A Molecular Oyster: A Neutral Anion Receptor Containing Two Cyclopeptide Subunits with a Remarkable Sulfate Affinity in Aqueous Solution

Abstract

An artificial anion receptor is presented, in which two cyclohexapeptide subunits containing l-proline and 6-aminopicolinic acid subunits in an alternating sequence are connected via an adipinic acid spacer. This compound was devised to stabilize the 2:1 sandwich-type anion complexes that are observed when the two cyclopeptide moieties are not covalently connected and to obtain a 1:1 stoichiometry for these aggregates. Electrospray ionization mass spectrometry and NMR spectroscopic investigations showed that the bridged bis(cyclopeptide) does indeed form defined 1:1 complexes with halides, sulfate, and nitrate. ROESY NMR spectroscopy and molecular modeling allowed a structural assignment of the sulfate complex in solution. The stabilities of various anion complexes were determined by means of NMR titrations and isothermal titration microcalorimetry in 50% water/methanol. Both methods gave essentially the same quantitative results, namely stability constants that varied in the range 105-102 M-1 and decreased in the order SO42- > I- > Br- > Cl- > NO3-. This order was rationalized in terms of the size of the anions with the larger anions forming the more stable complexes because they better fit into the cavity of the host. The ability of sulfate to form stronger hydrogen bonds to the NH groups of the receptor, in addition to its slightly larger ionic radius with respect to iodide, causes the higher stability of the sulfate complex. No significant effect of the countercation on complex stability was observed. Furthermore, complex stability is enthalpically as well as entropically favored. A comparison of the iodide and sulfate complex stabilities of the ditopic receptor with those of a cyclopeptide that forms 1:1 anion complexes in solution showed that the presence of a second binding site increases complex stability by a factor of 100-350.

Anion Recognition in Water: Recent Advances from a Supramolecular and Macromolecular Perspective

“…demonstrated that a cyclopeptide‐derived host 14 formed a 2:1 stoichiometric host–guest complex with halide and sulfate anions in D 2 O/CD 3 OD 80:20 solution through convergent hydrogen‐bonding interactions, aided by the hydrophobic effect (Figure 5). 30 They subsequently showed that 1:1 host–guest stoichiometric complexes could be prepared by joining two cyclopeptide macrocycles together with a flexible linker 31. The same research group has now reported a related host system 15 (Figure 5) which exhibits enhanced aqueous solubility, thus enabling the recognition of iodide and sulfate in 95:5 D 2 O/CD 3 OD (log  K =3.70 and 3.96 respectively) 32.…”

Anion recognition by cyclic peptides

“…3). 49 Stability constants of these complexes, determined by 1 H NMR titrations and isothermal titration microcalorimetry, are in the range of 10 5 -10 2 M À1 in 50% water-methanol and decrease in the order SO 4 2À 4 I À 4 Br À 4 Cl À 4 NO 3 À . This order was rationalised in terms of anion size, with larger anions having a better fit with the host cavity.…”

Supramolekulare Chemie von Anionen: von der Erkennung zur chemischen Anwendung

“…[53] Es wurde ein fünfeckiger "Cyanostern-Makrocyclus" synthetisiert (Abbildung 10), der große Anionen wie PF 6 À in Form eines Makrocyclus-AnionSandwichkomplexes im stçchiometrischen [56] In einer nachfolgenden Arbeit ermçglichte die kovalente Verknüpfung von zwei Cyclopeptiden mit Adipinsäure die Herstellung von Rezeptoren mit der Form einer "molekularen Auster", die in einem 50:50-Gemisch aus H 2 O und CH 3 OH mit log K a % 5 Sulfat binden kann (Abbildung 12 b). [57] Die Funktionsfähigkeit dieser Rezeptoren in solchen konkurrierenden Lçsungsmitteln wurde den hydrophoben Wechselwirkungen zwischen den Cyclopeptiden zugeschrieben, die das gebundene Anion einkapseln. [58] Jeong und Suk berichteten über die Bildung von auf Indolocarbazolen basierenden Foldameren, die mit Halogenidtemplaten in Wasser reagieren (z.…”