Crystallographic and Computational Analysis of Oxyma B Cocrystals with Nitrogen-Containing Coformers: The Relevant Role of <i>n</i> → π* Interactions in Their Diverse Supramolecular Architectures

Three new cocrystals of Oxyma-B, an important racemization suppressor for peptide synthesis, with 6-methylquinoline (I), 2,3,5,6-tetramethylpyrazine (II), and 1,10-phenanthroline (III) were synthesized and their single crystal structures analyzed. They show a rich network of noncovalent interactions, including classical and nonclassical hydrogen bonds (CH···O, OH···N, CH···N), CH···π, π-stacking, and, notably, lone pair···π (<i>n</i> → π*) interactions. Distinctive supramolecular synthons were identified, including the R₂ ²(7) motif found in both 6-methylquinoline/Oxyma-B and 2,3,5,6-tetramethylpyrazine/Oxyma-B cocrystals. In 1,10-phenanthroline/Oxyma-B, larger ring motifs such as R₄ ⁴(20) and R₅ ⁵(24) were observed, further supported by additional synthons of types <i>R</i> ₁ ²(5) and <i>R</i> ₁ ²(6). Hirshfeld surface analysis and density functional theory (DFT) calculations, including MEP surface, QTAIM, and NCIplot analyses, were carried out to quantify the intermolecular contributions and rationalize the experimental findings with a focus on the cooperative role of hydrogen bonding, π-stacking, and lone pair···π (<i>n</i> → π*) interactions in stabilizing and shaping the architectures of these new multicomponent crystalline materials.