Chitosan-based dithiophenolato nanoparticles: Preparation, mechanistic information of DNA binding, antibacterial and cytotoxic activities

Abstract The work aimed to synthesize the chitosan-based dithiophenolato nanoparticles (DTP-CS NPs), evaluate in-vitro DNA-binding mechanistically in detail, correlate the results with antibacterial and cytotoxic activity and try to answer the question: Is the metal center always important for binding?. DTP-CS NPs were prepared from dithiophenolate DTP and CS NPs as spherically shaped with the mean particle size of 150 ± 5 nm. Thermal and zeta potential measurements revealed an increase in the stability of DTP-CS NPs compared to DTP. Since almost all pharmaceuticals work via binding to a specific protein or DNA, in-vitro DNA binding DTP-CS NPs has been studied mechanistically and compared with DTP. With the aid of stopped-flow and other spectroscopic methods, a mechanism for the interaction was proposed. Both compounds bind via a static quenching mechanism through two reversible steps: a fast second-order binding is followed by a slow first-order isomerization reaction. The detailed binding parameters for the first and second steps of DTP-CS NPs and DTP were determined. Overall binding parameters for DTP-CS NPs (Ka = 357 × 103 M−1, Kd = 2.8 × 10−6 M, ΔG0 = −31.7 kJ mol−1) and DTP (Ka = 8.4 × 103 M−1, Kd = 119.2 × 10−6 M, ΔG0 = −22.4 kJ mol−1) were also determined and showed that the relative reactivity is approximately (DTP-CS NPs)/(DTP) = 40/1. The significantly negative ΔG values are consistent with a spontaneous binding reaction to both DTP–CS NPs and DTP, with DTP-CS NPs is very favorable. Moreover, antibacterial and cell viability assessments were performed on four bacterial strains and two cell lines, respectively. Antibacterial activity of DTP-CS NPs was extremely greater than DTP, especially in Gram-negative bacteria. Furthermore, DTP-CS NPs had significant cytotoxicity against HepG2 human hepatic cancer cells compared to DTP and also showed selectivity. A correlation with a related system is also reported and showed that the metal center may not always important for binding.