Conformational study of the four main dipyrone metabolites through theoretical methods: Electrostatic potential maps and NBO calculations

Studies on the spatial structure, through theoretical calculations, of the main four metabolites from Dipyrone (4-methyl-amino-antipyrine, 4-amino-antipyrine, 4-acetyl-amino-antipyrine and 4-formyl-amino-antipyrine), are reported. The potential energy surface (PES) was built and the HF method and 6-31G basis set were applied to determine the low energy structures in vacuum and solvent (Onsager and IPCM models). All compounds showed to be more stable in solvent media. The electrostatic potential maps (EPM) were calculated and the difference in electron concentration between the actives sites from the metabolites was observed and explained in terms of NBO analysis. The results are in perfect agreement with the literature data and the difference in electronic density around the active sites is probably responsible for the prevalence and larger activity of metabolites 4-methyl-amino-antipyrine and 4-amino-antipyrine in the drug-receptor binding.