Unveiling the supramolecular features of Oxyma-T: crystal structures, salt formation, and computational investigation of noncovalent interactions

Abstract

The single-crystal structures of Oxyma-T, the recent member of the Oxyma racemization-suppressor family for peptide synthesis, have been synthesized and structurally characterized by single-crystal X-ray diffraction (SCXRD). The crystalline materials include the anhydrous form of Oxyma-T, as well as two salts incorporating ammonium and pyridinium as hydrogen-bond donors. The electron-rich framework of Oxyma-T offers multiple sites for hydrogen bonding, giving rise to characteristic supramolecular motifs such as R (6) in the salts, and S(5) and S(6) ring motifs in the anhydrous form. In addition to these hydrogen-bonding networks, lone pair⋅⋅⋅ 1 π (n→ π (5) and R 1 *) interactions are revealed in the anhydrous structure, with energy estimated at –6.4 kcal/mol, acting cooperatively with conventional hydrogen bonds to stabilize the packing. Complementary density functional theory (DFT) calculations, including molecular electrostatic potential (MEP) surface mapping, QTAIM, and NCI plot analyses, further dissect the interplay of noncovalent interactions governing the stability and organization of these new Oxyma-T materials.