Iddon Ben, Hunter Christopher A
Yusuf Hamied Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, U.K.
J Am Chem Soc. 2024 Oct 4;146(41):28580-8. doi: 10.1021/jacs.4c11869.
Salt bridges formed by amidines and carboxylic acids represent an important class of noncovalent interaction in biomolecular and supramolecular systems. Isothermal titration calorimetry was used to study the relationships between the strength of the interaction, the chemical structures of the components, and the nature of the solvent. The stability of the 1:1 complex formed in chloroform changed by 2 orders of magnitude depending on the basicity of the amidine and the acidity of the acid, which is consistent with proton transfer in the complex. Polar solvents reduce the stabilities of salt bridges formed with -dialkylamidines by up to 3 orders of magnitude, but this dependence on solvent polarity can be eliminated if the alkyl groups are replaced by protons in the parent amidine. The enhanced stability of the complex formed by benzamidine is due to solvation of the NH sites not directly involved in salt bridge formation, which become significantly more polar when proton transfer takes place, leading to more favorable interactions with polar solvents in the bound state. Calculation of H-bond parameters using density functional theory was used to predict solvent effects on the stabilities of salt bridges to within 1 kJ mol. While H-bonding interactions are strong in nonpolar solvents, and solvophobic interactions are strong in polar protic solvents, these interactions are weak in polar aprotic solvents. In contrast, amidinium-carboxylate salt bridges are stable in both polar and nonpolar aprotic solvents, which is attractive for the design of supramolecular systems that operate in different solvent environments.
脒与羧酸形成的盐桥是生物分子和超分子体系中一类重要的非共价相互作用。采用等温滴定量热法研究了相互作用强度、组分化学结构与溶剂性质之间的关系。在氯仿中形成的1:1配合物的稳定性根据脒的碱性和酸的酸性变化了2个数量级，这与配合物中的质子转移一致。极性溶剂会使与二烷基脒形成的盐桥稳定性降低多达3个数量级，但如果在母体脒中用质子取代烷基，则可以消除这种对溶剂极性的依赖性。苯甲脒形成的配合物稳定性增强是由于未直接参与盐桥形成的NH位点的溶剂化作用，当发生质子转移时，这些位点的极性会显著增加，从而在结合状态下与极性溶剂形成更有利的相互作用。使用密度泛函理论计算氢键参数可将溶剂对盐桥稳定性的影响预测在1 kJ/mol以内。虽然氢键相互作用在非极性溶剂中很强，而疏溶剂相互作用在极性质子溶剂中很强，但这些相互作用在极性非质子溶剂中较弱。相比之下，脒鎓 - 羧酸盐盐桥在极性和非极性非质子溶剂中都很稳定，这对于设计在不同溶剂环境中运行的超分子体系具有吸引力。
