%0 Journal Article
%T Crystal Structure of Apraclonidine Hydrochloride
%A Noriaki Hirayama
%J Journal of Crystallography
%D 2013
%R 10.1155/2013/249672
%X Apraclonidine is used for the treatment of postsurgical elevated intraocular pressure. The crystal structure of its hydrochloride, C9H10Cl2N4¡¤HCl, was determined by X-ray analysis. The crystal belongs to space group with the cell dimensions , , £¿£¿, and ¡ã. The final (all reflections) value is 0.053. Apraclonidine has a more twisted structure than its related drug of clonidine. The nitrogen atom bridging the two rings is protonated. 1. Introduction Apraclonidine (2,6-dichloro-N1-(4,5-dihydro-1H-imidazol-2-yl)-1,4-benzenediamine) is a potent ¦Á-adrenergic agent similar to clonidine. The chemical structures of apraclonidine hydrochloride and clonidine are compared in Figure 1. Apraclonidine reduces aqueous humor formation. In clinical evaluation in the treatment of intraocular pressure, Robin et al. have showed that apraclonidine is effective in preventing the acute large postoperative intraocular pressure rise associated with argon laser iridotomy [1]. Apraclonidine is now used widely for the treatment of postsurgical elevated intraocular pressure. The additional amino group in apraclonidine makes it more polar than clonidine and reduces the penetration through the blood-brain barrier. Therefore, the pharmacological profile of apraclonidine is characterized by peripheral than central effects. Apraclonidine hydrochloride is clinically used now, but the crystal structure has not been determined yet. Therefore, the X-ray analysis of this drug was undertaken to disclose the inherent three-dimensional structure. Figure 1: Chemical diagrams of apraclonidine hydrochloride (a) and clonidine (b). 2. Method Apraclonidine hydrochloride was purchased from Sigma-Aldrich Co. The single crystals of the compound were grown from a methanol solution. A colorless platelet crystal with the size of 0.35 ¡Á 0.30 ¡Á 0.15£¿mm was mounted on a glass fiber and used for data collection. The structure was solved by direct methods, and non-H atoms were refined by a full-matrix least squares method with anisotropic temperature factors. Positions of H-atoms attached to carbon and nitrogen atoms were geometrically calculated and located from difference Fourier synthesis, respectively. All H-atoms were refined by the riding model. The crystal and experimental data are given in Table 1. Table 1: Crystal and experimental data. 3. Results and Discussion An ORTEP drawing [2] of apraclonidine hydrochloride is shown in Figure 2. Selected bond lengths, bond angles, torsion angles, and possible hydrogen bonds in the crystal structure are given in Table 2. Bond lengths and angles are within the
%U http://www.hindawi.com/journals/jcrys/2013/249672/