A bulky benzoate ligand for modeling the carboxylate-rich active sites of non-heme diiron enzymes [10]

Full text of DOI:10.1021/ja983333t

J. Am. Chem. Soc. 1998, 120, 13531-13532
13531
Scheme 1
A Bulky Benzoate Ligand for Modeling the
Carboxylate-Rich Active Sites of Non-Heme Diiron
Enzymes
John R. Hagadorn, Lawrence Que, Jr.,* and
William B. Tolman*
Department of Chemistry and Center for Metals
in Biocatalysis, UniVersity of Minnesota
207 Pleasant St. SE, Minneapolis, Minnesota 55455
ReceiVed September 18, 1998
A growing class of biologically important catalysts are the
dioxygen-activating non-heme diiron enzymes, noteworthy mem-
bers of which include methane monooxygenase (MMO), ribo-
nucleotide reductase (RNR), and stearoyl-ACP ∆9-desaturase
(∆9D).1 Carboxylate ligation to the diiron active site of these
enzymes is a common feature that allows for tremendous structural
flexibility during catalysis (via carboxylate shifts)2 and helps
stabilize the high oxidation states proposed for the intermediates
involved in the various reaction cycles. Previous synthetic routes
to diiron models of the biological centers have used polydentate
N-donors with simple unhindered carboxylates1b,f or semirigid
linked derivatives (cf. the xylyl-bridged ligand derived from
Kemp’s triacid).3 We have begun to pursue an alternative strategy
(albeit one with precedence in the organometallic chemistry
literature)4 involving the use of extreme steric hindrance about
the carboxylate ligand in order to control metal complex nucle-
arity, to stabilize biorelevant dioxygen adducts and derived
intermediates, and to mimic the protein scaffold that encapsulates
the metalloprotein active site. Here we report a new, very bulky
benzoate ligand5 that has enabled the preparation of coordinatively
unsaturated mono- and dinuclear iron(II) complexes, the latter
of which accurately mimics the structural characteristics of the
reduced forms of ∆9D6 and RNR.7 Additionally, studies of the
reactivity of this complex with dioxygen have revealed the
generation of a room-temperature stable purple species which
spectroscopic data suggest is a (µ-peroxo)diiron(III) complex.
-
The bulky carboxylate 2,6-dimesitylbenzoate (Mes2ArCO2
,
Scheme 1) was prepared from 2,6-Mes2C6H3I8 (Mes ) 2,4,6-
trimethylphenyl) by lithiation9 with BuLi followed by reaction
with dry CO2 in Et2O. The product was isolated in 82% yield as
the Et2O adduct [(Mes2ArCO2)Li(Et2O)]2 and characterized fully,
including by X-ray crystallography (Figure S1 and S2).10,11 The
extreme steric bulk of the ligand derived from the enforcement
of an orthogonal relationship between the Mes rings and the
benzoate aryl unit results in a dimeric structure distinct from the
polymeric topologies typically adopted by smaller carboxylates.12
The reaction of 1 equiv of [(Mes2ArCO2)Li(Et2O)]2 with FeCl2
or Fe(OTf)2 in CH2Cl2 in the presence of 1-methylimidazole
(MeIm) gave [(Mes2ArCO2)2Fe(MeIm)2] as colorless crystals
(Scheme 1); the same product was formed irrespective of the
amount of MeIm used (1 equiv or an excess).10 X-ray structural
characterization (Figure 1a) revealed a pseudo-tetrahedral iron
center coordinated to two carboxylates, each in monodentate
fashion with one short Fe-O distance (av 2.01 Å) and one much
longer [2.544(2) Å and 3.263(2) Å]. The influence of the large
carboxylate is manifested by a bowl-like cavity lined by the Mes
rings which only allows for the binding of two MeIm ligands.
The resulting low coordination number (CN) of 4 for the complex
contrasts with the higher CNs for related structurally characterized
complexes such as [Fe(O2CCH3)2(py)4] and [Fe2(O2CR)4(py)2] (R
) CMe3, Ph; py ) pyridine).13
(1) (a) Wallar, B. J.; Lipscomb, J. D. Chem. ReV. 1996, 96, 2625-2658.
(b) Feig, A. L.; Lippard, S. J. Chem. ReV. 1994, 94, 759-805. (c) Que, L., Jr.
