Shape-selective discrimination of small organic molecules [30]

Full text of DOI:10.1021/ja000002j

J. Am. Chem. Soc. 2000, 122, 11565-11566
11565
Scheme 1
Shape-Selective Discrimination of Small Organic
Molecules
Avijit Sen and Kenneth S. Suslick*
School of Chemical Sciences
UniVersity of Illinois at Urbana-Champaign
601 South Goodwin AVenue, Urbana, Illinois 61801
ReceiVed January 3, 2000
ReVised Manuscript ReceiVed October 3, 2000
Over the past few decades there has been remarkable progress
in the synthesis of molecular scaffolds based on superstructured
porphyrins.1 A number of these modified porphyrins have been
synthesized to mimic various aspects of the enzymatic functions
of heme proteins, especially oxygen binding (myoglobin and
hemoglobin), and substrate oxidation (cytochrome P-450).1,2 The
notable property of many heme proteins is their remarkable
substrate selectivity; the development of highly regioselective
synthetic catalysts, however, is still at an early stage. Discrimina-
tion of one site on a molecule from another and distinguishing
among many similar molecules presents a difficult and important
challenge to both industrial and biological chemistry.3 Although
the axial ligation properties of simple synthetic metalloporphyrins
are well documented in literature,4 size and shape control of
ligation to peripherally modified metalloporphyrins has been
largely unexplored, with few notable exceptions, where only
limited selectivities have been observed.5
We report here the synthesis, characterization, and remarkable
shape-selective ligation of silyl ether-metalloporphyrin scaffolds
derived from the reaction of 5,10,15,20-tetrakis(2′,6′-dihydroxy-
phenyl)porphyrinatozinc(II) with tert-butyldimethylsilyl chloride,
whereby the two faces of the Zn(II) porphyrin were protected
with six, seven, or eight siloxyl groups. This results in a set of
three porphyrins of nearly similar electronics but with different
steric encumbrance around the central metal atom present in the
porphyrin. Ligation to Zn by classes of different sized ligands
reveals shape selectivities as large as 107.
The size and shape selectivities of the binding sites of these
bis-pocket Zn silyl ether porphyrins were probed using the axial
ligation of various nitrogenous bases of different shapes and sizes
in toluene at 25 °C. Zn(II) porphyrins were chosen for this study
because, in solution, they generally bind only a single axial ligand.
Successive addition of ligand to the porphyrin solutions caused
a red-shift of the Soret band typical of coordination to zinc por-
phyrin complexes. There is no evidence from the electronic spectra
of these porphyrins for significant distortions of the electronic
structure of the porphyrin. The binding constants (Keq) and binding
composition (always 1:1) were evaluated using standard proce-
dures.10 The Keq values of the silyl ether porphyrins with nitrog-
enous bases of different classes are compared with the sterically
undemanding Zn(TPP) in Figure 1. It is worth noting the parallel
between shape selectivity in these equilibrium measurements and
prior kinetically controlled epoxidation and hydroxylation.2,11
While direct comparisons are not yet available, the selectivity
for equilibrated ligation appears to be substantially larger than
that for irreversible oxidations of similarly shaped substrates.
The binding constants of silyl ether porphyrins are remarkably
sensitive to the shape and size of the substrates relative to Zn-
(TPP) (Figure 1). The binding constants of different amines could
be controlled over a range of 101 to 107 relative to Zn(TPP). We
believe that these selectivities originate from strong steric
repulsions created by the methyl groups of the tert-butyldimeth-
ylsiloxyl substituents. The steric congestion caused by these bulky
silyl ether groups is pronounced eVen for linear amines and small
cyclic amines (e.g., azetidine and pyrrolidine).
A family of siloxyl-substituted bis-pocket porphyrins were
prepared according to the process in Scheme 1.6 Zn[(OH)6PP]
and Zn[(OH)8PP] were obtained5a from demethylation7 of corre-
sponding free base methoxy compounds followed by zinc(II)
insertion. The methoxy porphyrins were synthesized by acid
catalyzed condensation of pyrrole with respective benzaldehydes
following Lindsey procedures.8 Metalation was done in methanol
with Zn(O2CCH3)2. The tert-butyldimethylsilyl groups were
incorporated into the metalloporphyrin by stirring a DMF solution
of hydroxyporphyrin complex with TBDMSiCl in the presence
of imidazole.9 The octa (Zn(Si8PP)), hepta (Zn(Si7OHPP)), and
hexa (Zn(Si6PP)) silyl ether porphyrins were obtained from Zn-
[(OH)8PP] and Zn[(OH)6PP], respectively. The compounds were
purified by silica gel column chromatography and fully character-
There are very large differences in Keq for porphyrins having
three versus four silyl ether groups on each face (e.g., hexa- vs
(6) (a) Abbreviations: Zn(TPP), 5,10,15,20-tetraphenylporphyrinatozinc-
(II); Zn[(OH)6PP], 5-phenyl-10,15,20-tris(2′,6′-dihydroxyphenyl)porphyrina-
tozinc(II); Zn[(OH)8PP], 5,10,15,20-tetrakis(2′,6′-dihydroxyphenyl)porphyri-
natozinc(II); Zn(Si6PP), 5-phenyl-10,15,20-trikis(2′,6′-disilyloxyphenyl)porphyr-
inatozinc(II); Zn(Si7OHPP), 5,10,15-trikis(2′,6′-disilyloxyphenyl)-20-(2′-hy-
droxy-6′-silyloxyphenyl)porphyrinatozinc(II); Zn(Si8PP), 5,10,15,20-tetrakis-
(2′,6′-disilyloxyphenyl)porphyrinatozinc(II); TBDMSiCl, tert-butyldimethyl-
silyl chloride. (b) Characterization details provided as Supporting Information.
