Fritz Feigl, Brazil's Spot Tester Platinum Anti-Tumor Compounds: An

Nineteenth century tradition, died on>anuary 23,1971, in. Rio de Janeiro, after a long illness. ... in Ghent he helped the Belgian government develop ...
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JOHN H. WOTlZ Southern llllnoir University Carbondale. 62901

Fritz Feigl, Brazil's Spot Tester Joseph A. Sehufle New Mexico Highlands University and Laviuel G. Ionescu University of Detroit Dr. Fritz Feiel. one of the ereat Eurooean chemists of the Nineteenth century tradition, died on>anuary 23,1971, in Rio de Janeiro, after a long illness. He was one of the outstanding chemists of all time who called Latin America his home. He lived the last 30 years of his life in Brazil, working with his students and p"hlishing the results ot his work right UD t o the time of his death at the ace of 89. 'Feigi was horn in Vienna, on 15 May 1891, one of the last of the old fashioned Herr Professors, who expected and received the respect and undivided attention of his students. He studied chemistry a t the Technische Hochschule in Vienna and received his doctor of technical science degree there in 1920, for his thesis on spot testing methods of analysis. In his thesis Feigl worked out a scheme of analysis for elements of the ammonium sulfide and hydrogen sulfide groups on a micro scale. He conducted his reactions on filter paper and used color reagents to detect amounts of the order of 0.01 mg or less. He later extended these micromethods to include practically all anions and cations. He enlarged his filter paper technique to include spot tests on a porcelain plate with little indentations, which he called a in most analvtical soot . .d a t e .. a common oiece of eauioment . . laboratories today. Feiel defined an "identification limit" to describe the sensitivity of his tests. But essentially his methods were imorovements on the standard methods of qualitative chemical analysis, with quantitative determination a secondarv He concentrated much of his effort on find. ohiective. . ing organic compounds which give specific color reactions with the different elements. When such organic reagents gave similar reactions with more than one element, Feigl often determined the optimum p H range for a given element, or devised methods for masking interfering ions. He called this "conditioning of tests," and i t is a technique now widely used. One of the most important areas where Feigl's spot tests are used is in the field of paper chromatography. I t can he stated with confidence that Feigl's spot testing techniques contributed much to the ranid rise of the use of chromatoeraphy in recent years. Feiel's work a t Vienna ended when Hitler's "Anschluss" unite: Austria and Germany in 1938. Feigl moved to Belgium where a t the Soci6t.6 Belge de Recherche et #Etudes in Ghent he helped the Belgian government develop a material to he included in pas mask canisters to remove the ~ the German army, poisonous gas arsine. ~ e i r e a t i nbefore Feigl next moved to Vichy France where, pursued by the Condensed from a paper presented at the First Chemical Congress of the North American Continent, Symposium on "Latin American Chemistry," Mexico City, November 3kDecember 5, 1975.

174 / Journal of ChemicalEducation

German authorities, he contacted t h e Brazilian embassy in France which arranged for his escape through Spain and Portugal to Brazil. In Rio de Janeiro Feigl was invited by the famous Mario de Silva Pinto of the Brazilian Ministrv of Agriculture to become director of the Laboratory for Investigations in Microchemistrv of that ministrv. Feiel's methods of spot testing proved t o he useful in the geochemical . orosoectine being carried out in Brazil. The small . amount of equipmentneeded for these tests made them oarticularly valuable to scientific exoeditions sent out to kvaluate the vast mineral deposits in remote inland parts of Brazil. Large deposits of iron, manganese, molybdenum, tungsten, beryllium and uranium have heen discovered and evaluated by these expeditions. Feigl always felt that his spot reactions were a t least as good as other micro-precipitations methods, usually better, never inferior. Some authors have referred to these spot tests as "semi-microanalysis." Feigl never approved of this name. He thought semi-microanalysis referred to identification limits of 10-200 rrg, micrograms, whereas his spot . tests involved identification limits smaller than 10 ~ g In terms of concentration, Feigl's spot tests were effective in many cases into the parts per billion range. Feigl received many prizes and honors from societies and universities all over the world. He received many honors from his adopted country of Brazil, where he was regarded by many as one of the brightest stars in the firmament of Latin American Chemistry.

