The instability of an amide bond with dilute trifluoroacetic acid (TFA) is a rare chemical event. The native amide bonds are stable even in the neat TFA, which is one of the reagents that releases the peptides from the solid support in the solid-supported peptide synthesis method. In the repertoire of unnatural peptidomics, α-/β-hydrazino acids and their peptides are explored for the synthesis of N -amino peptide derivatives, and their amide bonds are stable in TFA (∼100%) as natural amide bonds. This report describes the synthesis of a β-hydrazino acid analogue as β-troponylhydrazino acid, containing a nonbenzenoid natural troponyl scaffold. The structural and conformational studies of their hybrid di-/tripeptides with the natural amino acid show that the 2-aminotroponyl residue is involved in hydrogen bonding. Surprisingly, the amide bond of β-troponylhydrazino peptides is cleavable with TFA (∼20%) through the formation of a new heterocyclic molecule N -troponylpyrazolidinone or troponylpyrazolidinone. Tropolone and related compounds are excellent biocompatible chromophores. Hence, β-troponylhydrazino acid could be employed for tuning the peptide structure and considered a promising chromophoric acid-sensitive protecting group of a free amine of amino acids/peptides. It could be applied for the estimation of the free amine group functionality by a UV–vis spectrophotometer.

Ampyrone is an amino-functionalized heterocyclic pyrazolone derivative that possesses therapeutic values such as analgesic, anti-inflammatory, and antipyretics. The chemical structure of ampyrone exhibits excellent hydrogen bonding sites and is considered as the potential scaffold of supramolecular self-assembly. Recently, this molecule has been derived into unnatural amino acids such as aminopyrazolone amino acid and its peptides. This report describes that one of its amino acids, O-alkylated ampyrone, containing hybrid (α/β) peptides forms organogel after sonication at 50–55°C with 0.7–0.9% (w/v) in ethyl acetate: hexane (1:3). The formation/morphology of such organogels is studied by nuclear magnetic resonance Fourier-transform infrared (FT-IR), circular dichroism (CD), scanning electron microscope (SEM), transmission electron microscopy (TEM), powder X-ray diffraction (Powder-XRD), and thermogravimetric analysis (TGA). Energy-minimized conformation of APA-peptides reveals the possibility of intermolecular hydrogen bonding. Hence, APA-peptides are promising peptidomimetics for the organogel-peptides.