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2nd INTERNATIONAL CONFERENCE ON BIOINORGANIC CHEMISTRY xes, except for the mono-complex which was regular octahedral, had shorter Ni-O bonds than Ni-N bonds, and the differences between the Ni-O and Ni-N distances were more enhanced in the tris-complex than in the bis-complex. Stepwise formation constants of the glycinato complexes decreased with the number of glycinato ions within the complexes. However, the stepwise formation reactions were more exothermic at a higher complex than a lower one in the case of nickel(II) and zinc(II) ions, except for the formation of Zn(gly)3. A more negative value in DII° at a higher complex is explained in terms of weakened M-OH, bonds in the complex, the water molecules being more easily replaced by an entering glycinate ion. A large rate constant of formation of a higher complex may also be due to water molecules which become more labile in the complex by the elongation of the M-0H 2 bond. The structures of the complexes thus determined were compared with those of metal complexes with other amino acids and biologically interesting ligands and with structures of carboxypeptidase, carbonic anhydrase and thermolysin in the crystalline state. REFERENCES [1] K. OZUTSUMI, H. OHTAKI, Bull. Chem. Soc. Jpn., 56, 3635 (1983). [2] K. OZUTSUMI, T. YAMAGUCHI, the H. OHTAKI, «Abstracts Of 3rd International EXAFS Conference», Stanford, U.S.A., July 15-20, 1984. [3] K. OZUTSUMI, H. OHTAKI, Bull. Chem. Soc. Jpn., 57, 2605 (1984). [4] K. [5] OZUTSUMI, T. FUJITA, T. H. OHTAKI, to be published. YAMAGUCHI, H. OHTAKI, Bull. Chem. Soc. Jpn., 52, 3539 (1979). [6] T. FUJITA, H. OHTAKI, Bull. Chem. Soc. Jpn., 53, 930 H. OHTAKI, Bull. Chem. Soc. Jpn., 55, (1980). [7] T. FunTA, 455 (1982). [8] T. FunTA, H. (1983). OHTAKI, Rev. Port. Quím., 27 (1985) Bull. Chem. Soc. Jpn., 56, 3276 6?) SL6 — MO H. KOZMWSKI G. FORMICKA-KOZCOWSKA Institute of Chemistry University of Wroclaw Joliot-Curie 14, 50-383 Wroclaw Poland L.D. PETTIT I. STEEL School of Chemistry University of Leeds LS2 9JT Leeds England CAN COPPER(II) IONS ACTIVATE BIOLOGICALLY SMALL PEPTIDE MOLECULES? Many small peptide molecules show very high biological activity, particularly in the central nervous system where many are active as neurotransmitters or as opioids. Very frequently these peptides contain proline or tyrosine residues. Copper is a biologically essential element which is distributed unevenly throughout the body, with relatively high concentrations being found in the brain. In some cases traces of copper have been shown to increase the activity of biologically active small molecules (e.g. aspirin and cimetidine [ 1 , 2]). The biologically active form of oligopeptides is usually of an organized structure containing e.g. one or more beta-turns. The proline residue encourages the formation of such beta-turns [3] and is unique among biological peptide residues in that it contains a secondary nitrogen atom which, when part of a peptide chain, is not bonded to an ionizable proton and hence cannot coordinate to copper(II). It therefore acts as a «break-point» to metal coordination since it allows the two ends of the chain to coordinate independently. Since a proline residue also encourages a beta-turn, the effect is to bring the two chains close together where they can be bridged by a copper ion [4-6]. Hence the copper can be regarded as locking the 19 SESSION LECTURES peptide into the biologically active conformation, so promoting its biological activity ]7]. The specificity of a proline residue as a «break-point» is also seen in its influence on the binding capability of other amino acid residues present in the peptide sequence, such as tyrosine [8] and lysine [9] residues. The involvement of ionized tyrosine phenolate oxygen in metal ion binding may be an important factor in peptides which display opioid activity such as casomorphin [10]. Copper(II) ions can also affect adversely the biological activity of peptides by binding (and so blocking) their active residues or can promote the activity by «bridging» the peptide to its receptors. This latter situation is most likely in the case of metal-TRF system [11,12]. KENNETH D. KARLIN YILMA GULTNEH RICHARD W. CRUSE JON C. HAYES JON ZUBIETA Department of Chemistry State University of New York (SUNY) at Albany Albany New York, 12222 U.S.A. DIOXYGEN BINDING AND ACTIVATION IN DINUCLEAR COPPER COMPLEX SYSTEMS REFERENCES L.W. OBERLEY, V. KISHORE, S.W.C. T.D. OBERLEY, A. PEZESHK, Inorg. Chim. Acta, 79, 45 (1983). [2] F.T. GREENAWAY, L.M. BROWN, J.C. DABROWIAK, M.R. THOMPSON, V.M. DAY, J. Am. Chem. Soc., 102, 7782 (1980). [3] R.Y. CHOU, G.D. FASMAN, J. Mol. Biol., 115, 135 (1977); M. LISOWSKI, LZ. SIEMION, K. SOBCZYK, Int. J. Pept. Protein Res., 21, 301 (1983) and references therein. [1] J.R.J. SL7 — MO SORENSON, LEUTHAUSER, [4] G. FORMICKA-KOZrAWSKA, MION, K. E. SOBCZYK, H. KOZrnwsKI, 1.Z. SIE- NAWROCKA, J. Inorg. Biochem., 15, 201 (1981). [5] M. BATAILLE, G. FORMICKA-KOZLOWSKA, H. KosroL.D. PETTIT, 1 . STEEL, J. Chem. Soc., Chem. Commun., 231 (1984). [6] L.D. PETTIT, 1 . STEEL, G. FORMICKA-KOZrOWSKA, T. wSKI, TATAROWSKI, M. BATAILLE, J. Chem. Soc., Dalton Trans., in press. [7] L.D. PETTIT, G. FORMICKA-KOZCOWSKA, Neuroscience Letters, 50, 53 (1984). [8] H. B. KOZPDWSKI, M. BEZER, HECQUET, [9] M. T. BATAILLE, L.D. TATAROWSKI, [10] G. L.D. PETTIT, M. BATAILLE, J. Inorg. Biochem., 18, 231 (1983). PETTIT, I. STEEL, H. KOZLOWSKI, J. Inorg. Biochem., in press. FORMICKA-KOZIDWSKA, L.D. PETTIT, 1. STEEL, B. K. NEUBERT, P. REKOWSKI, G. KUPRYSZEWSKI, J. Inorg. Biochem., 22, 155 (1984). [11] G. FORMICKA-KOZLOWSKA, L.D. PETTIT, M. BEZER, J. Inorg. Biochem., 18, 335 (1983). [12] T. TONOUE, S. MINAGAWA, N. KATO, K. OHKI, Pharmacol. Biochem. Behav., 10, 201 (1979). HARTRODT, Studies of the reactivity of dioxygen with model mono- and dinuclear copper(I) centers are of interest because of their relevance to the copper proteins such as hemocyanin, a dioxygen carrier, and tyrosinase and dopamine beta-hydroxylase which are monooxygenases involved in oxygen activation [1]. Such model studies may also help in the development of synthetic reagents or catalysts for the oxidation of organic substrates. Here, we will summarize our latest findings in several systems involving Cu(I)-dioxygen interactions or reactivity. The first deals with a monooxygenase model system where the reaction of dioxygen with a dinuclear Cu(I) complex II results in the oxygenation of the ligand and concomitant formation of the phenoxo- and hydroxo- bridged dinuclear complex III. Studies using isotopically labelled dioxygen and the observed stoichiometry of reaction (Cu:0 2 = 2:1) demonstrate that this reaction is directly analogous to that shown by the copper mono-oxygenase enzymes [2]. Recent insights into the mechanism of this reaction will be presented. The reaction of a dinuclear z NM^ - zw" Y rN 0 N ` ^/\ ) PY \ (\-% PY- PY pYCu - PY II 20 CHxCPx N 0 /1 PY l ^ H 1N /\5u PY^Cu •,) \ PY PY PY F1 PY IY 1II Rev. Port. Quim., 27 (1985)