Aza-BODIPY Route to Ageladine A.

The marine natural product ageladine A was synthesized by exploiting novel aza-BODIPY-type boron complexes that allowed the regioselective dibromination of the pyrrole unit, as confirmed by quantum chemical calculation (ωB97XD/TApr-cc-pVDZ). The parent tricycle was accessed by Suzuki-Miyaura cross-coupling employing Buchwald's precatalyst. The boron complex of ageladine A exhibited strong fluorescence that was greater than that of the natural product by a factor of ∼30 and that disappeared in the presence of 2-azido groups.

Biocompatible Coatings from Smart Biopolymer Nanoparticles for Enzymatically Induced Drug Release.

Nanoparticles can be used as a smart drug delivery system, when they release the drug only upon degradation by specific enzymes. A method to create such responsive materials is the formation of hydrogel nanoparticles, which have enzymatically degradable crosslinkers. Such hydrogel nanoparticles were prepared by ionotropic gelation sodium alginate with lysine-rich peptide sequences-either α-poly-L-lysine (PLL) or the aggrecanase-labile sequence KKKK-GRD-ARGSV↓NITEGE-DRG-KKKK. The nanoparticle suspensions obtained were analyzed by means of dynamic light scattering and nanoparticle tracking analysis. Degradation experiments carried out with the nanoparticles in suspension revealed enzyme-induced lability. Drugs present in the polymer solution during the ionotropic gelation can be encapsulated in the nanoparticles. Drug loading was investigated for interferon-ß (IFN-ß) as a model, using a bioluminescence assay with MX2Luc2 cells. The encapsulation efficiency for IFN-ß was found to be approximately 25%. The nanoparticles suspension can be used to spray-coat titanium alloys (Ti-6Al-4V) as a common implant material. The coatings were proven by ellipsometry, reflection-absorption infrared spectroscopy, and X-ray photoelectron spectroscopy. An enzyme-responsive decrease in layer thickness is observed due to the degradation of the coatings. The Alg/peptide coatings were cytocompatible for human gingival fibroblasts (HGFIB), which was investigated by CellTiterBlue and lactate dehydrogenase (LDH) assay. However, HGFIBs showed poor adhesion and proliferation on the Alg/peptide coatings, but these could be improved by modification of the alginate with a RGD-peptide sequence. The smart drug release system presented can be further tailored to have the right release kinetics and cell adhesion properties.