Simultaneous Ultrasensitive Detection and Elimination of Drug-Resistant Bacteria by Cyclometalated Iridium(III) Complexes

Abstract

Antimicrobial resistance has become a major threat to public health due to the rampant and empirical use of antibiotics. Rapid diagnosis of bacteria with the desired sensitivity and selectivity still, however, remains an open challenge. We report a special class of water-soluble metal-based aggregation-induced emission luminogens (AIEgens), namely, cyclometalated iridium­(III) polypyridine complexes of the type [Ir­(PQ)2(N^N)]Cl (1–3), where PQ = 2-phenylquinoline and N^N = 2,2′-bipyridine derivatives, that demonstrate dual capability for detection and elimination of drug-resistant bacteria in aqueous solutions. These AIEgens exhibit selective and rapid sensing of endotoxins, such as lipopolysaccharides (LPS) and lipoteichoic acid (LTA) released by the bacteria, with a detection limit in the lower nanomolar range. Targeting these naturally amplified biomarkers (approximately 1 million copies per cell) by iridium­(III) complexes induces strong AIE in the presence of different Gram-negative and Gram-positive bacteria including carbapenem-resistant A. baumannii (CRAB) and methicillin-resistant S. aureus (MRSA) at concentrations as low as 1.2 CFU/mL within 5 min in spiked water samples. Detection of bacteria by the complexes is also visible to the naked eye at higher (108 CFU/mL) cell concentrations. More notably, complexes 1 and 2 show potent antibacterial activity against drug-resistant bacteria with low minimum inhibitory concentrations (MICs) ≤ 5 μg/mL (1–4 μM) via ROS generation and cell membrane disintegrity. To the best of our knowledge, this work is the “first-in-class” example of a metal-based theranostic system that integrates selective, sensitive, rapid, naked-eye, wash-free, and real-time detection of bacteria using broad-spectrum antibiotics into a single platform. This dual capability of AIEgens makes them ideal scaffolds for monitoring bacterial contamination in aqueous samples and pharmaceutical applications.

Mitochondria-Targeted Photoactivatable Real-Time Monitoring of a Controlled Drug Delivery Platform

“…The events of phototriggered uncaging reaction encouraged us to study the uptake of MTPDDS in cancer cells. The uptake of any compound inside cells is greatly influenced by its lipophilicity. , Therefore, we determined the lipophilicity (log P o/w value) of MTPDDS by measuring its partition coefficient in an n-octanol/water system using the classical flask-shaking technique . The value of lipophilicity was found to be 3.7, indicating the lipophilic nature of MTPDDS .…”

“…24,25 Therefore, we determined the lipophilicity (log P o/w value) of MTPDDS by measuring its partition coefficient in an n-octanol/water system using the classical flask-shaking technique. 25 The value of lipophilicity was found to be 3.7, indicating the lipophilic nature of MTPDDS. Next, we examined the uptake of MTPDDS in human cervical cancer (HeLa) cells using fluorescence activated cell sorter (FACS) analysis.…”

Brief survey on organometalated antibacterial drugs and metal-based materials with antibacterial activity

“…[56][57][58] One of the alternative approaches to combating bacterial pathogens is based on inorganic [59][60][61][62] and organometallic compounds. [63][64][65][66][67][68][69][70][71][72][73][74][75][76][77][78] The latter are defined by the presence of at least one metal-carbon (M-C) bond. The biological activity of organometallic compounds has been a subject of many studies, especially in the field of anticancer therapy.…”

Aggregation‐Induced Emission‐Based Platforms for the Treatment of Bacteria, Fungi, and Viruses

“…fabricated a special iridium (Ir)‐based AIEgen which could produce ROS for bacterial elimination. [ 132 ] The Ir‐based AIEgens can detect bacterial endotoxins with a detection limitation as low as nanomolar range by a naked‐eye, wash‐free, and real‐time way. More notably, the Ir complexes exhibited potent antibacterial capability against drug‐resistant bacteria with MIC lower than 5 µg mL −1 .…”