The importance of the conformation Comparison of these spectra with simi of the metal complex in the transport lar spectra of the chromium enterobacprocess has been established by Dr. tin complex leads Raymond to con Thomas F. Emery of the University of clude that the natural enterobactin Utah, Logan, who worked with the si complex has a right-handed configura derochrome ferrichrome produced by tion. the smut fungus Ustilago sphaerogena. Additionally, an x-ray crystal struc Changes in substituents in the ferri ture analysis of both the model iron chrome molecule alter its transport and chromium complexes shows that properties. Moreover, the importance both are octahedral complexes having of the presence of an appropriate com- similar bond lengths and angles. This plexed metal with the ligand is indi finding, Raymond believes, supports cated by the fact that the unbound the validity of using chromic complexes complex is not transported into micro in such investigations. bial cells, whereas iron, gallium, and In related work, Raymond and his aluminum complexes are. coworkers have prepared and charac However, Raymond observes, studies terized the chromic-substituted coordi concerning the structure-function rela nation isomers of the siderochrome fer tionships of siderochromes have been rioxamine B. Ferrioxamine Β is a trihyhindered by the rapid rearrangement droxamate administered to patients and equilibration of the ferric complex, suffering from iron poisoning. Uptake which allows the iron to be exchanged studies of its chromic complex have easily and the complex to isomerize been conducted by Neilands and Dr. readily. To overcome these problems, John Leong, also at Berkeley. These Raymond and his coworkers have pre experiments show that neither the cis pared kinetically inert chromic com nor trans ferrioxamine Β isomer is transported into the cells of the bacte plexes of siderochromes. "This In this way, they have been able to rium Salmonella typhimurium. characterize ferrichrome and related implies that ferrioxamine is involved in siderochromes structurally. These tris the second type of transport process," hydroxamate complexes all were found Raymond observes. "It is not a mem to have a left-handed configuration brane transporting agent at all, and around the iron, Raymond says. (This now we must look for a membranemeans that when viewed down its bound iron chelating agent that ab threefold axis of symmetry, the tris sorbs the iron from the ferrioxamine D chelate complex of the metal looks like B." a left-handed propeller.) However, the left-handed configura tion does not appear to be a unique characteristic of siderochromes, ac cording to the Berkeley chemist. Enterobactin (the cyclic triester of 2,3-dihydroxy-N-benzoyl-7-serine) is a siderochrome that exists in a righthanded configuration. To determine the absolute configuration of this cate chol, produced by bacteria such as Escherichia coli, Raymond and his col leagues prepared model chromium and Although a number of compounds are iron tris catechol complexes and ob known that contain copper in its tritained the visible and circular di- positive oxidation state, the prepara chroism spectra of the resolved optical tion of a Cu(III) compound that is rela isomers of the chromium complex. tively stable in aqueous solution here-
Siderochromes aid in moving iron to cells
Chemical Congress-Mexico Siderochromes—the molecules in volved with microbial iron uptake—do not all possess the same absolute con figuration and are not always the agents that actually transport iron across cell walls. These results and other aspects of the chemistry of side rochromes were discussed in a sympo sium on bioinorganic chemistry by Dr. Kenneth N. Raymond of the University of California, Berkeley. When microbes invade living tissue, a battle ensues between host and in vader for available iron. Indeed, where host iron levels are higher than nor mal—because of liver or blood diseases, high iron intake through diet or injec tion, or other causes—the host can be especially susceptible to infection by bacteria and fungi. Ferric iron is extremely insoluble at the nearly neutral pH of tissue fluids and culture media. To obtain the iron that they need to survive, microbial cells synthesize phenolate and hydroxamate compounds called sidero chromes, which complex with the metal and facilitate its uptake into the microorganism. Some siderochromes are growth factors; others are potent and broad-spectrum antibiotics. According to results of investigations conducted by Dr. John B. Neilands, also at Berkeley, two mechanisms of action are possible for the sidero chromes, Raymond explains. In the first, siderochrome complexes with the iron and is the actual agent that carries the metal into the cell. In the second, siderochrome complexes with the iron, but brings it only to the cell surface where the iron is delivered to an alternate system that transports it through the membrane into the cell.
Stable Cu(lll) complex prepared
Chemical Congress-Mexico
Siderochromes are hydroxamates . . .
