Brock S. Howerton

Chemical precipitation of heavy metals from acid mine drainage.

The 1,3-benzenediamidoethanethiol dianion (BDET, known commercially as MetX) has been developed to selectively and irreversibly bind soft heavy metals from aqueous solution. In the present study BDET was found to remove > 90% of several toxic or problematic metals from AMD samples taken from an abandoned mine in Pikeville, Kentucky. The concentrations of metals such as iron, may be reduced at pH 4.5 from 194 ppm to below 0.009 ppm. The formation of stoichiomietric BDET-metal precipitates in this process was confirmed using X-ray powder diffraction (XRD), proton nuclear magnetic resonance (1H NMR), and infrared spectroscopy (IR).

Strained ruthenium complexes are potent light-activated anticancer agents.

Strained ruthenium (Ru) complexes have been synthesized and characterized as novel agents for photodynamic therapy (PDT). The complexes are inert until triggered by visible light, which induces ligand loss and covalent modification of DNA. An increase in cytotoxicity of 2 orders of magnitude is observed with light activation in cancer cells, and the compounds display potencies superior to cisplatin against 3D tumor spheroids. The use of intramolecular strain may be applied as a general paradigm to develop light-activated ruthenium complexes for PDT applications.

Irreversible precipitation of mercury and lead.

There are immediate concerns with current commercial reagents that are used for heavy metal precipitation; in particular the fact that the reagents are not specifically designed to bind the targeted metals. The current literature reveals that not only do commercial reagents lack sufficient ability to strongly bind the metals, but they also fail to provide long-term stability as ligand-metal complexes under a variety of moderate conditions. For this reason a new ligand was designed and synthesized: 1,3-benzenediamidoethanethiol (BDETH2). It offers multiple, concerted, bonding sites for heavy metals and forms a stable metal-ligand precipitate. In this study, the formation of compounds comprised of this ligand with the divalent metals, lead and mercury, was explored and the pH stability of the water insoluble precipitates was determined. The leaching properties of the metal-ligand precipitates were determined using inductively coupled plasma (ICP) spectroscopy and cold vapor atomic fluorescence spectroscopy (CVAF). The results indicate that a 50.00 ppm lead solution at a pH of 4.0 may be reduced to a concentration of 0.05 ppm (99.9% lead removal) and to 0.13 ppm (99.7% lead removal) at a pH 6.0. A 50.00 ppm mercury solution at pH 4.0 may be reduced to a concentration of 0.02 ppm (99.97% mercury removal) and to 0.02 ppm (99.97% mercury removal) at a pH of 6.0.

A pyridine-thiol ligand with multiple bonding sites for heavy metal precipitation.

There are immediate concerns with current commercial ligands that are used for heavy metal precipitation, especially the limited arrays of bonding sites. Previous research has indicated that not only do commercial reagents lack sufficient bonding criteria, but they also fail to provide long-term stability as ligand-metal complexes. For this reason, we have developed a pyridine-based thiol ligand (DTPY) which not only offers multiple bonding sites for heavy metals but also should form stable metal-ligand precipitates. In this study, we used the divalent metals cadmium and copper to model the reactivity and pH stability of divalent metal complexes with the DTPY ligand. Using inductively-coupled plasma spectrometry (ICP), results indicate that a 50.00ppm (parts per million) copper solution, pH of 4.5, can be reduced to below the ICP detection limits of 0.00093ppm (>99.99% removal), and a 50.00ppm cadmium solution, pH of 6.0, can be reduced to 0.06ppm (99.88%).

Modifying Charge and Hydrophilicity of Simple Ru(II) Polypyridyl Complexes Radically Alters Biological Activities: Old Complexes, Surprising New Tricks

Compounds capable of light-triggered cytotoxicity are appealing potential therapeutics, because they can provide spatial and temporal control over cell killing to reduce side effects in cancer therapy. Two simple homoleptic Ru(II) polypyridyl complexes with almost-identical photophysical properties but radically different physiochemical properties were investigated as agents for photodynamic therapy (PDT). The two complexes were identical, except for the incorporation of six sulfonic acids into the ligands of one complex, resulting in a compound carrying an overall −4 charge. The negatively charged compound exhibited significant light-mediated cytotoxicity, and, importantly, the negative charges resulted in radical alterations of the biological activity, compared to the positively charged analogue, including complete abrogation of toxicity in the dark. The charges also altered the subcellular localization properties, mechanism of action, and even the mechanism of cell death. The incorporation of negative charged ligands provides a simple chemical approach to modify the biological properties of light-activated Ru(II) cytotoxic agents.

