlines the glycoprotein’s potential therapeutic relevance

Effects of Human Lactoferrin on Neonatal and Adult Monocyte-to-Macrophage Differentiation and Macrophage Activation

vorgelegt von: Isabelle Sharon WesselyMasterarbeit Wien, FH Campus Wien 201

Dynamic porous organic polymers with tuneable crosslinking degree and porosity

We synthesised three different POPs via a nitroxide exchange reaction and modulated their crosslinking degree. That allowed us to investigate the influence of the crosslinking degree and the structure of the molecular components on the porosity.</jats:p

Dynamic Surface Modification of Metal–Organic Framework Nanoparticles via Alkoxyamine Functional Groups

External surface engineering of metal–organic framework nanoparticles (MOF NPs) is emerging as an important design strategy, leading to optimized chemical and colloidal stability. To date, most of the MOF surface modifications have been performed either by physical adsorption or chemical association of small molecules or (preformed) polymers. However, most of the currently employed approaches cannot precisely control the polymer density, and dynamic modifications at the surfaces on demand have been a challenging task. Here, we introduce a general approach based on covalent modification employing alkoxyamines as a versatile tool to modify the outer surface of MOF nanoparticles (NPs). The alkoxyamines serve as initiators to grow polymers from the MOF surface via nitroxide-mediated polymerization (NMP) and allow dynamic attachment of small molecules via a nitroxide exchange reaction (NER). The successful surface modification and successive surface polymerization are confirmed via time-of-flight secondary ion mass spectrometry (ToF-SIMS), size exclusion chromatography (SEC), and nuclear magnetic resonance (NMR) spectroscopy. The functionalized MOF NPs exhibit high suspension stability and good dispersibility while retaining their chemical integrity and crystalline structure. In addition, electron paramagnetic resonance spectroscopy (EPR) studies prove the dynamic exchange of two different nitroxide species via NER and further allow us to quantify the surface modification with high sensitivity. Our results demonstrate that alkoxyamines serve as a versatile tool to dynamically modify the surface of MOF NPs with high precision, allowing us to tailor their properties for a wide range of potential applications, such as drug delivery or mixed matrix membranes