Preparation and characterization of spiro-acridine derivative and 2-hydroxypropyl-β-cyclodextrin inclusion complex

• Published in: Journal of molecular structure Vol. 1222; p. 128945
• Main Authors: Melo, Camila de Oliveira, Rodrigues, Maria Salete da Silva, da Silva, Marcus Vinicius Santos, Marcelino, Henrique Rodrigues, Rabello, Marcelo Montenegro, de Moura, Ricardo Olímpio, Eleamen Oliveira, Elquio
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 15.12.2020
• Subjects: Acridine derivative; Fluorescence spectrophotometry; Inclusion complex; Molecular modeling; NMR spectroscopy; Acridine derivative; Fluorescence spectrophotometry; NMR spectroscopy; Molecular modeling; Inclusion complex
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2020.128945

•Spiro-acridine AMTAC-01 was complexed with 2-hydroxypropryl-β-cyclodextrin (HPβCD).•HPβCD complexed with AMTAC-01 in a 1:1 molar ratio as shown by molecular modeling.•¹H NMR, FT-IR, Raman, SEM, XRD, and fluorescence confirmed the inclusion complex. The spiro-acridine derivative (E)-1′-(benzylideneamino)-5′-oxo-1′,5′-dihydro-10H-spiro[acridine-9,2′-pyrrole]-4-carbonitrile (AMTAC-01) is a synthetic compound with limited water solubility, which restricts its physiological activities and therapeutic applications. Hence, we investigated the complexation of AMTAC-01 with 2-hydroxypropyl‑β‑cyclodextrin (HPβCD) using the freeze-drying method. Complex formation was characterized by scanning electron microscopy, X-ray diffractometry(XRD), nuclear magnetic resonance spectroscopy, Fourier transform infrared spectroscopy, Raman spectroscopy, and fluorescence spectrophotometry. Additionally, molecular modeling and phase solubility studies were performed. Molecular modeling demonstrated the most stable inclusion model, and phase solubility studies indicated that AMTAC-01 and HPβCD formed a 1:1 inclusion complex with an apparent stability constant of 1145.3 M − 1. XRD and spectroscopy results suggest intermolecular interactions between AMTAC-01 and HPβCD, with the formation of a 1:1 inclusion complex demonstrating an amorphous pattern and alterations in band distribution intensities compared with free drug. [Display omitted]