Piperazine is a pharmacophore that is widely used for combinatorial synthesis of potential drugs. For example, it has been shown that 4(2-Hydroxyethyl) Piperazine-1 Methanesulfonic Acid (HEMPS) possesses significant therapeutic value in the treatment of cancer and immunologically mediated diseases.

The electron density distribution helps to investigate details of intramolecular chemical bonding and intermolecular interactions that in many cases are important reasons of such phenomena as polymorphism, the formation of solvates and hydrates, solubility, and as a result, pharmacological activity. Also using Bader's theory “Atom in molecules”, we can determine the energies of intermolecular interactions from X-ray diffraction experiment and after that evaluate total crystal energy and compare it with  the enthalpy of sublimation.

Piperazine forms several hydrates that contains different amount of solvate water molecules. We have investigated the electron density distribution in the piperazine hydrates and compared characteristics, related to electronic structure of these materials, to their physical properties. For example, in piperazine monohydrate (C₄H₁₀N₂×H₂O), the two independent molecules of piperazine occupy special positions on the two inversion centers, thus four different hydrogen bonds (two N-H…O, and two O-H...N) occur in the crystal (Fig. 1). We have found that the energies of the O-H…N hydrogen bonds higher than the N-H…O hydrogen bonds.

Also we have studed the electron density distribution in the piperazine derivative  - HEMPS. The X-ray analysis revealed that HEMPS has a zwitterionic structure, in which the proton of the sulfonic acid group is transferred to one of the nitrogen atoms of the piperazine ring. Using the electron density distribution we compared atomic charges and energies on  the nitrogen atoms of the piperazinium ring.          

                        (a)                                                                                           (b) Fig.1 Deformation electron density distribution on hydrogen bonds O-H…N (a) and N-H…O (b)