A conformationally programmable ligand [21]

Full text of DOI:10.1021/ja0158713

J. Am. Chem. Soc. 2001, 123, 7463-7464
A Conformationally Programmable Ligand
Yong S. Chong, Mark D. Smith, and Ken D. Shimizu*
7463
UniVersity of South Carolina
Department of Chemistry and Biochemistry
Columbia, South Carolina 29208
ReceiVed March 23, 2001
ReVised Manuscript ReceiVed June 6, 2001
Figure 1. Schematic representation of a “programmable” ligand. At room
temperature the ligand adopts one of two conformations: syn- or anti-.
On heating in the presence of a metal, the syn-isomer is preferred. On
cooling this conformational preference is “locked-in” even on removal
of the metal ion.
Metals are well-known to induce conformational changes upon
ligand systems.1 This attribute has been utilized in sensors,2
molecular machines,3 synthetic receptors,4 and stabilization of
protein structures.5 However, these metal-induced conformations
are normally dependent on the presence of the metal ion. For
example, chelation of a metal by 2,2′-bipyridine stops rotation
about the C-C bond and leads to a planar conformation.6 Upon
removal of the metal ion the 2,2′-bipyridine “forgets” and reverts
to its conformationally flexible state. Demonstrated herein is a
ligand that can remember or retain its metal-induced conformation
even in the absence of the metal ion. In effect, the ligand can be
“taught” to hold a specific conformation.
Scheme 1a
Our strategy utilizes a ligand that is conformationally flexible
at elevated temperatures yet is conformationally rigid at room
temperature (Figure 1). This is achieved via restricted rotation,
which leads to two stable and separable conformational isomers:
a convergent syn- and a divergent anti-rotamer.7 Control over
ligand conformation can be exerted by heating the ligand in the
presence of a metal ion.8 The chelating syn-conformer is preferred,
and on cooling to room temperature, this conformer or shape is
locked in, even upon removal of the metal ion.
a (a) DMF, reflux, 12 h (99%), (b) K2CO3, DMF, 18 h (55%).
The specific ligand that was designed and synthesized was bis-
(pyridine) 1 (Scheme 1). Restricted rotation is present about the
two Caryl-Nimide bonds due to the steric interactions of the ether
oxygens with the imide carbonyls.9,10 As a consequence, the ligand
adopts stable syn- and anti-rotamers.
The ligand was readily assembled in two steps from amino
phenol 2 (Scheme 1). Condensation with 1,4,5,8-naphthalenetet-
racarboxylic dianhydride in DMF yielded syn-/anti-3.11 Subse-
quent alkylation with 3-chloromethylpyridine gave syn-1 and
anti-1 which were separated by column chromatography. The
rotamers were assigned on the basis of their dipole moments as
measured by their Rf on silica gel12 and later by an X-ray structure
of the anti-isomer.13 The stability of the conformational isomers
was determined by following the equilibration of the respective
(1) Eichhorn, G. L. Coord. Chem. ReV. 1993, 128, 167-173.
(2) For recent example see: (a) Zahn, S.; Proni, G.; Spada, G. P.; Canary,
J. W. Chem.sEur. J. 2001, 7, 88-93. (b) McFarland, S. A.; Finney, N. S. J.
Am. Chem. Soc. 2001, 123, 1260-1261. (c) Matsumoto, H.; Shinkai, S.
Tetrahedron Lett. 1996, 37, 77-80. Liquid crystalline phases: Liebmann,
A.; Mertesdorf, C.; Plesnivy, T.; Ringsdorf, H.; Wendorff, J. H. Angew. Chem.,
Int. Ed. Engl. 1991, 30, 1375-1377.
(3) Kelly, T. R.; Bowyer, M. C.; Bhaskar, K. V.; Bebbington, D.; Garcia,
A.; Lang, F. R.; Kim, M. H.; Jette, M. P. J. Am. Chem. Soc. 1994, 116, 3657-
3658.
(4) For recent examples, see: (a) Al-Sayah, M. H.; Branda, N. R. Angew.
Chem., Int. Ed. 2000, 39, 945-947. (b) Kubik, S. J. Am. Chem. Soc. 1999,
121, 5846-5855. For a general review, see: Robertson, A.; Shinkai, S. Coord.
Chem. ReV. 2000, 205, 157-199.
(5) (a) Eichhorn, G. L. Coord. Chem. ReV. 1993, 128, 167-173. (b)
Koshland, D. E. Angew. Chem., Int. Ed. Engl. 1995, 33, 2375-2378.
(6) Kaes, C.; Katz, A.; Hosseini, M. W. Chem. ReV. 2000, 100, 3553-
3590.
