Current treatment strategies for Glioblastoma (GBM)-including surgery, radiotherapy, and chemotherapy with oral administration of temozolomide (TMZ)-still lead to poor survival rates, making the development of more effective therapeutic methods an urgent need. This study presents a new approach for the treatment of GBM patients using a 3D-printed hydrogel-based mesh (GlioMesh), loaded with TMZ-releasing microparticles, that is capable of delivering TMZ over several weeks at the tumor site. Given the challenges associated with loading the amphiphilic TMZ in polymeric substrates, a novel encapsulation strategy is developed using an oil-in-oil emulsion method that improves the encapsulation efficiencies of TMZ in poly(lactic-co-glycolic acid) (PLGA) from <7% to about 61%. The cytotoxic effects of GlioMesh on GBM cells are evaluated in vitro by investigating the resultant levels of DNA break, autophagic activity, and mitochondrial damage. It is shown that GlioMesh produces significantly higher susceptibility to the drug in comparison with free TMZ by maintaining the level of autophagic activity and inducing larger degrees of mitochondrial damage. Sustained delivery of TMZ holds promise for suppressing chemoresistance to TMZ that is normally developed in GBM cells in systemic administration of the drug due to the induction of autophagy.

We report a direct tandem C−O/C−H activation approach to C−C bond formation using palladium catalysis. This reaction combines C−O oxidative addition at enol pivalates with concerted metalation−deprotonation of functionalized heterocycles to achieve base-free direct C−H alkenylation. Preliminary mechanistic studies revealed that the C−O oxidative addition to Pd(0) is reversible under these conditions and that C−H activation occurs directly from the Pd(II) C−O oxidative addition product. In situ 31 P NMR spectroscopy further revealed that the (Cy 3 P) 2 Pd-(alkenyl)(OPiv) species is a major catalyst resting state during the reactions.

Synthesis of organoboron derivatives is a key application of catalytic cross-coupling, with the Pd-catalyzed Miyaura borylation among the most versatile methods available. We have evaluated several Pd-based systems for borylation...

A stepwise build-up of multi-substituted Csp3 carbon centers is an attractive, conceptually simple, but often synthetically challenging type of disconnection. To this end, this report describes how gem-α,α-dimetalloid-substituted benzylic reagents...

Synthesis of organoboron derivatives is a key application of catalytic cross-coupling, with the Pd-catalyzed Miyaura borylation among the most versatile methods available. We have evaluated several Pd-based systems for borylation of alkenyl acetates and pivalates, with the optimal system heavily dependant on the substrate structure.

Synthesis of organoboron derivatives is a key application of catalytic cross-coupling, with the Pd-catalyzed Miyaura borylation among the most versatile methods available. We have evaluated several Pd-based systems for borylation of alkenyl acetates and pivalates, with the optimal system heavily dependant on the substrate structure.

In article 1900113 Mohsen Akbari and co‐workers develop a hydrogel‐based mesh containing temozolomide‐loaded poly(lactic‐co‐glycolic acid) microspheres with high encapsulation efficiency (GlioMesh) that can release anticancer drugs directly at a tumor site. GlioMesh can conform to the irregular structure of brain tissue because of its flexibility and release drugs for up to two months.

The use of oxygen-based electrophiles in cross-coupling remains challenging for substrates with strong C–O bonds, with few examples that can combine C–O activation with an-other strong-bond activation in tandem. We report the first example of a direct, tandem C–O/C–H activation approach to C–C bond formation using palladium catalysis. This reaction combines C–O oxidative addition at enol pivalates with con-certed metallation deprotonation of functionalized heterocycles to achieve base-free direct C–H alkenylation, with pivalic acid as the only byproduct. Mechanistic studies reveal that the Pd(II) C–O oxidative addition product is the major catalyst resting state, indicating that C–H activation is the turnover-limiting step.