‘Living’ macrolactonisation: thermodynamically-controlled cyclisation and interconversion of oligocholates

Brady, Paul A.; Bonar-Law, Richard P.; Rowan, Stuart; Suckling, C. J.; Sanders, Jeremy K. M.

doi:10.1039/cc9960000319

Cited by 148 publications

(125 citation statements)

References 22 publications

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“…4a Interestingly, more than ten years ago, Sanders and co-workers reported that, when cyclic oligocholate esters were subjected to transesterification, the trimer was always the most thermodynamically favorable species. 9 Although their cyclic oligocholates are connected by ester bonds and our linear cholate foldamers by amide, both Sanders' work and ours suggest that the cholate backbone prefers trimeric periodicity. Because of the large size of the repeat unit (ca.…”

Section: Resultsmentioning

confidence: 58%

Controlling the Conformation of Oligocholate Foldamers by Surfactant Micelles

Zhong

Zhao

2008

J. Org. Chem.

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Fluorescence resonance energy transfer (FRET) occurred readily in a cholate hexamer labeled with a naphthyl donor and a dansyl acceptor at the chain ends when the hexamer was solubilized by sodium dodecyl sulfate (SDS) micelles in water. Independence of the energy transfer efficiency over 1−70 mM SDS suggested that the energy transfer resulted from the folding of the hexamer instead of its intermolecular aggregation within the micelle. Upon addition of sodium chloride to the solution, energy transfer became less efficient, indicating unfolding of the oligocholate. In contrast, the oligocholate stayed folded in the micelle of nonionic Brij 30, in the presence or absence of NaCl. These results suggested that the oligocholate preferred to fold within the small spherical SDS micelles but unfold when the preference for spherical over rodlike micelles was not strong enough to overcome the tendency for the oligocholate to unfold. Disciplines Chemistry CommentsReprinted (adapted) Fluorescence resonance energy transfer (FRET) occurred readily in a cholate hexamer labeled with a naphthyl donor and a dansyl acceptor at the chain ends when the hexamer was solubilized by sodium dodecyl sulfate (SDS) micelles in water. Independence of the energy transfer efficiency over 1-70 mM SDS suggested that the energy transfer resulted from the folding of the hexamer instead of its intermolecular aggregation within the micelle. Upon addition of sodium chloride to the solution, energy transfer became less efficient, indicating unfolding of the oligocholate. In contrast, the oligocholate stayed folded in the micelle of nonionic Brij 30, in the presence or absence of NaCl. These results suggested that the oligocholate preferred to fold within the small spherical SDS micelles but unfold when the preference for spherical over rodlike micelles was not strong enough to overcome the tendency for the oligocholate to unfold.

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Section: Resultsmentioning

confidence: 58%

Controlling the Conformation of Oligocholate Foldamers by Surfactant Micelles

Zhong

Zhao

2008

J. Org. Chem.

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“…The rigidity resulting from the triangular geometry, for example, is true for both noncovalent and covalent macrocycles. The preference of the cholate backbone for the cyclic trimer 52 and the strong guanidiniumÀcarboxylate salt bridge suggest that 4 has a strong propensity to adopt the ring-closed conformation resembling 1. Strong "internal hydrophilicity", which provides the hydrophobic driving force for stacking, is found in both compounds.…”

Section: Scheme 2 Enzymatic Reactions Used In the Glucose Leakage Assaymentioning

confidence: 99%

Translocation of Hydrophilic Molecules across Lipid Bilayers by Salt-Bridged Oligocholates

