New protocol for chemists makes more sustainable research possible

AIMMS researchers Trevor Hamlin, Matthias Bickelhaupt and colleagues have published a step-by-step guide on how to perform the activation strain analysis

01/27/2020 | 3:46 PM

A team of theoretical chemists led by Trevor A. Hamlin and Matthias Bickelhaupt (AIMMS), has published a step-by-step guide on how to perform the activation strain analysis, which will serve as a “recipe for researchers” who want to analyze and understand the factors controlling the reactivity of literally any chemical reaction. This makes, among other things, environmentally sustainable research possible.

Chemists now have the tools to first rationally design chemical reactions using this protocol prior to carrying out the reaction in the laboratories. The authors hope that the availability of this easy to use protocol will cause a shift in the way new chemical reactions are being developed. The research has been published in Nature Protocols, the flagship protocol journal of the Nature Research Journals.

Scientific Impact
This theory-driven experimentation approach potentially represents a paradigm shift in chemical research, which the authors hope will ultimately lead to streamlined syntheses, lower costs, and a reduction in chemical waste, all of which will make chemical research more economically and environmentally sustainable.

Activation Strain Model
The protocol presented by the authors is based on the activation strain model (ASM) of chemical reactivity. This powerful method provides the user with insight into the driving force behind a chemical reaction, which not only allows for understanding the reaction of interest but also the rational design of other new reactions. Over the years, the ASM has successfully been applied to numerous inorganic, organic, biochemical, and supramolecular reactions.

Strain energy and interaction energy
In general terms, the rate of a chemical reaction is determined by the height of the reaction barrier that reactants must overcome in order to transform into products. Within the framework of the ASM, this reaction barrier is related to two factors, namely the strain energy and the interaction energy (see figure). The strain energy is the energy needed to deform the reactants that undergo a chemical reaction from their equilibrium geometry into the geometries they acquire to react. The interaction energy is the actual chemical interaction between the two deformed reactants.

Energy Decomposition Analysis
To obtain insight into this chemical interaction, the model can be extended with a matching energy decomposition analysis (EDA) scheme, in which the interaction energy between the reactants is decomposed into a number of physically meaningful terms, including the classical electrostatic interaction, steric (Pauli) repulsion, and the stabilizing orbital interactions.

More than a step-by-step guide
Besides acting as a step-by-step guide, this protocol provides researchers also with tips-and-tricks on which computational settings should be used for a number of specific chemical problems. Additionally, this work contains two fundamental examples, of which the first takes users by the hand and guides them through the procedure while the second serves as an advanced example, testing the knowledge of the user.

diagram trevor matthias
Activation strain diagram
Activation strain diagram where two generic chemical reactions (red and black) are compared and analyzed. The transition states are indicated with a dot.