I. INTRODUCTION
Fraxinellone (Figure 1), C14H16O3, is formed by the natural degradation of limonoids isolated from the Rutaceae and Meliaceae plants (Trudeau and Morken, Reference Trudeau and Morken2005). It has been reported that fraxinellone possesses a variety of therapeutic activities such as antifertility, antiplatelet aggregation, vascular relaxation, and fungicidal activity (Lü et al., Reference Lü, Wu and Liu2010). Considering the poor solubility of fraxinellone, the inclusion complex of β-cyclodextrin with fraxinellone can increase its solubility. Generally, the inclusion complexes of cyclodextrins with drugs are formed by non-covalent bond (Saenger and Steiner, Reference Saenger and Steiner1998). The crystal structure of β-cyclodextrin-p-aminobenzoic acid inclusion complex (Guo et al., Reference Guo, Su, Chen, Pan and Li2011) has been determined by our research group. This paper continues our work on the crystal structure determination of supramolecular compound directly from X-ray powder diffraction. The inclusion complex of β-cyclodextrin with fraxinellone has been prepared, whose molecular is more complex than p-aminobenzoic acid inclusion complex, and the crystal structure of the inclusion complex directly from powder X-ray diffraction data using a direct space global optimization method and refined by Rietveld refinement techniques has not been reported in the literature.
Figure 1. Structural formula of fraxinellone.
II. EXPERIMENTAL
A. Sample preparation
β-CD was purchased from Tianjin Bodi Chemical Holding Co. Ltd., China, and recrystallized twice from distilled water. Fraxinellone was isolated from the root bark of Dictamnus dasycarpus (Turcz.) and was identified by UV, FT-IR, MS, 1H-NMR, and 13C-NMR. The isolated fraxinellone was checked by RP-HPLC external standard method and the purity was 99.4%.
Fraxinellone (0.5000 g) was dissolved in acetone (4 ml), and then the solution was added to saturated β-CD (55 °C) aqueous solution drop by drop. The mixture was stirred at 50 to 55 °C for 1.5 h, then cooled down at 5 °C for 12 h. The solution was filtered and washed with water to remove the residual β-CD. The inclusion complex of fraxinellone-β-cyclodextrin was characterized by elemental analysis, FT-IR, and TG-DTA.
B. Diffraction data collection and reduction
X-ray powder diffraction measurement was performed on an X'Pert PRO (PANalytical, Almelo, Netherlands) diffractometer using CuKα 1 radiation (λ = 1.5406 Å) with an X'celerator detection system, operating at 40 kV, 40 mA. The diffraction data were collected over the angular range from 5 to 50°2θ with a step size of 0.013 13°2θ and a counting time of 11.22 ms per step at 295 K.
All the structure solution work was performed on Materials Studio 4.2 (Accelrys Co., Ltd., USA) in the State Key Laboratory of Polymer Materials Engineering (Sichuan University, China). The powder diffraction pattern was pretreated by subtracting the background, stripping off Kα 2 peaks, and smoothing. X-Cell method was used to index the pretreated powder diffraction pattern (Neumann, Reference Neumann2003; Pan et al., Reference Pan, Guo, Duan, Cheng and Li2012). MC/SA search algorithm in Powder Solve package (Engel et al., Reference Engel, Wilke, König, Harris and Leusen1999) was used to constantly adjust the conformation, position, and orientation of the molecular groups in the unit cell, which was selected by the indexing step, in order to reduce the difference between the calculated and the measured diffraction data. The results obtained from the Powder Solve step were subsequently refined by Rietveld refinement techniques. In the Rietveld refinement, cell parameters, atomic fraction coordinates, thermal vibration, and preferred orientation parameters were optimized simultaneously to obtain the optimum crystal structure. Only the indexing results are reported below and the crystal-structure results obtained by Rietveld refinement will not be reported in this paper.
III. RESULTS
The experimental powder diffraction pattern is depicted in Figure 2. Indexing results show that the inclusion complex is monoclinical with space group C2 and unit-cell parameters: a = 19.294(2) Å, b = 26.639(1) Å, c = 6.467(3) Å, β = 110.451(9)°, unit-cell volume V = 7930.34 Å3, Z = 4. The values of 2θ obs, d obs, I obs, h, k, l, 2θ cal, d cal, I cal, Δ2θ are listed in Table I.
Figure 2. X-ray powder diffraction pattern of inclusion complex of β-cyclodextrin with fraxinellone using CuKα 1 radiation (λ = 1.5406 Å).
Table I. Indexed X-ray powder diffraction data for inclusion complex of β-cyclodextrin with fraxinellone.
Only the peaks with I rel of 1 or greater are presented [a = 19.294(2) Å, b = 26.639(1) Å, c = 16.467(3) Å, β = 110.451(9)°, cell volume V = 7930.34 Å3 and Z = 4, space group C2]. All measured lines were indexed and are consistent with the C2 space group. The d-values were calculated using CuKα 1 radiation (λ = 1.5406 Å).