J. Chem. Soc., Dalton Trans. 1997, 3933-3940. (d) Lange, S. J.; Que, L., Jr.
Curr. Opin. Chem. Biol. 1998, 2, 159-172. (e) Kurtz, D. M., Jr. J. Biol. Inorg.
Chem. 1997, 2, 159-167. (f) Que, L., Jr.; True, A. E. Prog. Inorg. Chem.
1990, 38, 97-200.
When the smaller N-donor CH3CN (as a 5:1 toluene/CH3CN
mixture) was used in the synthesis instead of MeIm, the diiron-
(II) complex [(Mes2ArCO2)4Fe2(CH3CN)2] was isolated (Scheme
1).10 Its X-ray crystal structure (Figures 1b and 2) shows identical
iron sites related by a crystallographic inversion center, each
having a square pyramidal geometry (τ ) 0.04) with the CH3CN
ligand occupying the apical position and the remaining sites
occupied by the O atoms of the bidentate bridging or chelating
carboxylates. The space-filling model (Figure 2) dramatically
displays the steric “wall” imposed by the mesityl groups, forming
a hindered interior pocket just large enough to fit the rod-shaped
CH3CN ligands (revealed by removal of a Mes group in Figure
2b) that are forced to adopt bent geometries [cf. Fe(1)-N(1)-
C(51) ) 125.6(2)°]. The most remarkable aspect of the structure
is the similarity it possesses to the reduced forms of the active
sites of ∆9D and RNR-R2 (Figure S5).6,7 In addition to similar
ligand environments (one N-donor and a chelating carboxylate
per Fe, with two bidentate carboxylate bridges), the Fe-Fe
distances are all approximately 4 Å [(Mes2ArCO2)4Fe2(CH3CN)2,
4.122(1) Å; ∆9D, 4.2 Å; RNR-R2, 3.9 Å] due to their closely
analogous carboxylate bridging geometries. 1H NMR spectroscopy
shows a downfield signal at 50 ppm which disappears upon the
addition of CD3CN (in CDCl3 solution), demonstrating that the
nitrile remains coordinated in solution but is susceptible to
exchange despite its encapsulation by the steric wall of mesityl
goups.14
(2) Rardin, R. L.; Tolman, W. B.; Lippard, S. J. New J. Chem. 1991, 15,
417-430.
(3) (a) LeCloux, D. D.; Barrios, A. M.; Mizoguchi, T. J.; Lippard, S. J. J.
Am. Chem. Soc. 1998, 120, 9001-9014. (b) Herold, S.; Lippard, S. J. J. Am.
Chem. Soc. 1997, 119, 145-156. (c) Herold, S.; Pence, L. E.; Lippard, S. J.
J. Am. Chem. Soc. 1995, 117, 6134-6135. (d) Hagen, K. S.; Lachicotte, R.;
Kitaygorodskiy, A.; Elbouadili, A. Angew. Chem., Int. Ed. Engl. 1993, 32,
1321-1324.
(4) Selected reviews of low-coordinate transition metal complexes contain-
ing bulky ligands: (a) Power, P. P. Comments Inorg. Chem. 1989, 8, 177-
202. (b) Cummins, C. C. Prog. Inorg. Chem. 1998, 47, 685-836.
(5) For studies using related ligands for the preparation of dirhodium(II)
complexes, see: (a) Cotton, F. A.; Thompson, J. L. Inorg. Chim. Acta 1984,
81, 193-203. (b) Callot, H. J.; Albrecht-Gary, A.-M.; Al Joubbeh, M.; Metz,
B.; Metz, F. Inorg. Chem. 1989, 28, 3633-3640.
(6) Lindqvist, Y.; Huang, W.; Schneider, G.; Shanklin, J. EMBO J. 1996,
15, 4081-4092.
(7) Logan, D. T.; Su, X.-D.; Aberg, A.; Regnstrom, K.; Hajdu, J.; Eklund,
H.; Nordlund, P. Structure 1996, 4, 1053-1064.
(8) Du, C.-J. F.; Hart, H.; Ng, K.-K. D. J. Org. Chem. 1986, 51, 3162-
3165.
