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By Robert B. Parsons

"Canada doesn't really have a tax system for mining - it has eleven separate tax systems! The consequent maze adds some undefinable margin of difficulty to making investment decisions in Canada. But, this 11U1Ze is not likely to be simplified. Solution: learn it and sell it! Intricate Network of Winding PathwaysWebster's New World Dictionary defines the word ""maze"" as follows: ""a confusing, intricate network of winding pathways; labyrinth ... a state of confusion or bewilderment"". Webster's does not go on to give an example of a maze, but the dictionary could easily have referred to the taxation of a Canadian mining operation. The uninitiated would almost certainly look upon such taxation as a maze of the most perplexing sort.Twenty years ago, Canada's tax system was really quite simple. It is true that Canadian mining profits were subject to three levels of taxation (federal income tax, provincial income tax, and provincial mining tax), but this didn't pose a problem. Prior to 1974, at least the provincial income tax systems were somewhat the same in terms of rules .and rates, and even the provincial mining tax systems resembled one another. Mining profits were subject to pretty much the same rules, no matter what province or territory hosted the mine. Those were the “good old days” one could even dare to generalize about tax rates without fear of being labelled an imbecile!"

Jan 1, 1994

By J. H. Pateson, D. C. Comrie, D. J. Ritcey

"Geopolymers are inorganic semi-amorphous three dimensional silico-aluminates of the poly(sialate) type (-Si-O-Al-0-) or of the poly(sialate-siloxo) type (-Si-O-Al-O-Si-0-). Polycondensation occurs at low temperatures with geopolymers being stable up to 12oo0 c. Research, development and application technology pertaining to geopolymers is being undertaken jointly with Dr. Joseph Davidovits of The Institute for Applied Archaeological Sciences of Florida, U.S.A. This joint focused upon the chemical Barry University in Miami Shores, research and development program has stabilization and solidification of various waste products through geopolymerization. Of particular interest is the geopolymerization of mine wastes including tailings and waste rock derived from the processing of base metals, precious metals, potash, coal and uranium deposits.INTRODUCTIOND. Comrie Consulting Ltd., in cooperation and technical liaison with CANMET, Ottawa has been testing the application of geopolymers to mining wastes. Corporate efforts to date have concentrated upon reactive acid tailings, principally from the abandoned Kam-Kotia Mine site, and dewatered paint waste sludges. Test work conducted to date has successfully yielded geopolymer treated materials and wastes with increased chemical and structural stability. Wastes containing heavy metals, cyanides, arsenic and sulphur dioxide have been successfully geopolymerized."

Jan 1, 1988

By B. Loveday, G. W. Delaney, S. Cummins

"Applying DEM to prediction of tumbling mill performance is challenging because several different modes of breakage are active in the process. As our knowledge of breakage and computational capacity improve, it is worth revisiting previous simulation tasks which did not produce a satisfactorily realistic description of a measured process. At SAG 2006, we reported the simulated and measured outcomes of treating a well characterised ore in a 1.2 m diameter mill. This well instrumented, pilot scale mill at the University of KwaZulu-Natal has been combined with some new approaches to ore testing to allow different modes of breakage to be tested. The mill design allows the rate of generation of fine material to be measured in close to real time for autogenous and SAG mill charges. The updated simulation model estimates mass loss with particle evolution and embeds the cumulative damage and breakage.The simulated results are compared with the measured results. Issues such as relating modelling inputs to particle breakage characterisation data and the accuracy of the predictions of the models are discussed."

Jan 1, 2012

By Christopher McElman

Real-time mine management solutions have evolved over time from closed, proprietary solutions, to a "system of systems" that may include a wide variety of off-the-shelf components and technologies. Modular Mining Systems has embraced open standards for their NextGen products to bridge the technology gaps between these systems. However, the remaining logical gaps must be overcome, in order to achieve truly seamless integration between discrete systems. When dealing with volatile real-time management problems, the effectiveness of business process modeling and middle-ware can break down. Scientific principles of military command and control applied to mining domain help to achieve better alignment and reach the highest level of integration. The combination of open standards and off-the-shelf hardware and software with a deliberately structured command-and-control approach provides a clear evolutionary path from ad-hoc connected systems towards real-time management of a seamlessly integrated digital mine.

