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Solvent effects on host-guest residence time and kinetics: further insights from metadynamics simulation of Toussaintine-A unbiding from chitosan nanoparticle

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Abstract

Solvents play an important role in host-guest intermolecular interactions. The kinetics and residence time of Toussaintine-A (TouA) unbinding from chitosan was investigated by means of well-tempered metadynamics and thermodynamic integration using two solvents, polar aprotic (DMSO), and polar protic (water). The kinetic rates were found to be strongly dependent on the solvent polarity; hence, the unbinding rate proceeded much faster in DMSO compared to water. DMSO tends to participate less in a chemical reaction by weakening the intermolecular interaction between chitosan and TouA due to lack of acidic hydrogen resulting in a reduction of the transition state. On the other hand, water, which ought to donate hydrogen atoms, sustains a strong interaction and hence large barrier heights. Consequently, this reduces the unbinding rate and increases the residence time. Binding free energy from thermodynamic integration suggests a thermodynamic stable chitosan-TouA complex in water than in DMSO.

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Acknowledgements

DMS acknowledges the International Centre for Theoretical Physics (ICTP) for supporting his research visit and availing all research facilities. All authors are grateful to Prof. Alessandro Laio (SISSA) for his comments and discussion during the whole project.

Funding

DMS received the financial support from the world Bank, Tanzania, United Republic of Tanzania, through project no. PI:51847 and grant no. 5799-TZ.

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Authors and Affiliations

  1. School of Life Science and Bio-engeering, The Nelson Mandela African Institute of Science and Technology, P.O.Box 447, Arusha, Tanzania

    Daniel M Shadrack & Hulda Swai

  2. Department of Chemistry, Faculty of Natural and Applied Sciences, St John’s University of Tanzania, P.O.Box 47, Dodoma, Tanzania

    Daniel M Shadrack

  3. Department of Chemistry, Kenyatta University, P.O.Box 43844-00100, Nairobi, Kenya

    Lucy W Kiruri

  4. Chemistry Department, College of Natural and Applied Sciences, University of Dar es Salaam, P.O.Box 35061, Dar es Salaam, Tanzania

    Stephen S Nyandoro

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  1. Daniel M Shadrack
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  2. Lucy W Kiruri
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  4. Stephen S Nyandoro
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Contributions

DMS conceived the study and designed the experiment. DMS and LWK performed all the experiments. DMS developed the first version of the manuscript. DMS, LWK, SSN, and HSS revised and worked on the manuscript to final stage of submission.

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Correspondence to Daniel M Shadrack.

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Shadrack, D.M., Kiruri, L.W., Swai, H. et al. Solvent effects on host-guest residence time and kinetics: further insights from metadynamics simulation of Toussaintine-A unbiding from chitosan nanoparticle. J Mol Model 27, 127 (2021). https://doi.org/10.1007/s00894-021-04735-y

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