Werner Complexes Viewed Anew: Utilizing Cobalt Coordination Chemistry for 'Traceless' Stimuli-Responsive Bioconjugation Involving Therapeutic Nanoparticles, Protein PEGylation, and Drug-(Bio)polymer Conjugates
Alfred Werner received the Nobel Prize in 1913 for his pioneering work in developing coordination theory for metal complexes. A crucial experiment leading to the widespread acceptance of Werner's theory involved the resolution of a set of chiral cobalt complexes, specifically cis-[Co(en)(2)(NH3)X]X-2 (X=Cl, Br). The kinetic inertness of the Co complexes studied was likely a major contributor to the success of this endeavor by providing a robust system to probe ligand geometry. Here, we revisit this classic coordination chemistry and show how it can be utilized in the field of targeted drug delivery for the bioconjugation of amine-containing (bio)molecules. The chemistry proved to be quite robust, and could be used to crosslink albumin into nanoparticles (20-500nm in diameter) that exhibited exceptional stability under physiological conditions. The chemistry was pursued as a "traceless" linker that would degrade under reducing conditions, which was observed experimentally through the degradation of our cobalt crosslinked particles upon exposure to reduced glutathione. Bioconjugation of poly(ethylene glycol) (PEG) chains to a prototypical protein (transferrin) was also possible making this chemistry attractive for a host of applications in nanoparticle therapeutics.
展开▼
