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By John S. Stevenson

Zeballos mining camp is on the west coast of Vancouver island; 195 nautical miles northwest from Victoria.; The spectacularly rich gold-bearing veins that made Zeballos an important; gold camp were found early in 1934. Small pockets of very coarse; gold had been found earlier under large boulders at the mouth of Spud; creek; and in the autumn of 1933 rich gold-quartz float was found near the; mouth of the creek. The rocky beds of the steep creeks entering Spud creek; were searched for its source and as a result the veins on the White Star property; were found. The Goldfield vein on the Spud Valley property was discovered; in 1935; and the No. 1 vein on the Privateer in 1936. In the general; prospecting activity that quickly followed; other veins were found; not; only in Spud creek but in other creeks draining into Zeballos river.

Jan 1, 1954

By H. Kalsi

"IntroductionRoyal Oak Mines Inc. is currently operating the Parnour No.1 mine located 10.5 miles east of Tinunins, adjacent to Highway No. 101. The operation produces gold ore at a rate of 3300 tpd. A variety of mining methods including bulk open stopes with ITH drilling, narrow vein panel, longhole and open pits contribute to produce 1.2 rnillion ore tons annually. The milling process requires water at an average rate of 1 rnillion gallons per day (700 U.S. gpm). The Pamour No.1 mine has historically had two major problems with regard to water control. The flfSt is the underground pumping system's inability to handle excess inflows of water generated from spring thaws. When the thaw takes place over a short period of time, large inflows of water are created which quickly migrate underground and sometimes result in the loss of the lower loading pocket. During the spring runoff the pumps at Parnour No.1 work continuously for 24 hours at a rate of 1200 U.S. gpm. The system was further taxed in 1991 when the Hoyle mine was connected to the Parnour No. 1 mine and whatever excess capacity the pumping system had for the spring runoff was taken up handling the inflow of mine water generated by the Hoyle.The second problem facing the mine was the lack of water for the mill during the severe cold winter months and dry summer months. At those periods inflows of water into the mine decline and the underground water normally pumped to the mill is severely decreased. In times of dry spells mill personnel increase the water diversion from the Three Nations Lake in order to meet water demands and maintain tonnage throughout. In essence, the mine was going through an annual ""feast or famine"" situation and a solution was needed.A number of options were considered but were narrowed down to the two most practical. The first was to modify the existing pumping system and increase its capacity in order to handle the excessive runoff during spring thaw. This involved a heavy capital expenditure and would have caused additional operating costs (i.e. increased hydro). The option chosen by the management was to divert the spring runoff into an unused section of the mine called The West End. A bulkhead placed at the 2400 level would provide an ultimate underground water storage potential of 150 million gallons. This would also cut down the load on the existing pumping system, save electric consumption in pumping and provide water storage which could be used for milling during the two dry spells. Pumping stored water from the mine could be scheduled for off peak hours to take advantage of lower power rates. To meet these objectives an underground bulkhead capable of withstanding high water pressure up to 2000 ft head (866 psi) was constructed in the spring of 1992. The bulkhead site was at the 2400 level at the Pamour No.1 mine. A major consideration was the requirement to construct a safe bulkhead and to minimize water leakage from the bulkhead.Figure 1 shows the bulkhead location."

Jan 1, 1994

By Sebastian Siebert

Unmanned Aerial Vehicles (UAV) as a data acquisition platform and as a measurement instrument have become attractive for many surveying applications in civil engineering. However, their performance is not well understood for these particular applications. The specific scope of the presented work is the performance evaluation of a UAV system that was built to rapidly acquire mobile 3D mapping data for large earthmoving construction sites. Details to the components of the developed system (hardware and control software) are explained. A novel program for photogrammetric flight planning and its execution for the generation of 3D point clouds from digital mobile images is explained. A performance model for estimating the position error was developed and tested in several realistic construction environments. Results to these tests are presented as they relate in particular to large excavation and earth moving construction sites. Results and experiences with the developed UAV system are in particular useful for researchers or practitioners in need for successfully adapting UAV technology for their application(s).

