Relative hydrophilicities of cis and trans formamides

Abstract

Secondary formamides are widely encountered in biology and exist as mixtures of both cis and trans isomers. Here, we assess hydrophilicity differences between isomeric formamides through direct competition experiments. Formamides bearing long aliphatic chains were sequestered in a water-soluble molecular container having a hydrophobic cavity with an end open to the aqueous medium. NMR spectroscopic experiments reveal a modest preference (<1 kcal/mol) for aqueous solvation of the trans formamide terminals over the cis isomers. With diformamides, the supramolecular approach allows staging of intramolecular competition between short-lived species with subtle differences in hydrophobic properties.

Molecules in Confined Spaces: Reactivities and Possibilities in Cavitands

“…The assignments indicate that the cis end of the guest is more hydrophobic than the trans. 38 An application for the preference of the hydrophobic end for the interior is to use this bias as a means of protection from solvent-borne reagents. That is, using the cavitand as a protecting group.…”

Recent Advances in the Applications of Water‐soluble Resorcinarene‐based Deep Cavitands

“…[12] Recently, we determined the relative hydrophilic differences between isomeric formamides by binding in the synthetic cavitand H2 through direct competition experiments. [ 13 , 14 ] Long‐chain mono‐ and bis‐formamides were sequestered in the deep cavitand, driven by hydrophobic forces. The complexes show two sets of NMR signals in the upfield regions corresponding to the trans ‐ and cis ‐isomers (Figure 2 ).…”

“…Formamides exist as a mixture of both cis and trans isomers and cannot be separated under ordinary conditions owing to their rapid interconversion on the human timescale [12] . Recently, we determined the relative hydrophilic differences between isomeric formamides by binding in the synthetic cavitand H2 through direct competition experiments [13,14] . Long‐chain mono‐ and bis‐formamides were sequestered in the deep cavitand, driven by hydrophobic forces.…”

Self-assembly of a water-soluble endohedrally functionalized coordination cage including polar guests

“…The binding of longchain α,ω-bis-formamides to a water-soluble resorcin [4]arene deep cavitand was previously investigated by the Rebek group. 49 The cavitand displayed a reduced binding preference for the trans,cis isomer in front of the trans,trans counterpart.…”