Chemical Potential of the Solvent: A Crucial Player for Rationalizing Host-Guest Affinities
Chemical Potential of the Solvent: A Crucial Player for Rationalizing Host-Guest Affinities
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DOI：
10.1002/chem.201703184
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发表时间：
2017-11-27
影响因子：
4.3
通讯作者：
Piguet, Claude
中科院分区：
文献类型：
--
作者：
Baudet, Karine;Guerra, Sebastiano;Piguet, Claude
获得控制简单主客体（[HG]）缔合的热力学常数β（H，G）（1，1）的可靠值在医学、生物学、药学和化学中至关重要，因为效应物的最佳浓度（即，作用于受体的药物）被设定为1/β（H，G）（1，1）。极性溶剂中带电物质之间的分子间缔合，其中水是原型，在很大程度上遵守这一原则。任何偏离理想状态的情况都会改变溶液中的物种形成，这一点由德拜-休克尔的离子气氛理论所掌握。涉及中性物质在非极性（亲脂性）介质如膜、双层或有机聚合物中的相关缔合反应知之甚少。以[La（hfa）（3）dig]客体间的分子间缔合作用为基础，（hfa =六氟乙酰丙酮化物，dig=2-{2-甲氧基乙氧基}乙烷）和三齿多芳族主体受体L1-L3在二氯甲烷中作为概念验证，我们表明缔合反应的进展，如通过受体占据位点的摩尔分数的增加所测量的，破坏溶剂的化学势，使β（H，G）（1，1）似乎可能偏移两个数量级，从而导致错误的剂量反应处方。一个简单的化学模型，它认为一个子集的溶剂分子的表面接触的合作伙伴的缔合反应，恢复可靠的访问真实和可解释的热力学常数。伴随出现的浓度依赖性校正参数在真实的条件下重新建立了令人满意的剂量依赖性反应。这种对质量作用定律的“补充”提供了一种简单的方法，用于在非极性介质中进行主客体反应时，安全地处理各种伙伴的活度系数的不可预测变化。
Access to reliable values of the thermodynamic constants beta(H,G)(1,1), which control simple host-guest ([HG]) association, is crucial in medicine, biology, pharmacy, and chemistry, since the optimum concentration of an effector (i.e., a drug) acting on a receptor is set to 1/beta(H,G)(1,1). Intermolecular association between charged species in polar solvents, for which water is the archetype, largely obeys this principle. Any deviation from ideality, which alters the speciation in solution, is mastered by the Debye-Huckel theory of ionic atmosphere. Much less is known for related association reactions involving neutral species in non-polar (lipophilic) media such as membranes, bilayers, or organic polymers. Taking the intermolecular association between [La(hfa)(3)dig] guest (hfa = hexafluoroacetylacetonate, dig=2-{2-methoxyethoxy}ethane) and tridentate polyaromatic host receptors L1-L3 in dichloromethane as a proof-of-concept, we show that the progress of the association reactions, as measured by the increase in the mole fraction of occupied sites of the receptors, disrupt the chemical potential of the solvent to such an extent that beta(H,G)(1,1) may seemingly be shifted by two orders of magnitude, thus leading to erroneous dose-response prescriptions. A simple chemical model, which considers a subset of solvent molecules in surface contact with the partners of the association reaction, restores reliable access to true and interpretable thermodynamic constants. The concomitant emergence of a concentration-dependent corrective parameter reestablishes satisfying dose-dependent response under real conditions. This "complement" to the law of mass action offers a simple method for safely taking care of the non-predictable variations of the activity coefficients of the various partners when host- guest reactions are conducted in non-polar media.