Ab initio crystal structure determination of three pharmaceutical compounds from X-ray powder diffraction data

Crystal structures of drug compounds of increasing complexity have been solved ab initio from monochromatic X-ray diffraction data using a direct space approach. The geometry of the molecules introduced into the unit cell was optimised by quantum calculation. For structure solution, trial models were generated randomly using a simulated annealing algorithm. Torsion angles were allowed to vary simultaneously with translation and rotation of the molecular fragment within the cell. Provided that pattern indexing is solved and preferred orientation effects are minimised, the methodology can be applied almost routinely. A structure of a compound exhibiting a very high configurational flexibility has been solved recently (III). Examples reported are : I C14H14N3OCl C2/c V = 2512.5(3) Angstrom (3) 33 atoms 2 torsions R-wp = 7.72 % IIa C23H24N3O2SF P2(1) V = 1067.4(3) Angstrom (3) 54 atoms 5 torsions R-wp = 15.34 % IIb C23H24N3O2SF P-1 V= 1068.2(5) Angstrom (3) 54 atoms 5 torsions R-wp = 12.85 % III to be declassified P2(1) V = 2266.2(7) Angstrom (3) 117 atoms 18 torsions R-wp = 11.71 %.