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Nucleotide Interaction with Chitosan Layer Deposited on Fumed Silica Surface: Practice and Theory towards Establishing the Mechanism at the Molecular Level

preprint
submitted on 28.09.2020 and posted on 29.09.2020 by Tetyana Budnyak, Nataliya Vlasova, Lyudmila P. Golovkova, Olga Markitan, Glib V. Baryshnikov, Hans Ågren, Adam Slabon
The growing interest in gene therapy is coupled to the strong need for the development of safe and efficient gene transfection vectors. A composite based on chitosan and fumed silica has been found to be a prospective gene delivery carrier. This study presents an investigation of the nature of the bonds between a series of mono-, di- and triphosphate nucleotides with a chitosan layer deposited on a fumed silica surface. It was observed that the adsorption of most of the studied nucleotides is determined by the formation of one surface complex. Experimentally measured surface complex formation constants (logK) of the nucleotides were found to be in range 2.69–4.02 which is higher than that for the orthophosphate (2.39). Theoretically calculated nucleotide complexation energies for chitosan deposited on the surface range from 11.5 to 23.0 kcal·mol–1 in agreement with experimental data. The adsorption of nucleotides was interpreted using their calculated speciation in aqueous solution. Based on the structures of all optimized complexes determined from quantum-chemical PM6 calculations, electrostatic interactions between the surface-located NH3+ groups and –PO3H–/–PO32- fragments of the nucleotides was identified to play the decisive role in the adsorption mechanism. The saccharide fragment of monophosphates also plays an important role in the binding of the nucleotides to chitosan through the creation of hydrogen bonds; in the case of di- and triphosphates the role of the saccharide fragment decreases significantly.

Funding

A.S. thanks for financial support from MISTRA (project: SafeChem). HÅ and GB thanks for support to Olle Engkvist Byggmästare foundation (contract no. 189-0223). GB also thanks for the support to the Ministry of Education and Science of Ukraine (projects no. 0117U003908). The quantum-chemical calculations were performed with computational resources provided by the High Performance Computing Center North (HPC2N) in Umeå, Sweden, through the project “Multiphysics Modeling of Molecular Materials” SNIC 2019/2-41.

History

Email Address of Submitting Author

tetyana.budnyak@mmk.su.se

Institution

Stockholm University, MMK

Country

Sweden

ORCID For Submitting Author

0000-0003-2112-9308

Declaration of Conflict of Interest

The authors declare that they have no known competing financial interests or personal relationships which have, or could be perceived to have, influenced the work reported in this article.

Version Notes

The first version of manuscript (before peer review)

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