New solvated form of the antibiotic azithromycin. Clues about the role of the water retained inside the crystal

The structure of a new semihydrate solvated form of the antibiotic azithromycin is reported. The new form was obtained by partial dehydration of the crystal of the monohydrate-i-PrOH, when the sample was left in laboratory conditions (22–25 °C, 55–65% relative humidity) over a long period of time (about 40 months). The new semihydrate solvate form retains the crystalline structure of the monohydrate (unit cell parameters and space group) but shows changes in the position of the hydrogen atoms of some OH groups of the azithromycin molecules, leading to a new and different hydrogen bonding network. Moreover, in one of the two azithromycin molecules in the asymmetric unit (the one labelled as “b”), the dimethyl amine group (in the desosamine sugar) shows a significant positional change. This fact provides information about the role of the solvent in the building of the solvated forms of the azithromycin drug, and allows the mobility of this group to be associated with an inversion operation and not a rotation.