Optimizing side chains for crystal growth from water: a case study of aromatic amide foldamers

Abstract

A systematic approach to endow aromatic molecular architectures with both crystal growth ability from, and solubility in, water.

Carboxylate-functionalized foldamer inhibitors of HIV-1 integrase and Topoisomerase 1: artificial analogues of DNA mimic proteins

“…The asymmetric unit contained a molecule 4 folded as a single helix with no noticeable difference from the structures obtained from organic solvents. As with other helical aromatic amides (50,54), and unlike with α-helical peptides (55,56), electrostatic repulsion between the multiple charges is not conducive of a denaturation, or even of a structural change. This is despite the fact that charges are close enough to influence their apparent p K a values, as was measured for phosphonate side chains (33).…”

“…These bear Fmoc amine main chain protection and acid labile tert -butyl ester side chain protection instead of the tert -butyl-carbamate amine protection and diethyl-phosphonate ester protection used in solution (33). All of them are new except Q OAc and Q 5Ac (49,50). Of note are the different ether or carbon-carbon bond main chain-side chain linkages.…”

“…Of note are the different ether or carbon-carbon bond main chain-side chain linkages. These do not reflect a specific design but are simply a consequence of the synthetic route followed (49,50).…”

“…However, earlier attempts to grow crystals from unprotected anionic oligomers such as 1 have been unsuccessful. We assigned this difficulty to the relative length of the phosphonate side chain, which appears to be detrimental to crystal growth from water (50). This hypothesis was verified when attempting to grow crystals of the new carboxylate-functionalized oligomers: crystal growth from water was successful, but only in the case of hexadecaamide ( m Q Ac Q 5Ac ) 8 which bears the shortest side chains.…”

The influence of substituents on gelation and stacking order of oligoaramid – based supramolecular networks

“…However, the targeted design of functional gelators remains challenging and the synthesis of amphiphilic aramide oligomers has only been addressed by few groups. [16][17][18] Therefore, we present herein the synthesis of amphiphilic aromatic amide oligomers and the investigation of their aqueous gelation behavior by rhelology, scattering methods (SAXS) and imaging techniques such as AFM and SEM. Insight into the molecular aggregation mechanism was gained using full atomistic molecular dynamics simulations.…”