Coordination of Hydroxyquinolines to a Ruthenium Bis-dimethyl-phenanthroline Scaffold Radically Improves Potency for Potential as Antineoplastic Agents

A series of ruthenium coordination complexes containing hydroxyquinoline ligands were synthesized that exhibited radically improved potencies up to 86-fold greater than clioquinol, a known cytotoxic compound. The complexes were also >100-fold more potent than clioquinol in a tumor spheroid model, with values similar to currently used chemotherapeutics for the treatment of solid tumors. Cytotoxicity occurs through rapid processes that induce apoptosis but appear to be mediated by cell-cycle independent mechanisms. The ruthenium complexes do not inhibit the proteasome at concentrations relevant for cell death, and contrary to previous reports, clioquinol and other hydroxyquinoline compounds do not act as direct proteasome inhibitors to induce cell death.

Light-sensitive ruthenium complex-loaded cross-linked polymeric nanoassemblies for the treatment of cancer

This work focuses on improving the efficacy of photoactivatable Ru complexes for photodynamic therapy by employing cross-linked nanoassemblies (CNAs) as a delivery approach. The effects of complex photoactivation, hydrophobicity, and solution ionic strength and pH on complex loading and release from CNAs were analyzed. The cell cytotoxicity of CNA formulations was similar to free Ru complexes despite reduced or eliminated DNA interactions. The release rate and the amount of each Ru complex released (%) varied inversely with complex hydrophobicity, while the effect of solution ionic strength was dependent on complex hydrophobicity. Premature release of two photoactivatable prodrugs prior to irradiation was believed to account for higher activity in cells studies compared to DNA interaction studies; however, for photostable 1O2 generator-loaded CNAs this cannot explain the high cytotoxicity and lack of DNA interactions because release was incomplete after 48 hrs. The cause remains unclear, but among other possibilities, accelerated release in a cell culture environment may be responsible.

Covalent coating of coal refuse to inhibit leaching

Acid mine drainage (AMD) is a severe environmental problem that results from the oxidation of pyrite (FeS2) and various other metal sulfides. AMD is often associated with abandoned mines which produce acidic run-off waters that are rich in heavy metals. AMD also occurs in the areas surrounding coal refuse piles that have accumulated from coal cleaning processes. In the present work, the use of the disodium salt of the ligand 1,3-benzenediamidoethanthiol (Na2BDET) is explored as a possible coating to prevent the dissolution of pyrite in coal. Unlike phosphate- and silica-based compounds, Na2BDET is believed to form covalent Fe–BDET linkages along the pyrite lattice. It was found that Fe leaching from BDET-coated coal is reduced by 99.3% when submerged in a pH 6.5 solution, by 97.5% when submerged in a pH 3.0 solution, and 66.4% when subjected to acidic and oxidative conditions. The ligand coating treatment also reduced the leaching of other heavy metals, such as Mn, Cu, Ni, Zn where a reduction of 88.3%, 64.7%, 70.5% and 89.5%, respectively, was observed in leaching after a 14-day simulated acid rain test. Additional leaching reductions were observed for metals such as Zn, Cu, Co, etc. at pH 6.5 and 3.0 when subjected to both oxidative and acidic conditions.

Irreversible binding of mercury from contaminated soil

Abstract The 1,3-benzenediamidoethanethiol dianion (BDET 2− ) has been designed and synthesized to immobilize mercury from contaminated soils. In this study, mercury contaminated soil samples from the Appalachia Region of Eastern Kentucky were collected and tested with the sodium salt of this ligand. Multiple binding sites on the BDET 2− ligand have led to stable mercury–ligand precipitates that are capable of withstanding adverse oxidative and pH conditions. Results indicated that 99.6% of the mercury in the soil samples could be immobilized from an average starting concentration of 10.3 mg of mercury per gram of soil (mg Hg/g soil). The precipitates were tested for stability through leaching and oxidative-digestion tests, and yielded leaching rates less than 5×10 −11 g/ml at times 2, 30 and 60 days at a pH range of 0.0–10.0.

Soft metal preferences of 1,3-benzenediamidoethanethiol.

Recent studies indicate that the sodium salt of 1,3-benzenediamidoethanethiol (BDET) is both economical and effective in precipitating mercury and other heavy metals from water. Because wastewaters and contaminated natural waters may contain a variety of heavy metals, it is important to determine how different heavy metals may interact with BDET, and whether free metals may displace those that are bound. To explore this possibility, Cd-, Cu-, Pb-, Mn-, Hg- and Zn-BDET were leached separately under a nitrogen purge for up to 240 h in pH 3 aqueous solutions containing 0.100 mmol of all five heavy metals. The leaching studies indicate that dissolved Hg has a strong tendency to displace Cd, Cu, Mn, Pb, and Zn from the BDET structure.