Oct 1, 2009

By R. D. H. Wigmore

"The title of this paper probably sounds quite simple and self-explanatory. The problem, however, was not a simple one, and proved somewhat baffling and expensive over a period of years. After outlining the problem, and the methods which were used to overcome it, we will present our solution, or perhaps it would be more accurate to say the partial solution which we reached.We have in the cyanide circuit at Upper Canada two Dorr Single Tray Thickeners with 30 ft. diameter wood stave tanks 12 ft 4 1/ 2 in. deep. In the years prior to 1948, when the tonnage was 250 to 280 tons per day, two stage thickening was practised. As the tonnage was increased to 450, 500, and finally 560-600 the thickeners were used in parallel.Some settling problems were encountered, and in those days the means to combat these problems were very few. The only remedy was to dump in pounds and pounds of lime. Then along came a few reagents, and the writer remembers one in particular, - 11 Carboxel11 (carboxymethlycellulose). When water or solution was added to this reagent, the result was a gooey mass somewhat resembling tapioca. One drawback was that it stayed in this state, and didn't go anywhere. A method was finally developed of containing the mass (or mess) on a fine screen, and dissolving some of it was a fine spray of solution. The only thing the writer recalls was that it was not a very effective settling agent.Shortly after this time, along came the new flocculents, first a few, and then many, and our settling problems were over.But when the settling problem was solved at Upper Canada, some other problems were creeping up on us."

Jan 1, 1965

By E. Marcotte

"Technology developments and improvements are imperative to maintain a viable mineral processing industry. In order to achieve optimum implementation of technology in processing plants, safety conscious and efficient work forces are required. Effective management methods are required to prevent employee injuries, equipment or environmental damage and process losses. Good leadership also provides for employees to perform their work in the safest and most efficient manners to attain optimum recoveries of the valuable minerals and produce high quality mill products. Equipment and processes must be designed, operated and maintained as required to assure safe and efficient mineral processing.INTRODUCTIONThe Canadian mining industry must contend with many challenges to attain and maintain a competitive position in today's global market. Canadian Mineral Processors play a vital role in meeting the challenges and achieving optimum mineral productivity.Ongoing technology developments and improvements continue to be imperative to maintain a viable mineral processing industry. The efficient implementation of technology developments requires a safety conscious, skillful and productive work force.In addition to technical and human resources, challenges may also include governments, labour unions or environmental advocates who at times may appear to be misguided or unrealistic. Canadian Mineral Processors must not allow themselves to be overwhelmed by these apparent obstacles but must use their demonstrated ingenuity to achieve successful solutions.It should be recognized that the majority of the Canadian work force are, in fact, a potentially talented and skillful people with ambitions to excel. As leaders of people, we must provide the methodology, incentive and direction that will allow our work forces to realize their ambitions. If the potentials of our work forces are not recognized and leadership is not properly exercised much loss will occur. That is, safe effective and efficient work will not be achieved."

Jan 1, 1993

By A. C. Drost

The mining industry has been put under closer scrutiny in recent years, which has led to the adoption of a plethora of initiatives in countries around the world and by international organizations, some voluntary and others mandatory, governing economic, ethical, social and environmental practices of this industry. In order to plan appropriately, secure project financing, build value and manage risks, it is imperative to identify and understand the application of this new and evolving regime, which can be described under the general label of corporate social responsibility (?CSR?) law, and to incorporate compliance policies into the day-to-day operations of mining companies. Our paper and presentation will describe this new legal framework, which includes both ?soft? law and ?hard? law adopted at the international and domestic level that governs the actions of mining companies, particularly when operating in developing countries. While the notions of hard and soft law may seem abstract and grounded in legal theory, this paper shall demonstrate how these concepts concretely apply to companies in general, and to mining companies in particular. An analysis of the recent case law in this area as well as examples of corporate ?best practices? will illustrate the application of this body of law. As will be demonstrated through the case law, non-compliance of CSR law (both ?soft? law and ?hard? law) can lead to economic penalties, difficulties in accessing capital, loss of social licenses and even the withdrawal of permits and concessions. This confirms that now more than ever, ethics and sustainable practices in mining are fundamental to building a successful business model.

