Copper(I) and copper(II) complexes possessing cross-linked imidazole-phenol ligands: Structures and dioxygen reactivity

Article abstract of DOI:10.1021/ja034263f

Catalytic reduction of O₂ to H₂O, and coupling to membrane proton translocation, occurs at the heterobinuclear heme a₃-Cu_B active site of cytochrome c oxidase. One of the Cu_B ligated histidines is cross-linked to a neighboring tyrosine (C-N bond; tyrosine C6 and histidine ε-nitrogen), and the protic residue of this cross-linked His-Tyr moiety is proposed to participate as both an electron and a proton donor in the catalytic dioxygen reduction event. To provide insight into the chemistry of such a moiety, we have synthesized and characterized tetra- and tridentate pyridylalkylamine chelate ligands {L^N4OR and L^N3OR (R = H or Me)}, which include an imidazole-phenol (or anisole) cross-link and their copper(I/II) complexes. [Cu^I(L^N4OH)]B(C₆F₅)₄ (1) reacts with dioxygen at -80 °C in THF, forming an unstable trans-μ-1,2-peroxodicopper(II)complex, which subsequently converts to a dimeric copper(II)-phenolate complex [{Cu(L^N4O^-)}₂](B(C₆F₅)₄)₂ (5a). The close analogue [Cu^I(L^N4OMe)]B(C₆F₅)₄ (3) binds dioxygen reversibly at -80 °C in tetrahydrofuran. Stopped-flow kinetics of the reaction [Cu^I(L^N3OH)]ClO₄ (2) with O₂ in CH₂Cl₂ indicate a steady formation of the purple dimeric product [{Cu(L^N3O^-)}₂](ClO₄)₂ (5b), which has been analyzed in the temperature range from -40 to +20 °C, ΔH? = -9.6 (6) kJ mol^-1, ΔS? = -168 (2) J mol^-1 K^-1 (k_(-40°C) = 1.05(4) × 10⁶ and k_(+20°C) = 4.6(2) × 10⁵ M^-2 s^-1). The X-ray crystal structures of 1, [Cu^II(LN³OH)(MeOH)(OClO₃^-)](ClO₄) (4), 5a, and 5b are reported. Copyright

Full text of DOI:10.1021/ja034263f

Published on Web 04/29/2003
Copper(I) and Copper(II) Complexes Possessing Cross-Linked
Imidazole-Phenol Ligands: Structures and Dioxygen Reactivity
Kaliappan Kamaraj,† Eunsuk Kim,† Benedikt Galliker,§ Lev N. Zakharov,‡ Arnold L. Rheingold,‡
Andreas D. Zuberbu¨hler,§ and Kenneth D. Karlin*,†
Department of Chemistry, The Johns Hopkins UniVersity, Baltimore, Maryland 21218, Department of Chemistry,
UniVersity of Delaware, Newark, Delaware 19716, and Department of Chemistry, UniVersity of Basel,
4056 Basel, Switzerland
Received January 21, 2003; E-mail: karlin@jhu.edu
Cytochrome c oxidase is the terminal respiratory enzyme that
catalyzes the reduction of dioxygen to water and couples this redox
reaction to the membrane translocation of protons for subsequent
use in ATP synthesis.1,2 The O2 binding/reduction site is comprised
of a heme (heme a3) and a copper (CuB) in close association (∼4.5-
5.0 Å). Recent X-ray crystallographic3-6 and biochemical7 studies
reveal that one of the copper-bound histidines is covalently linked
to a tyrosine through a posttranslationally modified cross-link
between C6 of Tyr244 and the ꢀ-nitrogen of His240. The His-Tyr
moiety is proposed to either function in a structural role8,9 or provide
an electron and a proton during the O2-reduction cycle.10-13 There
Figure 1. ORTEP diagrams (50% thermal ellipsoids) showing the cationic
portions of [CuI(LN4OH)]B(C6F5)4 (1) (top) and [CuII(LN3OH)(MeOH)-
are a few recent reports about syntheses and physicochemical
investigations of organic models for the imidazole-phenol moiety;14-20
(OClO3-)](ClO4) (4) (bottom). Selected bond distances (Å): 1, Cu1-N1,
1.973(3); Cu1-N2, 2.191(3); Cu1-N3, 2.098(3); Cu1-N4, 1.944(2), 4,
yet studies of copper complexes of the latter have not been
described. Here, we report the first examples of Cu(I) and Cu(II)
complexes possessing an imidazole-phenol cross-link, their X-ray
structures, and initial chemical insights.
