Using nuclear forces to quantify the substituent effect
DOI: 10.1063/10.0005415
Using nuclear forces to quantify the substituent effect lead image
The substituent effect is known to influence the structure and the potential energy surface of a substrate. Even though a substituent is typically not involved directly in the reactivity of the substrate, it may significantly affect the substrate’s kinetics, thermochemistry, or selectivity.
Frutos and Fernandez-Gonzalez have developed a simple mechanical model that predicts the energy variations caused by a substituent based on the forces that it induces.
Over 50 years ago, the Hammett equation was developed to predict substituent effect in organic reactions. Even though the equation is still a useful tool for chemists, a theoretical and quantitative explanation of the substituent-substrate relationship remained a chemical enigma until now.
Substituents can exert mechanical forces over the rest of the molecule to which they are attached. The authors analyzed these forces in terms of the work produced. Using the alkaline hydrolysis of substituted ethyl benzoate as a case-study, the researchers proposed a simple physical model, where exerted force develops work along a reaction path.
The resulting analysis provided a priori description of the Hammett equation.
“Additionally, it offers a new tool to investigate with unprecedented detail the substituent effect, providing information of which internal coordinates, including bonds, angles, and torsions, are most relevant in the observed property changes,” said Luis Manuel Frutos, a co-author.
The authors plan to extend this concept to more complex situations like those seen in biological systems. They are currently investigating the substituent effect on photoactive proteins, where part of the molecular structure is treated as a substituent affecting the rest of the protein.
Source: “The concept of substituent-induced force in the rationale of substituent effect,” by Miguel Angel Fernandez-Gonzalez and Luis Manuel Frutos, Journal of Chemical Physics (2021). The article can be accessed at https://doi.org/10.1063/5.0052836 .
