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

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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.

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Authors and Affiliations

  1. Departamento de Farmacia, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, 5000, Córdoba, Argentina

    Norma R. Sperandeo

  2. Cátedra de Métodos de Investigación de Minerales, Facultad Ciencias Exactas, Físicas y Naturales, Universidad Nacional de Córdoba, Córdoba, Argentina

    Alicia Karlsson

  3. Agencia Córdoba Ciencia, CEPROCOR, Córdoba, Argentina

    Silvia Cuffini

  4. Department of Physics and Astronomy, SUNY at Stony Brook, 11974-3800, Stony Brook, NY

    Silvina Pagola & Peter W. Stephens

Authors
  1. Norma R. Sperandeo
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  2. Alicia Karlsson
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  3. Silvia Cuffini
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  4. Silvina Pagola
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  5. Peter W. Stephens
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Correspondence to Norma R. Sperandeo.

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Published: December 27, 2005

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Sperandeo, N.R., Karlsson, A., Cuffini, S. et al. The crystal structure and physicochemical characteristics of 2-hydroxy-N-[3(5)-pyrazolyl]-1,4-naphthoquinone-4-imine, a new antitrypanosomal compound. AAPS PharmSciTech 6, 82 (2005). https://doi.org/10.1208/pt060482

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  • DOI: https://doi.org/10.1208/pt060482

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