Terpolymerizations of (rac)-β-butyrolactone (BBL), cyclohexene oxide (CHO), and carbon dioxide were realized in one-pot reactions utilizing a Lewis acid BDI-Zn-N(SiMe) (1) catalyst. The type of polymerization can be regulated and switched between ring-opening polymerization (ROP) of BBL and CHO/CO copolymerization by the presence of CO in the reaction mixture. Applying 3 bar CO to the three-component system leads to similar reaction rates for copolymerization and ROP and therefore to a terpolymer with a statistical composition, whereas 40 bar CO affords exclusive copolymerization of CHO/CO. Two-dimensional NMR spectroscopy and polarimetry provided a deeper understanding of the underlying mechanism. Furthermore, copolymerization of cyclopentene oxide (CPO) and CO was performed, resulting in the highest reported TOF of 3200 h together with 99% polycarbonate selectivity. Terpolymerizations of CPO/CO and BBL were successfully conducted using the established reaction pathways.
The blood–brain barrier (BBB) is composed of brain endothelial cells, pericytes, and astrocytes, which build a tight cellular barrier. Therapeutic (macro)molecules are not able to transit through the BBB in their free form. This limitation is bypassed by apolipoprotein E (ApoE)‐functionalized polymeric nanoparticles (NPs) that are able to transport drugs (e.g., dalargin, loperamide, doxorubicin, and nerve growth factor) across the BBB via low density lipoprotein (LDL) receptor‐mediated transcytosis. Coating with polysorbate 80 or poloxamer 188 facilitates ApoE adsorption onto polymeric NPs enabling recognition by LDL receptors of brain endothelial cells. This effect is even enhanced when NPs are directly coated with ApoE without surfactant anchor. Similarly, covalent coupling of ApoE to NPs that bear reactive groups on their surface leads to significantly improved brain uptake while avoiding the use of surfactants. In this Progress Report several in vitro BBB models using brain endothelial cells or cocultures with astrocytes/pericytes/glioma cells are described, which provide insights regarding the ability of a drug delivery system to cross this barrier. In vivo models are described which simulate central nervous system‐relevant diseases such as Alzheimer's or Parkinson's disease and cerebral cancer.
Herein, we present a fundamental study of isostructural 2-methoxyethylamino-bis(phenolate)-lanthanide complexes [(ONOO)M(X)(THF)] (M = Lu, Y; R = Bu, CMePh, X = CHTMS, collidine; THF = tetrahydrofuran; TMS = trimethylsilyl) for rare-earth metal-mediated group-transfer polymerization (GTP). This analysis includes the differentiation of electron-donating and nondonating vinyl monomers and two metal centers with regard to the ionic radius (yttrium and lutetium). In addition, highly nucleophilic alkyl initiators are compared with electron-donating heteroaromatic initiators. Our examinations include the impact of these parameters on the activity, initiator efficiency, and tacticity of the obtained polymers. Density functional theory calculations and proposed catalyst structure determinations via X-ray analysis support these investigations. This facilitates the selection of the best metal and initiator combination to address efficient and stereospecific polymerization of a broad range of Michael monomers. [(ONOO)Lu(X)(THF)] shows the highest activity of 2220 h (normalized turnover frequency) for the polymerization of 2-vinylpyridine due to the higher Lewis-acidity of lutetium. Through C(sp)-H bond activation, catalysts with higher initiator efficiency in N,N'-dimethylacrylamide (DMAA) and diethylvinylphosphonate polymerization were synthesized. Remarkably, [(ONOO)Y(collidine)(THF)] was capable of stereospecifically polymerizing DMAA to highly isotactic poly(DMAA) (P = 0.94). Overall, the kinetics studies reveal a living-type GTP mechanism for all of the tested catalysts, enabling precise molecular-weight predeterminations with narrow molecular weight distributions (Đ ≤ 1.06).
2-Methoxyethylamino-bis(phenolate)-yttrium complexes were employed in the catalytic precision polymerization of 2-vinylpyridine (2VP). The C 1 -symmetric catalyst systems are able to isospecifically polymerize prochiral 2-vinylpyridine with moderate to high activities. Tacticities ranging from atactic to isotactic can be achieved (P m = 0.54-0.74). Mechanistic studies through 13 C NMR microstructure analysis of the resulting isotactic P2VP show an enantiomorphic site control mechanism.
C-H bond activation of 2-methoxyethylamino-bis(phenolate)-yttrium catalysts allowed the synthesis of BAB block copolymers comprised of 2-vinylpyridine (2VP; monomer A) and diethylvinylphosphonate (DEVP; monomer B) as the A and B blocks, respectively, by rare-earth-metal-mediated group-transfer polymerization (REM-GTP). The inherent multi-stimuli-responsive character and drug-loading and -release capabilities were observed to be dependent on the chain length and monomer ratios. Cytotoxicity assays revealed the biocompatibility and nontoxic nature of the obtained micelles toward ovarian cancer (HeLa) cells. The BAB block copolymers effectively encapsulated, transported, and released doxorubicin (DOX) within HeLa cells. REM-GTP enables access to previously unattainable vinylphosphonate copolymer structures, and thereby unlocks their full potential as nanocarriers for stimuli-responsive drug delivery in HeLa cells. The self-evident consequence is the application of these new micelles as potent drug-delivery vehicles with reduced side effects in future cancer therapies.
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