Analysis of the electron density of a water molecule encapsulated by two cholic acid residues

Cholic acid is a trihydroxy bile acid having three hydroxy groups at C-3, C-7 and C-12 carbon atoms, two methyl groups at C-10 and C-13 carbon atoms of the steroid nucleus, and a carboxylic group at C24 of the side alkyl chain. The distance between the oxygen atoms linked to C-7 and C-12 (~4.5 Å), perfectly matches with the edge distance between oxygen atoms in ice. This lead to a design of a cholic acid dimer in which one water molecule is encapsulated between two cholic residues, resembling an ice-like structure. The water molecule participates in four hydrogen bonds, the water simultaneously being acceptor from the O12-H hydroxy groups (two bonds with lengths of 2.177 Å and 2.114 Å) and the donor towards the O-7-H groups (two bonds with lengths of 1.866 Å and 1.920 Å).

It this communication we present the application of the “atoms in molecules” (AIM) theory to the former tetrahedral structure. The analysis of the calculated electron denstity, is performed through its gradient vector, and the Laplacian. The calculation of the complexation energy used correction of the basis set superposition error (BSSE) with the counterpoise method implemented in Gaussian 19. Laplacian of electronic density and critical points (AIM) were calculated using Multiwfn_3.8_dev software. As expected, four critical (3,-1) points located in the H^…O bond paths were identified. All calculated parameters are in concordance with those of similar systems and obey the proposed criteria for hydrogen bonds. The total energy for the interaction is -12.67 kcal/mol and is analyzed through proposed energy/electron density equations.