Chemical & Engineering
NEWS NOVEMBER 21, 1966
The Chemical World This Week Institute to study science role Columbia University has set up an in stitute to study the ethical and hu manistic implications of the scientific revolution. Creation of the Institute for the Study of Science in Human Affairs was made possible by a $1 mil lion founding grant from the Alfred P. Sloan Foundation. The aim of the institute is to help man understand more fully the scien tific forces that shape his life and to make better informed decisions on what the proper direction of scientific and technological developments should be. To carry out its aim, the institute will undertake many major studies. One will examine the human signifi cance of specific developments in bi ology and medicine, such as the role of computers in medical and clinical prac tice and education. The institute will study the social and economic changes related to sci entific and technological advances. It will also study the measurement of sci entific productivity. And it will try to determine what political, ethical, and cultural considerations affect the direc tion of scientific effort. The institute will also help develop Columbia's undergraduate instruction in the social implications of science for both science and nonscience majors. Commenting on this, Dr. David B. Truman, dean of Columbia College, says that the institute would study the setting up of undergraduate courses on the history of science and on the rela tion of governmental institutions to the scientific community. On the gradu ate level, the institute will prepare in terdisciplinary programs. The institute will initially be staffed by faculty members from both the sci ences and the humanities. In time, Columbia University president Gray son Kirk foresees the institute's activi ties becoming "a major interdiscipli nary program attracting the most dis tinguished scholars to named profes sorships and eliciting the cooperation of sister institutions." Its work may involve spending several million dol lars during the next 10 years. Provisions have already been made to appoint visiting scholars and to award graduate fellowships. The in stitute later hopes to set up internships
Christopher Wright Life-shaping forces for undergraduates. However, it will not award any degrees. Christopher Wright is director of the new institute. Mr. Wright was ex ecutive director of Columbia's Council for Atomic Age Studies, which, to gether with the advanced science writ ing program of Columbia's Graduate School of Journalism, will become part of the new institute. The bringing to gether of many talents in the institute, he says, will allow an individual scholar to accomplish more within the institute than by working alone.
Taube receives Kirkwood Award When an external oxidizing agent at tacks an oxidizable ligand coordinated with the pentaamminecobalt(III) res idue in solution, the cobalt (III) often acts as an internal oxidizing agent. To what extent the cobalt (III) takes part in the oxidation and becomes reduced to cobalt ( II ) is governed partly by the nature of the external oxidizing agent, Dr. Henry Taube of Stanford Univer sity told the New Haven Section of the ACS in his Kirkwood Award address at Yale University. These findings are among the many that have resulted from mechanism studies of the oxida tion of coordinated ligands in solution
done by Dr. Taube and his coworkers. A one-electron external oxidizing agent such as Ce (IV) tends to cause reduction to cobalt ( I I ) , Dr. Taube and his coworkers have found. By contrast, a two-electron external oxi dant such as chlorine or hydrogen per oxide catalyzed by Mo (VI) attacks only the oxidizable ligand, leaving the cobalt present as cobalt ( I I I ) . Dr. Taube is the fifth recipient of the John Gamble Kirkwood Medal. Established in 1962 in memory of the late chairman of the Yale chemistry department, the award recognizes out standing scientific accomplishment. Dr. Taube and his coworkers have studied the oxidation of a number of simple ligands associated with the pentaamminecobalt(III) residue. These ligands include bioxalate, iodide, wa ter, and ammonia. Besides Ce (IV), they have used external oxidants such as hydroxyl radicals, methyl radicals, and peroxydisulfate ion (alone and catalyzed by silver ion). In the oxidation of [ ( N H 3 ) 5 C o I ] 2 + by one-electron oxidants, for example, Dr. Taube and Dr. Albert Η aim found a striking difference between Ce (IV) as the external oxidant on the one hand, and HO, methyl radicals, and like agents on the other. When Ce (IV) is the oxidant in an acid solu tion, one half of the [ ( N H 3 ) 5 C o I ] 2 + which reacts is converted to [ ( N H 3 ) 5 CoOH 2 J 3 +; the other half forms Co 2 + and ammonium ions. When HO reacts, all of the Co (III) which is consumed is converted to Co 2 +. This contrast in behavior illustrates the dif ference which can arise between oxi dation by electron transfer as exempli fied by Ce (IV), and oxidation by group transfer as exemplified by HO, Dr. Taube says. More recently, Dr. Taube and his associates have begun to study the ox idation of more complex organic lig ands associated with pentaamminecob a l t ( I I I ) . In these ligands, the point of attack by the external oxidant is far removed from the ligand site which bears the Co ( I I I ) . One such ligand contains the pyridine ring with an ox idizable CH 2 OH group attached to the pyridine's C-4 position. When this complex is oxidized with Ce (IV) as the external oxidant, the complex breaks down, forming Co 2 +, and the NOV. 21, 1966 C&EN
19
TNM nitrates tyrosyl residues
Medalist Taube Oxidation in solution
