Crystallization of the Third Polymorphic Modification of L-Tryptophan: A Case of Non-order-disorder Polytypism

Abstract

The crystal structure of a new form of L-tryptophan, an essential amino acid metabolized to serotonin and melatonin, among other molecules with key biological activity, is described. So far, polymorphs α (P1 space group, Z′ = 16, reported in 2012) and β (P21 space group, Z′ = 2, reported in 2019) were known. We crystallized again the α form, together with a new α′ polymorph (P1 space group, Z′ = 4), which features a unit cell four times smaller than that of form α. The building block formed by the four molecules in the asymmetric unit of the new form α′ gives a 2D supramolecular framework based on hydrophilic layers held together by N-H···O hydrogen bonds. This diperiodic scaffold has a structure close to that of form α. However, the relative orientation of these layers along their stacking direction is different in both forms in such a way that L-tryptophan may be considered as a new example of a non-OD (order-disorder) polytypic organic material. Calculated crystal-state optical absorption over the UV range shows that the π → π* transition, which is known to involve orbitals localized on the indole moiety, is blue-shifted by 5 nm in form α compared to that in form α′. This corroborates that the structural modification of the hydrophobic layers, which include the indole groups, is responsible for the observed polymorphism.