Published on Web 02/11/2005
Albumin-Conjugated Corrole Metal Complexes: Extremely
Simple Yet Very Efficient Biomimetic Oxidation Systems
Atif Mahammed and Zeev Gross*
Contribution from the Department of Chemistry and Institute of Catalysis Science and
Technology, Technion-Israel Institute of Technology, Haifa 32000, Israel
Received August 1, 2004; Revised Manuscript Received December 23, 2004; E-mail: chr10zg@tx.technion.ac.il
Abstract: An extremely simple biomimetic oxidation system, consisting of mixing metal complexes of
amphiphilic corroles with serum albumins, utilizes hydrogen peroxide for asymmetric sulfoxidation in up to
74% ee. The albumin-conjugated manganese corroles also display catalase-like activity, and mechanistic
evidence points toward oxidant-coordinated manganese(III) as the prime reaction intermediate.
Introduction
strong binding site was identified for the 1:1 conjugates, and
the corresponding dissociation constants were found to be in
The chemistry of corroles has remained quite undeveloped
for decades, which may be appreciated by the very limited
number of reported derivatives and lack of corrole-based
applications.1 Recent years have evidenced three major advances
in the field: new synthetic routes for facile preparation of
triarylcorroles,2 efficient catalysis by the corresponding metal
complexes,3 and unique methodologies for preparation of
amphiphilic corroles.4 Regarding oxidation catalysis, manganese
corroles have received a large amount of attention for three
reasons: (a) the facile isolation of (oxo)manganese(V) corroles;5,6a
(b) the low reactivity of the above and mechanistic puzzles
regarding the identity of other oxygen-transferring intermedi-
ate;5,7 (c) the large increase of catalytic activity upon halogen
substitution of the â-pyrroles.6 In parallel, the amphiphilic bis-
sulfonated corrole 1 (Scheme 1) and its metal complexes were
shown to spontaneously form tightly bound noncovalent con-
jugates with human serum albumin (HSA).8 One particularly
the nanomolar range. These developments suggest that conjuga-
tion of metal complexes of corrole 1 with serum albumins might
be useful for inducing asymmetric catalysis in a biomimetic
fashion: the metal complex being responsible for catalysis and
the protein for a chiral environment. This hypothesis was proven
true: the albumin-conjugated iron and manganese complexes
1-Fe and 1-Mn catalyze the enantioselective oxidation of
prochiral sulfides by hydrogen peroxide to sulfoxides, synthons
of prime importance for asymmetric syntheses (Scheme 1).9
Compared to related biomimetic systems,10,11 this one has the
advantage of relying on the most accessible and cheapest
proteins and on extremely simple working procedures. An
additional outcome of the investigations is concerned with the
mechanism of action, primarily dealing with the identity of the
oxygen-atom-transferring intermediate.
Experimental Section
(1) (a) Paolesse, R. In The Porphyrin Handbook; Kadish, K. M., Smith, K.
M., Guilard, R., Eds.; Academic Press: New York, 2000; Vol. 2, Chapter
11. (b) Erben, C.; Will, S.; Kadish, K. M. In The Porphyrin Handbook;
Kadish, K. M., Smith, K. M., Guilard, R., Eds.; Academic Press: New
York, 2000; Vol. 2, Chapter 12. (c) Sessler, J. L.; Weghorn, S. J. Expanded,
Contacted, and Isomeric Porphyrins; Pergamon: Oxford, 1997.
(2) For the original breakthroughs, see: (a) Gross, Z.; Galili, N.; Saltsman, I.
Angew. Chem., Int. Ed. Engl. 1999, 38, 1427. (b) Paolesse, R.; Jaquinod,
L.; Nurco, D. J.; Mini, S.; Sagone, F.; Boschi, T.; Smith, K. M. Chem.
Commun. 1999, 1307. For recent reviews, see: (c) Gryko, D. T. Eur. J.
