Shaowei Bo

Design and Synthesis of Fluorinated Dendrimers for Sensitive F-19 MRI

To achieve high sensitivity for (19)F MRI, a class of novel dendritic molecules with multiple pseudosymmetrical fluorines was designed and efficiently synthesized. Through iterative bromination and Williamson ether synthesis under mild conditions, a fluorinated dendrimer with 540 pseudosymmetrical fluorines was conveniently prepared without performing the group protection in a convergent way. The dendrimer is characterized by a strong (19)F NMR peak and short relaxation times. Eventually, an appreciably enhanced (19)F MRI at an extremely low concentration (18.5 μM) was achieved, which demonstrated the potential utility of such dendritic molecules in highly sensitive (19)F MRI.

Discovery of a 19F MRI sensitive salinomycin derivative with high cytotoxicity towards cancer cells

Salinomycin is a promising anti-cancer agent which selectively targets cancer stem cells. To improve its potency and selectivity, an analog library of salinomycin was generated by site-specific modification and CuAAc derivatization. Through a cytotoxicity analysis of the library, a fluorinated analog with high potency, selectivity, and (19)F MRI sensitivity was discovered as a novel theranostic agent.

Application of Monodisperse PEGs in Pharmaceutics: Monodisperse Polidocanols

Polydisperse PEGs are ubiquitously used in pharmaceutical industry and biomedical research. However, the monodispersity in PEGs may play a role in the development of safe and effective PEGylated small molecular drugs. Here, to avoid the polydispersity in polidocanol, the active ingredient in a clinically used drug, a macrocyclic sulfate-based strategy for the efficient and scalable synthesis of monodisperse polidocanols, their sulfates, and their methylated derivatives, was developed. TLC and HPLC analysis indicated a complex mixture in regular polidocanol and high purities in monodisperse polidocanols and their derivatives. Assay on HUVEC, L929, and HePG2 cells showed that monodisperse polidocanols have much higher cytotoxicity and safety than that of regular polidocanol. It was found that the monodispersity of PEGs in polidocanols is crucial for achieving the optimal therapeutic results. Therefore, based on this case study, it would be beneficial to optimize PEGylated small molecular drugs with monodisperse PEGs in pharmaceutical research and development.

Monodisperse oligoethylene glycols modified Propofol prodrugs

The low water solubility of Propofol resulted in complicated formulation and adverse effects during its clinical application. To improve its water solubility and maintain its anesthetic effects, Propofol prodrugs with monodisperse oligoethylene glycols as solubility enhancer were designed and synthesized. Monodisperse oligoethylene glycols enable the concise manipulation of water solubility, biocompatibility and anesthetic effects. Through the physicochemical and biological assay, a few water soluble prodrugs of Propofol were identified as promising anesthetic to overcome the drawbacks associated with Propofol.