(c) X-ray structure of Zn(Si8PP) determined at 173(2) K from single crystals
grown from a mixture of CHCl3 and C6H5Cl (3:1, v/v). X-ray data collected
with a Bruker SMART system with a CCD detector; λ(Mo KR) ) 0.7107 Å.
Structure solved by direct methods (G. M. Sheldrick, 1998, SHELX-97-2;
Institute fur Anorg. Chemie, Gottingen, Germany) and refined by full-matrix
least squares against all F2 data. Crystal data for Zn(Si8PP): crystal dimension
0.20 × 0.22 × 0.24 mm, triclinic, space group P1h, a ) 13.114(3) Å, b )
13.577(3) Å, c ) 28.590(6) Å, R ) 78.703(8)°, â ) 83.449(8)°, γ ) 89.214-
(8)°, V ) 4959(2) Å3, Z ) 2, 2θmax ) 50°, R1 ) 0.0793, wR2 ) 0.1944 (due
to some disorder of one of the t-Bu groups), GOF ) 1.018, residual electron
density -0.417/0.671 eÅ3. Details provided as Supporting Information.
(7) Momenteau, M.; Mispelter, J.; Loock, B.; Bisagni, E. J. Chem. Soc.,
Perkin Trans. 1 1983, 189.
1
ized by UV-visible, H NMR, HPLC, and MALDI-TOF MS.
(1) (a) Suslick, K. S.; Reinert, T. J. J. Chem. Ed. 1985, 62, 974. (b) Collman,
J. P.; Zhang, X.; Lee, V. J.; Uffelman, E. S.; Brauman, J. I. Science 1993,
261, 1404.
(2) (a) Collman, J. P.; Zhang, X. In ComprehensiVe Supramolecular Chem-
istry; Atwood, J. L., Davies, J. E. D., MacNicol, D. D., Vogtel, F., Eds.; Per-
gamon: New York, 1996; Vol. 5, pp 1-32. (b) Suslick, K. S.; van Deusen-
Jeffries, S. In ComprehensiVe Supramolecular Chemistry; Atwood, J. L.,
Davies, J. E. D., MacNicol, D. D., Vogtel, F., Eds.; Pergamon: New York,
1996; Vol. 5, pp 141-170. (c) Suslick, K. S. In ActiVation and Functionaliza-
tion of Alkanes; Hill, C. L., Ed.; Wiley & Sons: New York, 1989; pp 219-241.
(3) Metalloporphyrins in Catalytic Oxidations; Sheldon, R. A., Ed.; Marcel
Dekker: New York, 1994.
(4) (a) Bampos, N.; Marvaud, V.; Sanders, J. K. M. Chem. Eur. J. 1998,
4, 325. (b) Stibrany, R. T.; Vasudevan, J.; Knapp, S.; Potenza, J. A.; Emge,
T.; Schugar, H. J. J. Am. Chem. Soc. 1996, 118, 3980.
(5) (a) Bhyrappa, P.; Vaijayanthimala, G.; Suslick, K. S. J. Am. Chem.
Soc. 1999, 121, 262. (b) Imai, H.; Nakagawa, S.; Kyuno, E. J. Am. Chem.
Soc. 1992, 114, 6719.
(8) Lindsey, J. S.; Wagner, R. W. J. Org. Chem. 1989, 54, 828.
(9) Corey, E. J.; Venkateswarlu, A. J. Am. Chem. Soc. 1972, 94, 6190.
(10) (a) Collman, J. P.; Brauman, J. I.; Doxsee, K. M.; Halbert, T. R.;
Hayes, S. E.; Suslick, K. S. J. Am. Chem. Soc. 1978, 100, 2761. (b) Suslick,
K. S.; Fox, M. M.; Reinert, T. J. Am. Chem. Soc. 1984, 106, 4522.
(11) (a) Bhyrappa, P.; Young, J. K.; Moore, J. S.; Suslick, K. S. J. Am.
Chem. Soc. 1996, 118, 5708-5711. (b) Suslick, K. S.; Cook, B. R. J. Chem.
