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

The X-ray crystal and molecular structure of a new polymorph of cis-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 C2) is conformationally polymorphic with the already known P212121 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 cis and trans isomers were performed using the same force field in vacuo, in aqueous solution, and for selected conformers in P212121 and C2 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 C2 unit cell helped to find the most plausible crystal packing motif.