Download peptide into the biologically active conformation, so promoting its

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