Successful prediction of the hydrogen bond network of the 3-oxo-12α-hydroxy-5β-cholan-24-oic acid crystal from resolution of the crystal structure of deoxycholic acid and its three 3,12-dihydroxy epimers

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Crystal structures of p-xylene-crystallized deoxycholic acid (3α,12α-dihydroxy-5β-cholan-24-oic acid) and its three epimers (3β,12α-; 3α,12β-; and 3β,12β-) have been solved. Deoxycholic acid forms a crystalline (P21) complex with the solvent with a 2:1 stoichiometry whereas crystals of the three epimers do not form inclusion compounds. Crystals of the 3β,12β-epimer are hexagonal, whereas the 3α,12β-and 3β,12α-epimers crystallize in the P212121 orthorhombic space group. The three hydrogen bond sites (two hydroxy groups, i. e. O3-H, and O12-H, and the carboxylic acid group of the side chain, O24bO24a-H) simultaneously act as hydrogen bond donors and acceptors.

The hydrogen bond network in the crystals was analyzed and the following sequences have been observed: two chains (abcabc… or acbacb…) and two rings (Symbol), which constitute a complete set of all the possible sequences which can be drawn for an intermolecular hydrogen bond network formed by three hydrogen bond donor/acceptor sites forming crossing hydrogen bonds. The orientation of O3-H (α or β) determines the sequence of the acceptor and the donor groups involved in the pattern: O24a→O12→O3→O24b when it is α and O24a→O3→O12→O24b when it is β.

These observations were used to predict the hydrogen bond network of p-xylene-crystallized 3-oxo,12α-hydroxy-5β-cholan-24-oic acid. This compound has two hydrogen bond donor and three potential hydrogen bond acceptor sites. According to the previous sequence set, this compound should crystallize in the monoclinic P21 system, should form a complex with the solvent, O24b should not participate in the hydrogen bond network, and the chain sequence O24a→O12→O3 would be followed. All predictions were confirmed experimentally.

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