Aug 1, 2013

By P. W. A. Walker

"The Riviera tungsten occurrence in the Cape Province of South Africa was discovered in October 1979 as a result of stream-sediment panned concentrate sampling. The Cape age granite and late Precambrian Malmesbury Group carbonates and chlorite schists which it intrudes and which host the mineralization are covered by between 10 m and 30 m of Tertiary/Recent alluvium and clay. The scheelite/powellite and molybdenite mineralization occurs in a greisenized granite cupola with an overprint of porphyry-type alteration as well as in minor skarns. The ore reserve is estimated to be 46 million tonnes at an average grade of 0.216% W03 and 0.020070 Mo. The deposit is uneconomic at current tungsten prices. IntroductionDuring the 19705, Union Carbide Corporation was a major producer, processor and supplier of tungsten and derivative products to end-user manufacturing industries. The corporation owned and operated two tungsten mines in the United States, and one in Brazil, and operated a plant in the United States which produced ammonium paratungstate (APT) which is an intermediate product in the production of tungsten wire and tungsten carbide for cutting tool insets and hard facings. In 1975 the three mines were ageing with short-life reserves and high production costs. The world market for tungsten was buoyant and prices, in constant dollar terms, had risen steadily over the past 15 years (Fig. 1).It was against this background that a decision was made to explore for tungsten in North America, South Mrica, Australia and Brazil."

Jan 1, 1994

By D. R. Rice

"The Smoky Valley Common Operation is managed and 50 percent owned by Echo Bay Mine' s Round Mountain Gold Corporation. The other partners with 25 percent each are Homestake Mining Company and Case Pomeroy. The operation in central Nevada includes an open pit, 3-stage open-circuit crushing train and heap leaching on asphalt pads. Presently, about 18,000 tons per day of 0.039 troy ounce gold per ton are transferred to the leach pads, and a similar tonnage of leach residue is transferred to a waste dump. One million tons of ore are being leached at any one time.Gold and silver cyanide are adsorbed from pregnant leach solution on activated coconut shell carbon granules. Pressure stripping desorbs values from loaded carbon to electrowinning solution.Three electrowinning cells are operated in parallel. Each contains six cathodes. Each cathode includes about 40 troy ounces (2.7 pounds) of Number 2 medium coarse steel wool. The wetted area of each cathode is about 24 by 30 inches. Solution flow is 2 to 3 gallons per minute per electrowinning cell. Average current flow is 25 amperes per cathode. The voltage is controlled in the range of 3 to 4 volts to maintain desired amperage.Twice a week two cathodes are pulled from each cell and drained. Each cathode is split into four portions. These are put in a steel pan coated with WD-40 and dried overnight.Each dried cathode portion is put into a paper sack. Each group of four sacks corresponding to a cathode is weighed together. The typical weight ratio of loaded cathode wool to new cathodes is 9 or 10 to 1. To each sack is added 35 troy ounces of silica, 45 troy ounces of anhydrous borax, 35 troy ounces of nitre, and 5 troy ounces of fluorspar. The sacks are taped shut."