Cu1-N1, 2.012(3); Cu1-N2, 2.001(3); Cu1-N3, 1.954(3), Cu1-O1,
2.323(3); Cu1-O5, 2.012(3). Interatomic distances (Å) between copper and
phenol: 1, Cu1‚‚‚O1, 5.94; 4, Cu1‚‚‚O6, 5.66. Dihedral angles (deg) between
the phenol and imidazole groups: 1, 83.1; 4, 73.0.
distorted trigonal pyramidal with three aromatic nitrogens in the
basal plane, while the Cu(II) ion in 4 is pentacoordinate, having
ligation from the three nitrogens of the chelate plus methanol and
perchlorate donors.28 The imidazole-phenol moiety in both com-
plexes, which includes imidazole-nitrogen copper-ligation, also
yields a proximate phenol to the copper ion. The resulting
Cu‚‚‚(O) distances are in the range of 5-6 Å, analogous to those
in the enzyme X-ray structures.3-6,29 Large dihedral angles (83.1°
and 73.0°) are observed between the phenol and imidazole rings
in 1 and 4, suggesting minimal electronic interaction exists between
the copper ion and the phenol in the solid state. For the proteins or
the simple organic cofactor models studied thus far, these dihedral
angles vary over a wide range, 36-66°.30
The ligands LN4OR and LN3OR were designed to have an
imidazole-phenol (or anisole) cross-link with either a tetra- or a
tridentate pyridylalkylamine-containing chelate, as shown, having
the advantage that we have previously studied copper-dioxygen
chemistry of close analogues.21-26 Syntheses of these ligands and
various copper complexes have been achieved.27 X-ray crystallo-
The redox properties and O2-reactivity of these complexes are
of general interest, because such information may eventually provide
insights into the O2-reduction process occurring at the enzyme CuB
site. We first note that the Cu(II)/Cu(I) redox potentials of [CuI(LN4
-
graphically determined structures of a Cu(I) complex, [CuI(LN4
-
OH)]B(C6F5)4 (1), the anisole analogue [CuI(LN4OMe)]B(C6F5)4 (3),
and [CuI(TMPA)(MeCN)]ClO4 (TMPA ) tris(2-pyridylmethyl)-
amine)21 are nearly identical {E1/2(1) = E1/2(3) = E1/2([CuI(TMPA)-
OH)]B(C6F5)4 (1), and a Cu(II) complex, [CuII(LN3OH)(MeOH)-
(OClO3-)](ClO4) (4), are shown in Figure 1. Both structures reveal
mononuclear copper ion centers. In 1, the Cu(I) geometry is
(MeCN)]+) ) -0.42 V versus FeCp2/FeCp2 in MeCN}. Inde-
+
pendent studies of a closely related imidazole complex (without a
phenol moiety) [(L)CuI]+, L ) [2-(1H-imidazol-4-yl)-ethyl]-bis-
(2-pyridylmethyl)amine, also give E1/2 ) -0.42 V. Thus, the
† The Johns Hopkins University.
‡ University of Delaware.
§ University of Basel.
9
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J. AM. CHEM. SOC. 2003, 125, 6028-6029
10.1021/ja034263f CCC: $25.00 © 2003 American Chemical Society

C O M M U N I C A T I O N S
Scheme 1
and X-ray crystallographic data files (CIF). This material is available
free of charge via the Internet at http://pubs.acs.org.
References
(1) Ferguson-Miller, S.; Babcock, G. T. Chem. ReV. 1996, 96, 2889-2907.
(2) Michel, H.; Behr, J.; Harrenga, A.; Kannt, A. Annu. ReV. Biophys. Biomol.
Struct. 1998, 27, 329-356.
(3) Yoshikawa, S.; Shinzawa-Itoh, K.; Nakashima, R.; Yaono, R.; Yamashita,
E.; Inoue, N.; Yao, M.; Jei-Fei, M.; Libeu, C. P.; Mizushima, T.;
Yamaguchi, H.; Tomizaki, T.; Tsukihara, T. Science 1998, 280, 1723-
1729.
imidazole-phenol (or anisole) cross-links in 1 and 3 do not directly
affect redox properties of copper, as expected from the large
imidazole/phenol dihedral angle (vide supra).31,32
(4) Ostermeier, C.; Harrenga, A.; Ermler, U.; Michel, H. Proc. Natl. Acad.
Sci. U.S.A. 1997, 94, 10547-10553.