Aug 1, 2013

By W. H. Hastings

Introductory In the amount of her coal reserves, Saskatchewan ranks third among the provinces of the Dominion, with a total, as estimated by D. B. Dowling, of 59,812,000,000 tons. All the coal so far discovered in the Province is lignite, and it would appear unlikely that bituminous or higher grade coals exist. General Occurrence of the Coal The location of the coal-bearing formations in Saskatchewan is shown on the accompanying map. It will be seen that the areas lie principally in the southern part of the Province. The more darkly shaded areas indicate locations where development is taking place, or where coal-seams are known to occur, either through outcrops in valley-sides or through having been encountered during boring operations. The coal-seams are not necessarily continuous throughout the shaded areas, but in all pans of these there are coal possibilities. It is quite possible that small outliers of the coal-bearing formations may occur further north in the Province, but, generally speaking, coal is not likely to be found outside the shaded areas.

Jan 1, 1929

By Prodipto Ghosh

This paper is prepared as a review of existing and traditional methods related to electrical maintenance strategy. Its primary focus is to explore newer ideas and how they point the way to a more efficient and effective manner of electrical maintenance. This discussion is primarily related to large electrical distribution assets typical of heavy industry such as mining.

Aug 1, 2013

By G. Vibert Douglas

"Gold occurs in Nova Scotia in three ways, saddle reefs, fissure veins, and fossil placers. Of these the saddle reefs are the commonest. They have been the source of most of the gold and have also been the subject of most of the literature on the gold occurrences.The Meguma or Gold-bearing series of Nova Scotia is a conformable succession of quartzite's and slates, possibly Precambrian in age, which have been folded into a number of anticlines and synclines that strike (Fig. 1) roughly east and west. This folding has been termed Acadian and is probably a westward continuation of the Caledonian revolution in Britain. It may have started in the Ordovician and continued through the Silurian and into the Lower Devonian. It was followed by the intrusion of the great Devonian granite batholiths. It is thought that the mineralization is connected with the late phases of the cooling of the granite. As the name saddle reef implies, the veins form on the crests and flanks of the anticlines, possibly in the synclinal troughs as well. The beds favoured by the solutions are the slates. The reason for this is apparent when it is realized that in order to fold over 30,000 feet of sediments (the thickness of the Meguma according to E. R. Faribault) through p radians of arc it is necessary to have a differential movement between the top and bottom beds of p times the thickness of the sediments. In the case of the Gold-bearing series, in which strong quartzite beds lie between incompetent slate beds, most of this differential movement was taken up in the slates. The evidence for this is the remarkably fine drag folding and the intense shearing and comminution of some of the beds of slate (Fig. 1). The quartzites exhibit some shearing and faulting, but there is little doubt that the greater permeability lay along the incompetent slate beds. The mineralizing solutions followed these beds and also passed from one slate bed to another through a joint or fault in the intervening bed of quartzite. These joining veins are called angulars in Nova Scotia. Within the veins the gold is in shoots and the real problem is to find out what controls the position and extent of the shoots."