Jan 1, 1986

By J. N. Cram

"The comments given are to help allay generally accepted ideas that the handling of arsenic as arsenic-trioxide (As2o3J in and from off gas pyrometallurgical operation fumes is difficult, hazardous and expensive. It need not be any of these things if the basic and rather unique chemic3l and physical properties are understood and taken care and advantage of through present day technologies. These particular characteristics are:-(1) As2o3 sublimes and re-condenses, at a relatively low temperature;(2) As2o3 is, for practical in-plant purposes, insoluble in water at ambient temperatures and quite soluble in water just below the boiling point;(3) residual suspended and dissolved As 2o3 can be removed from water by complete dissolution with very little sulfuric acid, followed by the addition of small amounts of ferrous sulfate and calcium chlorate, with oxidation to the ferric and arsenite state and precipitation of an insoluble ferric calcium arsenate, thereby lowering the As2o3 content of solutions to acceptable levels. Even lower levels of non-toxic forms of arsenic solids and residual As2o3 in the water solutions can be attained by also using phosphate, and lime, along with the above.A background re past arsenic processing methods, present day operations, plus predictions re future trends, and hazards, are outlined."

Jan 1, 1979

By Guy Chevalier

QCM?s pellet plant, located in Port-Cartier, Quebec, produces up to 8.6 million tons of iron ore pellets annually. Four different types are produced: three for blast furnace operations and one for direct reduction furnaces. The paper presents the scientific approach that led to the installation of new process equipment to improve the reducibility of direct reduction pellets (DR pellet). The findings, the equipment selection and some post start-up modifications are presented. This low silica DR pellet is used in Midrex and HyL shaft furnaces. A good DR pellet has to meet strict chemical, physical and metallurgical specifications. An important metallurgical property is its ability to release oxygen when exposed to reducing gases. Considering that the market for DR pellets is expanding and being aware that reducibility is critical for our clients, a program to improve the latter was undertaken. Test work showed that one factor which has a negative effect on reducibility is the proportion of particles larger than 75 microns. Knowing that the best way to reduce the amount of coarse particles was to close our open grinding circuits, we began evaluating the most suitable classification equipment applicable to our process operations. We settled on hydro-classifiers based on their very sharp cut and their low operating costs. In light of the hydro-classifiers performance it was also decided to replace the hydro-cyclones of an already closed circuit.

May 1, 2003

By P. Hickey, A. Oliver

"In March 1993, Ram Raising Limited was faced with a challenge. Placer Dome Incorporated, Dome Mine Division requested from Ram Raising that they design station excavation into the existing No. 8 shaft from No. 3 mine levels. This work had to be done without loss of production time in the underground department.Due to the time frame of the project, every detail had to be carefully considered, with extra care that all pros and cons had been worked out.Ram Raising submitted a work Plan that had been worked out with the Redpath Group which included the infrastructure requirements; the engineering design; the scheduling and sequence of work; and the excavation design and blasting procedures.A proposal was' put together by both Ram Raising and Placer Dome outlining the infrastructure requirements, including the engineering design, scheduling and sequence of the work, excavation design and blasting procedures. The proposal accepted by Placer Dome and, on July 3D, 1993 work commenced to breakthrough eight stations. Work continued until December 1993 with the completion off our stations. The project was then stopped to allow the station access drifts from No.3 mine to be completed. The second phase of the project began on May 27 and was completed on September 15, 1994.This paper shows how, through innovative design and the full cooperation between client and contractor, a project of this nature can be completed successfully."

Jan 1, 1995

RISKGATE is an interactive online risk management system developed by the Minerals Industry Safety and Health Centre (MISHC; University of Queensland) to assist the mining industry in implementing continual improvement in management of major unwanted events, and so maximising health and safety performance. A comprehensive body of knowledge has been compiled from diverse mining industry experts for risk management of tyres, collisions, fires, isolation, strata underground, ground control open cut, explosions, explosives, manual tasks and slips/trips/falls. This paper presents an overview of the body of knowledge captured from diverse mining industry experts for the management of unwanted strata incidents, and explosions in the underground environment. This knowledge is divided into a series of initiating events within both topics (as listed) with further degrees of classification based on design, operation, and management concerns. Strata Underground Initiating Events: Explosions Initiating Events Loss of strata control at longwall face Fire or ignition in a sealed area Loss of strata control in outbye roadways Fire or ignition in an unsealed goaf area Loss of strata control in roadways under development Fire or ignition in an extraction face Loss of control of overburden and caving behavior Fire or ignition in outbye Loss of pillar system stability Loss of control of goaf edge in pillar extraction Fire or ignition in a development panel or first working Loss of strata control in shafts The system guides the user in generating substantive and leading edge controls to assist industry stakeholders in the design, management and reporting of organisational and regulatory compliance requirements. From a broader industry perspective, RISKGATE provides an environment for knowledge capture and knowledge exchange to drive innovation and best practice in the identification, assessment and management of risk. By capturing operational knowledge from industry experts, RISKGATE provides a cumulative corporate memory at a time of high personnel turnover in the coal industry.

