Dual-Emissive Iridium(III) Complex with Aggregation-Induced Emission: Mechanistic Insights into Electron Transfer for Enhanced Hypoxia Detection in 3D Tumor Models

Accurate
oxygen detection and measurement of its concentration
is vital in biological and industrial applications, necessitating
highly sensitive and reliable sensors. Optical sensors, valued for
their real-time monitoring, nondestructive analysis, and exceptional
sensitivity, are particularly suited for precise oxygen measurements.
Here, we report a dual-emissive iridium(III) complex, IrNPh2, featuring “aggregation-induced emission” (AIE) properties
and used for sensitive oxygen sensing. IrNPh2 exhibits
dual emissions at 450 and 515 nm, with 515 nm triplet-state emission
demonstrating remarkable oxygen sensitivity due to its long-lived
excited state (12.12 μs) and high quantum yield (68%). Stern–Volmer
analysis reveals a notable quenching constant (Ksv = 12.44%–1) and an ultralow detection
limit of 0.0397%, emphasizing its superior performance. The oxygen
quenching mechanism is driven by electron transfer (ET), supported
by computational studies showing the lowest-unoccupied molecular orbital
(LUMO) alignment of IrNPh2 with the πg* orbitals of triplet oxygen, leading to superoxide radical (O2•–) formation. Electron paramagnetic
resonance (EPR) studies further confirm this pathway. Biological evaluations
using a three-dimensional (3D) U87-MG glioma spheroid model highlight
the ability of IrNPh2 to detect hypoxic regions, with significant
fluorescence enhancement under hypoxia and minimal cytotoxicity (>80%
viability at 100 μM). With high sensitivity, low detection limits,
and biocompatibility, IrNPh2 emerges as a promising candidate
for oxygen sensing in environmental and biomedical applications, especially
tumor hypoxia detection.