Jan 1, 1954

By Y. H. Hatzor

"This is an extended abstract for a keynote lecture delivered by the author during the 2015 ISRM congress in Montreal on the application of the numerical discontinuous deformation analysis (DDA) method in rock mechanics practice. Due to the large scope of the topic this lecture will focus on studies performed by the rock mechanics group at Ben-Gurion University, alone or in collaboration which other research groups, and is not intended to provide a comprehensive review of everything that has been done on the subject worldwide during the past two decades. A forthcoming textbook (Hatzor et al., in preparation) will attempt to provide such comprehensive coverage.DDA has been developed by Dr. Gen-hua Shi while he was doing his PhD studies under the supervision of Professor R. E. Goodman at U. C. Berkeley (Shi, 1988). Dr. Shi has invented a new numerical discrete element method which provides a solution for dynamic deformation of block systems, hence its applicability to rock mechanics practice. The method is similar in essence to the finite element method in its implicit formulation of the time integration scheme and where in every time step the minimum potential energy of the entire system is sought, but here every element is a finite block with six degrees of freedom. The blocks are assumed to be stiff (simply deformable) so that most of the energy is consumed by slip along pre-existing discontinuities, the frictional resistance of which is assumed to obey the Coulomb-Mohr failure criterion for rock joints. The greatest advantage of DDA over alternative numerical discrete element methods is its robust area (volume) integration which ensures great accuracy even when the blocks are of irregular shapes, including non-convex blocks which may contain holes. The greatest disadvantage is the necessity to solve in every time step very large matrices of unknowns, imposing great CPU demand when the block system involves a large number of blocks. Another disadvantage is the sensitivity of the solution to the choice of the penalty parameter which is implemented in DDA in the form of stiff springs that are attached to contacts once detected automatically.The inherently dynamic formulation of the DDA method lends itself to solution of dynamic problems in rock mechanics. Dynamic analysis with DDA can be performed in different ways corresponding to different rock mechanics problems and loading conditions. Three main classes of loading conditions which are relevant to rock mechanics applications are discussed here: 1) dynamic loading of a single bock which rests on a stationary foundation, 2) response of a block to dynamic loading of the foundations, 3) wave propagation through a block system.The most common approach is to introduce the dynamic force to a specific block in an otherwise fixed block system and check the resulting deformation, typically the time dependent displacement or rotation of the loaded block. This approach is particularly useful for dynamic rock slope stability studies when a stability of a specific rock block against earthquake vibrations is in question. The first 2D-DDA benchmark test of this approach was performed by Hatzor and Feintuch (2001) who introduced harmonic acceleration functions into a block which rests on an inclined plane. The analytical solution proposed for this problem by Hatzor and Feintuch (2001) was later generalized by Kamai and Hatzor (2008). The first 3D-DDA benchmarking for this approach was presented by Bakun-Mazor et al. (2012) who studied single and double face sliding of blocks which rest on stationary foundations and subjected to harmonic input acceleration functions."

Jan 1, 2015

By D. Nie, M. Ren, T. Mo

This paper studied the phenomenon of room temperature creep deformation at crack tip and its effect on fatigue crack growth rate of a X-70 pipeline steel using compact-tension (CT) specimen on a MTS 810 testing machine. Time-dependent deformation at the crack tip under constant load was observed in this steel at room temperature and the amount of deformation produced was seen to depend on loading rate and the magnitude of stress intensity factor. It is found that there exists a critical stress intensity factor below which the deformation decreases with time when the applied load remains constant. It is also found that the occurrence of room temperature creep obviously affects the subsequent fatigue crack growth rate. The observed behavior was explained based on dislocation theory.

Jan 1, 2005

By Stanley Davidson

Introduction The ore deposit mined by Falconbridge Nickel Mines, Limited, is one of the numerous nickel-copper sulphide bodies marginal to the large oyster-shaped mass of differentiated norite in the Sudbury district, famous as the world's most important nickel producing field. The unique character of the ore deposits of the district has resulted in its intensive geological study over a period of more than fifty years. The results of these studies have given rise to a voluminous geological literature and to a great deal of controversy as to the genesis of the ores. This description of the structural geology at the Falconbridge mine is presented in the hope that it may form a small part of the chain of evidence leading to a reasonably satisfactory explanation of the ore genesis. The mine, named after Falconbridge township in which the deposit occurs, lies along the southeast margin of the norite mass which, however, is here concealed beneath a deep mantle of glacial sands and gravels averaging over 100 feet in thickness. As a consequence, the deposit was not discovered by the early prospectors, and it was not until 1916-17 that E. J. Longyear, of Minneapolis, located the ore by drilling. The discovery was foreshadowed in 1899 by the work of Thomas A. Edison, who found indications of the deposit by what is believed to have been a combination of magnetic and electrical geophysical surveys. He sank a prospect shaft over what has to date proven to be the largest and richest ore section in the mine. A wet quicksand layer at the rock surface proved impenetrable, however, and the "Edison' shaft never reached bed-rock.

