TY - JOUR

T1 - Biocompatible Phosphorescent O2 Sensors Based on Ir(III) Complexes for In Vivo Hypoxia Imaging

AU - Самандарсангари, Можган

AU - Козина, Дарья Олеговна

AU - Соколов, Виктор Владимирович

AU - Комарова, Анастасия Денисовна

AU - Ширманова, Марина Вадимовна

AU - Критченков, Илья Сергеевич

AU - Туник, Сергей Павлович

PY - 2023/6/26

Y1 - 2023/6/26

N2 - In this work, we obtained three new phosphorescent iridium complexes ( Ir1- Ir3) of general stoichiometry [Ir(N^C) 2(N^N)]Cl decorated with oligo(ethylene glycol) fragments to make them water-soluble and biocompatible, as well as to protect them from aggregation with biomolecules such as albumin. The major photophysical characteristics of these phosphorescent complexes are determined by the nature of two cyclometallating ligands (N^C) based on 2-pyridine-benzothiophene, since quantum chemical calculations revealed that the electronic transitions responsible for the excitation and emission are localized mainly at these fragments. However, the use of various diimine ligands (N^N) proved to affect the quantum yield of phosphorescence and allowed for changing the complexes' sensitivity to oxygen, due to the variations in the steric accessibility of the chromophore center for O 2 molecules. It was also found that the N^N ligands made it possible to tune the biocompatibility of the resulting compounds. The wavelengths of the Ir1- Ir3 emission maxima fell in the range of 630-650 nm, the quantum yields reached 17% ( Ir1) in a deaerated solution, and sensitivity to molecular oxygen, estimated as the ratio of emission lifetime in deaerated and aerated water solutions, displayed the highest value, 8.2, for Ir1. The obtained complexes featured low toxicity, good water solubility and the absence of a significant effect of biological environment components on the parameters of their emission. Of the studied compounds, Ir1 and Ir2 were chosen for in vitro and in vivo biological experiments to estimate oxygen concentration in cell lines and tumors. These sensors have demonstrated their effectiveness for mapping the distribution of oxygen and for monitoring hypoxia in the biological objects studied.

AB - In this work, we obtained three new phosphorescent iridium complexes ( Ir1- Ir3) of general stoichiometry [Ir(N^C) 2(N^N)]Cl decorated with oligo(ethylene glycol) fragments to make them water-soluble and biocompatible, as well as to protect them from aggregation with biomolecules such as albumin. The major photophysical characteristics of these phosphorescent complexes are determined by the nature of two cyclometallating ligands (N^C) based on 2-pyridine-benzothiophene, since quantum chemical calculations revealed that the electronic transitions responsible for the excitation and emission are localized mainly at these fragments. However, the use of various diimine ligands (N^N) proved to affect the quantum yield of phosphorescence and allowed for changing the complexes' sensitivity to oxygen, due to the variations in the steric accessibility of the chromophore center for O 2 molecules. It was also found that the N^N ligands made it possible to tune the biocompatibility of the resulting compounds. The wavelengths of the Ir1- Ir3 emission maxima fell in the range of 630-650 nm, the quantum yields reached 17% ( Ir1) in a deaerated solution, and sensitivity to molecular oxygen, estimated as the ratio of emission lifetime in deaerated and aerated water solutions, displayed the highest value, 8.2, for Ir1. The obtained complexes featured low toxicity, good water solubility and the absence of a significant effect of biological environment components on the parameters of their emission. Of the studied compounds, Ir1 and Ir2 were chosen for in vitro and in vivo biological experiments to estimate oxygen concentration in cell lines and tumors. These sensors have demonstrated their effectiveness for mapping the distribution of oxygen and for monitoring hypoxia in the biological objects studied.

KW - Humans

KW - Hypoxia

KW - Ligands

KW - Neoplasms

KW - Oxygen

KW - Water

KW - hypoxia

KW - iridium complexes

KW - bioimaging

KW - phosphorescence

KW - phosphorescence lifetime imaging

KW - oxygen sensing

UR - https://www.mendeley.com/catalogue/4b86631e-8af3-38f1-9a39-36c2a7761584/

U2 - 10.3390/bios13070680

DO - 10.3390/bios13070680

M3 - Article

C2 - 37504079

VL - 13

JO - Biosensors

JF - Biosensors

SN - 2079-6374

IS - 7

M1 - 680

ER -