Modeling Triple Conformational Disorder in a New Crystal Polymorph of <i>cis</i>-Aquabis(l-isoleucinato)copper(II)

The X-ray crystal and molecular structure of a new polymorph of <i>cis</i>-aquabis­(l-isoleucinato)­copper­(II), obtained by recrystallization from an acetic acid–water mixture and determined at 120 and 295 K, revealed triple dynamic disorder over one isoleucinato ligand at both temperatures. The complicated multipart disorder was resolved with the help of extensive computational crystal structure simulations, which were undertaken for the first time to interpret disorder in a crystal of bioinorganic compound. The new polymorph (space group <i>C</i>2) is conformationally polymorphic with the already known <i>P</i>2<sub>1</sub>2<sub>1</sub>2<sub>1</sub> crystal form. To discover the conformers that can participate in self-associations in solution, and to rationalize an interplay of intramolecular and intermolecular interactions in the crystallization of different conformers, conformational analyses of <i>cis</i> and <i>trans</i> isomers were performed using the same force field in vacuo, in aqueous solution, and for selected conformers in <i>P</i>2<sub>1</sub>2<sub>1</sub>2<sub>1</sub> and <i>C</i>2 crystals. Three conformers identified in the disorder were estimated to form the most favorable intermolecular interactions in the solid state, and one of them (the most populated conformer in the disorder) also in aqueous solution. The crystal structure reproduction of all possible arrangements of the three conformers in <i>C</i>2 unit cell helped to find the most plausible crystal packing motif.