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submitted on 28.09.2020 and posted on 29.09.2020by 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.
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.