Aug 1, 2013

By L. McFarlane, D. Rollwagen

"Madawaska Mines produces a uranium precipitate (83-85% u3o8) using a magnesium oxide slurry to precipitate the uranium from solution. The solution, at approximately 9""0 g/l u3o8 is neutralized to a pH of 7.0. At the Eldorado Nuclear Refinery in Port Hope, the precipitate is not acceptable as a single feed to the refinery process. It was discovered that a 2% silica impurity caused emulsion problems in the solvent extraction column.After extensive studies of possible solutions, such as two-stage precipitation and solvent extraction, an acceptable solution was found. The selective precipitation of uranium at a pH of 3.5-4.0 using Hydrogen Peroxide produces an almost silica free product of higher purity (90-93% u3o8) to that of straight magnesium oxide precipitation. Introduction Madawaska Mines Limited is located four miles southwest of Bancroft, Ontario. The annual production of u3o8 is approximately 610,000 pounds. To produce the final product or yellowcake, nine separate steps are required. These are (1) grinding, (2) dewatering, (3) leaching, (4) acid filtration, (5) clarification, (6) ion exchange, (7) precipitation, (8) washing, and (9) drying and packaging. To illustrate these steps, a complete flowsheet of the mill is displayed on page three.The yellowcake is sent to Eldorado Nuclear Limited in Port Hope, Ontario for further concentrating and refining. As part of their routine specification check, a test called the amenability test is performed. This test indicates how a particular dissolved yellowcake product reacts to solvent extraction. The Madawaska yellowcake did not pass the test."

Jan 1, 1982

By Dani J. Alldrick, Alastair J. Sinclair, Colin I. Godwin

"The Stewart mining camp has a long history of precious and base metal mining. The camp is abundantly mineralized, with more than 200 widespread, varied, vein prospects, deposits and orebodies. These show wide variations in the mineralogy of ore, gangue and alteration assemblages, and wide variations in textures and structural settings. This report establishes the timing of the different metallogenic epochs and suggests a specific exploration application for systematic leadisotope analyses.Galena lead isotope ratios from a range of mineral occurrences indicate that all these varied deposits formed during two main mineralizing events. Lead isotope data from the Stewart mining camp do not provide absolute ages for the formation of mineral deposits, but the relative distributions of data are consistent with dates determined in other studies. One ore-forming episode occurred in the Early Jurassic and the other in the Middle Eocene. Both metallogenic epochs were brief, regional-scale phenomena. Some deposits from the younger mineralizing episode were emplacedadjacent to or superimposed on the older deposits.Field and laboratory studies show that the two metallogenic epochs are characterized by different base and precious metal suites: Early Jurassic gold-silver-zinc-lead-copper; and Middle Eocene silver-lead-zinc. Therefore, showings of different ages have different base and precious metal potentials and deserve different exploration emphasis. Lead isotope studies provide a reliable, cost-effective method for evaluating the age and commodity potential of small or recently discovered mineral showings and for setting exploration priorities on properties with several varied mineral occurrences. The determination of the age and metal potential of a prospect at an early stage of exploration may govern the urgency, intensity or even the necessity for further exploration work."

