Speaker
Description
The sigmatropic isomerization reaction of previtamin D3 to vitamin D3, when encapsulated within a dimer of β-cyclodextrin, exhibits a 40-fold enhanced rate compared to its counterpart in an isotropic organic solution [1]. Despite several hypotheses, the exact mechanism by which β-cyclodextrin dimer catalyzes the reaction remained elusive.
We have conducted a rigorous investigation of the isomerization dynamics of previtamin D3 within a β-cyclodextrin dimer through a combination of molecular dynamic simulations and statistical multi-structural transition state theory to address this knowledge gap. Two key programs in the field of Chemical Kinetics, namely TorsiFlex [2,3] and Pilgrim [4], play a crucial role in facilitating our investigations. TorsiFlex allows for an extensive conformational search encompassing both previtamin D and the reaction transition state, while Pilgrim enables precise calculations of thermal rate constants within systems comprising multiple conformations.
Our results verify the experimental observations and provide unprecedented insights into the β-cyclodextrin dimer catalytic mechanism.
Acknowledgements
The author thanks Xunta de Galicia for the financial support through a postdoctoral grant.
References
[1] X. Q. Tian and M. F. Holick, “Catalyzed Thermal Isomerization between Previtamin D3 and Vitamin D3 via β-cyclodextrin Complexation”, J. Bio. Chem. 270 (1995), 8706–8711.
[2] D. Ferro-Costas, A. Fernández-Ramos, “A Combined Systematic-Stochastic Algorithm for the Conformational Search in Flexible Acyclic Molecules”, Front. Chem. 8 (2020), 16.
[3] D. Ferro-Costas, I. Mosquera-Lois, A. Fernández-Ramos, “Torsiflex: an automatic generator of torsional conformers. Application to the twenty proteinogenic amino acids”, J. Cheminform. 13 (2021), 100.
[4] D. Ferro-Costas, D.G. Truhlar, A. Fernández-Ramos, “Pilgrim: A thermal rate constant calculator and a chemical kinetics simulator”, Comput. Phys. Commun. 256 (2020), 107457.
