Pyrazole amino acids: hydrogen bonding directed conformations of 3-amino-1H-pyrazole-5-carboxylic acid residue

Abstract

A series of model compounds containing 3-amino-1H-pyrazole-5-carboxylic acid residue with N-terminal amide/urethane and C-terminal amide/hydrazide/ester groups were investigated by using NMR, Fourier transform infrared, and single-crystal X-ray diffraction methods, additionally supported by theoretical calculations. The studies demonstrate that the most preferred is the extended conformation with torsion angles ϕ and ψ close to ±180°. The studied 1H-pyrazole with N-terminal amide/urethane and C-terminal amide/hydrazide groups solely adopts this energetically favored conformation confirming rigidity of that structural motif. However, when the C-terminal ester group is present, the second conformation with torsion angles ϕ and ψ close to ±180° and 0°, respectively, is accessible. The conformational equilibrium is observed in NMR and Fourier transform infrared studies in solution in polar environment as well as in the crystal structures of other related compounds. The observed conformational preferences are clearly related to the presence of intramolecular interactions formed within the studied residue. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.

Annular Tautomerism of 3(5)-Disubstituted-1H-pyrazoles with Ester and Amide Groups

“…To get more detailed information about these properties, the conformational properties of the 3-amino-1 H -pyrazole-5-carboxylic acid residue were investigated. It was found that the observed conformational preferences were clearly related to the presence of intramolecular interactions formed within the studied residue [29]. This shows that the N -unsubstituted 1 H -pyrazole moiety is able to create a specific type of hydrogen interaction and, then, association, which can be crucial for biological properties, or even broader for materials science.…”