For an active pharmaceutical ingredient, it is important to stabilize its specific crystal polymorph. If the potential interconversion of various polymorphs is not carefully controlled, it may lead to deterioration of the drug’s physicochemical profile and, ultimately, its therapeutic efficacy. The desired polymorph stabilization can be achieved via co-crystallization with appropriate crystallophoric excipients. In this work, we identified an opportunity for co-crystallization of anastrozole (ASZ), a well-known aromatase inhibitor useful in second-line therapy of estrogen-dependent breast cancer, with a classical XB donor, 1,2,4,5-tetrafluoro-3,6-diiodobenzene (1,4-FIB). In the X-ray structures of ASZ·1.5 (1,4-FIB) co-crystal, different non-covalent interactions involving hydrogen and halogen atoms were detected and studied by quantum chemical calculations and QTAIM analysis at the ωB97XD/DZP-DKH level of theory.

中文翻译：

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生物活性化合物的新晶体形式。第2部分：阿那曲唑作为N-取代的1,2,4-三唑在卤素键和与1,4-二碘四氟苯的Lp-π相互作用中

对于活性药物成分，重要的是稳定其特定的晶体多晶型物。如果不仔细控制各种多晶型物的潜在相互转化，可能会导致药物的理化特性下降，并最终导致其治疗效果下降。所需的多晶型物稳定化可通过与适当的晶体荧光赋形剂共结晶来实现。在这项工作中，我们确定了与经典XB供体1,2,4,5一起对阿那曲唑（ASZ）进行结晶的机会，阿那曲唑是一种著名的芳香酶抑制剂，可用于雌激素依赖性乳腺癌的二线治疗。 -四氟-3,6-二碘苯（1,4-FIB）。在ASZ的X射线结构中·1.5（1,4-FIB）共晶，通过量子化学计算和QTAIM分析在ωB97XD/ DZP-DKH理论水平上检测并研究了涉及氢和卤素原子的不同非共价相互作用。