title: Characterization, activity, and computer modeling of a molecular inclusion complex containing rifaldazine.
abstract: BACKGROUND
  The purpose of this study was to develop, characterize, and investigate a molecular inclusion complex containing rifaldazine with good solubility and antibacterial activity.
  
  
  METHODS
  Rifaldazine, a lipophilic molecule, was encapsulated into the hydrophobic cavity of β-cyclodextrin to form a molecular inclusion complex (RAABCD) with good solubility. RAABCD was prepared in a short time using a solid-state grinding method. The inclusion ratio, binding constant, and change in Gibbs free energy were determined by a phase solubility diagram and/or ultraviolet-visible spectroscopy. Differential scanning calorimetry and Fourier transform infrared spectroscopy of RAABCD were performed. Morphological features of RAABCD were observed by photomicroscopy. The most likely optimal configuration for RAABCD was simulated by computer modeling. Broth macrodilution testing was done to investigate the antibacterial activity of RAABCD.
  
  
  RESULTS
  The inclusion ratio, binding constant, and change in Gibbs free energy, determined by a phase solubility diagram and/or ultraviolet-visible spectroscopy were 1:1, 288.33/261.33 L/mol, and 32.29/31.73 kJ/mol, respectively. Differential scanning calorimetry and Fourier transformed infrared spectra of RAABCD confirmed the molecular interaction between rifaldazine and β-cyclodextrin. The morphological difference between irregular and amorphous-shaped RAABCD and columnar-shaped rifaldazine further confirmed the molecular encapsulation of rifaldazine. The most likely optimal configuration for RAABCD was confirmed by computer modeling. Broth macrodilution testing indicated that RAABCD had good antibacterial activity.
  
  
  CONCLUSIONS
  RAABCD had improved solubility and good activity, and might be a promising alternative for treatment of a range of bacterial infections.
authors: Department of Thoracic Surgery, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, People’s Republic of China.
authors: Qunyou
authors: Q
authors: Tan
authors: Dan
authors: D
authors: He
authors: Mingjun
authors: M
authors: Wu
authors: Lin
authors: L
authors: Yang
authors: Yong
authors: Y
authors: Ren
authors: Juan
authors: J
authors: Liu
authors: Jingqing
authors: J
authors: Zhang
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D002152:Calorimetry, Differential Scanning; D004926:Escherichia coli / Q000187:drug effects; D008958:Models, Molecular; D053769:Nanocapsules; D050997:Nanomedicine; D012293:Rifampin / Q000737:chemistry* / Q000494:pharmacology*; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013211:Staphylococcus aureus / Q000187:drug effects; D013816:Thermodynamics; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D000900:Anti-Bacterial Agents; D053769:Nanocapsules; D047392:beta-Cyclodextrins; D012293:Rifampin
keywords: Fourier transform infrared spectra; computer modeling; cyclodextrin inclusion complex; differential scanning calorimetry; rifaldazine; stoichiometric relationships
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