Related Experiment Video
Updated: May 27, 2026
05:51
Isotopic Effect in Double Proton Transfer Process of Porphycene Investigated by Enhanced QM/MM Method
Published on: July 19, 2019
Predicting Michael-acceptor reactivity and toxicity through quantum chemical transition-state calculations
Denis Mulliner1, Dominik Wondrousch, Gerrit Schüürmann
1UFZ Department of Ecological Chemistry, Helmholtz Centre for Environmental Research, Permoserstr. 15, 04318, Leipzig, Germany.
Organic & Biomolecular Chemistry
|November 4, 2011
Summary
Quantum calculations predict Michael acceptor toxicity by modeling glutathione reactions. This method accurately predicts reactivity, aiding in hazard assessment for chemicals like unsaturated carbonyls.
Area of Science:
- Computational Chemistry
- Toxicology
- Organic Chemistry
Background:
- Electrophilic reactivity of Michael acceptors is key to their toxicity.
- Understanding this reactivity is crucial for chemical safety assessments.
Purpose of the Study:
- To develop a computational method for predicting the electrophilic reactivity of Michael acceptors.
- To correlate this reactivity with toxicity data for hazard evaluation.
Main Methods:
- Quantum chemical calculations (B3LYP/6-31G**) of Michael addition reactions.
- Modeling reactions with methane thiol as a nucleophile.
- Empirical correction for α-substitution effects.
Main Results:
- Calculated reaction barriers (ΔE‡) correlate well with experimental glutathione reaction rate constants (k(GSH)).
- An empirical correction improved prediction accuracy (r² = 0.96) for log k(GSH).
- The method successfully predicted toxicity trends for a larger set of compounds.
Conclusions:
- In silico screening of Michael acceptor electrophilicity is feasible.
- This approach aids in predictive hazard evaluation, relevant for regulations like REACH.
- Early identification of toxicity-relevant reactivity is enabled.
Related Concept Videos
01:25Transition State Theory
Transition-state theory, also known as activated-complex theory, provides a molecular-level explanation of reaction rates in both gas-phase and solution-phase reactions. It extends earlier kinetic models by considering the formation of a short-lived, high-energy configuration during a reaction.The progress of a chemical reaction can be represented using a reaction profile, which plots potential energy against the reaction coordinate. As two reactant molecules approach one another, their...
01:08Conjugate Addition of Enolates: Michael Addition
The attack of a nucleophile at the β carbon of an α,β-unsaturated carbonyl compound is called conjugate addition. Conjugate addition reactions of active methylene compounds, such as β-diketones, β-keto esters, β-keto nitriles, and α-nitro ketones, are called Michael addition reactions.
02:24Predicting Reaction Outcomes
Kinetics describes the rate and path by which a reaction occurs. In contrast, thermodynamics deals with state functions and describes the properties, behavior, and components of a system. It is not concerned with the path taken by the process and cannot address the rate at which a reaction occurs. Although it does provide information about what can happen during a reaction process, it does not describe the detailed steps of what appears on an atomic or a molecular level. On the other hand,...
02:13Energy Diagrams, Transition States, and Intermediates
Free-energy diagrams, or reaction coordinate diagrams, are graphs showing the energy changes that occur during a chemical reaction. The reaction coordinate represented on the horizontal axis shows how far the reaction has progressed structurally. Positions along the x-axis close to the reactants have structures resembling the reactants, while positions close to the products resemble the products. Peaks on the energy diagram represent stable structures with measurable lifetimes, while other...
01:30Quantitative Aspects of Drug-Receptor Interaction
The receptor occupancy theory connects a drug's response to the number of occupied receptors. With higher drug concentrations, more receptors are occupied, leading to increased responses. The formation of drug-receptor complexes involves association and dissociation rates, which reach equilibrium when the forward and backward reactions are equal. The equilibrium association constant (Ka) and its inverse, the equilibrium dissociation constant (Kd), indicate drug affinity. Higher Ka and lower Kd...
01:16Cycloaddition Reactions: MO Requirements for Thermal Activation
Thermal cycloadditions are reactions where the source of activation energy needed to initiate the reaction is provided in the form of heat. A typical example of a thermally-allowed cycloaddition is the Diels–Alder reaction, which is a [4 + 2] cycloaddition. In contrast, a [2 + 2] cycloaddition is thermally forbidden.