Synthesis and triiron complexes of PDK, a new porphyrin-linked dicarboxylate ligand

Full text of DOI:10.1021/ja9816990

10260
J. Am. Chem. Soc. 1998, 120, 10260-10261
Synthesis and Triiron Complexes of PDK, a New
Porphyrin-Linked Dicarboxylate Ligand
nobis(Kemp’s triacid imide), and the preparation, structural
characterization, and preliminary reactivity studies of several
triiron PDK complexes.
Xiao-Xiang Zhang, Peter Fuhrmann, and Stephen J. Lippard*
The target ligand, R,R-5,15-bis(R-N-(Kemp’s triacid imido)-
o-tolyl)-2,8,12,18-tetraethyl-3,7,13,17-tetramethylporphyrin, H -
4
Department of Chemistry
Massachusetts Institute of Technology
Cambridge, Massachusetts 02139
(R,R-PDK), was synthesized by first coupling Kemp’s triacid
anhydride-chloride and a bis(diaminomethyl)phenyl-substituted
2
porphyrin in a manner similar to that employed for preparing H -
9,20
(
XDK), Scheme 1.1
The dimeso-substituted octaalkylporphyrin
ReceiVed May 18, 1998
unit 3, carrying a bromomethyl group at the ortho positions of
the two meso-phenyl groups, was obtained from (3,3′-diethyl-
4,4′-dimethyl-2,2′-dipyrrolyl)methane (2) and R-bromo-o-tolual-
dehyde (1). Porphyrins 3, a mixture of R,R- and R,â-atropiso-
mers, were separated by flash column chromatography on silica
gel. The structures of both R,R- and R,â-isomers, obtained as
the zinc complex and free base, respectively, of bromoporphyrin
3 were unambiguously identified by crystallographic chemical
analysis (Figures S1-S4, Supporting Information). The R,R-
isomer of bromomethyl porphyrin 3 was converted to its ami-
nomethyl derivative 5 through the intermediate imidoporphyrin
Many challenging chemical transformations are mediated by
metalloenzymes having two or more metal ions in close proxim-
ity.1 Carboxylate-bridged diiron centers in soluble methane
monooxygenase (sMMO) and ribonucleotide reductase (RNR)2
are two such examples where dioxygen is activated for subsequent
hydroxylation and tyrosyl radical generation reactions, respec-
tively. In sMMO, the chemistry is carried out at dinuclear iron
centers located within the hydroxylase enzyme, but electrons
required for catalytic turnover are supplied by a separate reductase
-4
5
protein. Previously, we reported the use of the convergent
dicarboxylate ligand XDK, where H XDK is m-xylylenediamine
2
bis(Kemp’s triacid imide), to assemble carboxylate-bridged diiron
complexes that mimic the properties of the sMMO and RNR
4
by Gabriel synthesis. The R,R-bis(aminomethyl)porphyrin 5
was then coupled with Kemp’s triacid anhydride-chloride to afford
(R,R-PDK) in overall ∼10% yield and gram quantities.
The triiron(II) complex [Fe (R,R-PDK)(Lut)(Br) (HBr)] was
obtained in 71% yield by reacting H (R,R-PDK) with anhydrous
FeBr in the presence of 2,6-lutidine in THF at reflux under an
inert atmosphere (Scheme 1).