(7) For examples of shape-based memory systems based on restricted
rotation, see: (a) Sugasaki, A.; Ikeda, M.; Takeuchi, M.; Robertson, A.;
Shinkai, S. J. Chem. Soc., Perkin Trans. 1 1999, 3259-3264. (b) Furusho,
Y.; Kimura, T.; Mizuno, Y.; Aida, T. J. Am. Chem. Soc. 1997, 119, 5267-
5268. (c) Yashima, E.; Maeda, K.; Okamoto, Y. Nature 1999, 399, 449-
451.
(8) Examples of induced conformation of atropisomers by organic guests:
(a) Hayashi, T.; Asai, T.; Borgmeier, F. M.; Hokazono, H.; Ogoshi, H. Chem.s
Eur. J. 1998, 4, 1266-1274. (b) Kuroda, Y.; Kawashima, A.; Urai, T.; Ogoshi,
H. Tetrahedron Lett. 1995, 36, 8449-8452. (c) Bampos, N.; Marvaud, V.;
Sanders, J. K. M. Chem.sEur. J. 1998, 4, 335-343.
(9) (a) Curran, D. P.; Geib, S.; N, D. Tetrahedron 1999, 55, 5681-5704.
(b) Degenhardt, C., III; Shortell, D. B.; Adams, R. D.; Shimizu, K. D. J.
Chem. Soc., Chem. Commun. 2000, 929-930. (c) Shimizu, K. D.; Dewey, T.
M.; Rebek, J. J. Am. Chem. Soc. 1994, 116, 5145-5149. (d) Verma, S. M.;
Singh, N. D. Aust. J. Chem. 1976, 29, 295-300. (e) Kishikawa, K.; Yoshizaki,
K.; Kohmoto, S.; Yamamoto, M.; Yamaguchi, K.; Yamada, K. J. Chem. Soc.,
Perkin Trans. 1 1997, 1233-1239. (f) Shimizu, K. D.; Freyer, H. O.; Adams,
R. D. Tetrahedron Lett. 2000, 41, 5431-5434.
1
isomers by H NMR, yielding a rotational barrier of 27.0 kcal/
mol,14 which corresponds to a half-life of 71 days at room
temperature (23 °C).15
Differences in coordination abilities of syn- and anti-1 were
evident by their differential solubilities in CDCl3 on addition of
1 equiv of [PdCl2(PhCN)2]. The convergent syn-bis(pyridine) 1
forms a soluble monomeric chelate complex; whereas the
divergent anti-1 forms an insoluble coordination polymer. Similar
differences in solubility have been demonstrated for macrocyclic
versus oligomeric supramolecular assemblies.
Structural characterization of the [PdCl2(syn-1)] complex was
provided by X-ray crystallography, which confirmed the mono-
(10) For examples of metal complexation to control the conformation of a
photoswitchable system, see: (a) Fyles, T. M.; Zeng, B. J. Org. Chem. 1998,
63, 8337-8345. (b) Shinkai, S.; Ogawa, T.; Kusano, Y.; Manabe, O.;
Kikukawa, K.; Goto, T.; Matsuda, T. J. Am. Chem. Soc. 1982, 104, 4.
(11) The rotational barrier of 3 was too low to enable separation of the
isomers at room temperature.
(12) Differences in dipole moments as measured by thin-layer chromatog-
raphy have been successfully utilized in the assignment of atropisomers in
many systems. (a) Sanders, G. M.; Van Dijk, M.; Machiels, B. M.; van
Veldhuizen, A. J. Org. Chem. 1991, 56, 1301-1305. (b) Shimizu, K. D.;
Dewey, T. M.; Rebek, J., Jr. J. Am. Chem. Soc. 1994, 116, 5145-5149.
(13) The crystal structure of anti-1 is in the Supporting Information.
1
(14) Measured in CDCl3 at 62 °C by H NMR.
(15) Calculated from the Arrhenius equation assuming an ideal value of A
) 2.08 × 1010 s-1 deg-1
.
10.1021/ja0158713 CCC: $20.00 © 2001 American Chemical Society
Published on Web 07/07/2001

7464 J. Am. Chem. Soc., Vol. 123, No. 30, 2001
Communications to the Editor
Figure 2. X-ray crystal structure of [PdCl2(syn-1)]. ORTEP representation
with 50% probability.
meric and chelating nature of the complex (Figure 2). The
pyridines hold the PdCl2 suspended over the naphthalene diimide
surface with N-Pd bond lengths of 2.02 Å. One chlorine atom
fills the space below the Pd atom and is poised 3.254 Å above
the naphthalene ring. Finally, the aryl rings are nearly perpen-
dicular to the naphthalene diimide surface with dihedral angles
of 91° and 81.3°.
