J. Am. Chem. Soc. 2001, 123, 1513-1514
1513
Scheme 1
“Hangman” Porphyrins for the Assembly of a Model
Heme Water Channel
Chen-Yu Yeh, Christopher J. Chang, and Daniel G. Nocera*
Department of Chemistry, 6-335
Massachusetts Institute of Technology
77 Massachusetts AVenue
Cambridge, Massachusetts 02139
ReceiVed September 1, 2000
ReVised Manuscript ReceiVed NoVember 7, 2000
via hydrogen bonding in the solid state and in solution, as well
as affording a monomeric iron(III) hydroxide porphyrin to be
characterized by single-crystal X-ray analysis.
The heme unit is one of the most ubiquitous and versatile
cofactors found in Nature.1,2 The amazingly diverse reactivities
displayed by heme-dependent enzymes (e.g., O2 transport and
storage,3,4 single outer-sphere electron transfer,5 metabolic oxida-
tion reactions6,7 and O2 reduction8,9) are governed by subtle and
precise changes in the microenvironments imposed by the tertiary
structures of the folded proteins surrounding the active site
porphyrinic cores. In many cases, this exquisite control is exerted
by noncovalent interactions such as hydrogen bonding; an
exemplary system is provided by the cytochrome P450 enzymes.7
Crystallographic studies of this family of monooxygenases give
evidence for the presence of internal solvent water channels that
finely tune heme electronic structure and redox potential, as well
as providing a possible proton-relay pathway during multielectron
catalysis.10-14 However, the challenge of constructing structural
and functional models15-23 for such complex, noncovalent ag-
gregates outside the biological milieu poses a daunting task for
the synthetic chemist. In this communication, we introduce novel,
minimalist heme/water channel models composed of porphyrins
and distal hydrogen-bonding groups anchored in a cofacial manner
to a rigid spacer. These pillared “Hangman” porphyrins have the
distinct ability to orient exogenous water in a controlled fashion
Our interest in the proton-coupled activation of small mol-
ecules24,25 has led us to recently develop methods for the facile
assembly of new symmetric cofacial bisporphyrins based on
dibenzofuran (DPD)26 and xanthene (DPX)27 spacers that exhibit
variable pocket sizes with minimal lateral displacements. A similar
approach may be used to produce asymmetric cofacial architec-
tures in which the rigid xanthene scaffold is used to “hang” a
hydrogen-bonding functionality over the porphyrin macrocycle
(HPX ) hanging porphyrin xanthene, Scheme 1). Porphyrin H2-
(HPX-CO2H) (1) is synthesized via a mixed-aldehyde condensa-
tion under standard Lindsey conditions.28,29 The carboxylic acid
complex provides access to a wide variety of functional groups;
for example, ester and amide derivatives are readily prepared from
1. Metalation of 1 with FeBr2 followed by alkaline workup affords
the corresponding monomeric iron(III)-hydroxide complex Fe-
OH(HPX-CO2H) 2. The steric buttressing provided by the
flanking mesityl groups precludes the formation of bisiron(III)
1
µ-oxo dimers.18,30-32 The H NMR of 2 is consistent with its
formulation as a hydroxide species; the downfield chemical shifts
of the â-pyrrole resonances (80.79, 82.40 ppm) are indicative31
of a monomeric high-spin Fe(III) porphyrin.
(1) Kadish, K. M.; Smith, K. M.; Guilard, R. The Porphyrin Handbook;
Academic Press: San Diego, 2000.
The structure of 2 is confirmed by single-crystal X-ray analysis
(Figure 1); a number of notable features merit discussion here.
To the best of our knowledge, we are unaware of another reported
crystal structure of a monomeric iron(III) hydroxide porphyrin.33
Furthermore, it is interesting to note that the hydrogen-bonding
network promotes selective binding of the axial hydroxide ligand
to the distal side of the HPX platform. The complex adopts a
distorted square pyramidal geometry with the pentacoordinate Fe
elevated 0.4947 Å out of the N4 plane and an average Fe-Npyrrole
bond length of 2.075 Å. The Fe-Ohydroxide bond length of 1.868
Å is shorter than the Fe-O distances found for Fe(III)-aqua
(2) Chapman, S. K.; Daff, S.; Munro, A. W. Structure and Bonding;
Springer-Verlag: Berlin Heidelberg, 1997; Vol. 88, pp 39-70.
(3) Dickerson, R. E.; Geis, I. Hemoglobin: Structure, Function, EVolution,
and Pathology; Benjamin/Cummings: Menlo Park, CA, 1983.
(4) Perutz, M. F. Nature 1970, 228, 726-734.
(5) Scott, R. A.; Mauk, A. G. Cytochrome c: A Multidisciplinary Approach;
University Science Books: Sausalito, CA, 1996.
(6) Sono, M.; Roach, M. P.; Coulter, E. D.; Dawson, J. H. Chem. ReV.
1996, 96, 2841-2887.