Jan 1, 1993

By T. Eger

Load Haul Dump vehicles (LHD) are extensively used in underground mining however equipment design and operating conditions contribute to restricted operator?s visibility. The inability to clearly see people, objects or hazards around the machine has contributed to a number of accidents including fatal injuries. In order to identify vehicle design characteristics resulting in restricted and blocked sightlines visibility assessments are traditionally completed in the field. However, field methods are unable to evaluate visibility under dynamic operating conditions and are limited in their ability to provide feedback on the impact of various operator characteristics such as sitting height, for example. Results of this research show computer simulation and virtual reality can be successfully used to evaluate visibility during the operation of LHD vehicles. In order to benefit from virtual reality applications the work environment, LHD vehicle and human posture need to be represented as accurately as possible. A computer simulation program with ergonomic ana lysis features, Classic JACK 3.1, was successfully used. Threedimensional CAD models of LHD vehicles were developed from manufacturer specifications and pictur es taken from LHD vehicles currently in use. The LHD models were imported into the JACK environment, a digital human was positioned in the cab of the LHD vehicle and the vehicle and human where driven over a typical mine route. Real-time feedback in the JACK program was used to identify what the operator could see under different operating conditions. Machine characteristics and operating scenarios resulting in impaired visibility were successfully identified with this method. The JACK program can also provide real-time feedback on the human?s joint forces and torques, strength requirements, postural comfort, and metabolic energy expenditure. As a result, this method could be used to successfully evaluate musculoskeletal injury risk factors along with system design recommendations to improve workplace safety and productivity in any setting. The LHD VRML files imported into JACK have also been combined with environment files into other VR software packages (e.g. Maverik) to view in a VRL facility, managed by MIRARCO at Laurentian University. The VR models using these packages can be viewed in stereo to provide better appreciation of spatial visibility issues.

May 1, 2003

By J. Gao

We present results from our investigation of the concept and practice of using surface-charged latex nanoparticles as building blocks for conductive membranes. Nanoparticles were synthesized by free-radical co-polymerization of two hydrophobic monomers, butyl acrylate (BA) and methyl methacrylate (MMA), a crosslinker, N, N'- methylenebisacrylamide (BIS), and a charged monomer, sulfonate styrene sodium salt (NaSS), in water. The resultant nanospheres were characterized with static and dynamic laser light scattering. Thin films were cast from concentrated particle dispersions, followed by incubation at ?110 °C. Conductivity, water uptake and final charge content were measured. The membranes have higher conductivities than both amorphous films cast from sulfonated BA-MMA-Styrene copolymer chains and BA-BIS-MMA-NaSS gel films. TEM images and neutron scattering spectra confirm the particulate structure of the membranes.

Jan 1, 2005

"The ore currently being milled at Delnite is a high pyrrhotite ore with the gold intimately associated with the pyrrhotite. To get maximum recovery of the gold with the lowest reagent cost, it is necessary to keep the pH as low as possible In the laboratory the best results were obtained with a pH of 10 but in the plant it was found that a pH of 11 was the minimum practical pH. With the n1anual control it was difficult to maintain this figure.The Mines Branch had a conductivity probe (see Fig. 1), developed by Dr. G .G. Eichholz that they wished to try out in plant operation.On June 17, 1963, the probe with all necessary control equipment was installed in the regrind circuit (see Fig. 2) at Delnite Mines. Crushed quick lime is fed at this point but it is also necessary to feed hydrated li1ne at two other points in the cyanide circuit in order to maintain the pH close to 11. 0 throughout the circuit. Only the feeding of the quick lime at the regrind mill was controlled in this test.One thing that concerned me with the operation of the probe was whether the reading on the probe chart would correspond to the pH. A look at the graph accompanying this paper will show that except for very minor variations the graphs of the chart reading and the pH reading are parallel. The upper graph shows that the pH reading and the lime titrations also correspond and that the cyanide titrations appear to have little effect on the pH reading.Table 1 gives the results obtained for the two months before and after the instal1ation of automatic control as well as the two months of control. Unfortunately there was a decided change in ore just after the automatic controls were removed. There was much less pyrrhotitc in the ore than usual thus changing the need for lime and cyanide."