The X-ray structure also revealed another unique characteristic
of syn-1, that it is an example of a trans-(spanning) bis(pyridine)
ligand. The PdCl2 is coordinated from opposite sides in a trans-
geometry (N-Pd-N bond angle ) 176.0°), due to the geometric
constrains of the rigid ligand framework. Trans-spanning bico-
ordinate ligands are quite rare.16 Examples of bis(nitrile),17 bis-
(phosphine),18 and bis(amine)19 ligands have been reported but
to our knowledge, this is the first example of a trans-spanning
bipyridine ligand.
NMR enabled in situ monitoring of the dynamic properties of
ligand 1 and its complexes. The following cycle was performed
in a single NMR tube to demonstrate the conformational
programmability of ligand 1 by metal chelation. Beginning with
trans-1 (Figure 3a), the addition of [PdCl2(PhCN)2] yielded the
corresponding coordination polymer (Figure 3b) as evidenced by
the complex and broadened spectra. This species was stable at
room temperature but could be transformed quantitatively into
[PdCl2(syn-1)] (Figure 3c), by heating for 25 h at 86 °C (∼15
half-lives) and then cooling to room temperature. The sharp set
of new signals were identical to those of the [PdCl2(syn-1)]
complex that was made independently by addition of [PdCl2-
(PhCN)2] to syn-1. Finally, the PdCl2 was removed by addition
TMEDA to yield free syn-1 (Figure 3d) with >98% diastereo-
meric excess.20 We have also taken mixtures of syn-1, and anti-1
shifted them entirely to syn-1, in a similar manner.
Figure 3. 1H NMR spectra in DMSO-d6 of (a) anti-1, (b) [{PdCl2(anti-
1)}n] formed from the addition of 1 equiv of [PdCl2(PhCN)2] to anti-1,
(c) [PdCl2(syn-1)] formed by heating [{PdCl2(anti-1)}n] for 25 h at 86
°C and (d) syn-1 formed by demetalation of [PdCl2(syn-1)]with TMEDA.
In effect, ligand 1 can be programmed by heating in the
presence of the PdCl2 template to form the syn-conformer. This
conformational preference is retained on cooling to room tem-
perature even on removal of the template. Alternatively, the anti-
isomer can be favored by heating the TsOH salt in toluene. Again,
the conformation is preserved on cooling to room temperature
and neutralization to yield 87% anti-enriched 1. The preference
for the anti-isomer, on protonation, is presumably due to the
destabilization of the syn-isomer by charge-charge repulsion. In
either case, the conformational preferences can be “erased” simply
by heating in the absence of metal ion or acid, returning the ligand
to an equilibrium mixture of syn- and anti-1.
In summary, ligand 1 can be programmed to adopt either a
convergent syn-conformer that forms chelates or a divergent anti-
conformer that forms coordination polymers. Preliminary exami-
nations have also demonstrated that ligand 1 demonstrates similar
dynamic characteristics with other metals such as Cu(II) or Ag-
(I). Potential applications of this structural programmability are
as molecular informational storage devices, or materials with
programmable properties.
Acknowledgment. We thank the NSF (DMR 9807470) for support.
Supporting Information Available: The contents include synthetic
procedures for the synthesis of ligand 1, characterization data including
1H NMR spectra, and crystallographic tables for [PdCl2(syn-1)] and anti-1
(PDF). X-ray crystallographic files in CIF format for [PdCl2(syn-1)] and
anti-1. This material is available free of charge via the Internet at
http://pubs.acs.org.
(16) (a) Bailar, J. C., Jr. Coord. Chem. ReV. 1990, 100, 1. (b) Ogino, H. J.
Coord. Chem. 1987, 15, 187.
(17) Shimizu, K. D.; Rebek, J., Jr. Proc. Natl. Acad. Sci. U.S.A. 1996, 93,
4257-4260.
JA0158713
(18) (a) Sawamura, M.; Hamashima, H.; Ito, Y. J. Am. Chem. Soc. 1991,
114, 8295. (b) Barrow, M.; Bu¨rgi, H. B.; Johnson, D. K.; Venanzi, L. M. J.
Am. Chem. Soc. 1976, 98, 2356.
(20) Interestingly, syn-1 is competitive with TMEDA for PdCl2 as both
complexes are observed in ∼1:1 ratio on addition of 1 equiv of TMEDA.
Thus, complete demetalation of [PdCl2(syn-1)] required an excess of TMEDA.
(19) Mochida, I.; Mattern, J. A.; Bailar, J. C., Jr. J. Am. Chem. Soc. 1975,
97, 3201.