(5) Soulimane, T.; Buse, G.; Bourenkov, G. P.; Bartunik, H. D.; Huber, R.;
Than, M. E. EMBO J. 2000, 19, 1766-1776.
Dioxygen reactivities of the CuI complexes were followed by
UV-vis spectroscopy. In THF at -78 °C, [CuI(LN4OMe)] B(C6F5)4
(3) binds O2 reversibly to yield a stable deep purple solution [λmax
) 537 nm (ꢀ ) 9500 M-1 cm-1), 610 nm (ꢀ ) 7500 M-1 cm-1)]
with spectral features indicative of a trans-µ-1,2-peroxodicopper-
(II) complex.21,27 Under the same conditions, introduction of O2 to
a solution of phenol complex [CuI(LN4OH)]B(C6F5)4 (1) gives a
spectrally similar intermediate (λmax ) 537, 610 nm),27 but it is
not stable and converts in minutes to a reddish-purple dimeric
copper(II) complex [{Cu(LN4O-)}2](B(C6F5)4)2 (5a) (λmax ) 510
nm, ꢀ ) 3000 M-1 cm-1) in a nearly quantitative yield (Scheme
1). The structure of the latter phenoxide-bridged dimer has been
confirmed by X-ray crystallography, exhibiting the Cu‚‚Cu distance
at 5.78 Å.27 A similar dimer complex (X-ray structure deter-
mined)27,33 is also obtained from the oxygenation of the tridentate
CuI complex [Cu(LN3OH)]ClO4 (2) (Scheme 1). UV-vis monitored
stopped-flow kinetics of the reaction of 2 with O2 in CH2Cl2
(6) Svensson-Ek, M.; Abramson, J.; Larsson, G.; Tornroth, S.; Brzezinski,
P.; Iwata, S. J. Mol. Biol. 2002, 321, 329-339.
(7) Buse, G.; Soulimane, T.; Dewor, M.; Meyer, H. E.; Blu¨ggel, M. Protein
Sci. 1999, 8, 985-990.
(8) Das, T. K.; Pecoraro, C.; Tomson, F. L.; Gennis, R. B.; Rousseau, D. L.
Biochemistry 1998, 37, 14471-14476.
(9) Pinakoulaki, E.; Pfitzner, U.; Ludwig, B.; Varotsis, C. J. Biol. Chem. 2002,
277, 13563-13568.
(10) Gennis, R. B. Biochim. Biophys. Acta 1998, 1365, 241-248.
(11) Proshlyakov, D. A.; Pressler, M. A.; DeMaso, C.; Leykam, J. F.; DeWitt,
D. L.; Babcock, G. T. Science 2000, 290, 1588-1591.
(12) MacMillan, F.; Kannt, A.; Behr, J.; Prisner, T.; Michel, H. Biochemistry
1999, 38, 9179-9184.
(13) Blomberg, M. R. A.; Siegbahn, P. E. M.; Babcock, G. T.; Wikstro¨m, M.
J. Am. Chem. Soc. 2000, 122, 12848-12858.
(14) McCauley, K. M.; Vrtis, J. M.; Dupont, J.; Van der Donk, W. A. J. Am.
Chem. Soc. 2000, 122, 2403-2404.
(15) Cappuccio, J. A.; Ayala, I.; Elliott, G. I.; Szundi, I.; Lewis, J.; Konopelski,
J. P.; Barry, B. A.; Einarsdottir, O. J. Am. Chem. Soc. 2002, 124, 1750-
1760.
(16) Aki, M.; Ogura, T.; Naruta, Y.; Le, T. H.; Sato, T.; Kitagawa, T. J. Phys.
Chem. A 2002, 106, 3436-3444.
(17) Collman, J. P.; Wang, Z.; Zhong, M.; Zeng, L. J. Chem. Soc., Perkin
Trans. 1 2000, 1217-1222.
(18) Elliott, G. I.; Konopelski, J. P. Org. Lett. 2000, 2, 3055-3057.
(19) Naruta, Y.; Tachi, Y.; Chishiro, T.; Shimazaki, Y.; Tani, F. Acta
Crystallogr., Sect. E: Struct. Rep. Online 2001, E57, o550-o552.
(20) Tomson, F.; Bailey, J. A.; Gennis, R. B.; Unkefer, C. J.; Li, Z.; Silks, L.
A.; Martinez, R. A.; Donohoe, R. J.; Dyer, R. B.; Woodruff, W. H.
