Frontiers in chemistry day. Oxygen bicentennial symposium - Journal

Report of the Third Biennial Conference on Chemical Education and the Second Centennial of Chemistry Celebration. Keywords (Audience):. Continuing ...
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Frontiers in Chemistry Day Oxygen Bicentennial Symposium R a p p o r t e u r : S. J. Benkovic, P e n n s y l v a n i a

State University

This was another event in which many references to Priestley and "dephlogisticated air" were heard. Oxygen obviously still commands such interest from outstanding scientists. Two lecturers in the Oxygen Bicentennial Symposium focussed on the physical and chemical properties of singlet oxygen, a form of oxygen which has higher energy and considerably greater reactivity than ground state triplet oxygen. Michael Kasha (Florida State Uniuersity) in his lecture "Singlet Molecular Oxygen Sensitized Luminescence~'' summarized some theoretical aspects, basic representations and spectral properties of the triplet and singlet forms. Special emphasis was given to energy transfer from singlet states to various dyes as a method for determining the particular singlet state present. In the following lecture Christopher S. Foote (Uniuersity of California, Los Angeles) in his lecture, "Singlet Oxygen and its Quenchers in Organic and Biological Chemistry," reviewed the chemical reactivity of singlet oxygen with organic compounds, and then went on to discuss its probable role in photodynamic toxicity, especially in the genetic disease porphyria. The use of &carotene to protect against this toxicity and the scientific basis for the protection was discussed. Also, Dr. Foote reported on some experiments involving bilirubin-sensitized formation and quenching of singlet oxygen. The balance between these is apparently just right to allow light therapy to be effective in treating neonatal jaundice without causing noticeable harmful side effects. The other two lectures were aimed at reactions of oxygen either in biological systems or in models of biological systems. Joe M. McCord (Duke Uniuersity Medical Center) presented a talk on "Superoxide. Suoeroxide Dismutase a n d Oxygen Toxicity" and T. G. 'Traylor (Uniuersity of California, San D i e ~ o )talked on "Reaction of Oxvaen .. with Hemes and Heme Proteins." Dr. McCord pointed out that the dramatic toxic effects produced by elevated concentrations of molecular oxygen present serious medical problems and are poorly understood chemically. A part of the problem appears to be due to the fact that many biological reductions of Oz do not reduce oxygen fully to produce HzO, a non-toxic product, but instead result in the formation of partially reduced, toxic intermediates: H202 from the two-electron reduction, and superoxide 02-, from the one-electron reduction. Nature has provided three families of protective enzymes to detoxify these reactive, partially-reduced intermediates. Superoxide dismutases catalyze the conversion of O z to 0 2 and HzOZ. Catalases and peroxidases then catalyze the further reduction of Hz02 to HzO. It appears that all organisms which metabolize Oz possess superoxide dismutase. Many microorganisms, however, do not possess enzymes to destroy HzOz, hut apparently rely on the diffusion out of the cell of this relatively more stable and less reactive intermediate. A mutant of E.xherichia coli which was deficient in superoxide dismutase was restricted to anaerobic growth and died on exposure to air. In mammalian metabolism it seemed likely to Dr. McCord that some of the toxic effects of Oz would result

from reactions taking place in the extracellular fluids, which contain a t best only traces of the protective enzymes. To compound the problem, 0 2 - and Hz02 are capable of reacting, if neither is scavenged to produce the OH. radical, an extremely potent oxidant. This mechanism was proposed to account for the extensive degradation suffered by synovial fluid upon exposure to a source of superoxide. A significant in uiuo source of superoxide is the polymorphonuclear leukocyte, or white blood, cell, which releases large amounts of 0 2 when metabolically activated, probably for bactericidal purposes. Dr. McCord suggested that this source of superoxide is quantitatively sufficient to account for synovial fluid degradation in certain types of inflamatory arthritic diseases. Dr. Traylor observed that since Priestley discovered that venous blood turns red in the presence of oxygen, the biological and chemical nature of this process has been under increasingly active investigation. With the elucidation of the structure of hemoglobin and myoglobin it became feasible to synthesize small molecules duplicating the structure of the active site for oxygen binding. Dr. Traylor's group has thus duplicated the myoglobin oxyaenation site in eeometrv. " . electronic effects. environment. and spectral properties by preparing the co"a1ently bound comoounds ovrroheme-3-N-imidazolvoroovlamide (1)and pyrroheme-3-(3-pyridy1)propyl)ester' (11i. compounds I and I1 reversibly bind oxygen a t temperatures -50" to 25°C as do the proper mixtures of n-alkyl imidazoles and simple heme compounds such as protoheme dimethyl ester, tetraphenylporphyrin iron(II), etc. in certain polar solvents (for example, dimethylformamide and N-methylpyrrolidone). In fact, the compound I reversibly binds oxygen a t 15°C in dimethylformamide (DMF) containing thirty percent water. The base-heme mixtures, unlike myoglobin and the model compounds I and I1 have extra equilibria which make dynamic studies very difficult. On the other hand, the kinetics and equilibria of oxygen and other ligand reactions with I and I1 can be compared directly with those of myoglobin and hemoglobin. The reactions studied are k,,,, heme + 0, == heme-0, (11 k,,,,

heme

+

k.,"

CO

= hemeCO ,,,,

('2)

First, the K = k,,n/k"rr for 0 2 is some 60 times larger with I than with II showing that basicity is important in oxygen binding. However, I and I1 hind carbon monoxide with almost the same K . Furthermore, the oxygen binding in, e.g., II is very dependent upon solvent polarity, K for 0% decreasing about 100-fold upon changing solvent fmm DMF to toluene. But carbon monoxide binding is changed little with solvent change. Thus the KO, as well as the KoJKcn ratio can be varied by greater than a factor of 103 hv changing ~ r o x i m a base l structure and solvent. This change exceeds the differences in the equilibria found in various normal and abnormal hemoalohins and suaeests that small changes in solvent polarity in the site or the Volume 52. Number I, January 1975 / 15

imidazole basicity could account for a major portion of the differences in oxygen and carbon monoxide binding strengths in different hemoglobins, myoglohins, etc. Preliminary measurements of k,, and kotr for CO and Oz using stopped flow methods were also reported. The kinetic results for oxygen resembled very much the corresponding k values for the last step in hemoglobin oxygenation as well as the corresponding k's for isolated chains. These results suggest that isolated chains and hemoglobin

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with three hemes oxygenated resemble simple hemes in a rather polar environment. Thus, the protein apparently serves to destabilize the heme-Oz bond in partially oxygenated hemoglohin, in abnormal hemoglobins, etc. in order to achieve the proper oxygen binding kinetics and equilibria. The papers presented in the Oxygen Bicentennial Symposium have been surveyed in Chemical and Engineering News, August 19, 1974, p. 24.