Dynamic Assessment of Bilayer Thickness by Varying Phospholipid and Hydraphile Synthetic Channel Chain Lengths

Weber, Michelle E.; Schlesinger, Paul H.; Gokel, George W.

doi:10.1021/ja044936+

Cited by 62 publications

(69 citation statements)

References 43 publications

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“…13 All reactions were conducted under dry N 2 unless otherwise stated. All reagents were the best (non-LC) grade commercially available and were distilled, recrystallized, or used without further purification, as appropriate.…”

Section: Methodsmentioning

confidence: 99%

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The influence of varied amide bond positions on hydraphile ion channel activity

et al. 2006

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Hydraphile compounds have been prepared in which certain of the amine nitrogens have been replaced by amide residues. The amide bonds are present either in the sidearm, the side chain, or the central relay. Sodium cation transport through phospholipid vesicles mediated by each hydraphile was assessed. All of the amide-containing hydraphiles showed increased levels of Na + transport compared to the parent compound, but the most dramatic rate increase was observed for sidearm amine to amide replacement. We attribute this enhancement to stabilization of the sidearm in the bilayer to achieve a better conformation for ion conduction. Biological studies of the amide hydraphiles with E. coli and B. subtilis showed significant toxicity only with the latter. Further, the consistency between the efficacies of ion transport and toxicity previously observed for non-amidic hydraphiles was not in evidence.

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Section: Methodsmentioning

confidence: 99%

“…1 H-NMR: 0.87 (6H, t), 1.25 (64H, bs), 1.43 (8H, quartet), 1.61 (4H, quartet), 2.31 (4H, t), 2.48 (8H, t), 2.78 (16H, m), 3.59−3.64 (56H, m). 13 Caption: Fractional Na + release, determined by the ISE method, for 1−4 (12 μM each). The concentration of DOPC vesicles was 0.4 mM.…”

Section: Nn'-bis{12-[n-(n'-dodecyl)-diaza-18-crown-6]-dodecyl}-diazamentioning

confidence: 99%

The influence of varied amide bond positions on hydraphile ion channel activity

et al. 2006

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“…An ion selective electrode (ISE) sensitive to Na + is inserted into the aqueous suspension [32]. The ionophore is added to the suspension and a measurement of Na + concentration is recorded every second.…”

Section: 63mentioning

confidence: 99%

“…In more recent studies, we used sodium ion-selective micro-electrodes to detect Na + release from liposomes [32]. When this method is used, Na + is trapped within phospholipid vesicles.…”

Section: Assessing Functionalitymentioning

confidence: 99%

Coordination and transport of alkali metal cations through phospholipid bilayer membranes by hydraphile channels

Gokel

Daschbach

2008

Coordination Chemistry Reviews

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Hydraphiles are synthetic ionophores that were designed to mimic some properties of protein channels that conduct such cations as sodium. They use macrocyclic (crown) polyethers as amphiphilic headgroups and as entry and exit portals. Their overall length is controlled by covalent links between the two headgroups (distal macrocycles) and the "central relay" unit, typically also an azacrown. The hydraphiles insert in the bilayer membranes of synthetic phospholipid vesicles or vital cells and mediate the transport of cations. The hydraphiles were intended to be models but they are functional channels. Because they are symmetric, they are non-rectifying but they show open-close behavior characteristic of natural channels. Because they are non-rectifying, when they insert into a microbial membrane, they lead to a rapid change in osmotic balance that proves fatal to bacteria.

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“…We have used NMR methods 16 and direct detection of Na + release by use of sodium-sensitive ion selective electrodes. 8 We have also used the planar bilayer clamp method to confirm channel-like behavior for these compounds. 17,18 The latter method provides considerable detail about ion transport through the bilayer but it is a complex technique that requires quite specialized instrumentation.…”

Section: Synthetic Access To Amidic Hydraphilesmentioning

confidence: 99%

Heterocyclic Amide Hydraphile Synthetic Cation Transporters

Wang¹,

Yamnitz²,

Gokel³

2007

HETEROCYCLES

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A family of hydraphile ionophores has been prepared in which various ∼CH 2 N∼ to ∼CON∼ replacements have been made to assess the effect on Na + transport through phospholipid bilayers. When the central relay (see graphical abstract) was a third macrocycle, symmetrical carbonyl for methylene replacements enhanced activity, but the presence of four or six amide residues diminished transport. When a pair of amides was incorporated into compounds having a 4,4′-bipiperidyl central relay, both significant increases and decreases were observed depending upon the amide positions. The presence of amides alters both the donor group type and strength and the conformation of the structural unit in which it occurs. These changes are shown to depend on the liposomes in which the Na + release studies were conducted. These changes are shown to affect the toxicity of the hydraphiles to E. coli.

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Dynamic Assessment of Bilayer Thickness by Varying Phospholipid and Hydraphile Synthetic Channel Chain Lengths

Cited by 62 publications

References 43 publications

The influence of varied amide bond positions on hydraphile ion channel activity

The influence of varied amide bond positions on hydraphile ion channel activity

Coordination and transport of alkali metal cations through phospholipid bilayer membranes by hydraphile channels

Heterocyclic Amide Hydraphile Synthetic Cation Transporters

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