Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States.
Biophysics Program, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States.
Biochemistry. 2023 Oct 3;62(19):2841-2853. doi: 10.1021/acs.biochem.3c00367. Epub 2023 Sep 11.
In addition to amide hydrogen bonds and the hydrophobic effect, interactions involving π-bonded sp atoms of amides, aromatics, and other groups occur in protein self-assembly processes including folding, oligomerization, and condensate formation. These interactions also occur in aqueous solutions of amide and aromatic compounds, where they can be quantified. Previous analysis of thermodynamic coefficients quantifying net-favorable interactions of amide compounds with other amides and aromatics revealed that interactions of amide spO with amide spN unified atoms (presumably C═O···H-N hydrogen bonds) and amide/aromatic spC (lone pair π, n-π*) are particularly favorable. SpC-spC (hydrophobic), spC-spC (hydrophobic, CH-π), spC-spC (hydrophobic, π-π), and spC-spN interactions are favorable, spC-spN interactions are neutral, while spO-spO and spN-spN self-interactions and spO-spC interactions are unfavorable. Here, from determinations of favorable effects of 14 amides on naphthalene solubility at 10, 25, and 45 °C, we dissect amide-aromatic interaction free energies into enthalpic and entropic contributions and find these vary systematically with amide composition. Analysis of these results yields enthalpic and entropic contributions to intrinsic strengths of interactions of amide spO, spN, spC, and spC unified atoms with aromatic spC atoms. For each interaction, enthalpic and entropic contributions have the same sign and are much larger in magnitude than the interaction free energy itself. The amide spO-aromatic spC interaction is enthalpy-driven and entropically unfavorable, consistent with direct chemical interaction (e.g., lone pair-π), while amide spC- and spC-aromatic spC interactions are entropy-driven and enthalpically unfavorable, consistent with hydrophobic effects. These findings are relevant for interactions involving π-bonded sp atoms in protein processes.
除酰胺氢键和疏水作用外，涉及酰胺、芳香族化合物和其他基团的π键合 sp 原子的相互作用也发生在蛋白质自组装过程中，包括折叠、寡聚化和凝聚体形成。这些相互作用也发生在酰胺和芳香族化合物的水溶液中，在那里可以对其进行量化。先前分析了定量描述酰胺化合物与其他酰胺和芳香族化合物之间净有利相互作用的热力学系数，结果表明酰胺 spO 与酰胺 spN 统一原子（推测为 C═O···H-N 氢键）和酰胺/芳族 spC（孤对 π，n-π*）的相互作用特别有利。spC-spC（疏水）、spC-spC（疏水、CH-π）、spC-spC（疏水、π-π）和 spC-spN 相互作用是有利的，spC-spN 相互作用是中性的，而 spO-spO 和 spN-spN 自相互作用和 spO-spC 相互作用是不利的。在这里，我们从 14 种酰胺在 10、25 和 45°C 下对萘溶解度的有利影响的测定中，将酰胺-芳香族相互作用自由能分解为焓和熵贡献，并发现这些随酰胺组成而系统变化。对这些结果的分析得出了酰胺 spO、spN、spC 和 spC 统一原子与芳香族 spC 原子相互作用的固有强度的焓和熵贡献。对于每个相互作用，焓和熵贡献具有相同的符号，并且比相互作用自由能本身大得多。酰胺 spO-芳香族 spC 相互作用是焓驱动的，熵不利，与直接的化学相互作用（例如，孤对-π）一致，而酰胺 spC-和 spC-芳香族 spC 相互作用是熵驱动的，焓不利，与疏水作用一致。这些发现与蛋白质过程中涉及π键合 sp 原子的相互作用有关。
