Clarithromycin form I determined by synchrotron X-ray powder diffraction

The structure of the metastable form I polymorph of the macrolide antibiotic clarithromycin, C38H69NO13, was determined by a powder diffraction method using synchrotron radiation. The space group of form I isP21212. The initial model was determined by a molecular replacement method using the structure of clarithromycin form 0 as a search model, and the final structure was obtained through Rietveld refinements. In the form I crystal structure, the clarithromycin molecules are aligned parallel along theaaxis in a head-to-tail manner with intermolecular hydrogen bonds between the hydroxy O atoms. The dimethylamine groups of the clarithromycin molecule interdigitate between neighbouring head-to-tail clarithromycin alignments. The novel crystal packing found in form I provides a mechanism that describes the transformation of form 0 to form I.