Jan 1, 1946

By M. S. Hedley

"The Lucky Jim mine is at Zincton in Slocan mmmg division; on the Kaslo-Nakusp branch of the Canadian Pacific railway. It is owned and operated by Zincton Mines; Limited; a subsidiary of Sheep Creek Gold Mines; Limited. The mine is far in the lead in the production of zinc in the Slocan. Its recorded production from concentrates and shipping ore was 102; 260; 191 pounds of zinc to the end of 1945.GENERAL GEOLOGY With the exception of acidic dykes the rocks near the Lucky Jim mine belong to the Slocan series, which is Triassic in age and consists principally of argillaceous rocks. It disconformably overlies greenstones of the Triassic Kaslo series about 3 miles to the northeast, and is cut by granitic rocks of the Nelson batholith 5 miles to the southeast.The sedimentary rocks in this area are best referred to on the whole as slates. They lie within the more fissile basal part of the Slocan series. The term 'slate belt' conveniently distinguishes this area of rocks characterized by slaty cleavage from the more massive argillites that are more characteristic of the Slocan as a whole. The contact between the slaty and massive argillites lies ½ mile southwest of the mine."

Jan 1, 1954

By L Gill

The four basic types of electric motors -squirrel-cage, wound rotor, synchronous and D.C. -are de-scribed, with particular reference to speed-torque characteristics. The three classifications of squirrel-cage motors, C.E.M.A. B, C and D, are compared, and methods of selection for specific drives are outlined. Wound rotor and synchronous motors are covered from the viewpoint of construction details, methods of operation and control required. The application of these motors to crushers, conveyors and ball mills is described and reasons for their selection are given. The application of D.C. motors to haulage equipment and mine hoist drives is included, and the basic principles of a variable voltage drive are illustrated. Efforts have been made through-out to provide specific examples of motor selection, with particular reference to the mining industry. THIS paper will attempt to answer the question -"which motor should be used for a specific drive?" Although it is impossible to cover the complete subject of electric motor application here, we hope to give some idea of the types of motors available and why certain types are used on specific applications.

Jan 1, 1963

By D. L. Marchioni

"The detection and quantification of the degree of weathering is an important aspect of coal exploration and mining. Tests for weathering which are suitable for the exploration camp should be fast, simple, and require minimal equipment and operator expertise. In this study, two tests which fulfill these requirements were evaluated using samples of Western Canadian coals. These tests, one based on the pH of a coal slurry and the other on the flotation of coal in a water/diesel oil mixture, do not appear to give consistent results and are not recommended as ideal weathering parameters.IntroductionThe weathering of coal results in a deterioration of those properties which render it suitable for use in industrial processes. Consequently, the detection and quantification of the degree of weathering is an important aspect of exploration and mining. Frequently, decisions related to the depth of the weathered zone must be made at the exploration camp and, therefore, tests for weathering which are fast, and require relatively inexpensive and portable equipment and minimal operator experience, would be very useful. The aim of the study reported here was to evaluate two tests used by U. S. Steel Corp. to detect coal weathering and which satisfy the requirements for use in an exploration camp. The study is a continuation of a more extensive examination of the detection of coal weathering by various methods, reported elsewhere (Marchioni, in press)."

Jan 1, 1981

By J. E. Gill, A. R. Byers

The Surf and Pugsley gold-copper mines; owned and operated by Surf Inlet Consolidated Gold Mines; Limited; are about 6 miles inland from; the head of Surf inlet; on Princess Royal island; Skeena mining division; British Columbia. Surf inlet is a fiord 360 miles in an air line northwest of; Vancouver.

