Formylation of functionalized P-H bonds — A novel approach to the design of synthons for use in biomedicine
Formylation of phosphorus-hydrogen bonds has become a versatile strategy to producing compounds with phosphorus-carbon bonds. However, the utility of such reactions on functionalized phosphines is a recent development. Our laboratory has developed new approaches to the synthesis of phosphorus(III) hydrides functionalized with main group backbones (e.g. thioether: (P2S2), alkyl amino (P2N2)). The formylation of P2S2 and P2N2 functionalized phosphorus(III) hydrides, using formaldehyde, produced hydroxymethyl-substituted (P(CH2OH)n)n compounds. Recent results suggest that formylation of P-H bonds occur under mild conditions in aqueous media without the aid of transition metal catalysts. The hydroxymethyl (HMP) functionalized P2S2 and P2N2 phosphines are highly soluble in water and display oxidative-stability in aqueous media. The HMP functionalized phosphines react with the early (e.g. Re(V)) and late transition metals (e.g. Rh(I), Pd(II), Pt(II), Ag(I) and Au(I)), under biphasic (aqueous-organic) solvent media to produce a new generation of water-soluble transition metal compounds. The electronic characteristics of HMP groups dictate high kinetic inertness and thermal stability in aqueous media and therefore provide a novel access to stabilize specific oxidation states of transition metals in aqueous media. Our laboratory has also concentrated its efforts on the application of HMP-based ligands in the design of site-directed and tumor-specific radiopharmaceuticals. This interest stems from the fact that the development ofin vivo-stable186/188rhenium (and99mTc) and199gold compounds and their conjugation to specific biomolecular vectors (e.g. peptides or proteins) will provide new avenues in the discovery of cancer diagnostic, and more importantly, therapeutic pharmaceuticals. Our studies have demonstrated that the HMP ligands upon complexation with technetium-99m and gold-198, produce complexes that are highly stable underin vivo conditions as evidenced through studies in experimental animal models. Details on ligand design and transition metal/organometallic chemistry as they relate to the development of aqueous-soluble transition metal/radiometal compounds with potential applications in nuclear medicine will be discussed.
Volume 134, 2022
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