Dearden J C
Environ Health Perspect. 1985 Sep;61:203-28. doi: 10.1289/ehp.8561203.
The history of the relationship of biological activity to partition coefficient and related properties is briefly reviewed. The dominance of partition coefficient in quantitation of structure-activity relationships is emphasized, although the importance of other factors is also demonstrated. Various mathematical models of in vivo transport and binding are discussed; most of these involve partitioning as the primary mechanism of transport. The models describe observed quantitative structure-activity relationships (QSARs) well on the whole, confirming that partitioning is of key importance in in vivo behavior of a xenobiotic. The partition coefficient is shown to correlate with numerous other parameters representing bulk, such as molecular weight, volume and surface area, parachor and calculated indices such as molecular connectivity; this is especially so for apolar molecules, because for polar molecules lipophilicity factors into both bulk and polar or hydrogen bonding components. The relationship of partition coefficient to chromatographic parameters is discussed, and it is shown that such parameters, which are often readily obtainable experimentally, can successfully supplant partition coefficient in QSARs. The relationship of aqueous solubility with partition coefficient is examined in detail. Correlations are observed, even with solid compounds, and these can be used to predict solubility. The additive/constitutive nature of partition coefficient is discussed extensively, as are the available schemes for the calculation of partition coefficient. Finally the use of partition coefficient to provide structural information is considered. It is shown that partition coefficient can be a valuable structural tool, especially if the enthalpy and entropy of partitioning are available.
简要回顾了生物活性与分配系数及相关性质之间关系的历史。强调了分配系数在定量构效关系中的主导地位，尽管也证明了其他因素的重要性。讨论了体内转运和结合的各种数学模型；其中大多数将分配作为主要的转运机制。这些模型总体上很好地描述了观察到的定量构效关系（QSARs），证实了分配在异生素体内行为中至关重要。分配系数与许多代表体积的其他参数相关，如分子量、体积和表面积、等张比容以及计算指数如分子连接性；对于非极性分子尤其如此，因为对于极性分子，亲脂性包含体积和极性或氢键成分。讨论了分配系数与色谱参数的关系，结果表明，这些通常可通过实验轻松获得的参数能够成功取代QSARs中的分配系数。详细研究了水溶性与分配系数的关系。观察到了相关性，即使对于固体化合物也是如此，这些相关性可用于预测溶解度。广泛讨论了分配系数的加和/构成性质以及计算分配系数的现有方案。最后考虑了使用分配系数来提供结构信息。结果表明，分配系数可以是一种有价值的结构工具，特别是如果有分配的焓和熵的话。
