*3.2. Supramolecular Synthons*

Supramolecular synthons are spatial arrangements of intermolecular interactions between complementary functional groups, and constitute the core of the retrosynthetic strategy for supramolecular structures [39]. With crystal structures defined as networks with the molecules as the nodes and the supramolecular synthons as the connections between them, retrosynthesis can be performed on network structures to produce appropriate molecular structures. The advantage of such an approach in crystal engineering is that comparisons between seemingly different crystal structures are facilitated. If we apply this observation to the systems studied here, we can establish some differences between them that can be attributed to the different constituent isomers.

With the structural data of the cocrystals studied here, we compare the main synthons that they present in their 3D network, which are displayed in Scheme 2. In cocrystal **1**, two heteromeric interactions are observed that give rise to two heterosynthons between *syn*amide with carboxylic acid (B) and between pyridine amide with hydroxy carboxylic acid (E). In cocrystal **2**, two heteromeric interactions are also observed, causing two heterosynthons, one between pyridine and carboxylic acid (C) and the other between *syn*-amide and hydroxy carboxylic acid (D). In cocrystal **3**, on the contrary, a homomeric interaction corresponding to typical amide–amide homosinton (A) and two heteromeric interactions stand out, one is the heterosinton pyridine with carboxylic acid (C), also observed in the cocrystals of **2**, and the other *anti*-amide with hydroxy carboxylic acid (F).

**Scheme 2.** Main supramolecular synthons in the cocrystals studied herein. Hydrogen bonds are shown as dotted lines.