Jan 1, 1954

By G. G. Campbell

"HistoricalBARYTES was mined in Nova Scotia as early as 1874 from a deposit at Five Islands, on the north shore of Minas Basin. The first record of the presence of the mineral at the Walton site appears in a report by Selwyn in l893, who states: ""Barytes in considerable quantity occurs in veins in lime-stones at Walton and Pembroke"". The exact site of the present workings was marked •on a map published by Fletcher in 1905.The economic •possibilities of this deposit, however, were not recognized until 1940, at which time we were at war with Germany, who up to that time had supplied 50 per cent of the world's requirements.At that time the Nova Scotia Department of Mines, recognizing the need for certain strategic minerals, induced Canadian Industrial Minerals, Limited, to send prospectors into 'the area to look for manganese. No manganese deposits were found, but a deposit of barytes was directed to their attention, and exploration and development work on the occurrence was proceeded with.IntroductionThe south shore of Minas Basin between the Avon river at Windsor and the Stewiacke river at Maitland has long been known as a potential source of mineral wealth. It had attracted the attention of mineralogists and in the past had produced considerable tonnages of manganese ore and gypsum. Depletion of ore in surface and near surface deposits resulted in a dwindling production, until today only deposits of gypsum are worked."

Jan 1, 1952

By T. Cutard, H. Marzagui, E. Ouedraogo, M. Roosefid, M. Prompt, C. Deteuf

The present work is achieved in the framework of a French national program on modeling and experimental characterization of the thermo-mechanical properties of refractory materials (PROMETHEREF). This research program is aimed to establish fair models and experimental database and to make it available to industrial partners for numerical simulation of industrial structures made of these materials. The present paper focuses on two silica-alumina refractory castables, an andalusite based one and a bauxite based one. We will present the first rheological characterization results achieved at room on normal and preheated samples of these two refractory castables. Refractory castables are characterized with the help of four points bending tests, compression tests and tensile tests.

Jan 1, 2004

By Hökmark. H., M. Lönnqvist

"The Swedish Nuclear Fuel and Waste Management Company are planning to construct a permanent storage facility for high-level nuclear waste at about 500 m depth in fractured crystalline rock. One potential concern for the long-term performance of the repository relates to large fracture shear displacements, since these may damage intersected waste containers. Although details in fracture surface geometries are known to influence slip magnitudes and distributions, fractures are commonly approximated as planar features with lab-scale properties due to lack of relevant field-scale data and to limitations in available modelling tools. The purpose of the work described in this paper is to explore the possibilities to use the distinct element code 3DEC to generate and analyze models with isolated, non-planar fractures and, based on the results of such models, get perspectives on the influence of basic disturbances such as ridges, steps and waves. Given the model set-up, fracture segments with orientations deviating from the critical one will contribute to stabilize the fracture. As a result, all analyzed non-planar fractures slip less than the critically oriented planar fracture. We demonstrate that the angle of deviation is the most influential parameter determining the slip magnitude for comparable surface geometries. Similarly inclined steps and ridges have almost equal slip reductions despite differences in surface area restricting the movement. Although it may be possible to translate the influence of such irregularities to an effective coefficient of friction that could be used as input to models with idealized planar fractures, additional analyses with randomly shaped and distributed asperities, different fracture sizes and with alternative stress loads, need to be carried out to devise a defensible strategy for this type of parameter variation. INTRODUCTIONThe Swedish Nuclear Fuel and Waste Management Company’s (SKB) concept for deep geological storage of high-level nuclear waste is the KBS-3 method according to which the waste will be encapsulated in copper canisters and deposited, surrounded by compacted bentonite clay, in vertical deposition holes at about 500 m depth in fractured crystalline rock (SKB 2011). A site has been selected in the Forsmark area, which is located some 120 km north of the Swedish capital Stockholm. One potential concern for the long-term performance of the repository that has been identified by SKB (SKB 2011) is related to large shear displacements along repository host rock fractures induced by a nearby earthquake, since these may cause mechanical damage to intersected waste containers. Due to lack of relevant data at the appropriate field scale and to limitations in available modelling tools, fractures are commonly approximated as planar features with lab-scale properties. The standard numerical tool, 3DEC (Itasca 2013), used in SKB’s rock mechanics analyses, for example, generates planar fractures by default. Results from dynamic 3DEC earthquake-models (Fälth et al. 2010) currently provide input to layout decisions, i.e., the diameter of the smallest planar fractures that must be avoided when deciding on waste container positions at different distances from potential earthquake faults. It is, however, well known that fracture surfaces are rough or undulating on a wide range of scales (e.g., Candela et al. 2012) and that such deviations from planarity influence the mechanical behaviour of the fractures (e.g., Dieterich and Smith 2009, Marshall and Morris 2012, Ritz and Pollard 2012). It will probably never be a realistic option to attempt to represent the geometrical complexity of a population of fractures of different size, shape and surface structure in any large-scale rock mechanical analysis relevant for the performance assessments of the nuclear waste repository. It may however be possible to find approximate ways to represent different styles and degrees of non-planarity by assigning mod"

