ABSTRACT
Over time platinum-based anticancer drugs have dominated the market, but their side effects significantly impact the quality of life of patients. Alternative treatments are being developed all over the world. The titanocene and auranofin families of compounds, discovered through an empirical search for other metal-based therapeutics, hold tremendous promise to improve the outcomes of cancer treatment. Herein we present a historical perspective of these compounds and review current efforts focused on the evolution of their ligands to improve their physiological solution stability, cancer selectivity, and antiproliferative performance, guided by a clear understanding of the coordination chemistry and aqueous speciation of the metal ions, of the cytotoxic mechanism of action of the compounds, and the external factors that limit their therapeutic potential. Newer members of these families of compounds and their combination in novel bimetallic complexes are the result of years of scientific research. We believe that this review can have a positive impact in the development and understanding of the metal-based drugs of gold, titanium, and beyond.
ABSTRACT
Small-scale gold mining in Portovelo-Zaruma, Southern Equador, performed by mercury amalgamation and cyanidation, yields 9-10 t of gold/annum, resulting in annual releases of around 0.65 t of inorganic mercury and 6000 t of sodium cyanide in the local river system. The release of sediments, cyanide, mercury, and other metals present in the ore such as lead, manganese and arsenic significantly reduces biodiversity downstream the processing plants and enriches metals in bottom sediments and biota. However, methylmercury concentrations in sediments downstream the mining area were recently found to be one order of magnitude lower than upstream or in small tributaries. In this study we investigated cyanide, bacterial activity in water and sediment and mercury methylation potentials in sediments along the Puyango river watershed, measured respectively by in-situ spectrophotometry and incubation with (3)H-leucine and (203)Hg(2+). Free cyanide was undetectable (<1 µg·L(-1)) upstream mining activities, reached 280 µg·L(-1) a few km downstream the processing plants area and was still detectable about 100 km downstream. At stations with detectable free cyanide in unfiltered water, 50% of it was dissolved and 50% associated to suspended particles. Bacterial activity and mercury methylation in sediment showed a similar spatial pattern, inverse to the one found for free cyanide in water, i.e. with significant values in pristine upstream sampling points (respectively 6.4 to 22 µgC·mg wet weight(-1)·h(-1) and 1.2 to 19% of total (203) Hg·gdry weight(-1)·day(-1)) and undetectable downstream the processing plants, returning to upstream values only in the most distant downstream stations. The data suggest that free cyanide oxidation was slower than would be expected from the high water turbulence, resulting in a long-range inhibition of bacterial activity and hence mercury methylation. The important mercury fluxes resultant from mining activities raise concerns about its biomethylation in coastal areas where many mangrove areas have been converted to shrimp farming.