Directed C–H activation has emerged as a major approach for developing synthetically useful reactions, owing to the proximity-induced reactivity and selectivity enabled by coordinating functional groups1–6. In contrast, development of palladium-catalyzed non-directed C–H activation has faced significant challenges associated with the lack of sufficiently active palladium catalysts7–8. Current palladium catalysts are only reactive with electron-rich arenes unless an excess of arene is used9–18, which limits synthetic applications. Herein, we disclose a 2-pyridone ligand that significantly enhances the reactivity of a palladium catalyst, allowing for Pd(II)-catalyzed non-directed C–H activation of a broad range of aromatic substrates using the various arenes as the limiting reagent. The significance of this finding is demonstrated by the direct functionalization of advanced synthetic intermediates, drug molecules, and natural products that cannot be utilized in excessive quantities. The potential of this methodology to be expanded to a variety of transformations is indicated by the development of both C–H olefination and C–H carboxylation protocols. Furthermore, the site selectivity in this transformation is governed by a combination of steric and electronic effects, with the pyridone ligand enhancing the influence of sterics on the selectivity, thus providing complementary selectivity to directed C–H functionalization.
Biomineralization offers an elegant example of how nature can design complex, hierarchical, and structurally/morphologically controllable materials. In this work, the surface of bioactive substrates prepared from poly(L‐lactic acid) and reinforced with Bioglass are modified by the graft polymerization of poly(N‐isopropylacrylamide), (PNIPAAm) after plasma activation. It is found that such treatment, together with temperature, could trigger the formation of apatite on the biodegradable substrate upon immersion in simulated body fluid above the PNIPAAm lower critical solution temperature (LCST); in contrast, no apatite is formed at room temperature. A control experiment on a material that is not subjected to surface treatment does not show any evidence of mineral deposition at the two analyzed temperatures. This “smart” biomineralization concept is combined with patterning methodologies to control the microstructure of the surface onto which PNIPAAm is grafted. In this case, the apatite is formed at 37 °C in the modified regions. We suggest that this concept could be extended in the biomimetic production of other minerals, where it would be triggered by another kind of stimulus (e.g., pH or ionic strength) in substrates with more complex geometries.
Chitosan coated alginate beads containing poly(N-isopropylacrylamide) (PNIPAAM), were prepared to be used as a controlled pH/temperature sensitive drug delivery system with improved encapsulation efficiency and delayed release rate. The studied beads were characterized by differential scanning calorimetry, scanning electron microscopy, and Fourier transform infrared spectroscopy. Water uptake and release studies using indomethacin as a model drug were also performed. The drug loading efficiency of the beads with the polyelectrolyte complex coating is significantly higher (84%) than that of the uncoated ones (74%). The equilibrium swelling of the developed materials was found to be pH- and thermo- responsive. For all the conditions it was found that the release profile was slower for the coated beads, indicating that the polyelectrolyte complex coating could slow down the release rate effectively. These results suggest that the studied smart system has potential to be used as an effective pH/temperature sustainable delivery system for biomedical applications.
A series of semi-interpenetrating, polymer network (semi-IPN), hydrogel beads, composed of calcium alginate (Ca-alginate) and poly(N-isopropylacrylamide) (PNIPAAM), were prepared for a pH/temperature-sensitive drug delivery study. The equilibrium swelling showed the independent pH- and thermo- responsive nature of the developed materials. At pH=2.1, the release amount of indomethacin incorporated into these beads was about 10% within 400 min, while this value approached to 95% at pH=7.4. The release rate of the drug was higher at 37 degrees C than that at 25 degrees C and increased slightly with increasing PNIPAAM content. These results suggest that the Ca-alginate/PNIPAAM beads have the potential to be used as an effective pH/temperature sustainable delivery system of bioactive agents. [GRAPHS: SEE TEXT] A summary of the temperature- and pH-dependence on the release of the drug over a period of 450 min. The effect of the temperature on the swelling of the beads is shown in the inset.
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