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Conformational Switching of a Foldamer in a Multicomponent System by pH-Filtered Selection between Competing Noncovalent Interactions.

Brioche J, Pike SJ, Tshepelevitsh S, Leito I, Morris GA, Webb SJ, Clayden J - J. Am. Chem. Soc. (2015)

Bottom Line: As a consequence of this noncovalent interaction, a global absolute screw sense preference, detectable by (13)C NMR, is induced in the foldamer.Addition of base, or acid, to the mixture of ligands competitively modulates their interaction with the binding site, and reversibly switches the foldamer chain between its left and right-handed conformations.As a result, the foldamer-ligand mixture behaves as a biomimetic chemical system with emergent properties, functioning as a "proton-counting" molecular device capable of providing a tunable, pH-dependent conformational response to its environment.

View Article: PubMed Central - PubMed

Affiliation: †School of Chemistry, University of Manchester, Oxford Road, Manchester M13 9PL, United Kingdom.

ABSTRACT
Biomolecular systems are able to respond to their chemical environment through reversible, selective, noncovalent intermolecular interactions. Typically, these interactions induce conformational changes that initiate a signaling cascade, allowing the regulation of biochemical pathways. In this work, we describe an artificial molecular system that mimics this ability to translate selective noncovalent interactions into reversible conformational changes. An achiral but helical foldamer carrying a basic binding site interacts selectively with the most acidic member of a suite of chiral ligands. As a consequence of this noncovalent interaction, a global absolute screw sense preference, detectable by (13)C NMR, is induced in the foldamer. Addition of base, or acid, to the mixture of ligands competitively modulates their interaction with the binding site, and reversibly switches the foldamer chain between its left and right-handed conformations. As a result, the foldamer-ligand mixture behaves as a biomimetic chemical system with emergent properties, functioning as a "proton-counting" molecular device capable of providing a tunable, pH-dependent conformational response to its environment.

No MeSH data available.


Related in: MedlinePlus

Conformational switching of foldamer F4* with threecompeting chiral ligands. [F4*] = 10 mM, CDCl3, 296 K; all subsequent additions are of 1.5 equiv relative to F4*. Portions of the 13C NMR spectra of the mixturescontaining the labeled signals of F4* are shown, withanisochronicity Δδ reported as the difference in chemicalshift between the major and minor labeled signals of F4*, δmaj – δmin, measuredin ppb. Protonated species available for interaction with the F4* binding site (represented by the pyridine in the coloredrectangle) are indicated by blue/green (for chiral species) or gray(for achiral species) disks, and acids HA are stackedin order of pKa. The number of protonsavailable is represented by the number of discs, building up fromthe bottom of the stack. Proposed conformation-inducing interactionswith F4* (whether these are hydrogen-bonded or ion-pairedis left undefined) are coded by matched colors: blue indicates inductionof a P screw-sense; green indicates induction ofan M screw-sense; red indicates no screw-sense induction.The most significant interaction is assumed to be between F4* and the top (typically the most acidic) protonated species in eachmultiply protonated stack. 7(g) is an exception: A1– is probably protonated rather than NH3,but the lack of screw sense preference in F4* suggestsinteraction preferentially with an NH4+ ion.
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fig7: Conformational switching of foldamer F4* with threecompeting chiral ligands. [F4*] = 10 mM, CDCl3, 296 K; all subsequent additions are of 1.5 equiv relative to F4*. Portions of the 13C NMR spectra of the mixturescontaining the labeled signals of F4* are shown, withanisochronicity Δδ reported as the difference in chemicalshift between the major and minor labeled signals of F4*, δmaj – δmin, measuredin ppb. Protonated species available for interaction with the F4* binding site (represented by the pyridine in the coloredrectangle) are indicated by blue/green (for chiral species) or gray(for achiral species) disks, and acids HA are stackedin order of pKa. The number of protonsavailable is represented by the number of discs, building up fromthe bottom of the stack. Proposed conformation-inducing interactionswith F4* (whether these are hydrogen-bonded or ion-pairedis left undefined) are coded by matched colors: blue indicates inductionof a P screw-sense; green indicates induction ofan M screw-sense; red indicates no screw-sense induction.The most significant interaction is assumed to be between F4* and the top (typically the most acidic) protonated species in eachmultiply protonated stack. 7(g) is an exception: A1– is probably protonated rather than NH3,but the lack of screw sense preference in F4* suggestsinteraction preferentially with an NH4+ ion.

Mentions: Encouraged by theresponsiveness of this three-component system, we investigated thepotential for acidity-driven conformational switching in a four-componentsystem composed of F4*, (R)-HA1, (S)-HA4, and (S)-HA6. Starting with a solution of F4* (1.0 equiv)in CDCl3 (Figure 7a) we added (R)-HA1 (1.5 equiv), inducing an M screw sense in F4* (Figure 7b), followed by (R)-HA4 (1.5 equiv),inverting the screw-sense of F4* from M to P (Figure 7c). Now, additionof (S)-N-triflyl phosphoramide HA6 (1.5 equiv) to this mixture induces a second helical inversionfrom P back to M (Figure 7d), with a value of Δδ = −112ppb. We presume that HA6 takes control of the conformationof the foldamer F4* by protonating the HA4↔F4* pairing of the weaker acid HA4 and inducing a conformational preference characteristic of the new(probably largely ion-paired62) HA6↔F4* interaction (cf. Table 1, entry 4).


