Molecular Recognition by Zn(II)‐Capped Dynamic Foldamers

Abstract

Two α‐aminoisobutyric acid (Aib) foldamers bearing Zn(II)‐chelating N‐termini have been synthesized and compared with a reported Aib foldamer that has a bis(quinolinyl)/mono(pyridyl) cap (BQPA group). Replacement of the quinolinyl arms of the BQPA‐capped foldamer with pyridyl gave a BPPA‐capped foldamer, then further replacement of the linking pyridyl with a 1,2,3‐triazole gave a BPTA‐capped foldamer. Their ability to relay chiral information from carboxylate bound to Zn(II) at the N‐terminus to a glycinamide‐based NMR reporter of conformational preference at the C‐terminus was measured. The importance of the quinolinyl arms became readily apparent, as the foldamers with pyridyl arms were unable to report on the presence of chiral carboxylate in acetonitrile. Low solubility, X‐ray crystallography and 1H NMR spectroscopy suggested that interfoldamer interactions inhibited carboxylate binding. However changing solvent to methanol revealed that the end‐to‐end relay of chiral information could be observed for the Zn(II) complex of the BPTA‐capped foldamer at low temperature.

Reaction, Recognition, Relay: Anhydride Hydrolysis Reported by Conformationally Responsive Fluorinated Foldamers in Micelles

“…The binding of a given chiral ligand to ( R )‐ 1 and ( S )‐ 1 will produce diastereomeric complexes that may give measurably different NMR spectra [35] . The first chiral ligand to be studied was N ‐( tert ‐butoxycarbonyl)‐L‐proline (Boc‐L‐Pro 2 , Figure 2a,b), whose binding to Zn(II)(BQPA)‐capped Aib foldamers in CD 3 CN has been well‐characterized [31,37c,38] . Receptors ( R )‐ 1 and ( S )‐ 1 were also soluble in CD 3 CN (and THF, see the SI) but insoluble in CD 3 OD and CDCl 3 .…”

Enantioselective conjugate addition to nitroolefins catalysed by helical peptides with a single remote stereogenic centre

“…24 Since the Aib residue is achiral, a racemic mixture of right- ( P ) or left- ( M ) handed screw-senses is formed; these rapidly interconvert at room temperature in solution. However, attaching a chiral group either covalently 25 or non-covalently 26 to one terminus creates a relay of chiral conformations that propagate down the peptide body to the other terminus, leading to one screw-sense becoming favoured over the other. 27 For example, Clayden and co-workers have shown that a single l -alanine residue at the C-terminus can produce a significant enhancement in the proportion of P helix ( P : M of 88 : 12).…”