Biochemistry 2002, 41, 14383-14390.
indicates a steady formation of the purple dimer product [{Cu(LN3
-
O-)}2](ClO4)2 (5b) (λmax ) 510 nm, ꢀ ) 1300 M-1 cm-1), which
can be readily analyzed in the temperature range from -40 to +20
°C, ∆Hq ) -9.6(6) kJ mol-1, ∆Sq ) -168(2) J mol-1 K-1 (k(-40 °C)
) 1.05(4) × 106 and k(+20 °C) ) 4.6(2) × 105 M-2 s-1. At the lowest
temperatures (-90 °C), there is evidence for an intermediate, whose
UV-vis spectrum (λmax ) ∼360-380 nm) points to the presence
of a µ-η2:η2 side-on peroxo dicopper(II) species.23 Further kinetic
and mechanistic analyses and investigations are needed, but we
suggest that for both 1 and 2, reactions of O2 give peroxo-dicopper-
(II) Cu-O2-Cu intermediates, preorganized for subsequent depro-
tonation of the ligand phenol (LN4OH or LN3OH) and following
formation of dimer products 5a or 5b.34
(21) Tyekla´r, Z.; Jacobson, R. R.; Wei, N.; Murthy, N. N.; Zubieta, J.; Karlin,
K. D. J. Am. Chem. Soc. 1993, 115, 2677-2689.
(22) Wei, N.; Murthy, N. N.; Tyekla´r, Z.; Karlin, K. D. Inorg. Chem. 1994,
33, 1177-1183.
(23) Karlin, K. D.; Kaderli, S.; Zuberbu¨hler, A. D. Acc. Chem. Res. 1997, 30,
139-147.
(24) Zhang, C. X.; Liang, H.-C.; Kim, E.-i.; Shearer, J.; Helton, M. E.; Kim,
E.; Kaderli, S.; Incarvito, C. D.; Zuberbuehler, A. D.; Rheingold, A. L.;
Karlin, K. D. J. Am. Chem. Soc. 2003, 125, 634-635.
(25) Liang, H.-C.; Zhang, C. X.; Henson, M. J.; Sommer, R. D.; Hatwell, K.
R.; Kaderli, S.; Zuberbuehler, A. D.; Rheingold, A. L.; Solomon, E. I.;
Karlin, K. D. J. Am. Chem. Soc. 2002, 124, 4170-4171.
(26) Liang, H.-C.; Karlin, K. D.; Dyson, R.; Kaderli, S.; Jung, B.; Zuberbu¨hler,
A. D. Inorg. Chem. 2000, 39, 5884-5894.
In summary, we have prepared novel copper complexes with
imidazole-phenol cross-links as initial models for the CuB site in
cytochrome c oxidase. We have begun systematic studies on redox
properties, dioxygen reactivity, and other aspects which may be
relevant to the enzyme chemistry.32 Heme-containing models with
appended copper chelates having imidazole-phenol groups are also
being synthesized for investigation.
(27) See Supporting Information.
(28) X-band EPR spectrum of 4 (MeOH, 19 K): g ) 2.06, g| ) 2.26, A| )
173 G.
(29) Cu‚‚O(Tyr) distances are 5.70-5.94,3 5.02,4 5.66,5 and 5.786 Å.
(30) His-Tyr dihedral angles (deg) from enzyme X-ray structures: 44,3 66,4
and 57.5 Dihedral angles (deg) from the organic model compounds: 36.315
and 42.2.19
(31) Only irreversible electrochemical behavior is observed for the tridentate
copper complex 2. Epa ) -0.42 V and Epc ) -0.74 V versus FeCp2/
+
FeCp2 in DMF, ia/ip ) 1.1.
(32) Generation, characterization, and electronic interaction of a Cu(II)-
phenoxyl radical species are currently under investigation.
Acknowledgment. We are grateful to the National Institutes
of Health (K.D.K., GM28962 and GM60353) and the Swiss
National Science Foundation (A.D.Z.) for support of this research.
(33) X-ray quality crystals of 5b were obtained from MeCN/Et2O, giving a
complex with ligated acetonitrile, [{Cu(LN3O-)(MeCN)}2](ClO4)2.
(34) Tests for hydrogen peroxide as expected products were negative, but we
separately observe that 5a and 5b effect the decomposition of H2O2.
Supporting Information Available: Synthetic details, UV-vis
spectra, Eyring kinetic plot, ORTEP diagrams of 5a and 5b (PDF),
JA034263F
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