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A systematic investigation to assess the degree of similarity between polymorphs was carried out. A similarity indices (IX) approach was applied in ten series of polymorphs with different characteristics and number of molecules in the asymmetric unit. Geometric (ID), contact area (IC), and stabilization energy (IG) parameters were used. It was possible to situate each comparison in different regions of similarity within the polymorphism phenomenon and determine the boundaries between quasi-isostructural polymorphs and polymorphs of low similarity. The multiparameter IDCG index was used as a robust tool to determine the total similarity within the polymorphism phenomenon. The highest contribution of the stabilization energy parameter (45%) toward the final value of similarity (IDCG) was observed, followed by the contact area index (32%). The geometric index contributed approximately 23% to the final value of IDCG. This information reinforces the importance of the contact area and stabilization energy in assessing the degree of similarity between crystalline structures. A new descriptor (IQ) based on the comparison of the energetic contribution of intermolecular interaction types present in each crystal structure is presented. IQ can be a versatile tool and applicable even for systems that do not share any similarity.

A series of seven N-phenylamides [R–C(O)NHPh, in which R: CH3, C(CH3)3, Ph, CF3, CCl3, CBr3, and H] were used as models in this study. Molecular packing and intermolecular interactions were evaluated by theoretical calculations, solution NMR, and quantum theory of atoms in molecules analyses. Crystallization mechanisms were proposed based on the energetic and topological parameters using the supramolecular cluster as demarcation. Concentration-dependent 1H NMR experiments corroborated the proposed interactions between molecules. For all compounds (except for R: H, which initially formed tetramers), layers (two-dimensional) or chains (one-dimensional) were formed in the first stage of the proposed crystallization mechanisms. The presence of strong intermolecular NH···O═C interactions promoted the first stages. The study in solution provided different values of association constant (Kass) governed by the hydrogen bond NH···O═C, showing that the stronger interactions are directly influenced by the substituen...

The quest for concepts of isostructurality in organic crystals has been long and mostly based on geometric data, even with the development of modern software. This field of study is of great interest to the pharmaceutical industry and for the prediction of crystal structures. Despite this, there is still no methodology that provides broad quantitative and comparable similarity data between two complete crystalline structures. The present study demonstrated that the similarity between two crystalline structures could be estimated from the similarity between the two "supramolecular clusters". Quantitative indexes for similarity comparisons of crystal structures were shown using nine 5-aryl-1-(1,1-dimethylethyl)-1H-pyrazoles as a model. This proposal includes the quantitative data of a geometric parameter (ID), a contact area parameter (IC), and an energetic parameter (IG). The proposed indexes exhibited good perspective regarding the similarity data and distinct regions of similarity. The range of similarity was set at IX ≥ 0.80, 0.80 > IX > 0.60, and IX ≤ 0.60 (X = D, C, or G). Indexes with a value near 1.0 indicate systems with isostructural, isocontact, and isoenergetic behavior. The results indicated that supramolecular structures with high similarity must have high values for all three indexes (ID, IC, and IG).