Crowned spiropyran fluoroionophores with a carboxyl moiety for the selective detection of lithium ions

Stubing, Daniel B.; Heng, Sabrina; Abell, Andrew D.

doi:10.1039/c6ob00468g

Cited by 36 publications

(12 citation statements)

References 28 publications

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“…Fluorescent sensors are excellent choices to image Li + in live cells or tissues, as they provide sensitive detection with high spatiotemporal resolution. Despite demonstrated success in using fluorescent sensors to detect divalent metal ions such as Ca 2+ , Zn 2+ , and Cu 2+ , , effective sensors for detecting monovalent metal ions, especially Li + , is quite limited. − Among the fluorescent Li + sensors, sensors based on organic crown, such as chiral diaza-9-crown-3 derivatives, [2.1.1]-cryptates, KLI-1 and KLI-2, methyl-1-aza-12-crown-4, and 1-(9-anthryl)-4-ferrocenyl-2-aza-1,3-butadiene, have received the most attention. − However, they have limited selectivity over other competing monovalent ions, such as Na + and K + , which are present in biological systems in much higher concentrations than that of Li + , and most of them have limited solubility in water and thus do not work well under physiological conditions. To our knowledge, Sabrina Heng lithium (SHL), based on merocyanine and spiropyran isomers changing upon Li + binding, was the first and is the only intracellular Li + optical sensor reported .…”

Section: Introductionmentioning

confidence: 99%

DNAzyme-Based Lithium-Selective Imaging Reveals Higher Lithium Accumulation in Bipolar Disorder Patient-Derived Neurons

et al. 2021

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Lithium has been a drug for bipolar disorders (BD) for over 70 years; however, its usage has been limited by its narrow therapeutic window (between 0.6 and 1.2 mM). Understanding the cellular distribution of lithium ions (Li + ) in patient cells will offer deep insight into this limitation, but selective imaging of Li + in living cells under biomedically relevant concentration ranges has not been achieved. Herein, we report in vitro selection and development of a Li + -specific DNAzyme fluorescent sensor with >100-fold selectivity over other biorelevant metal ions. This sensor allows comparative Li + visualization in HeLa cells, human neuronal progenitor cells (NPCs), and neurons derived from BD patients and healthy controls. Strikingly, we detected enhanced accumulation of Li + in cells derived from BD patients compared with healthy controls in differentiated neurons but not NPCs. These results establish the DNAzyme-based sensor as a novel platform for biomedical research into BD and related areas using lithium drugs.

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Section: Introductionmentioning

confidence: 99%

DNAzyme-Based Lithium-Selective Imaging Reveals Higher Lithium Accumulation in Bipolar Disorder Patient-Derived Neurons

et al. 2021

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“…Details on the synthesis of SHL are reported in the synthesis section of the Supplemental Information. In brief, the Li 1 sensor was prepared from 1-aza-15-crown-5 and 1-(2-hydroxyethyl)-2,3,3-trimethyl-3H-indol-1ium to give SHL with an overall yield of 20% using a modification to existing methodology (Heng et al, 2013;Stubing et al, 2016).…”

Section: Resultsmentioning

confidence: 99%

Development of a Photoswitchable Lithium-Sensitive Probe to Analyze Nonselective Cation Channel Activity in Migrating Cancer Cells

Pei

Heng

Ieso

et al. 2019

Molecular Pharmacology

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This is the first work to use a newly designed Li 1-selective photoswitchable probe Sabrina Heng Lithium (SHL) in living colon cancer cells to noninvasively monitor cation channel activity in real time by the appearance of lithium hot spots detected by confocal microscopy. Punctate Li 1 hot spots are clustered in the lamellipodial leading edges of HT29 human colon cancer cells and are colocalized with aquaporin-1 (AQP1) channels. AQP1 is a dual water and cyclic-nucleotidegated cation channel located in lamellipodia and is essential for rapid cell migration in a subset of aggressive cancers. Both the Li 1 hot spots and cell migration are blocked in HT29 cells by the AQP1 ion channel antagonist AqB011. In contrast, Li 1 hot spots are not evident in a poorly migrating colon cancer cell line, SW620, which lacks comparable membrane expression of AQP1. Knockdown of AQP1 by RNA interference in HT29 cells significantly impairs Li 1 hot spot activity. The SHL probe loaded in living cells shows signature chemical properties of ionic selectivity and reversibility. Dynamic properties of the Li 1 hot spots, turning on and off, are confirmed by time-lapse imaging. SHL is a powerful tool for evaluating cation channel function in living cells in real time, with particular promise for studies of motile cells or interlinked networks not easily analyzed by electrophysiological methods. The ability to reset SHL by photoswitching allows monitoring of dynamic signals over time. Future applications of the Li 1 probe could include high-throughput optical screening for discovering new classes of channels, or finding new pharmacological modulators for nonselective cation channels.

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“…Abell combined the nitrophenol chromogenic moiety and crown ether receptor first reported by Pacey [ 24 ] and introduced a spiropyran group which cleaves to bind Li + in preference to other metal cations [ 48 , 49 ]. Investigation of chromoionophore 35 ( Scheme 15 ) showed that exposure to ultra-violet (UV) light at 365 nm in the presence of Li + generated increases in fluorescence which could be reversed with white light.…”

Section: Sensorsmentioning

confidence: 99%

Lithium Ion Sensors

Kamenica

Kothur

Willows

et al. 2017

Sensors

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The detection and monitoring of lithium in environmental and clinical settings is becoming increasingly important. In this review, sensors incorporating conductive polymers and lithium bronzes are discussed, together with electrochemical and spectroscopic approaches. Ionophore-based methods have been employed extensively, with varying degrees of selectivity and sensitivity, and these are discussed in depth.

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Crowned spiropyran fluoroionophores with a carboxyl moiety for the selective detection of lithium ions

Abstract: The absorbance and fluorescence spectra of carboxylated spiropyrans containing methyl-1-aza-12-crown-4, methyl-1-aza-15-crown-5, methyl-1-aza-18-crown-6 moieties are compared in the presence of alkali metal ions.

Cited by 36 publications

References 28 publications

DNAzyme-Based Lithium-Selective Imaging Reveals Higher Lithium Accumulation in Bipolar Disorder Patient-Derived Neurons

DNAzyme-Based Lithium-Selective Imaging Reveals Higher Lithium Accumulation in Bipolar Disorder Patient-Derived Neurons

Development of a Photoswitchable Lithium-Sensitive Probe to Analyze Nonselective Cation Channel Activity in Migrating Cancer Cells

Lithium Ion Sensors

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