A halogen bond-mediated highly active artificial chloride channel with high anticancer activity

Ren, Changliang; Ding, Xin; Roy, Arundhati; Shen, Jie; Zhou, Shaoyuan; Chen, Feng; Li, Sam Fong Yau; Ren, Haisheng; Yang, Yi Yan; Zeng, Huaqiang

doi:10.1039/c8sc00602d

Cited by 98 publications

(89 citation statements)

References 57 publications

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“…Considerable interest has been invested in developing ion‐transport machinery for selective transport of chloride in lipid bilayer membranes . This endeavor is not only to understand the fundamental transport mechanism in biology but also for possible medical applications in either channelopathies or as anticancer agents . However, synthetic iodide channels are still underexplored, considering that only two iodide‐selective channels have been reported thus far .…”

Section: Introductionmentioning

confidence: 99%

Polyhydrazide‐Based Organic Nanotubes as Efficient and Selective Artificial Iodide Channels

Roy¹,

Joshi

et al. 2020

Angew Chem Int Ed

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Reported herein is a series of pore‐containing polymeric nanotubes based on a hydrogen‐bonded hydrazide backbone. Nanotubes of suitable lengths, possessing a hollow cavity of about a 6.5 Å diameter, mediate highly efficient transport of diverse types of anions, rather than cations, across lipid membranes. The reported polymer channel, having an average molecular weight of 18.2 kDa and 3.6 nm in helical height, exhibits the highest anion‐transport activities for iodide (EC50=0.042 μm or 0.028 mol % relative to lipid), whcih is transported 10 times more efficiently than chlorides (EC50=0.47 μm). Notably, even in cholesterol‐rich environment, iodide transport activity remains high with an EC50 of 0.37 μm. Molecular dynamics simulation studies confirm that the channel is highly selective for anions and that such anion selectivity arises from a positive electrostatic potential of the central lumen rendered by the interior‐pointing methyl groups.

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Section: Introductionmentioning

confidence: 99%

Polyhydrazide‐Based Organic Nanotubes as Efficient and Selective Artificial Iodide Channels

Roy¹,

Joshi

et al. 2020

Angew Chem Int Ed

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“…It is known that halogen atoms form halogen bonds with electron donors and their halogen bonding ability increases from chlorine to bromine to iodine. [20] Although the thyroid hormones,T4and T3, are known to form halogen bonds with their transport proteins transthyretin (TTR) and thyroxine-binding globulin (TBG), [21] it is not known whether halogen bonding is responsible for the cellular uptake of thyroid hormones by MCT8. [18] Although halogen bonds have attracted significant attention in drug discovery, [19] it remains unclear whether they play key roles beyond their applications in improving drug-target interactions.Matile and co-workers and others showed that halogen bonds can be used for ion transport in synthetic membrane systems.…”

Section: Angewandte Chemiementioning

confidence: 99%

“…[18] Although halogen bonds have attracted significant attention in drug discovery, [19] it remains unclear whether they play key roles beyond their applications in improving drug-target interactions.Matile and co-workers and others showed that halogen bonds can be used for ion transport in synthetic membrane systems. [20] Although the thyroid hormones,T4and T3, are known to form halogen bonds with their transport proteins transthyretin (TTR) and thyroxine-binding globulin (TBG), [21] it is not known whether halogen bonding is responsible for the cellular uptake of thyroid hormones by MCT8. Thep resent study indicates that halogen bonds may play crucial roles in cellular uptake of organohalogen compounds.T he DFT [22] calculations on the halogenated compounds 4-15 indicate that the halogen bonding ability of the iodo compounds is greater than that of the corresponding bromo or chloro compounds.…”

Section: Angewandte Chemiementioning

confidence: 99%

The Remarkable Effect of Halogen Substitution on the Membrane Transport of Fluorescent Molecules in Living Cells

2018

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Small-molecule-based fluorescent probes have become important tools in biology for sensing and imaging applications.H owever,t he biological applications of many of the fluorescent molecules are hampered by lowcellular uptake and high toxicity.Inthis paper,wes howf or the first time that the introduction of halogen atoms enhances the cellular uptake of fluorescent molecules and the nature of halogen atoms plays acrucial role in the plasma membrane transport in mammalian cells.T he remarkably higher uptake of iodinated compounds compared to that of their chloro or bromo analogues suggests that the strong halogen bonding ability of iodine atoms may play an important role in the membrane transport. This study provides an ovel strategy for the transport of fluorescent molecules across the plasma membrane in living cells.

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“…Halogen bond (XB) interactions are prevalent in many areas of chemistry, [1][2][3][4][5][6][7] demonstrating important applications in catalysis, [8][9][10][11] crystal engineering [12][13][14] and rational drug design. [15][16][17][18] From a fundamental point of view, it has as well become a topic of main interest in the computational chemistry community. [19][20][21] Politzer and co-workers showed that the halogen lone-pairs, perpendicular to the covalent RÀ X bond, form a belt of negative electrostatic potential, leaving on the extension of the RÀ X bond an area of positive electrostatic potential.…”

Section: Introductionmentioning

confidence: 99%

On the Interplay between Charge‐Shift Bonding and Halogen Bonding

et al. 2020

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The nature of halogen-bond interactions has been analysed from the perspective of the astatine element, which is potentially the strongest halogen-bond donor. Relativistic quantum calculations on complexes formed between halide anions and a series of Y 3 CÀ X (Y=F to X, X=I, At) halogen-bond donors disclosed unexpected trends, e. g., At 3 CÀ At revealing a weaker donating ability than I 3 CÀ I despite a stronger polarizability. All the observed peculiarities have their origin in a specific component of CÀ Y bonds: the charge-shift bonding.Descriptors of the Quantum Chemical Topology show that the halogen-bond strength can be quantitatively anticipated from the magnitude of charge-shift bonding operating in Y 3 CÀ X. The charge-shift mechanism weakens the ability of the halogen atom X to engage in halogen bonds. This outcome provides rationales for outlier halogen-bond complexes, which are at variance with the consensus that the halogen-bond strength scales with the polarizability of the halogen atom.

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A halogen bond-mediated highly active artificial chloride channel with high anticancer activity

Abstract: Modularly tunable monopeptidic scaffold enables rapid and combinatorial evolution of a halogen bond-mediated highly active chloride channel, exhibiting an excellent anticancer activity toward human breast cancer.

Cited by 98 publications

References 57 publications

Polyhydrazide‐Based Organic Nanotubes as Efficient and Selective Artificial Iodide Channels

Polyhydrazide‐Based Organic Nanotubes as Efficient and Selective Artificial Iodide Channels

The Remarkable Effect of Halogen Substitution on the Membrane Transport of Fluorescent Molecules in Living Cells

On the Interplay between Charge‐Shift Bonding and Halogen Bonding

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