H
4
active sites.6
-8
In the present study, we were interested in
designing and preparing a ligand in which the m-xylylenediamine
linker of XDK was replaced by a metalloporphyrin moiety. Such
a construct would have the potential to activate dioxygen and
other small molecules within a trimetallic cavity while offering
the possibility to supply additional reducing equivalents such as
the reductase in the sMMO system. Although complexes in which
a metalloporphyrin is linked to a second metal-binding functional-
3
2
4
2
2
1-23
An X-ray crystal structure
determination (Figure 1) revealed that iron had both inserted into
the porphyrin and formed the desired carboxylate-bridged di-
2
+
nuclear unit, {Fe
2
2 2
(µ-O CR) } . The coordination sphere of one
9
-12
ity have been of recent interest
and several porphyrin
iron atom in the latter unit is completed by a terminal halide ion
and the nitrogen atom of a 2,6-lutidine ligand. The other non-
heme iron atom is coordinated to a bromide ion, Br(1), and to
the bromine atom, Br(3), tentatively assigned (see below) to an
HBr molecule produced in the reaction and housed in the cavity
formed by the three iron atoms. The dimensions of the cavity
are defined by the distances Fe(1)‚‚‚Fe(2) ) 5.490(3) Å,
Fe(1)‚‚‚Fe(3) ) 4.494(3) Å, and Fe(2)‚‚‚Fe(3) ) 3.744(3) Å. The
bromine atom Br(3) also weakly coordinates to the heme iron,
Fe(1), expanding its coordination number to 5, and the hydrogen
atom H(001) appears to interact with Fe(2), allowing it also to
achieve 5-coordination. Steric protection within the cavity is
afforded in part by the two methyl carbon atoms of the ligand,
C(104) and C(204), which are within van der Waals contact of
one another at 3.78 Å (Figure S5). A similar triiron complex
compounds containing an appended Kemp’s triacid1 unit have
been synthesized for the purpose of molecular recognition,1
there was no prior example of the kind of trinucleating system
we envisioned. Herein we report the efficient synthesis of the
desired ligand, designated R,R-PDK for porphyrin-based diami-
3,14
5-18
[
FeI
Fe
3
(R,R-PDK)(Lut)(I)
2
2
(HI)] was obtained when using anhydrous
as the iron source. An X-ray crystal structure determination
(
1) Lippard, S. J.; Berg, J. M. Principles of Bioinorganic Chemistry;
(Figures S6 and S7) revealed essentially the same geometry as
in the bromide analogue (Supporting Information).
University Science Books: Mill Valley, CA 94941, 1994.
(
(
(
(
(
2) Feig, A. L.; Lippard, S. J. Chem. ReV. 1994, 94, 759-805.
3) Que, L., Jr.; Dong, Y. H. Acc. Chem. Res. 1996, 29, 190-196.
4) Wallar, B. J.; Lipscomb, J. D. Chem. ReV. 1996, 96, 2625-2657.
5) Lund, J.; Dalton, H. Eur. J. Biochem. 1985, 147, 291-296.
6) LeCloux, D. D.; Barrios, A. M.; Mizoguchi, T. J.; Lippard., S. J. J.
(15) Liang, Y.; Chang, C. K. Tetrahedron Lett. 1995, 36, 3817-3820.
(16) Chang, C. K.; Liang, Y.; Aviles, G.; Peng, S.-M. J. Am. Chem. Soc.
1995, 117, 4191-4192.
Am. Chem. Soc. 1998, 120, 9001-9014.
(17) Shipps, G.; Rebek, J., Jr. Tetrahedron Lett. 1994, 35, 6823-6826.
(18) Lindsey, J. S.; Kearney, P. C.; Duff, R. J.; Tjivikua, P. T.; Rebek, J.,
Jr. J. Am. Chem. Soc. 1988, 110, 6575-6577.
(
(
7) Herold, S.; Lippard, S. J. J. Am. Chem. Soc. 1997, 119, 145-156.
8) Watton, S. P.; Masschelein, A.; Rebek, J., Jr.; Lippard, S. J. J. Am.
Chem. Soc. 1994, 116, 5196-5205.
(19) Rebek, J. J.; Marshall, L.; Wolak, R.; Parris, K.; Killoran, M.; Askew,
B.; Nemeth, D.; Islam, N. J. Am. Chem. Soc. 1985, 107, 7476.
(20) Zhang, X.-X.; Lippard, S. J., unpublished results.
(
9) Lee, S. C.; Holm, R. H. J. Am. Chem. Soc. 1993, 115, 5833-5834.
10) Nanthakumar, A.; Fox, S.; Karlin, K. D. J. Chem. Soc., Chem.
(
Commun. 1995, 499-510.
(21) Collman, J. P.; Herrmann, P. C.; Boitrel, B.; Zhang, X. M.; Eber-
spacher, T. A.; Fu, L.; Wang, J. L.; Rousseau, D. L.; Williams, E. R. J. Am.
