Experimental and Theoretical Thermochemistry of the Isomers 3- and 4-Nitrophthalimide.

This work presents a thermochemical study of two derivatives of phthalimide: the isomers 3-nitrophthalimide and 4-nitrophthalimide. The enthalpies of formation for these compounds in the solid phase were obtained by combustion calorimetry. Using ths thermogravimetry technique, the enthalpies of vaporization were obtained. The enthalpies of sublimation were calculated from enthalpies of fusion and vaporization. From experimental data and by ab initio methods, the enthalpies of formation in the gas phase were calculated. With these results, it was possible to determine their relative stability, and it was found that 4-nitrophthalimide is more stable than its isomer 3-nitrophthalimide. This tendency is similar to that of 3-nitrophthalic anhydride and 4-nitrophthalic anhydride, as reported in a previous work by our research group. The enthalpy of isomerization was also obtained, and a good correlation with that of phthalic anhydride derivatives was found. Finally, with the values obtained, the enthalpic difference resulting when the imide group is substituted by an anhydride group was determined.

Molecular docking study of the binding of aminopyridines within the K+ channel.

We present a molecular docking study aimed to identify the binding site of protonated aminopyridines for the blocking of voltage dependent K(+) channels. Several active aminopyridines are considered: 2-aminopyridine, 3-aminopyridine, 4-aminopyridine, 3,4-diaminopyridine, and 4-aminoquinoleine. We apply the AutoDock force field with a lamarckian genetic algorithm, using atomic charges for the ligands derived from the electrostatic potential obtained at the B3LYP/cc-pVDZ level. We find a zone in the alpha-subunit of the K(+) channel bearing common binding sites. This zone corresponds to five amino acids comprised between residuals Thr107 and Ala111, in the KcsA K(+) channel (1J95 pdb structure). The 2-aminopyridine, 3-aminopyridine, 4-aminopyridine, and 3,4-diaminopyridine bind to the carboxylic oxygens of Thr107 and Ala111. In all cases aminopyridines are perpendicular to the axis of the pore. 4-aminoquinoleine binds to the carboxylic oxygen of Ala111. Due to its large size, the molecular plane is parallel to the axis of the pore. The charge distributions and the structures of the binding complexes suggest that the interaction is driven by formation of several hydrogen bonds. We find 2-aminopyridine, 3-aminopyridine, 4-aminopyridine, and 3,4-diaminopyridine with similar binding energy. Considering the standard error of the estimate of the AutoDock force field, this energy should lie, as a rough estimation, in the interval 3-7 kcal mol(-1). On the other hand, 4-aminoquinoleine seems to have a smaller binding energy.