Near-Infrared Emitting Ir(III) Complexes Bearing a Dipyrromethene Ligand for Oxygen Imaging of Deeper Tissues In Vivo

Abstract

Phosphorescence lifetime imaging microscopy (PLIM) using a phosphorescent oxygen probe is an innovative technique for elucidating the behavior of oxygen in living tissues. In this study, we designed and synthesized an Ir(III) complex, PPYDM-BBMD, that exhibits long-lived phosphorescence in the near-infrared region and enables in vivo oxygen imaging in deeper tissues. PPYDM-BBMD has a π-extended ligand based on a mesomesityl dipyrromethene structure and phenylpyridine ligands with cationic dimethylamino groups to promote intracellular uptake. This complex gave a phosphorescence spectrum with a maximum at 773 nm in the wavelength range of the so-called biological window and exhibited an exceptionally long lifetime (18.5 μs in degassed acetonitrile), allowing for excellent oxygen sensitivity even in the near-infrared window. PPYDM-BBMD showed a high intracellular uptake in cultured cells and mainly accumulated in the endoplasmic reticulum. We evaluated the oxygen sensitivity of PPYDM-BBMD phosphorescence in alpha mouse liver 12 (AML12) cells based on the Stern−Volmer analysis, which gave an O 2 -induced quenching rate constant of 1.42 × 10 3 mmHg −1 s −1 . PPYDM-BBMD was administered in the tail veins of anesthetized mice, and confocal one-photon PLIM images of hepatic tissues were measured at different depths from the liver surfaces. The PLIM images visualized the oxygen gradients in hepatic lobules up to a depth of about 100 μm from the liver surfaces with a cellular-level resolution, allowing for the quantification of oxygen partial pressure based on calibration results using AML12 cells.

Iridium(III)-Based Infrared Two-Photon Photosensitizers: Systematic Regulation of Their Photodynamic Therapy Efficacy

“…For YF1 – 4 , however, most ESs with low energy level were contributed by the N ∧ N ligands, resulting in a more obvious difference in emission wavelengths from each other . All Ir­(III)-PSs in this study exhibited a lifetime (τ) range from 814 to 970 ns in aqueous solution (Table S7), comparable to Ir­(III)-PSs recently reported by different research groups. ,,− Such a relatively long ES lifetime can facilitate photosensitization and photoinduced electron transfer processes on light activation.…”

Near-infrared metal agents assisting precision medicine: from strategic design to bioimaging and therapeutic applications

“…In 2022, Yoshihara et al developed an Ir( iii ) complex 14 for in vivo oxygen imaging. 117 Complex 14 , which features a π expansive ligand based on a mesomesityl dipyrromethene and phenylpyridine ligands, had been shown to enhance intracellular uptake. Complex 14 exhibited a maximum absorption wavelength at 577 nm.…”

Recent Advances in Organometallic NIR Iridium(III) Complexes for Detection and Therapy

“…The demand and supplement of oxygen is thought to be closely linked to a variety of serious diseases, such as cancers, neurological diseases, arteriosclerosis, cerebral infarction, ischemic heart disease, chronic kidney disease, and diabetic retinopathy. The monitoring of oxygen concentration in the body can effectively diagnose and trace the metastasis of pathological tissues as well as more accurate personality therapy [ 78 , 79 ].…”