(7) Ortiz de Montellano, P. R. Cytochrome P450: Structure, Mechanism,
and Biochemistry, 2nd ed.; Plenum: New York, 1995.
(8) Ferguson-Miller, S.; Babcock, G. T. Chem. ReV. 1996, 96, 2889-2907.
(9) Babcock, G. T.; Wikstro¨m, M. Nature 1992, 356, 301-309.
(10) Poulos, T. L. Curr. Opin. Struct. Biol. 1995, 5, 767-774.
(11) Vidakovic, M.; Sligar, S. G.; Li, H.; Poulos, T. L. Biochemistry 1998,
37, 9211-9219.
(24) Cukier, R. I.; Nocera, D. G. Annu. ReV. Phys. Chem. 1998, 49, 337-
369.
(12) Schlichting, I.; Berendzen, J.; Chu, K.; Stock, A. M.; Maves, S. A.;
Benson, D. E.; Sweet, R. M.; Ringe, D.; Petsko, G. A.; Sligar, S. G. Science
2000, 287, 1615-1622.
(13) Oprea, T. I.; Hummer, G.; Garc´ıa, A. E. Proc. Natl. Acad. Sci. U.S.A.
1997, 94, 2133-2138.
(14) Dmochowski, I. J.; Crane, B. R.; Wilker, J. J.; Winkler, J. R.; Gray,
H. B. Proc. Natl. Acad. Sci. U.S.A. 1999, 96, 12987-12990.
(15) Chang, C. K.; Kondylis, M. P. Chem. Commun. 1986, 316-318.
(16) Chang, C. K.; Liang, Y.; Aviles, G.; Peng, S.-M. J. Am. Chem. Soc.
1995, 117, 4191-4192.
(17) Collman, J. P.; Wang, Z. Chemtracts: Org. Chem. 1999, 12, 229-
263.
(25) Chang, C. J.; Deng, Y.; Shi, C.; Chang, C. K.; Anson, F. C.; Nocera,
D. G. Chem. Commun. 2000, 1355-1356.
(26) Deng, Y.; Chang, C. J.; Nocera, D. G. J. Am. Chem. Soc. 2000, 122,
410-411.
(27) Chang, C. J.; Deng, Y.; Heyduk, A. F.; Chang, C. K.; Nocera, D. G.
Inorg. Chem. 2000, 39, 959-966.
(28) Lindsey, J. S.; Wagner, R. W. J. Org. Chem. 1989, 54, 828-836.
(29) Detailed procedures for the preparation of all ligands and iron
complexes will be described in an upcoming full report. Characterization data
for compound 2 is given here. Anal. Calcd. for C76H84N4O5Fe: C, 76.68; H,
7.20; N, 4.71. Found: C, 76.78; H, 7.19; N, 4.69. HRFABMS (M+), m/z:
calcd for C71H70N4O3Fe, 1082.4797; found, 1082.4824.
(30) Balch, A. L. Inorg. Chim. Acta 1992, 198-200, 297-307.
(31) Cheng, R.; Latos-Grazynski, L.; Balch, A. L. Inorg. Chem. 1982, 21,
2412-2418.
(18) Groves, J. T.; Han, Y. In Cytochrome P450: Structure, Mechanism,
and Biochemistry, 2nd ed.; Ortiz de Montellano, P. R., Ed.; Plenum: New
York, 1995; pp 3-48 and references therein.
(19) Momenteau, M.; Reed, C. A. Chem. ReV. 1994, 94, 659-698 and
references therein.
(32) Calderwood, T. S.; Bruice, T. C. Inorg. Chem. 1985, 25, 3722-3724.
(33) An alternative formulation of the structure is an iron(III)-aqua
complex with a bound hydroxide to a carboxylic acid (or bound water to a
carboxylate). However, the spectral data (NMR and UV-vis) and Fe-O bond
length (see refs 34 and 35) are inconsistent with an iron(III)-aqua formulation.
Buchler and Scheidt have reported the structure of a monomeric iron(III)-
hydroxide complex of a sterically encumbered porphodimethene: Buchler, J.
W.; Lay, K. L.; Lee, Y. J.; Scheidt, W. R. Angew. Chem., Int. Ed. Engl. 1982,
21, 432.
(20) Walker, F. A.; Bowen, J. J. Am. Chem. Soc. 1985, 107, 7632-7635.
(21) Matsui, M.; Higashi, M.; Takeuchi, T. J. Am. Chem. Soc. 2000, 122,
5218-5219.
(22) Matsu-ura, M.; Tani, F.; Nakayama, S.; Nakamure, N.; Naruta, Y.
Angew. Chem., Int. Ed. 2000, 39, 1989-1991.
(23) For elegant examples of hydrogen-bonded cavities in non-heme
systems, see: MacBeth, C. E.; Golombek, A. P.; Young, V. G., Jr.; Tang, C.;
Kuczera, K.; Hendrich, M. P.; Borovik, A. S. Science 2000, 289, 938-941.
10.1021/ja003245k CCC: $20.00 © 2001 American Chemical Society
Published on Web 01/30/2001