CH 2 OH group is oxidized to CHO, Dr. Taube and his coworkers, J. E. French and Dr. Richard Robson, find. It's important to learn whether the two oxidants, the external, C e ( I V ) , and the internal, Co ( I I I ) , act in concert or separately. If attack by the external oxidizing agent and internal electron transfer to Co (III) are separate processes, pentaamminecobalt(III) bound at some remote position can be used as a probe to explore the mechanism of oxidation of oxidizable groups. When internal electron transfer is a fast process, this probe can provide a clear distinction between oneelectron and two-electron oxidation processes, Dr. Taube points out. Dr. Taube and a number of coworkers, including Patricia Saffir and Dr. R. P. M. Fraser at the University of Chicago and Dr. Darwin Thusius at Stanford have used competition experiments to study the rate of internal electron transfer. In these experiments, internal electron transfer in the intermediate product formed by the attack of the external one-electron oxidant competes with further reaction of this intermediate product with an external oxidant such as oxygen. These experiments lead to estimates of the half-life for the internal electron transfer act. Comparing these rates for different oxidizable group locations is of interest to chemists, Dr. Taube says. At Stanford, Dr. DeForest Rudd is extending oxidation studies of coordinated ligands to systems in which ruthenium (III) is the internal oxidizing center. The aim of this work, Dr. Taube explains, is to find what the effect on the oxidation mechanism will be when the acceptor orbital in the internal oxidant has TT symmetry as does ruthenium (III) rather than * & symmetry as in cobalt ( I I I ) . 20 C&EN NOV. 21, 1966
Riochemists at Harvard Medical School have found tetranitromethane (TNM) to be a highly selective, specific, and mild reagent for the nitration of tyrosyl residues of proteins at pH 8. Methods for chemically modifying these tyrosyl residues are important since the residues are known to both stabilize the structure of the proteins and participate in their biological function. Dr. James F. Riordan, Dr. Mordechai Sokolovsky, and Dr. Bert L. Vallee have previously done work on the nitration of tyrosine and other related phenols [/. Am. Chem. Soc, 88, 4104, (1966)]. These studies have proved directly pertinent to the nitration of proteins. By chromatography, the Boston biochemists have identified 3-nitrotyrosine as a reaction product of TNM with tyrosyl- containing peptides and proteins. The compound exhibits an absorption band with a maximum at 428 m/x and a molar absorptivity of 4100. This chromophore serves as a convenient and accurate quantitative measure of the nitration reaction [Biochemistry, 5, 3582 (1966)]. Comparison of the spectrophotometric results of the nitration reaction with those obtained by amino acid analyses establishes the optimum experimental conditions and that the nitration is quantitative. Although nitration with TNM also affects cysteinyl residues, controlling the pH of the reaction serves to make it selective. At pH 6, cysteinyl residues are oxidized but the tyrosyl residues are not affected. Generation in a protein of a chromophore which absorbs in the visible spectrum opens a number of experimental approaches. For example, if the group modified is functional, then substrates, substrate analogs, and inhibitors may affect the chromophore^ spectral properties. Since the nitrotyrosyl residue can be ionized, methods such as perturbation spectra could be used to investigate the microscopic environment of active center residues. Current work by Dr. Riordan and his coworkers bears out this prediction. Addition to mononitrocarboxypeptidase of /?-phenylpropionate, a competitive inhibitor of the enzyme, shifts the pK of the nitrotyrosyl residue from 6.3 to 7.2. This pK shift is a very sensitive indicator of vicinal changes, they note. Additional work under way by the three biochemists points to the potential offered by reduction of a substituent nitro group to an amino group. Reduction should modify the phenolic pK, the characteristics of the chromo-
phoric group, and the enzymic activity (if the tyrosyl residue is biologically active). And what is most important, the resulting aminophenol should have unique chemical properties permitting further specific chemical modification. Recent results by the three biochemists show that nitration of carboxypeptidase with a fourfold molar excess of TNM doubles esterase activity while reducing peptidase activity between 5 and 10%. Amino acid analysis reveals the presence of one mole of 3-nitrotyrosine per mole of enzyme. Other residues are not modified. Moreover, /^-phenylpropionic acid protects against these changes in activity. In another study [Biochemistry, 5, 3574 (1966)], Dr. Sokolovsky and Dr. Vallee have extended a method for determining histidine and tyrosine residues in proteins developed by Dr. H. Horinishi and coworkers [Biochim. Biophys. Acta, 86, 477 (1964)]. Basis of the method is coupling of diazonium- lH-tetrazole ( D H T ) with histidine and tyrosine residues and quantitative conversion to the respective bisazo derivatives. Measurement of the absorption spectra of the derivatives at 550 and 480 m/x then simultaneously determines the histidine and tyrosine content of a protein.
Economy slowing The economy has been running so fast that in the past year or so a certain amount of dizziness has set in, says Edwin H. Sonnecken, director of corporate business planning for Goodyear. The dizziness is conventionally described as inflation. And Mr. Sonnecken says that it is no wonder that
Edwin H. Sonnecken Dizziness has set in
