Absolute Configuration of Small Molecules by Co-Crystallization.

Area of Science:

• Organic Chemistry
• Crystallography
• Structural Analysis

Background:

• X-ray crystallography is the gold standard for determining absolute configuration of chiral molecules.
• Crystallization of small organic molecules for X-ray analysis can be challenging and time-consuming.

Purpose of the Study:

• To develop a rapid and efficient method for obtaining crystals of small molecules for X-ray crystallography.
• To enable the assignment of absolute configuration for chiral compounds that are difficult to crystallize.

Main Methods:

• Co-crystallization of various small molecules with tetraaryladamantanes as crystallization chaperones.
• Screening of 52 diverse compounds for co-crystal formation.
• Utilizing a combination of Nuclear Magnetic Resonance (NMR) spectroscopy and X-ray crystallography.

Main Results:

• High success rate for co-crystal inclusion (88%) and high-resolution structure determination (77%) across diverse compounds.
• Rapid structure determination in under three days from small sample amounts (3 mg).
• Successful co-crystallization with a wide range of molecules, from n-decane to nicotine.

Conclusions:

• Tetraaryladamantanes serve as effective crystallization chaperones for small molecules.
• This method significantly accelerates the process of determining absolute configuration via X-ray crystallography.
• The approach is robust, efficient, and applicable to a broad spectrum of chiral analytes.