The metabolism and polarity of the all-cis tetra-fluorocyclohexane motif is explored in the context of its potential as a motif for inclusion in drug discovery programmes. Biotransformations of phenyl all-cis tetra-, tri- and di- fluoro cyclohexanes with the human metabolism model organism Cunninghamella elegans illustrates various hydroxylated products, but limited to benzylic hydroxylation for the phenyl all-cis tetrafluorocyclohexyl ring system. Evaluation of the lipophilicities (log P) indicates a significant and progressive increase in polarity with increasing fluorination on the cyclohexane ring system. Molecular dynamics simulations indicate that water associates much more closely with the hydrogen face of these Janus face cyclohexyl rings than the fluorine face owing to enhanced hydrogen bonding interactions with the polarised hydrogens and water.

中文翻译：

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极化“Janus face”全顺四氟环己基环的代谢和亲水性，药物发现的候选基序†

全顺式四氟环己烷基序的代谢和极性在其作为包含在药物发现计划中的基序的潜力的背景下进行了探索。苯基全顺式四氟、三氟和二氟环己烷与人体代谢模型生物Cunninghamella elegans 的生物转化说明了各种羟基化产物，但仅限于苯基全顺式四氟环己基环系统的苄基羟基化。亲脂性评估（log  P) 表明极性随着环己烷环系统上氟化作用的增加而显着且逐渐增加。分子动力学模拟表明，由于与极化氢和水的氢键相互作用增强，水与这些 Janus 环己基环的氢面的结合比氟面更紧密。