Long-range effects on the capture and release of a chiral guest by a helical molecular capsule.
Helically folded molecular capsules based on oligoamide sequences of aromatic amino acids which are capable of binding tartaric acid in organic solvents with high affinity and diastereoselectivity have been synthesized, and their structures and binding properties investigated by (1)H NMR, X-ray crystallography, circular dichroism, and molecular modeling. We found that elongating the helices at their extremities by adding monomers remote from the tartaric binding site results in a strong increase of the overall helix stability, but it does not influence the host-guest complex stability. The effect of this elongation on the binding and release rates of the guest molecules follows an unexpected non-monotonous trend. Three independent observations (direct monitoring of exchange over time, 2D-EXSY NMR, and molecular modeling) concur and show that guest exchange rates tend to first increase upon increasing helix length and then decrease when helix length is increased further. This investigation thus reveals the complex effects of adding monomers in a helically folded sequence on a binding event that occurs at a remote site and sheds light on possible binding and release mechanisms.
Université Bordeaux, CBMN, UMR 5248, Institut Européen de Chimie Biologie, 2 rue Escarpit, 33607 Pessac, France.
Yann
Y
Ferrand
Nagula
N
Chandramouli
Amol M
AM
Kendhale
Christophe
C
Aube
Brice
B
Kauffmann
Axelle
A
Grélard
Michel
M
Laguerre
Didier
D
Dubreuil
Ivan
I
Huc
D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry*; D024322:Amino Acids, Aromatic / Q000138:chemical synthesis / Q000737:chemistry*; D001665:Binding Sites; D018360:Crystallography, X-Ray; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D017510:Protein Folding; D017433:Protein Structure, Secondary; D013644:Tartrates / Q000737:chemistry* / Q000302:isolation & purification
D000577:Amides; D024322:Amino Acids, Aromatic; D013644:Tartrates; C029768:tartaric acid