Chem. Soc. 1994, 116, 9783-9784.
(22) Collman, J. P.; Zhang, X.; Herrmann, P. C.; Uffelman, E. S.; Boitrel,
B.; Straumanis, A.; Brauman, J. I. J. Am. Chem. Soc. 1994, 116, 2681-2682.
(23) Collman, J. P.; Herrmann, P. C.; Fu, L.; Eberspacher, T. A.; Eubanks,
M.; Boitrel, B.; Hayoz, P.; Zhang, X. M.; Brauman, J. I.; Day, V. W. J. Am.
Chem. Soc. 1997, 119, 3481-3489.
(
11) Martens, C. F.; Murthy, N. N.; Obias, H. V.; Karlin, K. D. Chem.
Commun. 1996, 629-630.
12) Collman, J. P.; Fu, L.; Herrmann, P. C.; Zhang, X. M. Science 1997,
(
2
75, 949-951.
(
(
13) Kemp, D. S.; Petrakis, K. S. J. Org. Chem. 1981, 46, 5140-5143.
14) Rebek, J. Jr.; Askew, B.; Killoran, M.; Nemeth, D.; Lin, F.-T. J. Am.
Chem. Soc. 1987, 109, 2426.
S0002-7863(98)01699-0 CCC: $15.00 © 1998 American Chemical Society
Published on Web 09/17/1998

Communications to the Editor
J. Am. Chem. Soc., Vol. 120, No. 39, 1998 10261
to deprotonate the porphyrin and carboxylic acid functionalities.
The assignment of this feature was supported by satisfactory
elemental analysis and several additional lines of evidence. The
M o¨ ssbauer spectrum of solid [Fe
displays two overlapping quadrupole doublets with isomer shifts
3
2
(R,R-PDK)(Lut)(Br) (HBr)]
characteristic of three high-spin Fe(II) centers (doublet A: δ )
1
)
.08 mm/s, ∆E
Q
) 2.05 mm/s; doublet B: δ ) 1.09 mm/s, ∆E
Q
2.48 mm/s; area ratio: doublet A/doublet B ) 2/1; 77 K). These
six positive charges are balanced by four negative charges from
the tetraanionic PDK ligand and the two terminal bromide ligands.
Unless residual electron density in the crystal lattice modeled as
pentane is some unidentified cation, an unlikely possibility in view
of the analytical data, the central halide ion or some other ligand
residue must be protonated. A peak corresponding to H(001)
was located between X(3) and Fe(2) in the difference Fourier
maps at the position indicated in Figure 1 which behaved well
for X ) Br when assigned as a hydrogen atom in subsequent
least-squares refinements of the structure. This result alone is
insufficient to support its location, however, since alternative sites
could not be excluded. Accurate positioning and identification
of the H atom will have to await the results of a more definitive
neutron diffraction analysis, if large enough crystals can be grown.
Figure 1. ORTEP showing 30% probability thermal ellipsoids for non-
3 2
hydrogen atoms of [Fe (R,R-PDK)(Lut)(Br) (HBr)]. For clarity, hydrogen
atoms except H(001), the carbon atoms of the coordinated 2,6-lutidine,
all of the atoms of R,R-PDK except for the carboxylate group plus the
R-carbon atoms and the porphyrin core have been omitted. Selected
interatomic distances (Å) and angles (deg): Fe(1)sBr(3), 2.567(2); Fe-
A series of related, trinuclear PDK complexes, [M
3
(R,R-PDK)-
+
j
(µ -X)(L1) (L2) ] , M ) Mn, Fe, Co, Ni, Cu, and/or Zn; X )
i m n
-
Br, Cl, or F; L1, L2 ) Lut, py, THF, H O, and/or OTf ; i ) 2
2
or 3; m ) 1 or 2; n ) 1 or 2; j ) 0 or 1), have also been prepared
(
(
2)sN(401), 2.133(10); Fe(2)sO(102), 2.004(9); Fe(2)sO(202), 2.013-
9); Fe(2)sBr(2), 2.456(2); Fe(2)sH(001), 1.63(16); Fe(3)sBr(1),
and structurally characterized. They too have metals inserted into
the porphyrin and contain the desired carboxylate-bridged di-
2
2
.366(2); Fe(3)sBr(3), 2.495(2); Fe(3)sO(101), 2.011(9); Fe(3)sO(201),
.003(8); Br(3)sH(001), 1.50(16); N(401)sFe(2)sO(102), 128.6(4);
2+
nuclear unit, {M
Fe (R,R-PDK)(Lut)(Br)
these reactions are currently under investigation.