Jan 1, 2015

By W. L. Ennis

Introduction This paper outlines the causes of underground fires at Noranda Mines and the precautionary measures taken to guard against such fi res. Shafts There are six shafts (Figures and lA) on the property, of which N os. 1 and 2 are abandoned. Nos. 3, 4, and 5 are the present working openings from surface and No 6 is an internal shaft. No. 3 is used primarily as a service shaft, while Nos.?1 and 5 are the main hoisting shafts. Orebodies The orebodies are of two distinct types. There are the massive sulphide bodies, and the areas of mineralized rhyolite containing gold values and a silica content high enough for fluxing purposes. The massive sulphide bodies contain chalcopyl'ite, pyrite, pyrrhotite, and minor amounts of sphalerite and magnetite. The concentration of particular sulphides varies even within the same body. It is the areas high in pyrite, and to a lesser degree those, high in pyrrhotite, that are of particular interest.

Jan 1, 1950

By Michael Fuller

Roadmap ? Examples of Partnership from UBC ?? Event Sponsorship ?? Recruitment & Connections ?? Opportunities ? National Recruitment Survey Results ? Conclusion with Key Points Event Sponsorship ? Annual Canadian Mining Games competition ?? 160 senior mining engineering students, from 10 universities ? Field Trips ?? 2nd year: Open pit ? Highland Valley Copper ?? 3rd year: Underground ? Myra Falls, Quinsam Coal ?? 4th year: Self-organized ? Chile, China, Poland, Brazil

May 1, 2008

By Junto Nishiwaki, Shinji Kumai

"Mechanical and physical properties of the impact welded dissimilar metal joints are controlled by joint interface morphology. An intermediate layer (IML) is often formed at the joint interface and this deteriorates the interface quality in some metal combinations. Numerical and experimental studies were performed in order to examine the formation mechanism of the wavy interface and intermediate layer for explosive welded Al/Cu dissimilar metal joints. The impact welding process consists of (1) high-speed oblique collision of metal plates, (2) metal jet emission and large deformation and temperature increase at collision point and (3) rapid cooling at the joint interface. Euler-Lagrange coupling method, smooth particle hydrodynamic (SPH) method and modified laplacianFoam (LF) method were linked together to simulate a series of processes from (1) to (3), and the final interface morphology including the formation of IML was reproduced. The wavy morphology (wave-height, wavelength) and the position and composition of IML formed at the joint interface of Al/Cu joints were quantitatively in good agreement with those reproduced by numerical analysis. Our simulation results are useful for the control of the interface morphology, reduction of the amount of IML, and improvement of the mechanical properties of the impact welded dissimilar metal joints.INTRODUCTIONImpact welding is a kind of solid state joining method providing extremely high joint strength for both similar-and dissimilar metal combinations. Explosive welding and magnetic pulse welding are representative methods to achieve the impact welding. By a high-speed oblique collision between two metal plates, a metal jet is emitted from the collision point. The metal jet can remove any oxide films and contaminations on the plates and produce an active refreshed surface. Consequently, good metallurgical bonding can be achieved even for dissimilar metals (Crossland, 1982). Solid metals deform like fluids under the high pressure condition at the collision point and characteristic wavy interface is formed. In addition to the wavy interface, an intermediate layer (IML) is often formed at the joint interface in some metal combinations. Elimination or reduction of the amount of IML at the joint interface is desired since the excessive IML formation along the joint interface causes a large reduction in physical and mechanical properties. Formation of IML is considered to result from characteristic thermal history at the joint interface including partial melting due to the local temperature increase and successive rapid cooling behavior at the joint interface. In order to control the IML formation at the joint interface, it is necessary to reveal both heating and cooling processes at the joint interface. However, it is impossible to observe the phenomenon occurring at the joint interface and also difficult to investigate the temperature change at the joint interface directly during the impact welding. Therefore, simulation or numerical analysis is indispensable to overcome this problem. In the present study, the explosive welded Al/Cu joint, which is prone to form IML at the joint interface, was selected for the research. By using a newly developed numerical analysis method, not only the formation process of wavy interface, but also the local temperature increase and successive temperature decrease at the joint interface were reproduced. The formation process of IML was investigated by using both numerical analytic and experimental results."

