A racemic spirohydantoin derivative with two aromatic substituents, a tetralin and a 4‐methoxybenzyl unit, was synthesized and its crystal structure was determined. To define the relationship between molecular stereochemistry and spatial association modes, development of the crystal packing was analyzed through cooperativity of intermolecular interactions. Homo and heterochiral dimeric motifs were stabilized by intermolecular N−H⋅⋅⋅O, C−H⋅⋅⋅O, C−H⋅⋅⋅π interactions and parallel interactions at large offsets (PILO), thus forming alternating double layers. The greatest contribution to the total stabilization came from a motif of opposite enantiomers linked by N−H⋅⋅⋅O bonds (interaction energy=−13.72 kcal/mol), followed by a homochiral motif where the 4‐methoxybenzyl units allowed C−H⋅⋅⋅π , C−H⋅⋅⋅O interactions and PILO (interaction energy=−11.56 kcal/mol). The number of the contact fragments in the environment of the tetralin unit was larger, but the 4‐methoxybenzyl unit had greater contribution to the total stabilization. The statistical analysis of the data from the Cambridge Structural Database (CSD) showed that this is a general trend. The compound is a potential inhibitor of kinase enzymes and antigen protein‐coupled receptors. A correlation between the docking study and the results of the CSD analysis can be drawn. Due to a greater flexibility, the 4‐methoxybenzyl unit is more adaptable for interactions with the biological targets than the tetralin unit.

中文翻译：

---

衍生自α-四氢萘酮的螺旋乙内酰脲的自组装和生物识别：手性和分子间相互作用的相互作用。

合成了具有两个芳族取代基，四氢化萘和4-甲氧基苄基单元的外消旋螺乙内酰脲衍生物，并确定了其晶体结构。为了定义分子立体化学与空间缔合模式之间的关系，通过分子间相互作用的协同性分析了晶体堆积的发展。分子间的N-H··⋅·O，C·H····O，C-H···· π相互作用和平行相互作用在大偏移量（PILO）下稳定了同构和杂手性二聚体基序，从而形成了交替的双层。对总稳定度的最大贡献来自通过N-H·⋅·O键连接的相对对映体的基序（相互作用能= -13.72 kcal / mol），其次是同手性基序，其中4-甲氧基苄基单元允许C-H ⋅⋅⋅ π，CH-·⋅·O相互作用和PILO（相互作用能= -11.56 kcal / mol）。四氢萘单元环境中接触片段的数量较大，但4-甲氧基苄基单元对总稳定度的贡献更大。来自剑桥结构数据库（CSD）的数据的统计分析表明，这是大趋势。该化合物是激酶和抗原蛋白偶联受体的潜在抑制剂。可以得出对接研究与CSD分析结果之间的相关性。由于具有更大的灵活性，与四氢化萘单元相比，4-甲氧基苄基单元更适合与生物靶标相互作用。