(9) Ruhlandt-Senge, K.; Ellison, J. J.; Wehmschulte, R. J.; Pauer, F.; Power,
P. P. J. Am. Chem. Soc. 1993, 115, 11353-11357.
(10) Synthetic procedures and characterization data for all compounds are
provided in the Supporting Information.
(11) Similar bulky carboxylates have been reported: (a) Lu¨ning, U.;
Wangnick, C.; Peters, K.; von Schnering, H. G. Chem. Ber. 1991, 124, 397-
402. (b) Chen, C.-T.; Siegel, J. S. J. Am. Chem. Soc. 1994, 116, 5959-5960.
(12) (a) Kansikas, J.; Hermansson, K. Acta Crystallogr. 1989, C45, 187-
191. (b) Galigne´, P. J. L.; Mouvet, M.; Falgueirettes, J. Acta Crystallogr.
1970, B26, 368-372. (c) Plattner, D. A.; Petter, W.; Seebach, D. Chimia 1994,
48, 138-141.
(13) (a) Singh, B.; Long, J. R.; Papaefthymiou, G. C.; Stavropoulos, P. J.
Am. Chem. Soc. 1996, 118, 5824-5825. (b) Randall, C. R.; Shu, L.; Chiou,
Y.-M.; Hagen, K. S.; Ito, M.; Kitajima, N.; Lachicotte, R. J.; Zange, Y.; Que,
L., Jr. Inorg. Chem. 1995, 34, 1036-1039.
Like the diiron(II) sites in the enzymes, [(Mes2ArCO2)4Fe2(CH3-
CN)2] reacts rapidly with O2.15 Oxygenation (1 atm) of a solution
10.1021/ja983333t CCC: $15.00 © 1998 American Chemical Society
Published on Web 12/11/1998

13532 J. Am. Chem. Soc., Vol. 120, No. 51, 1998
Communications to the Editor
Figure 3. UV-vis spectra of (Mes2ArCO2)4Fe2(CH3CN)2 (dashed line)
and the product of its oxygenation (solid line) in CH2Cl2 (0.55 mM) at
-50 °C. Inset: difference resonance Raman spectrum of the product of
oxygenation (18O2 - 16O2, frozen chlorobenzene, λex ) 514.5 nm).
vibration at 885 cm-1 which shifts by 14 cm-1 upon the use of
18O2. No other isotope-sensitive vibrations were observed. Al-
though energetically consistent with O-O vibrations reported for
known Fe2(µ-1,2-peroxo) complexes16 and recently characterized
diiron enzyme intermediates,17 the isotope shift is much smaller
than expected for a pure O-O stretch.18 There was no evidence
of decay of the purple species after 12 h at -50 °C. Even upon
warming to ambient temperature, the species was quite stable,
decomposing only slowly (t1/2 ≈ 30 h) to a brown solution at 25
°C. The stability of the intermediate undoubtedly stems from the
steric hindrance of the carboxylate ligands that shields the
dioxygen adduct from exogenous agents that would promote its
decay.
In conclusion, we have shown the utility of bulky benzoate
ligands for the preparation of unsaturated, carboxylate-rich, iron-
(II) complexes which were previously inaccessible. The diiron-
(II) derivative readily reacts with molecular oxygen to form a
stable purple species which we tentatively assign as a (µ-peroxo)-
diiron(III) species. Further characterization of this and other
species are in progress.
Figure 1. Representations of the X-ray crystal structures of (a) (Mes2-
ArCO2)2Fe(MeIm)2‚0.5C5H12 and (b) (Mes2ArCO2)4Fe2(CH3CN)2‚C7H8
(50% ellipsoids, hydrogen atoms, and solvate molecules not shown for
clarity). Selected bond distances (Å) for [(Mes2ArCO2)2Fe(MeIm)2]: Fe-
(1)-O(1), 2.028(2); Fe(1)-O(2), 2.544(2); Fe(1)-O(3), 1.989(2); Fe-
(1)-O(4), 3.263(2); Fe(1)-N(1), 2.066(2); Fe(1)-N(3), 2.057(2) Å.
Selected bond distances for [(Mes2ArCO2)4Fe2(CH3CN)2]: Fe(1)-Fe-
(1A), 4.122(1); Fe(1)-O(1), 2.121(2); Fe(1)-O(2), 2.153(2); Fe(1)-O(3),
2.035(2); Fe(1)-O(4A), 2.026(2); Fe(1)-N(1), 2.093(3).
