X-ray crystal structure of cytotoxic oxidized cholesterols: 7- ketocholesterol and 25-hydroxycholesterol

The cytotoxic cholesterol derivative, 7-ketocholesterol, crystallizes in a monoclinic unit cell, space group P2₁ with a = 11.405 Å, b = 6.288 Å, c = 35.393 Å and β = 92.75°(Z = 4). Its room temperature crystal structure was solved by direct methods, i.e. the minimal principle via the Shake-and- Bake (SnB) algorithm. In contrast to the continuous chain pattern found for the cholesterol monohydrate structure, hydrogen bonding in the 7- ketocholesterol structure is localized to specific sites via one water molecule that forms linkages between two O3 hydroxyl groups and one keto oxygen. The final weighted R factor for 4562 reflections was 0.144. The 25- hydroxycholesterol also crystallizes in a monoclinic unit cell (P2₁), with a = 10.840 Å, b = 14.533 Å, c = 16.093 Å and β = 95.91°(Z = 4). The low temperature structure was solved by DIRDIF. In this instance, molecular packing is anti-parallel in layers stabilized by hydrogen bonding networks via both hydroxyl functions, differing both from cholesterol monohydrate and the 7-ketocholesterol. The final weighted R-factor for 6566 reflections was 0.034. The final weighted R-factor for 6566 reflections was 0.034. Functional differences of the oxysterols therefore, may be expressed by observed variations in the molecular packing and geometry.