Jan 1, 1964

By L. Long

Stirred milling of nickel laterites offers possibilities for improving liberation and selective size reduction of soft nickel-bearing minerals in laterites. Batch grinding tests were performed in a Netzsch LME4 stirred mill on siliceous goethitic (SG), goethitic (G), and saprolitic (SAP) nickel laterite samples (- 2000 ?m particle size) to evaluate the effect of stirrer speed, solid content, water salinity and grinding time. A fine mineral product (-38 µm) was used to evaluate the effect of selective grinding and Ni upgrade. The optimum grinding time for the highest Ni upgrade was 0.25 min, 0.1 min and 0.1 min for the SG, G, and SAP nickel laterite, respectively. A new feed (38-2000 µm) for each nickel laterite sample was prepared for batch grinding tests under the optimum grinding conditions. Upon grinding the 38-2000 µm feed, the - 38 µm product confirmed the effect of selective grinding and nickel upgrade. Size classification followed by stirred milling is a suggested process for Ni upgrade. The best Ni upgrade result was achieved on the SG nickel laterite among the three samples. The Ni grade increased from 0.85% to 1.37%, with 27.8% Ni recovery. Bottle roll leach tests showed that for SG and SAP samples selective grinding had no dramatic effect on Ni extraction due to the slow leach rate of hard mineral particles. Stirred milling of G sample increased the surface area of goethite, resulting in higher Ni extraction. Gravity concentration through a Knelson Concentrator was not effective in the further treatment of the stirred milling products either due to the poor operating conditions or due to the mineralogy characteristics of the feed samples. The energy requirement in the stirred milling was investigated. The first pass of the signature plots study is critical for the purpose of selective grinding, because the best result on selective grinding is achieved in the early stage of the grinding process.

Aug 1, 2013

By Simon P. Fricker

Gold drugs have been used for the treatment of rheumatoid arthritis since the mid 20th century as disease-modifying antirheumatic drugs (DMARD) class. Methotrexate is often the preferred DMARD, and with the advent of new therapies gold drugs are now used infrequently. Since the introduction of auranofin in 1985 there has been no new clinically approved gold drug. In spite of this apparent lack of progress there has been a great deal of interest in the use of gold compounds for cancer therapy and early promising indications were achieved with a gold phosphine complex [Au(dppe)2]Cl. This compound was not entered for clinical trials, however, due to problems with cardiotoxicity highlighted during pre-clinical toxicology studies. Gold(III) is isoelectronic (d8) with platinum(II) and likewise forms square planar complexes. It is therefore tempting to speculate that such complexes would have similar antitumor activity to cisplatin. In order to stabilise the gold(III) oxidation cycloaurated complexes were synthesised with a single mononegative bidentate ligand, damp, (2-[(dimethylamino)methyl]phenyl), and two monodentate anionic ligands e.g. Cl or acetate. The damp ligand forms part of a five-membered chelate ring. The monodentate ligands are readily hydrolysed and are available for substitution. These compounds had limited anti-tumor activity in in vivo against human tumor xenografts. Mechanistic studies indicated that these compounds had a different mechanism of action to cisplatin. An alternative molecular target for these compounds is biologically important thiol-containing molecules such as the cysteine protease cathepsin B. Modifications were made to the Au(III) damp structure to give compounds with a six-membered chelate ring. These compounds were shown to be inhibitors of cathepsin B. Compounds were also tested for cytotoxicity against a panel of human tumor cell lines. Three compounds were selected for further evaluation against a human colon tumor xenograft. The compounds showed modest anti-tumor activity but with no marked improvement over the parent Au(III)damp complexes. Initial indications are that Au(III) compounds targeted against disease-specific thiol-containing biological molecules have potential as drugs, particularly for cancer. However, further work is required to produce a target-specific drug with a suitable pharmacological activity and toxicity profile.

Oct 1, 2003