The rate-limiting reaction step means that if one elementary step in a mechanism progresses much slower than the others, then this step determines the total reaction rate. A rate-limiting step can be the formation or breaking of a critical structure such as a specific base pair in RNA folding. Therefore, it is crucial to identify this important step to study the reaction mechanism of the entire reaction. The determination of the rate-limiting step in a chemical reaction depends on a clear understanding of the kinetics of each reaction. The experimental data obtained under different conditions introduce the uncertainty of kinetic parameters. Identification of the rate-limiting steps has been a long standing problem in most of chemical process. The emergence of computer simulation has effectively made up for the lack of experiments, and can obtain detailed information about the entire reaction process at the atomic level. By analyzing the structure of the reaction intermediates and transition states, the rate-limiting steps of the reaction can be determined combined with kinetic methods. Several remarkable computational methods have been developed to search for the transition states and analyze the mechanism of the entire reaction. Scientists can therefore model the uncertainty of the kinetic data and quantitatively predict reaction steps.
Figure 1. Values of the various terms are used to identify a change in the rate-limiting step. (Sbirrazzuoli, N; et al. 2019)
At Alfa Chemistry, we have abilities in performing a diversity of calculation methods including Monte Carlo method, isoconversional kinetic analysis, density functional theory and predictive methods. Our fast and high-quality services include the following:
- Monte Carlo method
We use a novel and efficient Monte Carlo sampling program to simulate almost all possible meaningful states of a chemical process, and compute the corresponding values of the kinetic constants of each reaction step to identify the rate-liming reaction steps. The proposed methodology is developed based on process control and accounts explicitly for physicochemical and thermodynamic constraints.
- Isoconversional kinetic analysis
We use an advanced isoconversion kinetic analysis method to clarify complex reaction mechanisms and quickly identify rate-limiting steps. Our scientists can simulate various and complex mechanism, and analyze any complex chemical or physical transformation. Our method focuses on the correlation between the reaction rate, the activation energy dependency, rate constants for the chemically control part of the reaction and the diffusion control part, activation energy and pre-exponential factors of each step and change in rate-limiting steps. Moreover, some of the parameters we calculate can help to identify changes in the rate-limiting steps of the overall aggregation mechanism measured by thermal analysis techniques.
- Density functional theory (DFT)
Alfa Chemistry supports the DFT-B3LYP method to study the mechanism of the enzyme-catalyzed rearrangement reaction. The optimization of the structure and the calculation of the single point energy are respectively completed on the two basis sets of 6-31G(d) and 6-311++G(2d,2p).
1. We construct a theoretical model of polyatoms to study its catalytic mechanism based on the crystal structure of the reactants.
2. The natural bond orbit theory (NBO) method is applied to perform the charge population analysis, further verifying the correctness of the speculated mechanism.
3. Our scientists then conduct accurate calculation to obtain an intermediate with a tetrahedral structure.
4. We finally draw the potential energy surface curve of the total reaction, and determine the rate-limiting step of the entire reaction by comparison according to the energy calculation of each optimized structure.
- Predictive methods
Our teams are also capable of using a hierarchy of predictive methods to provide estimates of transition-state free energies for reaction pathways, and study reaction kinetics and rate-limiting steps.
1. First, the free energy of each intermediate species is estimated using a combination of machine learning and group additivity methods.
2. These intermediate species energies are then used to calculate reaction free energies for each reaction using stoichiometric relations.
3. Transition-state energies can be predicted using established linear transition-state scaling relations.
4. Finally, significant pathways are determined using approximations from absolute rate theory by tracking the highest transition state in the free energy diagram for each mechanism.
Why Choose Us?
- We have developed a particularly broad expertise in the modelling of surfaces and interfacial processes, aiming to providing reliable services of quantum mechanical modelling of chemical reactions.
- Our experienced groups can identify rate-limiting reaction step accurately by comparing the kinetic characteristics of different elementary reactions.
Identification of rate-limiting reaction steps provides an effective way to optimize the chemical process. Our identification of rate-limiting reaction steps services remarkably reduce the cost, promote further experiments, and enhance the understanding of chemical process for customers worldwide. Our personalized and all-around services will satisfy your innovative study demands. If you are interested in our services, please don't hesitate to contact us. We are glad to cooperate with you and witness your success!
- Sbirrazzuoli, N; et al. Advanced Isoconversional Kinetic Analysis for the Elucidation of Complex Reaction Mechanisms: A New Method for the Identification of Rate-Limiting Steps. Molecules. 2019, 24(9): 1683.