Uses
1H-Imidazole-2-carboxylic acid is a heterocyclic compound derived from histidine that serves as the core metallo-β-lactamase binding pharmacophore (MBP) scaffold influencing MBL inhibition[2][3]. The compound acts as a ligand with histidine to form mixed-ligand coordination complexes with Fe(III), Co(II), and Ni(II) ions[3].
Synthesis Reference(s)
The Journal of Organic Chemistry, 60, p. 1090, 1995
DOI: 10.1021/jo00109a052
Synthesis
General procedure for the synthesis of imidazole-2-carboxylic acid from 2-imidazolecarboxaldehyde: 30% aqueous H2O2 solution (10 g) was slowly added dropwise to stirred aqueous 2-imidazolecarboxaldehyde (2.88 g, 0.030 mol) solution (10 ml). The reaction was continued at room temperature for 72 hours. After completion of the reaction, water was removed by distillation under reduced pressure at room temperature to give a white crystalline solid. The resulting solid was washed with stirred diethyl ether/water (4:1) mixture to remove residual peroxide. Note: Heating may cause decarboxylation to occur. The yield was 97.5%. Melting point (MP) was 156-158 °C. 1H NMR (400 MHz, D2O): δ 7.56 (2H, s, imidazolium ring-H); 13C NMR (400 MHz, D2O): δ 158.86, 141.02, 120.49 ppm. IR (KBr, cm-1): 3392 (m), 3124 (m), 2861 ( m), 1618 (s), 1502 (m), 1462 (m), 1421 (s), 1388 (s), 1322 (m), 1108 (s), 925 (s), 910 (s), 819 (m), 797 (s), 774 (m). Calculated values for elemental analysis (C4H6N2O3, 130.11): C, 36.92%; H, 4.65%; N, 21.53%. Measured values: C, 37.18%; H, 4.94%; N, 21.47%.
References
[1] Journal of Inorganic Biochemistry, 2015, vol. 145, p. 11 - 18
[2]Li, R., Su, H., Chen, W., Yan, Y.-H., Zhou, C., Mou, L., Yang, H., Qian, S., Wang, Z., Yang, L., & Li, G.-B. (2022). Design, Synthesis, and Biological Evaluation of New 1H-Imidazole-2-Carboxylic Acid Derivatives as Metallo-β-Lactamase Inhibitors. Bioorganic & Medicinal Chemistry, 72, 116993.
https://doi.org/10.1016/j.bmc.2022.116993 [3]El‐Lateef, H. M. A., Khalaf, M. M., & Abdou, A. (2024). Preparation, Characterization, <i>In Vitro</i> Biological Evaluation, DFT Calculations, and Molecular Docking Investigations of 1H‐Imidazole‐2‐Carboxylic acid and Histidine‐Based Mixed‐Ligand Complexes. Chemistry & Biodiversity, 22(1).
https://doi.org/10.1002/cbdv.202402049
