Remote Control of the Planar Chirality in Peptide‐Bound Metallomacrocycles and Dynamic‐to‐Static Planar Chirality Control Triggered by Solvent‐Induced 3₁₀‐to‐α‐Helix Transitions

Abstract

Abstract:The dynamic planar chirality in ap eptide-bound Ni II -salphen-based macrocycle can be remotely controlled. First, ar ight-handed (P)-3 10 -helix is induced in the dynamic helical oligopeptides by ac hiral amino acid residue far from the macrocyclic framework. The induced planar chirality remains dynamic in chloroform and acetonitrile,but is almost completely locked in fluoroalcohols as ar esult of the solventinduced transition of the peptide chains from a3 10 -helix to aw ider a-helix, which freezes the rotation of the pendant peptide units around the macrocycle.Long-range communication is ubiquitous in biological systems,f or example in allosteric enzymes.[1] Such longrange information transfer has been successfully achieved in artificial helical systems based on the chiral domino effect, [2] through which an excess of either ar ight-(P)o rl eft-handed (M)h elical conformation can be induced in dynamic helical polymers and oligomers including peptides that are composed of achiral components by covalently or noncovalently introducing chiral residues at the chain ends.T aking advantage of this unique chiral domino effect, we recently succeeded in the multistep remote control of the dynamic metal-centered chirality (D or L)ofcomplexes coordinated by 2,2'-bipyridine (bpy) ligands bearing dynamic helical oligopeptides.[3] We anticipated that this multistep remote-control strategy based on the chiral domino effect would be applicable to control other types of complex supramolecular chirality, [4] such as the planar chirality of macrocycles. [5] To this end, we synthesized novel dynamic peptide-bound Ni II -salphen-based macrocycles [6] (Figure 1a)i nw hich the planar chirality results from the relative orientations of the peptide-bound phenylene units,w hich can rotate around the macrocyclic plane via the peptide chains passing through the inside of the macrocyclic cavity,t hus producing four interconvertible diastereomers [(pS,pS,pS), (pR,pS,pS), (pR,pR,pS), and (pR,pR,pR)].Tw od ynamic peptides with the sequence (Ac 6 c) n -l-ValAib-OTg( n = 4a nd 6) [7] were employed as pendants of the macrocycles based on ap revious study [3] (Figure 1a). The peptide-bound Ni II -salphen-based macrocycles were prepared by the reactions of the peptide-bound disalicylaldehydes 1 6mer and 2 8mer with ortho-phenylenediamine in the presence of nickel(II) acetate,p roducing the desired metallomacrocycles 3 6mer and 4 8mer (Figure 1a), respectively,inhigh yields (92-97 %).

Synthesis and properties of chiral nanoparticles based on (pS)- and (pR)-decasubstituted pillar[5]arenes containing secondary amide fragments

“…This conclusions coincides well with the data previously published and semi-empirical calculations (PM6 method in MOPAC2012) performed elsewhere for similar compounds. 36 However, these spin systems were unresolved while the region of amide protons was clearly expressed. This facilitated further study.…”

Self-Assembling Peptide-Appended Metallomacrocycle Pores for Selective Water Translocation

“…The synthesis previously reported by Yashima et al is quantitatively leading to the trimeric macrocycle in high yields (92−97%). 24 The unprecedented dynamic planar chirality observed with compound 1 is crucial for maintaining the pR/pS interconversion in this system, while it might be strongly suppressed when the compound is embedded in a bilayer membrane environment.…”

“…The hydrophobic nature of the peptide arms may provide not only an important solubility of these compounds in the membrane but also, more importantly, a rational design strategy for developing macrocycle-based ion channels that make use of 3 10 -to-helix transitions to regulate the opening of the pores and implicitly the selectivity of the transport . Other hydrophobic peptides scaffolded around synthetic pillarene − or cyclodextrins have been developed and inserted into bilayers.…”

A Constrained and “Inverted” [3+3] Salphen Macrocycle with an ortho‐Phenylethynyl Substitution Pattern

“…The reversible character of imine condensation with dynamic exchange of C=N bonds meets the requirements for dynamic covalent reactions, which has been exploited to prepare shape‐persistent 2D and 3D molecular systems of high complexity in high yields, such as macrocycles tiered architectures, capsules, and molecular cages . One of the main synthetic challenges is to obtain selectively one type of macrocycle of a given size in good yield.…”