Org. Chem. 2002, 1735. (d) Ghosh, A. Angew. Chem., Int. Ed. 2004, 43,
1918.
(3) For a recent review about oxidation catalysis, see: (a) Gross, Z.; Gray, H.
B. AdV. Synth. Catal. 2004, 346, 165. For catalytic cyclopropanation and
aziridination, see: (b) Simkhovich, L.; Mahammed, A.; Goldberg, I.; Gross,
Z. Chem. Eur. J. 2001, 7, 1041. (c) Simkhovich, L.; Gross, Z. Tetrahedron
Lett. 2001, 42, 8089.
Materials. Human serum albumin (essentially fatty acid free), pig
serum albumin (essentially fatty acid free, essentially globulin free),
sheep serum albumin (essentially fatty acid free), bovine serum albumin,
and rabbit serum albumin (essentially fatty acid free) were purchased
from Sigma. All the sulfides and H2O2 (30% in water) were obtained
from Aldrich. The preparation of compound 1 and its manganese(III)
complex 1-Mn was described in previous publications.4
Preparation of 1-Fe: One portion of FeCl2 (30 mg, 23.7 mmol)
was added at once to a pyridine solution (10 mL) of 1 (30 mg, 31.4
µmol), and the mixture was heated immediately to reflux for 5 min
under argon, followed by evaporation of the solvent. The product was
purified by two subsequent silica gel columns (the eluent was methanol
for the first column and ethanol/CH2Cl2 1:1 for the second column),
affording 31 mg (30.7 µmol, 98% yield) of the iron(III) complex
of 1. 19F NMR (CD3OD): δ ) -106.2 (brs, ortho-F), -115.4
(4) (a) Mahammed, A.; Goldberg, I.; Gross, Z. Org. Lett. 2001, 3, 3443. (b)
Saltsman, I.; Mahammed, A.; Goldberg, I.; Tkachenko, E.; Botoshansky,
M.; Gross, Z. J. Am. Chem. Soc. 2002, 124, 7411.
(5) Gross, Z.; Golubkov, G.; Simkhovich, L. Angew. Chem., Int. Ed. 2000,
39, 4045.
(6) (a) Liu, H.-Y.; Lai, T.-S.; Yeung, L.-L.; Chang, C. K. Org. Lett. 2003,
617. (b) Golubkov, G.; Bendix, J.; Gray, H. B.; Mahammed, A.; Goldberg,
I.; DiBilio, A. J.; Gross, Z. Angew. Chem., Int. Ed. 2001, 40, 2132.
(7) (a) Collman, J. P.; Zeng, L.; Decre´au, R. A. Chem. Commun. 2003, 2974.
(b) Wang, S. H.; Mandimutsira, B. S.; Todd, R.; Ramadhanie, B.; Fox, J.
P.; Goldberg, D. P. J. Am. Chem. Soc. 2004, 126, 18.
(9) Ferna´ndez, I.; Khair, N. Chem. ReV. 2003, 103, 3651.
(10) Dembitsky, V. M. Tetrahedron 2003, 59, 4701.
(11) (a) Yang, H. J.; Matsui, T.; Ozaki, S.; Kato, S.; Ueno, T.; Phillips, G. N.,
Jr.; Fukuzumi, S.; Watanabe, Y. Biochemistry 2003, 42, 10174. (b) Hayashi,
T.; Matsuda, T.; Hisaeda, Y. Chem. Lett. 2003, 32, 496. (c) Coulter, E. D.;
Cheek, J.; Ledbetter, A. P.; Chang, C. K.; Dawson, J. H. Biochem. Biophys.
Res. Commun. 2000, 279, 1011.
(8) Mahammed, A.; Gray, H. B.; Weaver, J. J.; Sorasaenee, K.; Gross, Z.
Bioconjugate Chem. 2004, 15, 738.
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10.1021/ja045372c CCC: $30.25 © 2005 American Chemical Society
J. AM. CHEM. SOC. 2005, 127, 2883-2887
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