Jan 1, 2018

By Peter J. Barnard

Mitochondria play a key role in the regulation of apoptosis (cell death) and in diseases characterised by abnormal apoptotic responses such as cancer. Mitochondrial membrane permeabilisation (MMP), regulated by the mitochondrial permeability transition pore complex, is widely accepted as being central to the process of cell death. As a result there has been considerable recent interest in targeting mitochondrial cell death pathways in the development of new chemotherapeutic agents.(1) There is potential to overcome the two overriding problems in cancer chemotherapy?the common occurrence of drug-resistant tumour cells and the lack of selectivity of cancer drugs in differentiating between tumour cells and normal tissues. Significantly, carcinoma cells have an elevated mitochondrial membrane potential relative to normal cells and lipophilic cations are concentrated within mitochondria in response to mitochondrial membrane potentials. There is potential for the selective targeting to tumour cells with compounds having optimal lipophilic-hydrophilic character. Research stemming from the early 1980?s points to two distinct classes of Au(I) phosphine antitumour agents where an antimitochondrial mode of action has been implicated: (i) neutral linear two-coordinate Au(I) complexes such as triethylphosphinegold(I) chloride and the tetraacetylthioglucose gold(I) phosphine complex, Auranofin; (ii) cationic tetrahedral bis-chelated Au(I) phosphine complexes related to [Au(dppe)2]+.(2) Recently it has been reported that Auranofin, at submicromolar concentrations, induces MMP observed as mitochondrial swelling and dissipation of membrane potential.(3, 4) Both events are completely inhibited by cyclosporin-A, the specific inhibitor of MMP. The permeability changes were shown to occur at concentrations associated with the selective inhibition of mitochondrial thioredoxin reductase.(3) Auranofin is a potent and specific inhibitor of this enzyme due to Au(I) binding to the active-site selenol group.(5) The redox state of mitochondrial thiols may be critical in the control of MMP.(3) In general, swelling is stimulated by thiol blocking or oxidising agents and is prevented by thiol reducing agents.(1) Mitochondrial thioredoxin reductase may play an import role in the redox control of the permeability of mitochondrial membranes.(3) Our interest is in investigating the antitumour potential of Au(I) phosphine compounds using a number of different approaches. In recent work we have evaluated a series of hydrophilic analogs of [Au(dppe)2]+ containing pyridylphosphine ligands which have demonstrated greater tumour selectivity than the parent compound. To investigate the possible antimitochondrial mode of action we are studying the effect of [Au(dppe)2]+ and related compounds on isolated rat liver mitochondria. To assess whether the lipophiliccationic nature of the compounds determines the antitumour activity, we have synthesized a series of novel Au(I) complexes based on heterocyclic carbene rather than phosphine ligands. The similar chemistry and structural features of the two classes of complexes allow us to assess whether the phosphine ligands are essential for the antitumour properties.

Oct 1, 2003