Soc., Chem. Commun. 1987, 200-202. (c) Cook, B. R.; Reinert, T. J.; Suslick,
K. S. J. Am. Chem. Soc. 1986, 108, 7281-7286. (d) Suslick, K. S.; Cook, B.
R.; Fox, M. M. J. Chem. Soc., Chem. Commun. 1985, 580-582.
10.1021/ja000002j CCC: $19.00 © 2000 American Chemical Society
Published on Web 11/05/2000

11566 J. Am. Chem. Soc., Vol. 122, No. 46, 2000
Communications to the Editor
Figure 2. Molecular models of Zn(Si6PP) (left column) and Zn(Si8PP)
(right column). Pairs of images (top to bottom) are cylinder side-views,
side-views, and top-views, respectively; space filling shown at 70% van
der Waals radii, with porphyrin carbon atoms (purple), oxygen atoms
(red), silicon atoms (green), and Zn (dark red). The X-ray single-crystal
structure of Zn(Si8PP) determined at 173(2) K is shown;6c for Zn(Si6-
PP), an energy-minimized structure was obtained using Cerius 2 from MSI.
Figure 1. Ligand binding constants for siloxyl porphyrins compared to
Zn(TPP): (a) aliphatic primary and secondary amines; (b) alicyclic
secondary amines, and (c) aromatic amines. Errors in Keq were typically
(10% (i.e., (0.05 log units): open bar, Zn(TPP); dotted bar, Zn(Si6-
PP); horizontally ruled bar, Zn(Si7OHPP); and solid bar, Zn(Si8PP).
sites is clear, even for compact aromatic ligands with non-ortho-
methyl substituents (Figure 1c).
octasilyl ether porphyrins), as expected based on obvious steric
arguments (Figure 1). Even between the hexa- over heptasilyl
ether porphyrins, however, there are still substantial differences
in binding behavior. We suggest that this is probably due to
doming of the macrocycle in the hexa- and heptasilyl ether
porphyrins, which lessens the steric constraint relative to the
octasilyl ether porphyrin. Such doming will be especially
important in porphyrins whose two faces are not identical. The
free hydroxy functionality of the heptasilyl ether may play a role
in binding of bifunctionalized ligands (e.g., free amino acids);
for the simple amines presented here, however, we have no
evidence of any special effects.
These silyl ether porphyrins showed remarkable selectivities
for normal, linear amines over their cyclic analogues. For a series
of linear amines (n-propylamine through n-decylamine), Keq values
were very similar for each of the silyl ether porphyrins. In
comparison, the relative Keq for linear versus cyclic primary
amines (Figure 1a, n-butylamine vs cyclohexylamine) were
significantly different: Keqlinear/Keqcyclic ranges from 1 to 23 to 115
to >200 for Zn(TPP), Zn(Si6PP), Zn(Si7OHPP), and Zn(Si8PP),
respectively. The ability to discriminate between linear and cyclic
compounds is thus established.
The molecular structures of these silyl ether porphyrins explain
their ligation selectivity. We have solved the X-ray single-crystal
structure of Zn(Si8PP) in the triclinic P1h space group.6c As shown
in Figure 2, Zn(Si6PP) (energy minimized molecular model) and
Zn(Si8PP) (single crystal X-ray structure) have dramatically
different binding pockets. In the octasilyl ether porphyrin, the
top access on both faces of the porphyrin is very tightly controlled
by the siloxyl pocket. In contrast, the metal center of the hexasilyl
ether porphyrin is considerably more exposed for ligation.
In summary, a series of bis-pocket siloxylmetalloporphyrin
complexes were prepared with sterically restrictive binding
pockets on both faces of the macrocycle. Ligation to Zn by various
nitrogenous bases of different sizes and shapes was investigated.
Shape selectivities as large as 107 were found, compared to
unhindered metalloporphyrins. Fine-tuning of ligation properties
of these porphyrins was also possible using pockets of varying
steric demands. The shape selectivities shown here rival or surpass
those of any biological system.
Acknowledgment. We thank Dr. Richard Milberg (UIUC, Mass Spec-
troscopy Lab) for MALDI-TOF spectral measurements and Drs. J. H.
Chou and S. R. Wilson for assistance in solving the crystal structure.
This work was supported by the National Institute of Health (HL 5R01-
25934) and in part by the U.S. Army Research Office (DAAG55-97-
0126).
A series of cyclic secondary amines (Figure 1b) demonstrate
the remarkable size and shape selectivities of this family of bis-
pocket porphyrins, whereas the binding constants to Zn(TPP) with
those amines are virtually similar. In contrast, the Keq values for
silyl ether porphyrins strongly depend on the ring size and its
peripheral substituents. The effect of these shape-selective binding
Supporting Information Available: Synthesis, characterization, and
X-ray crystallographic details (PDF). This material is available free of
charge via the Internet at http://pubs.acs.org.
JA000002J