PUBLICATION
Phosphorescent biscyclometallated iridium(iii) ethylenediamine complexes functionalised with polar ester or carboxylate groups as bioimaging and visualisation reagents
- Authors
- Tang, T.S., Leung, K., Louie, M., Liu, H., Cheng, S.H., Lo, K.K.
- ID
- ZDB-PUB-141219-1
- Date
- 2015
- Source
- Dalton transactions (Cambridge, England : 2003) 44(11): 4945-56 (Journal)
- Registered Authors
- Cheng, Shuk Han
- Keywords
- none
- MeSH Terms
-
- Animals
- Biological Transport
- Carboxylic Acids/chemistry*
- Cattle
- Drug Design
- Esters
- Ethylenediamines/chemistry*
- HeLa Cells
- Humans
- Hydrogen-Ion Concentration
- Hydrophobic and Hydrophilic Interactions
- Indicators and Reagents/chemistry
- Iridium/chemistry*
- Luminescent Agents/chemistry
- Luminescent Agents/metabolism
- Luminescent Agents/pharmacology
- Molecular Imaging/methods*
- Organometallic Compounds/chemistry*
- Organometallic Compounds/metabolism
- Organometallic Compounds/pharmacology
- Oxidative Phosphorylation/drug effects
- Serum Albumin, Bovine/metabolism
- Singlet Oxygen/chemistry
- Zebrafish
- PubMed
- 25522324 Full text @ Dalton Trans.
Citation
Tang, T.S., Leung, K., Louie, M., Liu, H., Cheng, S.H., Lo, K.K. (2015) Phosphorescent biscyclometallated iridium(iii) ethylenediamine complexes functionalised with polar ester or carboxylate groups as bioimaging and visualisation reagents. Dalton transactions (Cambridge, England : 2003). 44(11):4945-56.
Abstract
We report the synthesis, characterisation and photophysical properties of new phosphorescent biscyclometallated iridium(iii) ethylenediamine (en) complexes functionalised with polar ester or carboxylate groups [Ir(N^C)2(en)](n)(X) (n = +1, X = Cl(-), HN^C = methyl 4-(2-pyridyl)benzoate Hppy-COOMe (), methyl 2-phenyl-4-quinolinecarboxylate Hpq-COOMe (); n = -1, X = Li(+), HN^C = 4-(2-pyridyl)benzoate Hppy-COO(-) (), 2-phenyl-4-quinolinecarboxylate Hpq-COO(-) ()). In aqueous solutions, the carboxylate complexes and displayed emission quenching (ca. 7 and 74 fold, respectively) and lifetime shortening upon protonation, and their pKa values were determined to be 5.13 and 3.46, respectively. The pq complexes and exhibited hypsochromic shifts in their emission maxima and a significant increase in emission intensity (ca. 84 and 15 fold, respectively) upon nonspecific binding to the protein bovine serum albumin (BSA). Inductively coupled plasma-mass spectroscopy (ICP-MS) and laser-scanning confocal microscopy (LSCM) results revealed that the ester complexes and were efficiently internalised by the human cervix epithelioid carcinoma (HeLa) cells through energy-requiring pathways and subsequently localised in endosomes and mitochondria, respectively. They showed good biocompatibility in the dark, but became significantly cytotoxic upon photoirradiation due to the generation of singlet oxygen. In contrast, in aqueous solutions of physiological pH, the carboxylate complexes and existed as the anionic form and hardly entered cells due to limited membrane permeability, as evidenced by the intense emission surrounding the plasma membrane of the cells. They showed negligible cytotoxicity and the cell viability remained over 95% for an incubation period of 24 hours. In view of the low cytotoxicity and strongly emissive nature of the hydrophilic ppy-COO(-) complex in an aqueous medium, the potential application of the complex as a visualisation reagent has been demonstrated using zebrafish (Danio rerio) as an animal model.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping