Design and synthesis of ionophores with multiple receptor sites: solution nuclear magnetic resonance studies of their interaction with chloride, sodium and potassium ions

Abstract

lonophores of the bis(crown ether) type, with polyamine linkers, examples of which are known to bind simultaneously to a cation and its counter anion, have been prepared. One-pot reductive amination, used to couple a benzo-crown aldehyde with aliphatic (both linear and cyclic) and aromatic polyamines, proved to be the most efficient route. A strong inhibition of one synthetic route (amine benzylation) was observed.The competitive interaction between chloride and other anions for binding with the protonated ionophores was examined using 35CI N M R spectroscopy. Sandwich complexing of potassium contrasting with single-face complexation of sodium was demonstrated by 13C N MR spectroscopy.Biological systems frequently organise a molecule with two distinct subunits by a strong ionic or co-ordinative type interaction with a metal ion, which holds the units in position for some other biological strategy. For example the two halves of the iron protein of the nitrogenase complex are organised by an Fe,S, cluster linked to cysteines coming from each half, forming a receptor site into which fits the ATP/ADP unit involved in energy transfer for the hydrogenation of dinitrogen. Such examples have prompted chemical mimicry. In this work a promising bis(crown ether) structure was designed to co-ordinate anions within a cavity produced by organisation of the two ends of the molecule with a strong interaction. In the examples tried ' this 'organisation' is a sandwiching of an alkalimetal cation between two crown ethers. Molecules containing two crown ether moieties, separated by a linking group, are known to sandwich potassium but crystallographic evidence of the structure has been sparse. A recent crystal structure determination of a rubidium complex of a Schiffbase-linked bis(crown ether) shows a double sandwich structure, not previously demonstrated.' This has a potential binding site between the two aromatic fragments which link the two crowns of each individual bis(crown ether), which may be represented as shown in Scheme 1, which we have used previously to describe our designThe 1 : 1 sandwich structure (see Scheme 1) has also been demonstrated crystallographically.6 This paper gives details of synthetic routes to, and the separation and characterisation of, multireceptors which should exhibit multiple binding as outlined by us previously in a preliminary report.' 1980,47,81.

Heteroditopic rhenium(I) and ruthenium(II) bipyridyl calix[4]arene receptors for binding cation–anion ion pairs

“…The residue was stirred in diethyl ether and the solvent removed under vacuum to give the product as a white solid (0.91 g, 94% yield). 1 H NMR (300 MHz, CDCl 3 ): δ 1.32 (m, 9H, OCH 2 CH 3 ), 3.32 (d (J = 13), 2H, CCH 2 C), 3.35 (d (J = 13), 4H, CCH 2 C) and 6.48-7.14 (m, 12H, ArH) Microanalysis: C 42 H 44 O 12 ؒ0.5H 2 O requires C 67.28, H 6.05%; found C 67.39, H 5.93%, [4]arene 3. Compound 2 (1.00 g, 1.35 mmol) was refluxed in oxalyl chloride for 2 hours.…”

“…Stimulated by the need to design new selective extraction and transportation reagents for metal salt species of environmental and biological importance, ion pair recognition, the simultaneous binding of cationic and anionic guest species by ditopic receptors, is a rapidly developing new field of coordination chemistry. [1][2][3][4][5][6][7][8][9][10][11][12][13] Novel co-operative and allosteric metal salt complexing behaviour whereby the binding of the metal cation charged guest can enhance, through electrostatic and conformational effects, the subsequent coordination of the pairing anion has been demonstrated by a number of ditopic crown ether functionalised boron, 1 uranyl, 2 polyammonium, 3 amide, 6-12 urea 11 and amide 4, 13 -urea calix [4]arene 5 based receptor systems. In addition such systems have recently been shown to solubilise and transport alkali metal salts across lipophilic membranes.…”

2-{2,4,6-Tris(bromomethyl)-3,5-bis[(1,3-dioxoisoindolin-2-yl)methyl]benzyl}isoindoline-1,3-dione toluene monosolvate

“…The synthesis of ditopic receptors, which interact simultaneously with cationic and anionic guests in so called ion-pair recognition processes, is a rapidly developing area of research (McConnell & Beer, 2012). A number of ditopic receptors based on a macrocylic or acyclic scaffold have been designed and studied (Kinnear et al (1994), Kirkovits et al (2001), Hossain & Schneider (1998), Tsukube et al (1999) and Smith (2010)) Interesting applications, such as binding of amino acids in their zwitterionic state, salt extraction and membrane transport, have been reported in the literature (for a recent review, see McConnell & Beer, 2012). In this context, the title compound is a particularly useful building block for the construction of a large number of receptors with different recognition units, because it provides a base for many synthetic modifications of the molecule structure.…”

Cooperative halide, perrhenate anion–sodium cation binding and pertechnetate extraction and transport by a novel tripodal tris(amido benzo-15-crown-5) ligand

“…Ion pair recognition, the simultaneous complexation of cationic and anionic guest species by multisite receptors, is a new, emerging and topical field of coordination chemistry. [1][2][3][4][5][6] These heteroditopic ligands can be designed to exhibit novel cooperative and allosteric behaviour whereby the binding of one charged guest can influence, through electrostatic and conformational effects, the subsequent coordination of the pairing ion. Such systems have potential as new selective extraction and transportation reagents for ion pair species of environmental importance.…”