Cho

Zhao

2011

Langmuir

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Macrocyclic oligocholates were found in a previous work (Cho, H.; Widanapathirana, L.; Zhao, Y. J. Am. Chem. Soc.2011, 133, 141−147) to stack on top of one another in lipid membranes to form nanopores. Pore formation was driven by a strong tendency of the water molecules in the interior of the amphiphilic macrocycles to aggregate in a nonpolar environment. In this work, cholate oligomers terminated with guanidinium and carboxylate groups were found to cause efflux of hydrophilic molecules such as glucose, maltotriose, and carboxyfluorescein (CF) from POPC/POPG liposomes. The cholate trimer outperformed other oligomers in the transport. Lipid-mixing assays and dynamic light scattering ruled out fusion as the cause of leakage. The strong dependence on chain length argues against random intermolecular aggregates as the active transporters. The efflux of glucose triggered by these compounds increased significantly when the bilayers contained 30 mol % cholesterol. Hill analysis suggested that the active transporter consisted of four molecules. The oligocholates were proposed to fold into "noncovalent macrocycles" by the guanidinium−carboxylate salt bridge and stack on top of one another to form similar transmembrane pores as their covalent counterparts. Disciplines Chemistry CommentsReprinted ( Synthetic transmembrane pores with an inner diameter of 1 nm or larger have attracted a great deal of attention in recent years. 1,2 Part of the motivation comes from the fact that their biological congeners, membrane-associated pore-forming proteins, are involved in critical functions such as signaling, metabolism, and bacterial or viral infection. 3À7 Since it is notoriously difficult to obtain detailed structural information for complex membrane proteins, chemists have sought to construct simpler biomimetic nanopores and study their behavior under more easily controlled conditions. Knowledge generated from such studies not only is useful to the understanding of biological pore formation but also helps create materials with potential applications ranging from single-molecule detection of DNAs and RNAs 8À14 to drug delivery. 15 Crown ethers and open chain compounds, which worked extremely well for ion channels, 16À21 normally are too flexible for nanopore formation. To keep the pore open, the structure must be able to withstand the external membrane pressure when incorporated into a bilayer. 22 Despite the significant efforts devoted to synthetic nanopores, limited designs exist currently. An early example was Ghadiri's cyclic D/L-peptides, which self-assembled into transmembrane pores large enough for glucose and glutamic acid to pass through. 23,24 In recent years, the β-barrel pores constructed from oligo(phenylene) derivatives by Matile and coworkers 25À27 proved particularly versatile and useful in many applications including sensing 26 and catalysis. 27 Other examples include the porphyrin-based nanopores by Satake and Kobuke, 28 Gong's π-stacked aromatic heterocycles, 29 the metal-coordinated nanopores by Fy...

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“…They thus embody a sort of (supra)molecular Darwinism! The VCL concept described herein bears relation to processes and approaches such as the formation of clathrates by assembly of a solid-state host structure around included substrates (6)(7)(8), the template-directed oligonucleotide synthesis (9), the generation of RNA aptamers (10), the computational progressive build-up of a host in a binding site (11), the self-assembly of an inorganic catalyst (12) or of ionophores (13), the template-induced formation of a metallomacrocycle (14) or of macrocyclic lactams (15), the construction of a binding site via metal ion coordination of the components (16), the equilibrated condensation of multiple components to yield macrobicyclic cryptands (17) or macrocyclic oligocholates (18), or the formation of a binding site by noncovalent self-assembly in a molecular monolayer (19) (see also section 9.4.1 in ref. 5).…”

mentioning

confidence: 99%

Virtual combinatorial libraries: Dynamic generation of molecular and supramolecular diversity by self-assembly

Huc¹,

Lehn²

1997

Proc. Natl. Acad. Sci. U.S.A.

444

217

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Molecular and supramolecular diversity may be generated, respectively, by reversible, covalent or noncovalent self-assembly of basic components whose various potential combinations in number and nature represent a virtual combinatorial library. This concept is applied to the induction of inhibitors of carbonic anhydrase (CA) by reversible recombination of aldehyde and amine components. It is found that the presence of CA favors the formation of those condensation compounds that may be expected to present the strongest binding to the CA active site. The virtual combinatorial library approach may represent a powerful methodology for the discovery of substrates, inhibitors, receptors, catalysts, and carriers for a variety of processes.

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‘Living’ macrolactonisation: thermodynamically-controlled cyclisation and interconversion of oligocholates

Abstract: Cyclocholates are efficiently and rapidly synthesised from suitable monomers by transesterification under thermodynamic, equilibrating conditions using a potassium methoxidexrown ether complex.

Cited by 148 publications

References 22 publications

Controlling the Conformation of Oligocholate Foldamers by Surfactant Micelles

Controlling the Conformation of Oligocholate Foldamers by Surfactant Micelles

Translocation of Hydrophilic Molecules across Lipid Bilayers by Salt-Bridged Oligocholates

Virtual combinatorial libraries: Dynamic generation of molecular and supramolecular diversity by self-assembly

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