A spin-labeled adduct of the therapeutic drug, Melphalan, was synthesized using a three-step synthetic route. Step one involves the protection of the amine group under basic conditions with Di-tert-butyl carbonate as the protecting group. Step two involves the addition of the spin label compound 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPOL) to the carboxylate group of Melphalan via a Steglich esterification with the assistance of the coupling agent, N,N'-Dicyclohexylcarbodiimide, and a catalyst, 4-Dimethylaminopyridine, under the inert atmosphere of nitrogen gas. The final step comprises the restoration of the amine group by using a strong acid to remove the protecting group and obtaining the final product after purification of the Melphalan-TEMPOL adduct. To ensure that the spin label compound was successfully coupled to Melphalan, structural analyses of the intermediates and final product have been carried out using 1H NMR and EPR (Electron Paramagnetic Resonance) for detecting free radical activity of the single electron spin of the nitroxyl group of TEMPOL. The main objectives of this project are: a) to improve the bioavailability, retention time and permeability of Melphalan during drug delivery with the assistance of nanoparticle drug delivery techniques; and b) to develop MRI techniques using the Melphalan-TEMPOL adduct enclosed polymeric nanoparticles.

Synthesis and magnetic resonance analyses of Melphalan-TEMPOL for site-targeted drug delivery

248th National Meeting (2014)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.