METHOD OF DETERMINING THE THREE-DIMENSIONAL STRUCTURE OF MOLECULES IN CRYSTALLINE INCLUSION COMPLEXES

Abstract

The invention is directed to a method for elucidating the three-dimensional structure of compounds by X-ray diffraction (X-ray SCD) characterized in that the compound is co-analyte crystallized with tetraaryladamantanes according to general formula I Wherein R and R′ are identical or different residues selected from the group consisting of O-R1, S-R1, NHR1, NR1R2, F, Cl, Br or I and R1, R2 stand for identical or different, substituted on not substituted aliphatic or aromatic residues having 1 to 25 carbon atoms and the the three-dimensional structure of the compound is obtained by X-ray diffraction (X-ray SCD).

##STR00001##

Claims

1. A method for elucidating the three-dimensional structure of compounds by X-ray diffraction (X-ray SCD) characterized in that the compound is co- crystallized with tetraaryladamantes according to general formula I ##STR00003## Wherein R and R′are identical or different residues selected from the group consisting of O-R1, S-R1, NHR1, NR1R2, F, Cl, Br or I and R1, R2 stand for identical or different, substituted on not substituted aliphatic or aromatic residues having 1 to 25 carbon atoms and the the three-dimensional structure of the compound is obtained by X-ray diffraction (X-ray SCD).

2. The method according to claim 1 characterized in that the compound is co- crystallized with tetraaryladamantes into a single-crystal.

3. The method according to claim 1 characterized in that the compounds are chiral molecules and the absolute configuration or relative configuration of the compounds is obtained.

4. The method according to claim 1, characterized in that the compound to be co-crystallized has a molecular weight of less than 500 g/mol.

5. The method according to claim 1, characterized in that the compound to be co-crystallized is a liquid.

6. The method according to claim 1, characterized in that the compound and the tetraaryladamantanes are co-crystallized in the absence of a solvent.

7. The method according to claim 1, characterized in that the compound and the tetraaryladamantanes are co-crystallized by providing a mixture of the compound, the tetraaryladamantanes and a solvent and subsequent evaporation of the solvent followed by heating or incubation at room temperature.

8. The method according to claim 1, characterized in that the compound is a mixture of enantiomers or a mixture of diastereomers.

Description

EXAMPLES

[0028] Representative Protocol

[0029] A sample of 1,3,5,7-tetrakis(2,4-diethoxyphenyl)adamantane (TEO) (2 mg, 0.0025 mmol) in a glass vial is treated with (R)-(+)-a-methylbenzylamine (30 μL, 29 mg, 0.24 mmol). The resulting suspension is heated on a hot plate with a surface temperature of 150° C. until a homogenous solution forms. The hot plate is switched off, and the solution is allowed to cool to room temperature while on the plate. The crystals formed are harvested and analysed by X-ray diffractometry.

[0030] Diffraction data were collected on a KAPPA APEXII DUO diffractometer from Bruker (Karlsruhe, Germany) at 130 K and Cu Kα (λ=1.54178 Å). Cell refinement and data reduction were performed with the SAINT program package. Absorption correction was performed with SADBAS. The structure was solved by direct methods using SHELXL97. An isotropic refinement by least-squares methods were also carried out in SHELXL97. This procedure was followed by anisotropic refinements on F2 of all non-hydrogen atoms. The positions of the H-atoms were calculated geometrically with riding models. The graphics of the crystal structure were generated with the program Mercury 4.0.0.

[0031] FIG. 1, below, shows the structure of the guest and the host molecule and crystallographic data for either of the two enantiomers of methylbenzylamine.

[0032] The entire procedure from the crystallization to the final crystal structure, including the determination of the absolute configuration of the guest, took less than two days.

[0033] FIG. 2 shows the procedure for structure elucidation. FIGS. 3 and 4 show additional examples for the successful elucidation of the three-dimensional structure of analytes using the procedure.

[0034] FIG. 4 shows an example for the successful determination of the relative configuration for a racemic mixture of enantiomers using the method of the invention. The analyte was identified as being of the trans-configuration by co-crystallizing a racemic mixture or a mixture containing racemates of either relative configuration in unequal concentrations (trans as major component and cis as minor component).