Surprising impact of remote groups on the folding–unfolding and dimer-chain equilibria of bifunctional H-bonding unimers

Abstract

Oligoamide 1, consisting of two H-bonding units linked by a trimethylene linker, was previously found to form a very stable, folded dimer. In this work, replacing the side chains and end groups of 1 led to derivatives that show the surprising impact of end groups on the folding and dimer-chain equilibria of the resultant molecules.

Hydrogen-Bonded Duplexes with Lengthened Linkers

“…In contrast, protons b and d , which form intramolecular H-bonds, have negligible shifts in the same concentration range. Nonlinear regression analysis of the concentration-dependent chemical shift values of proton c yielded a dimerization constant of 322 ± 10 M –1 for 5a (Table ) that is much larger than that of 5′ (∼25 M –1 in CDCl 3 ) . The formation of duplex 5a·5a is confirmed by the NOESY spectrum of 5a (10 mM) recorded in CDCl 3 (Figure S1), which revealed cross-strand NOEs between protons a and h , c and i , and g and h , that are consistent with the expected antiparallel alignment of two strands of 5a (Figure ).…”

“…We developed a series of H-bonded duplexes consisting of linear oligoamide strands. ,, Basic H-bonding units linked via glycine residues result in oligoamide strands having H-bonding sequences defined by arrays of H-bond donors (D) and acceptors (A). An oligoamide specifically pairs with another strand carrying a complementary H-bonding sequence, leading to self-complementary duplexes such as the quadruply H-bonded 1·1 , 2·2 , or heterocomplementary duplexes such as 3·4 (Figure ) and their longer analogues …”

“…Oligoamide 5a was first designed and examined (Figure ). Based on coupling steps we reported before for preparing strands 1 through 4 , H-bonding units derived from 5-aminosalicylic acid were connected with a linker derived from 4-aminobutyric acid into 5a (Scheme S1 and the Supporting Information (SI)). With its ADAD array, strand 5a should dimerize into H-bonded duplex 5a·5a .…”

“…Our original quadruply H-bonded duplexes have association constants that are 2 orders of magnitude, i.e., in the 10 4 M –1 range, larger than the dimerization constant of 5a·5a . The low stability of 5a·5a , which impairs its effectiveness as an association unit, can be attributed to the linker based on 4-aminobutyric acid.…”

“…Strands 5b , 6 , and 7 were synthesized based on procedures similar to those we reported before (Scheme S1 and the SI).…”