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.
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