Solution conformations of oligomers of α ‐aminoisobutyric acid°

Abstract

The N‐acetyl(Aib)nN' ‐methylamides (with n= 1, 2 and 3) and the N‐acetyl‐(Aib)3 methyl ester have been synthesized using an oxazolone procedure. An experimental conformational analysis of this series of oligomers has been carried out in water, DMSO‐d6 and CDCI3 using n.m.r. techniques, and in chloroform using i.r. spectroscopy. Deuterium exchange rates of amide protons in DMSO‐d6 and the rates of change of these proton chemical shifts with temperature in water, DMSO‐d6 and CDCI3 indicate that the oligomeric N'‐methylamides adopt conformations that have no hydrogen bonds when n = 1, one hydrogen bond when n = 2, and two hydrogen bonds when n = 3, and that Ac(Aib)3OMe has a conformation with one hydrogen bond. An analysis of the N‐H stretching region of the i.r. spectra of these compounds in CHCI3 also suggests the existence of these conformational states. These data imply that the peptides adopt the 310‐helical and not the α‐helical conformation in solution. This conclusion supports the hypothesis that the Aib residue has asymmetric geometry at the Cα atom in solution, similar to that reported in the literature for the crystalline state.

N–H⋯X interactions stabilize intra-residue C5 hydrogen bonded conformations in heterocyclic α-amino acid derivatives

“…5). A similar NH frequency value was previously indicated for a C5 conformer in derivatives of 2-aminoisobutyric acid [19][20][21] and diethylglycine. 27 The present observations for 1-3, aided by further insights from theoretical gas phase studies (ESI Section S2.5 †), suggest that this is the characteristic signature of a C5 interaction in a,a-disubstituted amino acid derivatives in solution.…”

“…In this area, one of the most enigmatic phenomena is the intra-residue interaction between the N-H and C]O dipoles known as the C5 H-bond. 14 Pioneering studies [15][16][17][18][19][20][21] and salutary subsequent work [22][23][24] on model compounds suggested that this weak interaction succumbs easily to C7 or C10 H-bonds which stabilize folded structures in solution (Fig. 1).…”

Handedness preference and switching of peptide helices. Part II: Helices based on noncodedα‐amino acids

“…For (Aib) n homo‐peptides in helix‐supporting solvents (e.g. CDCl 3 ), the same conformation (3 10 ‐helix) is largely prevailing . Using Fourier transform infrared spectroscopy (FTIR) absorption and 1 H NMR, we established that populations close to 90% and 100% of 3 10 ‐helical conformers are attained at the hexamer and octamer level, respectively.…”

Single-Conformation Spectroscopy of Capped Aminoisobutyric Acid Dipeptides: The Effect of C-Terminal Cap Chromophores on Conformation

“…Synthesis of the molecules was carried out at Fairfield University. The most direct synthesis of the three peptide samples was to couple the oxazolone of Ac-Aib–Aib-OH to the three different amine caps in dry MeCN (overnight reflux). , After isolation, the peptides were purified using flash silica gel chromatography. Crystals for X-ray analysis were grown via diffusion of diethyl ether into a solution of methylene chloride.…”