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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) 2nd INTERNATIONAL CONFERENCE ON BIOINORGANIC CHEMISTRY Cu(II) derivative of the ligand I with aqueous hydrogen peroxide also gives high yields of the oxygenated product III. By contrast, neither the reaction of dioxygen with a Cu(I) monomeric analog of I nor the reaction of H 2 0 2 with the Cu(II) form give hydroxylated products. Together, the evidence suggests that a peroxo-bridged dinuclear Cu(II) unit is involved as an intermediate in the reaction of II - III [3]. Thus, due to the interest in stabilizing and characterizing peroxo-Cu(II) compounds (i.e. dioxygen adducts resulting from the addition of 0 2 to Cu(I),), we have studied the intermediate products of the reaction of dioxygen with Cu(I) complexes of dinucleating ligands such as II and IV. We have isolated and structurally characterized a Cu(I) dinuclear complex of ligand IV (V); it S, Cu Cu REFERENCES [1] K.D. KARLIN, ^ pY ^^ V J. ZUBIETA (eds.), «Copper Coordination Chemistry: Biochemical and Inorganic Perspectives», Adenine Press, Guilderland, NY, 1983. [2] K.D. KARLIN, J.C. HAYES, J.W. MCKOwN, J.P. Y. GULTNEH, HUTCHINSON, J. R.W. ZUBIETA, CRUSE, J. Am. Chem. Soc., 106, 2121-2128 (1984). [3] N.J. BLACKBURN, HAYES, Y. K.D. KARLIN, GULTNEH, J. M. CONCANNON, ZUBIETA, J.C. J.C.S. Chem. Commun., 939-940 (1984). [4] K.D. KARLIN, R.W. CRUSE, J.C. GULTNEH, J. ZUBIETA, J. Am. Chem. Soc., 106, 3372-3374 (1984). scs 0\ t N N P adducts (VII) with VI. In addition, they can be formed by reaction with the peroxo- complex VI, resulting in the quantitative release of 0 2 . SL8 — MO L =PPh,,CO S. MARTIN NELSON so Chemistry Department Queen's University N/^PY PY'--" N O \ ^ \ C úCu l ^ ^ L VII Belfast BT9 5AG \ L=PPh^,CO PYN Cúp` ú N ^Py tp ^ py VI contains a bridging phenoxo group and a vacant potential bridging position (Cu...Cu = 3.6 A). Compound V reacts with 0 2 resulting in the formation of a dinuclear Cu(II)-peroxo complex VI that is stable at low temperature. It is characterized by a strong charge-transfer absorption band at 505 nm. Confirmation of the complex's formulation as a peroxo species also comes from resonance Raman spectroscopy [4]. The binding of dioxygen to VI is quasi-reversible, and cycling between V and VI can be achieved and followed spectrophotometrically. Additional evidence for the reversibility of the dioxygen binding equilibrium comes from the reaction of either V or VI with CO or PPh 3 . These form Rev. Port. Quím., 27 (1985) Northern Ireland DI-COPPER COMPLEXES OF MACROCYCLIC LIGANDS AS MODELS FOR TYPE 3 COPPER PROTEINS It is well established that the biological action of many metalloproteins is associated with the occurrence of the metal atoms in pairs or clusters. Prominent amongst these are the copper proteins containing di-copper (Type 3) sites such as the 0 2 -transport protein hemocyanin and oxygenase and oxidase proteins such as tyrosinase, dopamine (3-hydroxylase, laccase, etc. [1]. Studies of synthetic di-copper complexes have contributed to our understanding of the active site chemistry of the natural systems including the nature of the interaction of 0 2 and oxidisable substrates with the dimetallic site [2]. 21