The development of new strategies for the functionalization of the historically inert C—H bond arises as an excellent way to create new carbon—carbon and carbon— heteroatom bonds. With increasingly chemo- and site-selective methods that enables the late-stage functionalization of C—H bonds, the modification of specific sites in natural products and pharmaceuticals without altering their scaffold emerges as a powerful means for the diversification of complex molecules. In this review, we will introduce concepts of late-stage modifications, the use of C—H bond functionalization to forge new carbon—carbon and carbon—heteroatom bonds using metal catalysis and photochemistry in simple examples and their applications in natural products and pharmaceuticals. The aim of the review is to update and display to the reader the contributions and implications of this methodology to organic synthesis. CH C H carboncarbon carbon chemo siteselective site selective latestage late stage molecules modifications carbonheteroatom synthesis

The diruthenium(II,III)-ibuprofen (RuIbp) metallodrug shows anticancer activity in vitro and in vivo. The encapsulation into lipid nanoparticles enhanced the efficacy in glioblastoma, breast and prostate cancer cells. Here we report data for RuIbp hydrophobicity, solubility in alcohol/water, and behavior in 1-5% ethanol/water and ethanol/cell culture medium. RuIbp is capable of spontaneously generate self-assembled RuIbpNP nanoparticles when drug ethanolic solutions are added to water or cell growth culture medium at 1-5% ethanol. The phenomenon was investigated, and the nanoparticles characterized. RuIbpNP nanoparticles formed at 100-200 µmol L−1 RuIbp are colloidally stable and nearly spherical showing zeta potential about +40 mV and particle size about 100 (aqueous suspension) and 180 nm (culture medium). The integrity of the [Ru2(Ibp)4] framework was confirmed by spectroscopy and mass spectrometry. Significant amount of metallodrug was found in suspension (85%, culture medium; 54%, culture medium with cells). The uptake by U87MG glioblastoma cells was 6% at 24 h. The spontaneous nanosizing of RuIbp in the form of nanosuspensions may explain the biological activity of this highly hydrophobic metallodrug. The present findings expand the knowledge on the behavior of RuIbp, opening new directions to exploit the properties of the metallodrug targeting cancer therapy.