Fluorescence Imaging and Photodynamic Inactivation of Bacteria Based on Cationic Cyclometalated Iridium(III) Complexes with Aggregation‐Induced Emission Properties

Abstract

Antibacterial photodynamic therapy (PDT) is one of the emerging methods for curbing multidrug‐resistant bacterial infections. Effective fluorescent photosensitizers with dual functions of bacteria imaging and PDT applications are highly desirable. In this study, three cationic and heteroleptic cyclometalated Ir(III) complexes with the formula of [Ir(CˆN)2(NˆN)][PF6] are prepared and characterized. These Ir(III) complexes named Ir(ppy)2bP, Ir(1‐pq)2bP, and Ir(2‐pq)2bP are comprised of three CˆN ligands (i.e., 2‐phenylpyridine (ppy), 1‐phenylisoquinoline (1‐pq), and 2‐phenylquinoline (2‐pq)) and one NˆN bidentate co‐ligand (bP). The photophysical characterizations demonstrate that these Ir(III) complexes are red‐emitting, aggregation‐induced emission active luminogens. The substitution of phenylpyridine with phenylquinoline isomers in the molecules greatly enhances their UV and visible‐light absorbance as well as the photoinduced reactive oxygen species (ROS) generation ability. All three Ir(III) complexes can stain both Gram‐positive and Gram‐negative bacteria efficiently. Interestingly, even though Ir(1‐pq)2bP and Ir(2‐pq)2bP are constitutional isomers with very similar structures and similar ROS generation ability in buffer, the former eradicates bacteria much more effectively than the other through white light‐irradiated photodynamic inactivation. This work will provide valuable information on the rational design of Ir(III) complexes for fluorescence imaging and efficient photodynamic inactivation of bacteria.

The fast-growing field of photo-driven theranostics based on aggregation-induced emission

“…Ir(III) complexes have aroused great research interest in phototherapy owing to their favorable characteristics, such as their high ISC ability and tunable photophysical properties. [199][200][201][202][203][204][205][206] In 2017, Chao et al reported a series of Ir(III) complexes with AIE characteristics for cancer cellspecific mitochondria-targeted PDT. The obtained AIE-active Ir(III) complexes exhibited gradually red-shifted emission peaks and gradually decreased quantum yields in the aggregate state from Ir1 to Ir3.…”

Restricting Bond Rotations by Ring Fusion: A Novel Molecular Design Strategy to Improve Photodynamic Antibacterial Efficacy of AIE Photosensitizers

“…For instance, rose bengal and chlorin e6 (20 μM) inactivated only 0.6 and 1.2 log 10 of S. aureus with high light doses of 30 and 20 J/cm 2 , respectively. It is worth noting that the light dose needed to effectively kill S. aureus (>3.0 log 10 ) with CPVBP2 (1.2 J/cm 2 ) is also significantly lower than many reported photosensitizers, including traditional photosensitizers, such as porphyrin, − phthalocyanine, − phenothiazinium, − boron-dipyrromethene, − indocyanine green, − and AIE photosensitizers. ,− …”

“…Instruments. 1 H and 13 C NMR spectra were measured using a Bruker BioSpin AVANCE III 400 MHz spectrometer and a JEOL EZC400S 400 MHz spectrometer. High-resolution mass spectra (HRMS) were obtained on a Bruker Impact II Mass Spectrometer.…”

“…Antibacterial photodynamic therapy (aPDT), which uses photosensitizers (PSs), light, and oxygen to generate reactive oxygen species (ROS) to kill bacteria, has received increasing attention because of its advantages of noninvasiveness, low drug resistance, and minimal systemic toxicity. , However, traditional PSs, such as phthalocyanines, boron-dipyrromethenes, and porphyrins tend to aggregation in aqueous media, thus reducing their bacteria-killing efficacy. , The π–π stacking in the aggregation state leads to fluorescence quenching and reduces the ability of ROS generation. , On the contrary, aggregation restricts the intramolecular motions of aggregation-induced emission photosensitizers (AIE-PSs), which suppresses nonradiative decay to boost the generation of fluorescence and ROS. , In recent years, AIE-PSs have been successfully applied to bacterial imaging and ablation. ,− However, the antibacterial efficacy of AIE-PSs is still unsatisfactory. Most reported antibacterial rates of AIE-PSs did not exceed 2.0 log 10 , except for a membrane-anchored AIE-PS called a TBD anchor, which was reported to be able to kill 3.0 log 10 of Staphylococcus aureus ( S. aureus ) at a concentration of 2 μM and kill 3.0 log 10 of Escherichia coli ( E. coli ) at 5 μM with a 15 J/cm 2 light dose .…”

Boosting the photodynamic therapy of near-infrared AIE-active photosensitizers by precise manipulation of the molecular structure and aggregate-state packing

“…[36][37][38] To achieve an efficient PDT process, photosensitizers (PSs) [39][40][41][42] with excellent reactive oxygen species (ROS) generation ability are highly desired. 43,44 In biologically relevant processes, however, the chemical structures, the physiological environments, [45][46][47] and the self-assembled forms [48][49][50] of PSs have a salient influence on the inherent properties including the ROS generation ability as well as the emission behaviors. 51,52 For example, the photophysical behaviors in both isolated and aggregate states are easily tuned by molecular engineering such as simple alteration of substituent positions and species.…”