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

Abstract

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 (</span><em style="color:rgb( 21 , 21 , 21 )">n</em><span style="color:rgb( 21 , 21 , 21 )"> → π*) interactions. Distinctive supramolecular synthons were identified, including the R22(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 R44(20) and R55(24) were observed, further supported by additional synthons of types </span><em style="color:rgb( 21 , 21 , 21 )">R</em><span style="color:rgb( 21 , 21 , 21 )">12(5) and </span><em style="color:rgb( 21 , 21 , 21 )">R</em><span style="color:rgb( 21 , 21 , 21 )">12(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 (</span><em style="color:rgb( 21 , 21 , 21 )">n</em><span style="color:rgb( 21 , 21 , 21 )"> → π*) interactions in stabilizing and shaping the architectures of these new multicomponent crystalline materials.