N~C
N—C
1
II
1 II
(3
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0
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N— C
0
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II
C&EN Dec. 8, 1975
ι 0
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Ferrioxamine Β
26
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. . . and phenolates
tofore has eluded the efforts of chemists. Now, however, Dr. Dale W. Margerum of Purdue University, West Lafayette, Ind., has found that Cu(II) complexed with deprotonated amides and deprotonated peptides can be oxidized easily to Cu(III) complexes. For example, in neutral solution, the deprotonated Cu(III) complex of tetraglycine, [Cu(III)(H- 3 G4)] _ , shows a half-life of about two hours at 25° C, Margerum told a symposium on bioinorganic chemistry. Moreover, the [CuiïïUIKH-aGé)]1-'2complex shows a standard electrode potential of 0.631 volt—a value 0.140 volt less than that for the [Fe(III,II)aquo] couple, and a potential 0.3 to 0.5 volt more accessible than that predicted from previous measurements. The stability of the Cu(III)-peptide complexes and their low redox potentials may be of biological interest, says Margerum. In the absence of light, molecular oxygen will convert Cu(II)tetraglycine to the [Cu(III)(H_ 3 G 4 )]complex. Such a reaction may provide a means to activate molecular oxygen, says the Purdue chemist. Additionally, the possibility of a two-electron transfer in which Cu(III) is reduced to Cu(I) eliminates the necessity of postulating a biological redox pathway involving a high-energy free radical intermediate, he suggests. Such a Cu(III)/Cu(I) couple has been proposed for the enzyme galactose oxidase by Dr. Gordon A. Hamilton at Pennsylvania State University. Margerum observes that [Cu(III)(H_3G 4 )]- oxidizes sulfite to sulfate, and Sn(IL) to Sn(IV) with a one-to-one stoichiometry, but has no effect on galactose. The proposed [Cu(III)(H_ 3 G 4 )]complex shows an electronic absorption band at 365 nm characteristic of a Cu(III) species, according to Margerum. Electron paramagnetic resonance and kinetic properties also confirm the presence of Cu(III), he believes. The potential of the ' [Cu(in)(H- 3 G 4 )]complex was determined using a reversible redox system with [Ir(lV,III)Cl6] 2 "' 3 - . In subsequent work, Margerum and his coworkers have measured the potential of tetra-L-alanine, pentaglycine, hexaglycine, triglycineamide, glycylglycyl-L-histidine, and other complexes using cyclic voltammetry and a glassy carbon electrode. The redox potentials of these peptide complexes vary from 1.02 to 0.58 volt, Margerum says. Very strong electron-donating groups are needed to stabilize the Cu(III), he says, and generally, the higher the number of deprotonated amide or peptide groups, the lower the potential. In the case of tetra-L-alanine, the presence of methyl groups helps to give the lowest potential thus observed—0.58.volt. "It appears," he says, "that where Cu(III) may exist in nature, it is more likely to be coordinated to deprotonated peptides rather than only to lysine and histidine groups that stabilize Cu(II)." π
Shielding region Η
Deshielding
Deshielding
region
region
h ti tt External magnetic field III
Study confirms magnetic deshielding by triple bonds As a corollary to the magnetic shielding effects commonly ob served in the nuclear magnetic resonance spectra of terminal acetylenes, a deshielding effect for protons located alongside a triple bond would be expected. Both effects may be ascribed to the secondary magnetic field arising from the fieldinduced circulation of the pi electrons of the triple bond (I). To confirm the existence of magnetic deshielding by triple bonds, Dr. Frank B. Mallory and Mary B. Baker of Bryn Mawr (Pa.) College observed the pro ton nuclear magnetic resonance spectrum of 4-ethynylphenanthrene (II). They found that the H-5 chemical shift (10.35 ppm downfield from tetramethylsilane) is 1.71 ppm further downfield than the corresponding shift for H-5 in phenanthrene alone. In the compound 5-ethynyl-1,4-dimethylnaphthalene ( I I I ) , the protons of the methyl group located at the 4 position were 0.45 ppm downfield from those in the 1-methyl group. The smaller effect arises from a rotational averaging, they believe, and demonstrates, as expected, that deshielding is a function of the distance of the proton from the triple bond.
Chemical Congress-Mexico
Cancer risk higher for pot smokers
Chemical Congress-Mexico Although previous research has sug gested that marijuana cigarettes can be more carcinogenic than regular tobacco cigarettes, until now it hasn't been known why. Chemists from Indiana University, Bloomington, and the Uni versity of Leeds (England) told a sym posium on gas chromatography that marijuana could be more mutagenic be cause it contains more polynuclear aromatic hydrocarbons. This conclusion was reached by Indi ana's Dr. Milos Novotny and Dr. Mil ton L. Lee, and Leeds' Dr. Keith D. Bartle after analyzing smoke conden sates from 2000 marijuana and 2000 to bacco cigarettes using liquid chroma tography, nuclear magnetic resonance spectroscopy, and the combination of high-resolution gas chromatographymass spectrometry. The researchers chose to study the polynuclear aromatic hydrocarbons be cause they are known to be a major group of chemical carcinogens and be cause they are commonly formed in
various combustion processes and therefore likely to be present in the products of burning cigarettes. Using their own fractionation and purification procedures, Novotny, Lee, and Bartle collected polynuclear aro matic fractions containing three rings and more from the smoke condensate from marijuana and tobacco cigarettes. These portions amounted to 73.7 mg from the marijuana cigarettes and 56.9 mg from the tobacco cigarettes. The cigarettes were prepared from equal weights of tobacco and Mexican mari juana. The marijuana was standard material obtained from the National Institute of Mental Health, Rockville, Md., and contained 2.8% A 9 -tetrahydrocannabinol. Standard tobacco ciga rettes were obtained from the TobaccoHealth Research Institute at the Uni versity of Kentucky, Lexington. The cigarettes were smoked by a smoking machine, and the smoke collected in a chilled acetone trap. Included in the more than 150 poly nuclear aromatic hydrocarbons found in marijuana smoke condensate were sev eral heavier compounds that are prac tically absent in tobacco smoke. Among them are indeno [1,2,3-cd] pyrene, a known carcinogen, and dibenzopyrene, which researchers at the Na tional Cancer Institute have shown can produce respiratory cancer in ham sters. Dec. 8, 1975C&EN
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