A DNase-mimetic artificial enzyme for the eradication of drug-resistant bacterial biofilm infections.

The construction of multifunctional nano-enzymes is a feasible strategy for fighting multi-drug resistant (MDR) bacterial biofilm-associated infections. Extracellular DNA (eDNA) is an important functional part of biofilm formation, including the initial adherence of bacteria to subsequent development and eventual maturation. A nano-enzyme platform of graphene oxide-based nitrilotriacetic acid-cerium(IV) composite (GO-NTA-Ce) against bacterial biofilm infection has been developed. When located at the site of bacteria-associated infection, GO-NTA-Ce could inhibit the biofilm formation and effectively disperse the formed biofilm by degrading the eDNA. In addition to Ce-mediated deoxyribonuclease (DNase)-like activity, near-infrared laser irradiation of GO-NTA-Ce could produce local hyperthermia to kill the bacteria that lost the protection by the biofilm matrix. In addition, graphene is also a new green broad-spectrum antimicrobial material that can exert its antimicrobial effects through physical damage and chemical damage. In short, our GO-NTA-Ce nano-enzyme platform is capable of effectively eradicating drug-resistant bacterial biofilm infections through the triple action of DNase-like enzyme properties, photothermal therapy, and graphene-based antimicrobial activity, and the nano-composite has excellent potential for the treatment of MDR bacterial biofilm infections.

Unlocking the full potential of lipid-based formulations using lipophilic salt/ionic liquid forms.

Lipid-based formulations (LBF) are widely used by industry and accepted by the regulatory authorities for oral drug delivery in the pharmaceutical and consumer healthcare market. Innovation in the LBF field is however needed in order to meet the demands of modern drugs, their more challenging problem statements and growing needs for achieving optimal pharmacokinetics (i.e., no food-effects, low variability) on approval. This review describes a new lipophilic salt / ionic liquid approach in combination with LBF, and how this salt strategy can be used to better tailor the properties of a drug to LBFs. The potential advantages of lipophilic salts are discussed in the context of dose escalation studies during toxicological evaluation, reducing the pill burden, increasing drug absorption of new drugs and in life-cycle management. Commentary on lipophilic salt synthesis, scale-up, LBF design and the regulatory aspects are also provided. These topics are discussed in the broad context of bringing the widely recognized advantages of LBFs to a broader spectrum of drugs.

Asymmetric Total Synthesis of Propindilactone†G, Part†1: Initial Attempts towards the Synthesis of Schiartanes.

Our first-generation synthetic study towards the total synthesis of propindilactone G (1) and its analogues is reported. The key synthetic steps were an intramolecular Pauson-Khand reaction (PKR) and a vinylogous Mukaiyama reaction (VMAR). The stereoselective synthesis of the CDE ring moiety with an all-carbon quaternary center through a PKR was difficult, whilst a VMAR afforded a product with the opposite stereochemistry at the C20 position on the side chain. These results led us to redesign our synthetic strategy for the total synthesis of compound 1.

Total synthesis of (±)-decinine via an oxidative biaryl coupling with defined axial chirality.

The total synthesis of (±)-decinine has been achieved. The key steps in the synthesis involved the formation of lasubine II via a gold catalyzed annulation of 1-(but-3-yn-1-yl)piperidine and the formation of the 12-membered ring of decinine (1) with complementary atropselectivity via a VOF3-mediated oxidative biaryl coupling reaction.