Acknowledgment. We thank the NIH (GM47365 to W.B.T., GM38767
to L.Q., and F32-GM19374 to J.R.H.) and the NSF (NYI Award to
W.B.T.) for financial support. We also are grateful for the assistance of
Dr. R. Y. N. Ho for obtaining resonance Raman spectral data.
Note Added Proof. A related approach was reported recently: Lee,
D.; Lippard, S. J. J. Am. Chem. Soc. 1998, 120, 12153-12154.
Supporting Information Available: Synthetic procedures and char-
acterization and crystallographic data for all new compounds (28 pages,
print/PDF). See any current masthead page for ordering information and
Web access instructions.
JA983333T
(14) In further support of the substitution lability of the CH3CN ligand,
addition of MeIm (1-2 equiv per Fe) converts [(Mes2ArCO2)4Fe2(CH3CN)2]
to [(Mes2ArCO2)2Fe(MeIm)2] (by NMR spectroscopy in CDCl3).
(15) In contrast, the mononuclear complex is unreactive under the same
conditions.
(16) (a) Dong, Y.; Me´nage, S.; Brennan, B. A.; Elgren, T. E.; Jang, H. G.;
Pearce, L. L.; Que, L., Jr. J. Am. Chem. Soc. 1993, 115, 1851-1859. (b)
Kitajima, N.; Tamura, N.; Amagai, H.; Fukui, H.; Moro-oka, Y.; Mizutani,
Y.; Kitagawa, T.; Mathur, R.; Heerwegh, K.; Reed, C. A.; Randall, C. R.;
Que, L., Jr.; Tatsumi, K. J. Am. Chem. Soc. 1994, 116, 9071-9085. (c)
Hayashi, Y.; Kayatani, T.; Sugimoto, H.; Suzuki, M.; Inomata, K.; Uehara,
A.; Mizutani, Y.; Kitagawa, T.; Maeda, Y. J. Am. Chem. Soc. 1995, 117,
11220-11229. (d) Kim, K.; Lippard, S. J. J. Am. Chem. Soc. 1996, 118, 4914-
4915. (e) Dong, Y.; Yan, S.; Young, V. G., Jr.; Que, L., Jr. Angew. Chem.,
Int. Ed. Engl. 1996, 35, 618-620. (f) Ookubo, T.; Sugimoto, H.; Nagayama,
T.; Masuda, H.; Sata, T.; Tanaka, K.; Maeda, Y.; Okawa, H.; Hayashi, Y.;
Uehara, A.; Suziki, M. J. Am. Chem. Soc. 1996, 118, 701-702.
(17) (a) Moe¨nne-Loccoz, P.; Baldwin, J.; Ley, B. A.; Loehr, T. M.;
Bollinger, J. M., Jr. Biochemistry 1998, 37, 14659-14663. (b) Broadwater,
J. A.; Ai, J.; Loehr, T. M.; Sanders-Loehr, J.; Fox, B. G. Biochemistry 1998,
37, 14664-14671.
Figure 2. Top: space-filling representation of [(Mes2ArCO2)4Fe2(CH3-
CN)2] drawn as in Figure 1b, except rotated 90° about the Fe-Fe vector.
Bottom: same view, except one Mes group is omitted to reveal a CH3-
CN ligand (shown with N ) blue, C ) gray, H ) pale blue).
of the complex in CH2Cl2 at -50 °C resulted in the immediate
and irreversible formation of an EPR silent purple species with
λmax ) 540 nm (ꢀ ) 2300 M-1 cm-1, Figure 3), properties similar
to those associated with a number of well-characterized (µ-
peroxo)diiron(III) complexes.16 Characterization by resonance
Raman spectroscopy (Figure 3 insert) reveals an isotope-sensitive
(18) A small isotope shift also was reported for a proposed Fe/Cu O2-
adduct: Collman, J. P.; Herrmann, P. C.; Boitrel, B.; Zhang, X.; Eberspacher,
T. A.; Fu, L.; Wang, X.; Rousseau, D. L.; Williams, E. R. J. Am. Chem. Soc.
1994, 116, 9783-9784.