Hybrid titania-zirconia nanoparticles coated adsorbent for highly selective capture of nucleosides from human urine in physiological condition.

Modified nucleosides are important biomarkers of cancers. For their analysis, boronate adsorbents were widely used to selectively capture them from urine, but often suffered from serious secondary hydrophobic interaction and harsh alkaline extraction condition. In this work, the hybrid titania-zirconia nanoparticles coated on porous silica spheres (TiO2-ZrO2/SiO2) were developed for the first time as a selective adsorbent for nucleosides under neutral conditions based on specific recognition of its Lewis acid sites to the cis-diol group. It was found here that TiO2-ZrO2 has higher binding constants than pure TiO2 or ZrO2, and a significant improvement of binding efficiencies was obtained by decreasing calcination temperature to 400 °C. Moreover, physiological pH of urine (pH 6-7) was found optimal to adsorb nucleosides and resist other Lewis base interferences. By self-assembly of TiO2-ZrO2 nanoparticles on silica, unprecedentedly high binding capacity (35 mg/g) for nucleosides was obtained due to high surface area (350 m(2)/g) and abundant Lewis acid sites on the surface. Due to efficient reduction of secondary hydrophobic interaction on the inorganic surface, cis-diol nucleosides could be captured from 500-fold non-cis-diol interferences. In the real sample application, nine nucleosides have been quantified with relative recoveries in 83%-126%, and 42 ribosylated metabolites had been identified with only 100 μL of urine at physiological pH. Among them, two nucleosides have never been identified in most previous studies using boronate adsorbents for capture.