Conformational polymorphism in a Schiff-base macrocyclic organic ligand: an experimental and theoretical study

Polymorphism in the highly flexible organic Schiff-base macrocycle ligand 3,6,9,17,20,23-hexa-azapentacyclo(23.3.1.1(11,15).0(2,6).0(16,20))triaconta-1(29),9,11,13,15(30),23,25,27-octaene (DIEN, C(24)H(30)N(6)) has been studied by single-crystal X-ray diffraction and both solid-state and gas-phase density functional theory (DFT) calculations. In the literature, only solvated structures of the title compound are known. Two new polymorphs and a new solvated form of DIEN, all obtained from the same solvent with different crystallization conditions, are presented for the first time. They all have P\bar 1 symmetry, with the macrocycle positioned on inversion centres. The two unsolvated polymorphic forms differ in the number of molecules in the asymmetric unit Z', density and cohesive energy. Theoretical results confirm that the most stable form is (II°), with Z' = 1.5. Two distinct molecular conformations have been found, named `endo' or `exo' according to the orientation of the imine N atoms, which can be directed towards the interior or the exterior of the macrocycle. The endo arrangement is ubiquitous in the solid state and is shared by two independent molecules which constitute an invariant supramolecular synthon in all the known crystal forms of DIEN. It is also the most stable arrangement in the gas phase. The exo form, on the other hand, appears only in phase (II°), which contains both the conformers. Similarities and differences among the occurring packing motifs, as well as solvent effects, are discussed with the aid of Hirshfeld surface fingerprint plots and correlated to the results of the energy analysis. A possible interconversion path in the gas phase between the endo and the exo conformers has been found by DFT calculations; it consists of a two-step mechanism with activation energies of the order of 30-40 kJ mol(-1). These findings have been related to the empirical evidence that the most stable phase (II°) is also the last appearing one, in accordance with Ostwald's rule.