In conclusion, the complexes [Fe (R,R-PDK)(Lut)(X)
X ) Br or I) represent the first examples of triiron species which
bring together features of both heme iron and carboxylate-bridged
2
(µ-O
2 2
CR) } . Preliminary studies reveal that
(HBr)] reacts with O , CO, and NO, and
2 2
[
3
N(401)sFe(2)sO(202), 121.3(4); O(102)sFe(2)sO(202), 102.4(4); Br-
(
(
2)sFe(2)sN(401), 95.3(3); Br(2)sFe(2)sO(102), 99.0(3); Br(2)sFe-
2)sO(202), 104.2(2); H(001)sFe(2)sN(401), 89(5); H(001)sFe(2)s
3
2
(HX)]
(
O(102), 75(5); H(001)sFe(2)sO(202), 79(5); Br(2)sFe(2)sH(001),
74(5); Br(1)sFe(3)sBr(3), 106.94(8); Br(1)sFe(3)sO(101), 130.1(3);
1
1
1
non-heme diiron metalloenzyme cores in a single entity. They
offer the possibility of comparing directly the reactivity of these
two major types of biological iron and of achieving new chemistry
not available for either center in isolation. The proposed binding
mode of the HX molecule has implications for several areas of
current interest, including transition-state theory, small molecule
Br(1)sFe(3)sO(201), 104.9(3); Br(3)sFe(3)sO(101), 102.1(3); Br(3)s
Fe(3)sO(201), 119.4(3); O(101)sFe(3)sO(201), 94.7(4); Br(3)sH(001)s
Fe(2), 167(5); Fe(1)sBr(3)sFe(3), 125.20(8); Fe(1)sBr(3)sH(001),
1
57(5); Fe(3)sBr(3)sH(001), 77(6). See text for discussion of H(001)
identification and placement.
24-27
Scheme 1
activation, and hydrogen bonding in organometallic systems.
The nonplanar conformational distortion of the porphyrin core
caused by formation of the carboxylate-bridged diiron unit {Fe (µ-
and other chemical and structural details will be
2
2
+
O
2
CR)
2
}
20
discussed in more detail elsewhere.
Acknowledgment. This work was supported by grants from the
National Science Foundation, National Institute of General Medical
Science and AKZO. We thank Professor C. K. Chang at Michigan State
University for providing us with the dipyrrolylmethane starting material
and Dr. T. J. Mizoguchi for collecting and analyzing the M o¨ ssbauer data.
X.-X.Z. is grateful to the National Institutes of Health for support under
training grant CA09112 and for postdoctoral fellowship GM18375.
Supporting Information Available: Synthetic and X-ray structural
details for all compounds (71 pages, print/PDF). See any current
masthead page for ordering information and Web access instructions.
JA9816990
(
24) Crabtree, R. H.; Siegbahn, P. E. M.; Eisenstein, O.; Rheingold, A. L.;
Koetzle, T. F. Acc. Chem. Res. 1996, 29, 348-354.
25) Peris, E.; Lee, J. C.; Rambo, J. R.; Eisenstein, O.; Crabtree, R. H. J.
Am. Chem. Soc. 1995, 117, 3485-3491.
26) Braga, D.; Grepioni, F.; Tedesco, E.; Biradha, K.; Desiraju, G. R.
Organometallics 1997, 16, 1846-1856.
27) Murphy, V. J.; Hascall, T.; Chen, J. Y.; Parkin, G. J. Am. Chem. Soc.
1996, 118, 7428-7429.
(
(
The presence of a neutral HX molecule in the cavity of the
R,R-PDK ligand was unexpected, especially since the reaction
was carried out in the presence of excess lutidine added as a base
(