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AAPS PharmSciTech. 2005 December; 6(4): E655–E663.
Published online 2005 December 27. doi:  10.1208/pt060482
PMCID: PMC2750615

The crystal structure and physicochemical characteristics of 2-hydroxy-N-[3(5)-pyrazolyl]-1,4-naphthoquinone-4-imine, a new antitrypanosomal compound

Abstract

This study was designed to investigate the physical characteristics and crystalline structure of 2-hydroxy-N-[3(5)-pyrazolyl]-1,4-naphthoquinone-4-imine (PNQ), a new active compound againstTrypanosoma cruzi, the causative agent of American trypanosomiasis. Methods used included differential scanning calorimetry, thermogravimetry, hot stage microscopy, polarized light microscopy (PLM), Fourier-transform infrared (FTIR) spectroscopy, and high-resolution X-ray powder diffraction (HR-XRPD). According to PLM and HR-XRPD data, PNQ crystallized as red oolitic crystals (absolute methanol) or prisms (dimethyl sulfoxide [DMSO]-water) with the same internal structure. The findings obtained with HR-XRPD data (applying molecular location methods) showed a monoclinic unit cell [a=18.4437(1)Å, b=3.9968(2) Å, c=14.5304(1) Å, α=90°, β=102.71(6)°, γ=90°, V=1044.9(1) Å3, Z=4, space group P21/c], and a crystal structure (excluding H-positions) described by parallel layers in the direction of theb-axis, with molecules held by homochemical (phenyl-phenyl and pyrazole-pyrazole) van der Waals interactions. In addition, FTIR spectra displayed the NH-pyrazole stretch overlapped with the OH absorption at 3222 cm−1, typical of-NH and-OH groups associated through H-bondings; and a carbonyl stretching absorption at 1694 cm−1, indicating a non-extensively H-bonded quinonic C=O, which was in accordance with the solved crystal structure of PNQ. The existence of such cohesive forces shed light on the thermo-analytical data, which revealed that PNQ is a stable solid, unaffected by oxygen that decomposed without melting above 260°C.

Keywords: anti-Trypanosoma cruzi agent, high-resolution X-ray powder diffraction, crystal structure, differential scanning calorimetry

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Selected References

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