Conferring Phosphorogenic Properties on Iridium(III)‐Based Bioorthogonal Probes through Modification with a Nitrone Unit

Lee, Lawrence Cho-Cheung; Lau, Jonathan Chun-Wai; Liu, Huawei; Lo, Kenneth Kam‐Wing

doi:10.1002/ange.201509396

Cited by 17 publications

(2 citation statements)

References 55 publications

(20 reference statements)

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“…Coordination compounds able to emit from the excited triplet state have found applications in molecular bioimaging. Among these, species with d 6 and d 8 electronic configurations have been described, including Re(I), Pt(II), and Ir(III) complexes. − Such transition-metal complexes are usually quenched upon aggregation because of triplet–triplet annihilation processes, which become more probable for longer excited-state lifetimes. On the other hand, Pt(II) complexes can stack into luminescent aggregates because of their d 8 electronic configuration, which leads to planar coordination compounds where aggregation favors the interaction between d z 2 orbitals protruding out of the molecular plane.…”

Section: Introductionmentioning

confidence: 99%

Oxygen-Insensitive Aggregates of Pt(II) Complexes as Phosphorescent Labels of Proteins with Luminescence Lifetime-Based Readouts

Delcanale

Galstyan

Daniliuc

et al. 2018

ACS Appl. Mater. Interfaces

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The synthesis and photophysical properties of a tailored Pt(II) complex are presented. The phosphorescence of its monomeric species in homogeneous solutions is quenched by interaction with the solvent and therefore absent even upon deoxygenation. However, aggregation-induced shielding from the environment and suppression of rotovibrational degrees of freedom trigger a phosphorescence turn-on that is not suppressed by molecular oxygen, despite possessing an excited-state lifetime ranging in the microsecond scale. Thus, the photoinduced production of reactive oxygen species is avoided by the suppression of diffusion-controlled Dexter-type energy transfer to triplet molecular oxygen. These aggregates emit with the characteristic green luminescence profile of monomeric complexes, indicating that Pt-Pt or excimeric interactions are negligible. Herein, we show that these aggregates can be used to label a model biomolecule (bovine serum albumin) with a microsecond-range luminescence. The protein stabilizes the aggregates, acting as a carrier in aqueous environments. Despite spectral overlaps, the green phosphorescence can be separated by time-gated detection from the dominant autofluorescence of the protein arising from a covalently bound green fluorophore that emits in the nanosecond range. Interestingly, the aggregates also acted as energy donors able to sensitize the emission of a fraction of the fluorophores bound to the protein. This resulted in a microsecond-range luminescence of the fluorescent acceptors and a shortening of the excited-state lifetime of the phosphorescent aggregates. The process that can be traced by a 1000-fold increase in the acceptor's lifetime mirrors the donor's triplet character. The implications for phosphorescence lifetime imaging are discussed.

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Section: Introductionmentioning

confidence: 99%

Oxygen-Insensitive Aggregates of Pt(II) Complexes as Phosphorescent Labels of Proteins with Luminescence Lifetime-Based Readouts

Delcanale

Galstyan

Daniliuc

et al. 2018

ACS Appl. Mater. Interfaces

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“…Phosphorescent cyclometalated Ir(III) complexes are regarded as excellent probes for biological imaging and sensing, due to their outstanding photophysical properties, including relatively high quantum yields, long emission lifetimes, large Stokes shifts, two-photon absorption and high photobleaching resistance8910. On the other hand, cyclometalated Ir(III) complexes are also considered to be potent anticancer candidates as they can target subcellular organelles, inhibit protein activities and act as photodynamic therapeutic agents11121314151617.…”

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confidence: 99%

Ester-Modified Cyclometalated Iridium(III) Complexes as Mitochondria-Targeting Anticancer Agents

Wang

Chen

et al. 2016

Sci Rep

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Organometallic iridium complexes are potent anticancer candidates which act through different mechanisms from cisplatin-based chemotherapy regimens. Here, ten phosphorescent cyclometalated iridium(III) complexes containing 2,2′-bipyridine-4,4′-dicarboxylic acid and its diester derivatives as ligands are designed and synthesized. The modification by ester group, which can be hydrolysed by esterase, facilitates the adjustment of drug-like properties. The quantum yields and emission lifetimes are influenced by variation of the ester substituents on the Ir(III) complexes. The cytotoxicity of these Ir(III) complexes is correlated with the length of their ester groups. Among them, 4a and 4b are found to be highly active against a panel of cancer cells screened, including cisplatin-resistant cancer cells. Mechanism studies in vitro indicate that they undergo hydrolysis of ester bonds, accumulate in mitochondria, and induce a series of cell-death related events mediated by mitochondria. Furthermore, 4a and 4b can induce pro-death autophagy and apoptosis simultaneously. Our study indicates that ester modification is a simple and feasible strategy to enhance the anticancer potency of Ir(III) complexes.

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Bioorthogonal Turn‐On Probe Based on Aggregation‐Induced Emission Characteristics for Cancer Cell Imaging and Ablation

Yuan

Cheng

et al. 2016

Angewandte Chemie

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Bioorthogonal turn-on probes have been widely utilized in visualizing various biological processes.Most of the currently available bioorthogonal turn-on probes are blue or green emissive fluorophores with azide or tetrazine as functional groups.H erein, we present an alternative strategy of designing bioorthogonal turn-on probes based on red-emissive fluorogens with aggregation-induced emission characteristics (AIEgens). The probe is water soluble and non-fluorescent due to the dissipation of energy through free molecular motion of the AIEgen, but the fluorescence is immediately turned on upon click reaction with azide-functionalized glycans on cancer cell surface.T he fluorescence turn-on is ascribed to the restriction of molecular motion of AIEgen, which populates the radiative decay channel. Moreover,t he AIEgen can generate reactive oxygen species (ROS) upon visible light (l = 400-700 nm) irradiation, demonstrating its dual role as an imaging and phototherapeutic agent.

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Conferring Phosphorogenic Properties on Iridium(III)‐Based Bioorthogonal Probes through Modification with a Nitrone Unit

Cited by 17 publications

References 55 publications

Oxygen-Insensitive Aggregates of Pt(II) Complexes as Phosphorescent Labels of Proteins with Luminescence Lifetime-Based Readouts

Oxygen-Insensitive Aggregates of Pt(II) Complexes as Phosphorescent Labels of Proteins with Luminescence Lifetime-Based Readouts

Ester-Modified Cyclometalated Iridium(III) Complexes as Mitochondria-Targeting Anticancer Agents

Bioorthogonal Turn‐On Probe Based on Aggregation‐Induced Emission Characteristics for Cancer Cell Imaging and Ablation

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