Ligand-Mediated TiO2 Functionalization of Silica Nanoparticles for Efficient and Selective Natural Product Separation

Introduction: Post synthesis titania (TiO₂) functionalization of silica nanoparticles (SNPTs) is a facile, yet robust process to obtain a stable system capable of binding natural products of therapeutic interest, such as flavonoids. However, these particles are not efficient in utilizing all of the TiO₂-sites due to clustering or layer formation, and may not be selective in what they bind. Here, we present an approach to produce isolated TiO₂-sites for maximum efficiency by directing single TiO₂ groups towards silica surface using the polar head-group of a TiO₂-surfactant complex. Separately, specificity can be obtained using TiO₂- flavonoid complex during “one-pot” functionalization with TiO₂ sites created by a soft molecular imprint of the desired compound. The use of complexes instead of TiO₂ precursor alone for functionalization should promote dispersion of TiO₂ throughout the system and allow for engineering selectivity towards target metabolites. The ability to improve the accessibility and selectivity of TiO₂ on the particle surface is necessary in designing an advanced and versatile nano-carrier for natural products.

Methods: Silica nanoparticles were synthesized and functionalized simultaneously in a “one-pot” approach following traditional Stöber synthesis of silica nanoparticles, followed by addition of TiO₂ precursor complexed with either a surfactant or flavonoid to the newly formed silica particles. The surfactant/flavonoids were removed from the particle surface by calcination, and the resulting particles were characterized by scanning/transmission electron microscopy, UV-Vis absorbance, N₂ adsorption, and chemical analysis. Particle-flavonoid interactions, capacity, efficiency and selectivity were quantified by equilibrium adsorption isotherms of the flavonoids to differently functionalized nanoparticles.

Results and Discussion: Monodisperse SNPTs were successfully synthesized, consisting of 110 nm particles with different TiO₂ amounts and complexing ligands. Flavonoid adsorption studies demonstrated that binding efficiency is higher for these particle compared to the literature results with post-synthesis functionalization. While selective binding due to imprinting was not observed, binding isotherms of different flavonoids reveal in selective binding based on the structure of the flavonoid, which can be further utilized in a multistep extraction process. This work provides the framework for the design of TiO₂ functionalized silica nanoparticles for the efficient and selective binding of target molecules.

Conclusion: We have developed an approach to obtain well-isolated TiO₂ binding sites on silica nanoparticle surfaces using a one-pot synthesis with simultaneous ligand-guided functionalization. These nanoparticles were demonstrated to efficiently utilize titania for adsorption of flavonoid molecules due to the superior accessibility of surface TiO₂. Moving forward, these concepts will be transferred to mesoporous silica nanoparticle systems to improve the capacity while exploring additional routes of surface functionalization to achieve targeted specificity.