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RESEARCH PRODUCT

Evidence of Weak Halogen Bonding: New Insights on Itraconazole and its Succinic Acid Cocrystal

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Exact knowledge of the crystal structure of drugs and lead compounds plays a significant role in the fields of crystal engineering, docking, computational modeling (drug–receptor interactions), and rational design of potent drugs in pharmaceutical chemistry. The succinic acid cocrystal of the systemic antifungal drug, itraconazole, reported by Remenar et al. (J. Am. Chem. Soc.2003, 125, 8456–8457) (CSD: IKEQEU), represents one of the classical examples displaying a molecular fitting mechanism in the solid state. In this work, we disclose the X-ray single-crystal structure of the cis-itraconazole–succinic acid (2:1) cocrystal and found that it differs slightly from the previously reported structure by the location of the elements (C, H, and N) in the 1,2,4-triazol-5-one ring. By making use of the new solid-state structure, we have also applied an enhanced disorder model, which, in turn, uncovered the intriguing halogen bond (XB) interactions (0.86 × van der Waals distance of C–Cl···N), which were previousl...