Conformational Switching of a Foldamer in a Multicomponent System by pH-Filtered Selection between Competing Noncovalent Interactions.

Brioche J, Pike SJ, Tshepelevitsh S, Leito I, Morris GA, Webb SJ, Clayden J - J. Am. Chem. Soc. (2015)

Conformational switching of foldamer F4* with threecompeting chiral ligands. [F4*] = 10 mM, CDCl3, 296 K; all subsequent additions are of 1.5 equiv relative to F4*. Portions of the 13C NMR spectra of the mixturescontaining the labeled signals of F4* are shown, withanisochronicity Δδ reported as the difference in chemicalshift between the major and minor labeled signals of F4*, δmaj – δmin, measuredin ppb. Protonated species available for interaction with the F4* binding site (represented by the pyridine in the coloredrectangle) are indicated by blue/green (for chiral species) or gray(for achiral species) disks, and acids HA are stackedin order of pKa. The number of protonsavailable is represented by the number of discs, building up fromthe bottom of the stack. Proposed conformation-inducing interactionswith F4* (whether these are hydrogen-bonded or ion-pairedis left undefined) are coded by matched colors: blue indicates inductionof a P screw-sense; green indicates induction ofan M screw-sense; red indicates no screw-sense induction.The most significant interaction is assumed to be between F4* and the top (typically the most acidic) protonated species in eachmultiply protonated stack. 7(g) is an exception: A1– is probably protonated rather than NH3,but the lack of screw sense preference in F4* suggestsinteraction preferentially with an NH4+ ion.
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fig7: Conformational switching of foldamer F4* with threecompeting chiral ligands. [F4*] = 10 mM, CDCl3, 296 K; all subsequent additions are of 1.5 equiv relative to F4*. Portions of the 13C NMR spectra of the mixturescontaining the labeled signals of F4* are shown, withanisochronicity Δδ reported as the difference in chemicalshift between the major and minor labeled signals of F4*, δmaj – δmin, measuredin ppb. Protonated species available for interaction with the F4* binding site (represented by the pyridine in the coloredrectangle) are indicated by blue/green (for chiral species) or gray(for achiral species) disks, and acids HA are stackedin order of pKa. The number of protonsavailable is represented by the number of discs, building up fromthe bottom of the stack. Proposed conformation-inducing interactionswith F4* (whether these are hydrogen-bonded or ion-pairedis left undefined) are coded by matched colors: blue indicates inductionof a P screw-sense; green indicates induction ofan M screw-sense; red indicates no screw-sense induction.The most significant interaction is assumed to be between F4* and the top (typically the most acidic) protonated species in eachmultiply protonated stack. 7(g) is an exception: A1– is probably protonated rather than NH3,but the lack of screw sense preference in F4* suggestsinteraction preferentially with an NH4+ ion.
Mentions: Encouraged by theresponsiveness of this three-component system, we investigated thepotential for acidity-driven conformational switching in a four-componentsystem composed of F4*, (R)-HA1, (S)-HA4, and (S)-HA6. Starting with a solution of F4* (1.0 equiv)in CDCl3 (Figure 7a) we added (R)-HA1 (1.5 equiv), inducing an M screw sense in F4* (Figure 7b), followed by (R)-HA4 (1.5 equiv),inverting the screw-sense of F4* from M to P (Figure 7c). Now, additionof (S)-N-triflyl phosphoramide HA6 (1.5 equiv) to this mixture induces a second helical inversionfrom P back to M (Figure 7d), with a value of Δδ = −112ppb. We presume that HA6 takes control of the conformationof the foldamer F4* by protonating the HA4↔F4* pairing of the weaker acid HA4 and inducing a conformational preference characteristic of the new(probably largely ion-paired62) HA6↔F4* interaction (cf. Table 1, entry 4).

Bottom Line: As a consequence of this noncovalent interaction, a global absolute screw sense preference, detectable by (13)C NMR, is induced in the foldamer.Addition of base, or acid, to the mixture of ligands competitively modulates their interaction with the binding site, and reversibly switches the foldamer chain between its left and right-handed conformations.As a result, the foldamer-ligand mixture behaves as a biomimetic chemical system with emergent properties, functioning as a "proton-counting" molecular device capable of providing a tunable, pH-dependent conformational response to its environment.

View Article: PubMed Central - PubMed

Affiliation: †School of Chemistry, University of Manchester, Oxford Road, Manchester M13 9PL, United Kingdom.

ABSTRACT
Biomolecular systems are able to respond to their chemical environment through reversible, selective, noncovalent intermolecular interactions. Typically, these interactions induce conformational changes that initiate a signaling cascade, allowing the regulation of biochemical pathways. In this work, we describe an artificial molecular system that mimics this ability to translate selective noncovalent interactions into reversible conformational changes. An achiral but helical foldamer carrying a basic binding site interacts selectively with the most acidic member of a suite of chiral ligands. As a consequence of this noncovalent interaction, a global absolute screw sense preference, detectable by (13)C NMR, is induced in the foldamer. Addition of base, or acid, to the mixture of ligands competitively modulates their interaction with the binding site, and reversibly switches the foldamer chain between its left and right-handed conformations. As a result, the foldamer-ligand mixture behaves as a biomimetic chemical system with emergent properties, functioning as a "proton-counting" molecular device capable of providing a tunable, pH-dependent conformational response to its environment.

No MeSH data available.


Related in: MedlinePlus