Platinum Anti-Tumor Compounds: An Unexpected Discovery Christine F. Ledger and J o h n Webb Australian National Uniuersity Canberra, 2600 Australia With cancer's threat so immediate and its cure so elusive. it is to he exuected that any indication of the cell-division process's being hindered in the course of scientific exoeriment will incite interest and demand further attention. i n 1965, while investigating the rate of bacterial growth in the presence of electric fields, Rosenherg and co-workers noted that bacteria in the Escherichia coli culture heing tested were exhibiting abnormal elongation (i.e., the cells were not dividing readily) while the growth rate remained unaffected (I)). The group went to considerable and painstaking lengths to determine the cause of this unexpected observation. Subsequent research has led to the emergence of a class of inorganic compounds with tumorinhibiting properties. On first ohservine the filamentous erowth. the a O U D investigated the possibility of uv light,temperature, or maenesium concentration (all of which were alreadv known to stimulate this abnormal type of growth) heing responsi-

hle for the behavior. All returned negative results and possible electrolysis products hecame the focus of attention. It was indeed established that a stable chemical species was being produced by electrolysis and inhibiting the celldivision. By the potassium iodide-starch test, it was confirmed that an oxidizing agent was being generated a t a rate similar to that of the elongation process. Also, just as the extent of filamentous growth was proportional to the frequency of the voltage applied, the concentration of the, as yet, unknown chemical species was likewise proportional. By a process of elimination, i.e., electrolyzing separately each component of the "C" medium in which they were working, the group decided that the platinum electrodes which, ironically, had been originally chosen because of platinum's chemical "inertness", were being attacked by chloride ions to form [PtC16I2-. Direct inoculation of (NH&[PtCls] in appropriate concentration to the bacterial culture indeed resulted in filamentous growth, hut not to the same extent as the electrolysis products. The (NH&[PtC16] was converted by photochemical processes to the neutral species-[Pt(II)C12(NHa)21 and [Pt(IV)CId(NH&-which were identical to the electrolysis products (2). These compounds were synthesized and found to he active only in the cis-configuration. I t was thus verified that particular platinum compounds had heen responsible for the original observations. This initial intriguing discovery prompted further research into platinum compounds and, in 1967, Rosenherg reported that, of various chloro-ammine complexes of Pt(IV), the cis-isomer of [PtC14(NHa)z]most markedly inhibited cell division in Escherichia coli while having little

effect on growth (3).This complex, along with three others, viz. cis-[Pt(II)C12(NH3)2]. [Pt(II)C12(NH~CHzCH2NHz)], and [Pt(IV)C14(NH2CH2CH2NH2)]was later tested for inhibition of sarcoma 180 and leukaemia LIZ10 in mice (4). All the complexes yielded hopeful results-tumor growth was inhibited markedlv. Platinum compounds were certainly looking promising as cancer-inhihitine agents, and it remained to investieate their effects on &man malignancies. The p l a t i n u g ( ~ ~ ) compound, cis-[Pt(II)Clz(NH3)z] has proved the most promising in many animal trials and was chosen by the National Cancer Institute to enter into clinical trials. For example in 1972 Rossof, Slaytou, and Perlia reported (5) their clinical experience with this compound. Although they advised caution in administering the compound due to possible delayed or cumulative toxicity and renal complications, they affirmed that anti-tumor activity was apparent. The number of metal-containing compounds reported to possess anti-tumor activity a t least in experimental animals, continues to increase ( 6 ) .Hence, from that original experiment, unrelated to either platinum compounds or cancer research, has arisen the new and exciting field of inorganic reagents as possible tumor-inhibitors. Liferafure Cifed (1) Rosenhrg. B., Vancamp. L.. and Kiigsr, T.. Nolure. 205,698 (1965). I21 Rosenberg, B., personal mrnrnunicsiion. (3) Ro~enberg,8.. Vancamp. L.. Grimley, E., end Thornson. A. J., J R i d C h ~ m .242. , 1947 119671 ~,~

I41 Rosenborg, B., VanCasp, L., Trosko, J. E., and Mansour, V. H..

Nolure.

222, 385

(19691.

15) Ro8sof.A. H.,Slayton.R. E.,and Pedia.C. P.. Concar. 30, ,461 11972) 16) Cleare. M. J.. Coord. Chem Re". 12.349 119741.

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