Erythromycin A dimethyl sulfoxide disolvate 1.43-hydrate

The title compound, C37H67NO13·2C2H6OS·1.43H2O, is a macrolide antibiotic with better solubility and better dermal penetration abilities than erythromycin A itself. The asymmetric unit of this form contains one erythromycin A molecule, two dimethyl sulfoxide (DMSO) solvent molecules, a fully occupied water molecule and a partially occupied water molecule with an occupancy factor of 0.432 (11). The 14-membered ring of the erythronolide fragment has a conformation which differs considerably from that in erythromycin A dihydrate [Stephenson, Stowell, Toma, Pfeiffer & Byrn (1997 ▶). J. Pharm. Sci. 86, 1239–1244]. One of the two DMSO molecules is disordered over two orientations; the orientation depends on the presence or absence of the second, partially occupied, water molecule. In the crystal, erythromycin molecules are connected by O—H⋯O hydrogen bonds involving the hydroxy groups and the fully occupied water molecule to form layers parallel to (010). These layers are connected along the b-axis direction only by a possible hydrogen-bonding contact involving the partially occupied water molecule.

The title compound, C 37 H 67 NO 13 Á2C 2 H 6 OSÁ1.43H 2 O, is a macrolide antibiotic with better solubility and better dermal penetration abilities than erythromycin A itself. The asymmetric unit of this form contains one erythromycin A molecule, two dimethyl sulfoxide (DMSO) solvent molecules, a fully occupied water molecule and a partially occupied water molecule with an occupancy factor of 0.432 (11). The 14membered ring of the erythronolide fragment has a conformation which differs considerably from that in erythromycin A dihydrate [Stephenson, Stowell, Toma, Pfeiffer & Byrn (1997). J. Pharm. Sci. 86, 1239-1244. One of the two DMSO molecules is disordered over two orientations; the orientation depends on the presence or absence of the second, partially occupied, water molecule. In the crystal, erythromycin molecules are connected by O-HÁ Á ÁO hydrogen bonds involving the hydroxy groups and the fully occupied water molecule to form layers parallel to (010). These layers are connected along the b-axis direction only by a possible hydrogen-bonding contact involving the partially occupied water molecule.  Symmetry codes: (i) x þ 1; y; z; (ii) x À 1; y; z; (iii) x; y; z þ 1.
bond from the hydroxy group O6-H6A and acts as a donor for two hydrogen bonds to two symmetry-related erythromycin molecules (Table 1).
The erythromycin molecule shows one intramolecular O-H···O hydrogen bond. The remaining hydroxy groups are involved in intermolecular hydrogen bonds. One of them links the erythromycin molecules along the c-axis direction. The other three hydroxy groups are directed towards the two DMSO solvate molecules and towards water molecule O7W.
The latter water molecule links the erythromycin molecules along the a-axis direction. Thus, the structure contains hydrogen bonded layers parallel to the (010) plane. The only intermolecular contact between adjacent layers along the baxis direction is the before mentioned possible O8W···O14 i hydrogen bond, involving the partially occupied water molecule.
A second crystal of the title compound was measured at 177 K. The resulting crystal structure was similar to the structure determined at room temperature. The occupancy factor of the partially occupied water molecule refined to 0.400 (7). No phase transition was observed on cooling of the crystal from room temperature to 177 K.

Experimental
Erythromycin A was recrystallized from a dimethyl sulfoxide/water mixture. The crystal used for the data collection was sealed in a glass capillary tube with a drop of mother liquor.

Refinement
The H atoms were positioned geometrically and treated as riding with C primary -H = 0.98 Å, C secondary -H = 0.97 Å, C methyl -H = 0.96 Å, O-H = 0.82 Å, U iso (H) = 1.2U eq (C non-methyl ) and U iso (H) = 1.5U eq (C methyl ,O). The H atoms at water molecule O7W were taken from a difference Fourier synthesis and were refined, using an O-H distance restraint of 0.84 (1) Å.
The O and C atoms of the disordered DMSO solvate molecule were refined as anisotropic split atoms, using 20 restraints to bond distances and atomic displacement parameters. The occupancy factors refined to 0.482 (4) for atoms O15, C40, C41 and to 0.518 (4) for atoms O15′, C40′, C41′. The occupancy factor of the water molecule O8W refined to 0.432 (11).
H atoms associated with the partially occupied water molecule (O8W) could not be located in difference Fourier maps and were not assigned.

Computing details
Data collection: SMART (Siemens, 1995); cell refinement: SAINT (Siemens, 1995); data reduction: SAINT (Siemens, 1995); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97  The asymmetric unit of (I) at 296 K with the numbering scheme of the atoms. Displacement ellipsoids are drawn at the 50% probability level and H atoms are shown as small spheres of arbitrary radii. Atoms belonging to the second orientation of the disordered DMSO solvate molecule have been omitted for clarity.   (9) Special details Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes. Refinement. Refinement of F 2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F 2 , conventional R-factors R are based on F, with F set to zero for negative F 2 . The threshold expression of F 2 > σ(F 2 ) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F 2 are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger.