Electrokinetics in antimicrobial resistance analysis: A review

Infections caused by antimicrobial resistance are a serious problem in the world. Currently, commercial devices for antimicrobial susceptibility testing and resistant bacteria identification are time-consuming. There is an urgent need to develop fast and accurate methods, especially in the process of sample pretreatment. Electrokinetic (EK) is a family of electric-field-based kinetic phenomena of fluid or embedded objects, and EK applications have been found in various fields. In this paper, EK bacteria manipulation, including enrichment and separation, is reviewed. Focus is given to the rapid electric-based minimum inhibitory concentration measurement. The future directions and major challenges in this field are also outlined.     

Bayesian Self-Optimization for Telescoped Continuous Flow Synthesis

The optimization of multistep chemical syntheses is critical for the rapid development of new pharmaceuticals. However, concatenating individually optimized reactions can lead to inefficient multistep syntheses, owing to chemical interdependencies between the steps. Herein, we develop an automated continuous flow platform for the simultaneous optimization of telescoped reactions. Our approach is applied to a Heck cyclization-deprotection reaction sequence, used in the synthesis of a precursor for 1-methyltetrahydroisoquinoline C5 functionalization. A simple method for multipoint sampling with a single online HPLC instrument was designed, enabling accurate quantification of each reaction, and an in-depth understanding of the reaction pathways. Notably, integration of Bayesian optimization techniques identified an 81 % overall yield in just 14 h, and revealed a favorable competing pathway for formation of the desired product.     

Synthesis of Ferrocene 1,3-Derivatives by Distal C−H Activation**

The third position of cyclopentadienyl ring of a monosubstituted ferrocene has remained as an inaccessible chemical space for direct functionalization. Until recently, functionalizing the C(3)-position while bypassing the predominantly active C(2)-position is the most challenging task. Herein, we report a distal C−H functionalization of monosubstituted ferrocenes using an easily removable directing group with precise site-selectivity, under a Pd^II/ mono-N-protected amino-acid ligand catalytic system. The robust synthetic protocol leads to the synthesis of ferrocene 1,3-derivatives with broad scope in olefins while functionalizing ferrocenyl methylamine in moderate to good yields via a highly strained ferrocene appended 12-membered palladacycle intermediate.     

A Novel Electroanalytical Biosensor Based on ZIF-8/Acetylcholinesterase Bio-nanohybrids for Early Management of Hirschsprung Disease

Hirschsprung's disease (HD) is characterised by missing nerve cells in the colon of infants and children which results in strained bowel movement. Under such situations, undiagnosed and untreated cases often lead to a cascade of gastrointestinal infections eventually resulting in Hirschsprung-assisted enterocolitis which has significantly high mortality rate. This is further exacerbated by the absence of suitable, sensitive and efficient technologies to detect the pathological segment of the intestine, which could significantly reduce surgery duration in the operation theatre, as well as associated risks to patients. It therefore becomes a matter of extreme importance to develop a point-of-care platform for early and efficient management/identification of the occurrence of HD in neonates and older children during its onset, before it proves fatal with life-threatening outcomes. The present work reports an electrochemical enzymatic biosensor using Zeolitic Imidazolate Framework-8 (ZIF-8) modified with acetylcholinesterase enzyme (AchE), for detection of HD as a function of the key biomarker – acetylcholine. The developed sensor was initially characterized using Cyclic Voltammetry (CV) and Electrochemical Impedance Spectroscopy (EIS), while the analytical performance and insights onto interfacial redox kinetics were assessed using Differential Pulse Voltammetry (DPV) and EIS respectively. The sensor exhibited limit of detection and sensitivity of 0.19 μM and sensitivity of 0.42 μA/μM/mm² with a shelf life of 1 month, while remaining unperturbed in the presence of common interferants. The performance of developed sensor was also examined in spiked serum samples and was observed to yield a high degree of linearity.