Transition metal complexes with bioactive ligands: mechanisms for selective ligand release and applications for drug delivery

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Abstract

The unique properties of transition metal complexes, such as environment-responsive ligand exchange kinetics, diverse photochemical and photophysical properties, and the ability to form specific interactions with biomolecules, make them interesting platforms for selective drug delivery. This minireview will focus on recent examples of rationally designed complexes with bioactive ligands, exploring the different roles of the metal, and mechanisms of ligand release. Developments in the techniques used to study the mechanisms of action of metal–drug complexes will also be discussed, including X-ray protein crystallography, fluorescence lifetime imaging, and X-ray absorption spectroscopy.

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Prodrugs: design and clinical applications.

Jarkko Rautio, Hanna Kumpulainen, Tycho Heimbach … (2008)

Prodrugs are bioreversible derivatives of drug molecules that undergo an enzymatic and/or chemical transformation in vivo to release the active parent drug, which can then exert the desired pharmacological effect. In both drug discovery and development, prodrugs have become an established tool for improving physicochemical, biopharmaceutical or pharmacokinetic properties of pharmacologically active agents. About 5-7% of drugs approved worldwide can be classified as prodrugs, and the implementation of a prodrug approach in the early stages of drug discovery is a growing trend. To illustrate the applicability of the prodrug strategy, this article describes the most common functional groups that are amenable to prodrug design, and highlights examples of prodrugs that are either launched or are undergoing human trials.