Two crystallographic forms and the absolute structure of 5α,14α-androstane

Area of Science:

• Crystallography
• Solid-state chemistry
• Molecular structure analysis

Background:

• Polymorphism is common in organic molecules, influencing physical properties.
• Understanding crystal structures is crucial for material science and pharmaceutical development.
• 5α,14α-Androstane is a steroid compound with potential biological relevance.

Purpose of the Study:

• To investigate the polymorphic behavior of 5α,14α-Androstane.
• To characterize the different crystalline forms and their formation conditions.
• To computationally assess the relative stability of the observed polymorphs.

Main Methods:

• Vapor diffusion crystallization technique.
• Single-crystal X-ray diffraction for structural determination.
• High-resolution mass spectrometry (HR-MS) for impurity identification.
• Density Functional Theory (DFT) for lattice free energy calculations.

Main Results:

• Two distinct polymorphic forms of 5α,14α-Androstane were identified.
• Form I (major) crystallizes as twinned plates (P21, Z=4), susceptible to radiation damage.
• Form II (minor) crystallizes as needles (P212121, Z=3) and contains 5α,14α-androstan-17-one impurity, which can be eliminated by altering the solvent system.
• DFT calculations indicate that both pure forms are energetically similar (isoergic).

Conclusions:

• 5α,14α-Androstane exhibits complex crystallization behavior with the formation of two polymorphs.
• The presence of an oxidation product can influence crystal formation and purity.
• Pure crystalline forms of 5α,14α-Androstane can be selectively obtained.
• Computational methods support the energetic comparability of the pure polymorphic forms.