Structure−Function Relationship of Amino Acid−[2]Rotaxanes

Abstract

Synthetic methodology was developed to construct amino acid-[2]rotaxanes that have phenylalanine and 3,5-di-tert-butylbenzene as blocking groups and dibenzo-24-crown-8, derivatized with either N-acetylargininyl or a carboxylic group, as the ring. A relative measure of the intramolecular interaction energies between the functional groups in DMSO/water mixtures is obtained by comparing their pK(a) values. Rotaxane structures were investigated through 2D NMR analysis and molecular dynamics simulations. Association constants for complexes of amino acids and rotaxanes in various protonation states were determined in a variety of solvent systems by (1)H NMR analysis. The unique intracomponent interactions that exist in the rotaxanes and their ability to act as artificial receptors are discussed.

Thermodynamics of Complexes between Dibenzo‐24‐crown‐8 Derivatives and 1,2‐Bis(pyridinium)ethanes

“…Analytical-grade CH 3 CN was dried with calcium hydride and then distilled fractionally to give the anhydrous solvent for calorimetry. Of the macrocyclic hosts in Scheme 1,, [14] diformyl-dibenzo-24-crown-8 (2), [15] dinitro-dibenzo-24-crown-8 (3), [16] dimethyl-dibenzo-24-crown-8 (4), [17] and diamino-dibenzo-24-crown-8 (5) [16] were prepared according to the literature procedures. No efforts were made to separate the cis/trans isomers.…”

Recent Advances in the Synthesis of Ammonium-Based Rotaxanes

“…Some examples of such rotaxanes are shown in Figure 2. In their model, the ring motion is used as a mimic of the peptide loops that cover protein binding sites [73]. Thus, they synthesized multiple crown ethers with different pending groups, including amino acids, and studied their ability to act as artificial receptors.…”

Assembly of [2]Rotaxanes in Water

“…The released water molecules participate in the hydrogen‐bonding network of the water bulk, which results in an enthalpy gain. Most known water‐soluble rotaxane systems that rely on the hydrophobic effect comprise cyclodextrin, pillar[ n ]arene, or cucurbit[ n ]uril as host molecules, and for some of these systems acidic media or organic co‐solvents are required , . Prominent examples of synthetically modifiable water‐soluble macrocycles are the quaternary ammonium‐functionalized dicationic spiro‐cyclophanes developed and extensively studied by Diederich and co‐workers , .…”

“…Most known water-soluble rotaxane systems that rely on the hydrophobic effect comprise cyclodextrin, [43][44][45][46] pillar[n]arene, [47][48][49] or cucurbit[n]uril [50][51][52] as host molecules, and for some of these systems acidic media or organic co-solvents are required. [51,[53][54][55] Prominent examples of synthetically modifiable water-soluble macrocycles are the quaternary ammonium-functionalized dicationic spiro-cyclophanes developed and extensively studied by Diederich and co-workers. [56,57] The dichloride of cyclophane 1 [56] (Scheme 1) forms 1:1 inclusion complexes with aromatic compounds, for example, 2,6-disubstituted naphthalene derivatives, in protic solvents due to a nonclassical hydrophobic effect.…”