Ind. Eng. Chem. Res. 2000, 39, 3471-3478
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Modified Calix[4]pyrroles Jonathan L. Sessler,*,† Pavel Anzenbacher, Jr.,† Hidekazu Miyaji,† Karolina Jursı´kova´ ,† Ellen R. Bleasdale,‡ and Philip A. Gale*,§ Department of Chemistry and Biochemistry and Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, Texas 78712-1167, and Inorganic Chemistry Laboratory, Department of Chemistry, University of Oxford, South Parks Road, Oxford, OX1 3QR, United Kingdom, and Department of Chemistry, University of Southampton, Southampton, SO17 1BJ, United Kingdom
The synthesis and chemical properties of a variety of chemically modified calix[4]pyrroles are described. The effects of structural changes, specifically the presence and absence of substituents on the meso-like and β-pyrrolic carbons, on anion affinities are detailed as is their effect on macrocycle conformation. Also described are unsymmetrical systems, bearing an aliphatic and aromatic substituent on each of the four meso-like carbon atoms. In this case, the properties of the resulting configuration isomers are discussed in terms, again, of the resulting effects on macrocycle conformation and substrate binding affinity. Finally, the use of appropriately functionalized calix[4]pyrrole systems as rudimentary fluorescence-based anion sensors is presented. Introduction Calix[4]pyrroles, a class of tetrapyrrolic macrocycles similar to porphyrinogens that was first synthesized by Baeyer in 1886,1 have emerged recently as very attractive anion receptors.2-4 These simple-to-make systems exist in the so-called 1,3-alternate conformation in the absence of an anion but adopt a conelike conformation in the presence of an anionic guest. This ability to undergo conformational changes and complex anions has also been demonstrated not only in the solid state but also in organic solution.2-10 Indeed, in early work, involving the study of system 1,5 it was found that the fluoride anion was bound with high affinity in dichloromethane and that other Lewis basic substrates, such as chloride anion and dihydrogen phosphate anion, were also complexed (Table 1). An interesting corollary of this first study was the finding that slight variations in structure, e.g., the use of 2 rather than 1, led to demonstrable changes in anion affinity (Table 1). The extent to which this phenomenon was general, however, and whether it reflected steric, electronic, or structurerelated conformational effects was unknown at the time. These findings inspired us to investigate how changes in calix[4]pyrrole structure affected anion binding. Concurrently, we also began to explore whether appropriately modified calix[4]pyrroles could be used as anion sensors. In this paper the results of these studies are reported, some of which have been previously published in preliminary form.5-10
spiro-cyclohexyl substituents. Consistent with this thinking was the fact that replacing the β-pyrrolic hydrogens by bromine atoms (as in, e.g., 3) or methoxy substitutents (as in, e.g., 4) served, respectively, to greatly
Results and Discussion At the time of our initial publication on calix[4]pyrrole-mediated anion binding,5 it was considered likely that the difference in affinity manifested by 1 and 2 reflected an electronic effect, specifically the disparate electron-donating properties of the meso-methyl and * To whom correspondence should be addressed. † The University of Texas at Austin. ‡ University of Oxford. § University of Southampton.
increase greatly or decrease substantially the anion binding affinities (Table 1).6 On the other hand, in later experiments it was found that the meso-octaethyl- and meso-octa-n-propyl-substituted systems (compounds 5 and 6) displayed anion binding affinities that were only slightly diminished as compared to the original mesooctamethyl system 1.11
10.1021/ie000102y CCC: $19.00 © 2000 American Chemical Society Published on Web 08/18/2000
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Ind. Eng. Chem. Res., Vol. 39, No. 10, 2000
Table 1. Stability Constants (Ka) for Complexes Formed between Compounds 1-4, 7, and 8 (M-1) and Chloride, Fluoride, and Dihydrogen Phosphate Anions (in the Form of Their Tetrabutylammonium Salts) in Dichloromethane-d2 at 22 °Ca compound FClH2PO4-
1
2
3
4
7
8
17 000 350 97
3 600 120 2 > 7 > 8). This finding, consistent with the proposal that the diminished anion affinity displayed by 2 relative to 1 is caused by an increase in the energetic barrier needed to “flip” between the resting 1,3-alternate and final cone conformations, serves at the very least to underscore how the nature of the meso substituents can have a dramatic steric, as opposed to electronic, effect on the binding characteristics of calix[4]pyrrole-based receptors. In an effort to understand further the role of meso substituents, it was considered useful to prepare calix[4]pyrroles systems bearing substituted aryl groups in the meso positions.4,10 The idea here was that such rigid substituents would provide a structured scaffold above and around the calix[4]pyrrole macrocycle that would not only influence the ease of conformer interconversion but also mediate direct, and possibly disparate, electronic effects (as the result of, e.g., differences in dipole orientations). Scheme 1
a mixture of four configurational isomers denoted as RβRβ, RRββ, RRRβ, and RRRR to indicate the relative position of the bulky aryl substituent. The yield of the respective isomers was found to depend strongly on the nature of the acetophenone substituent X, the polarity of the reaction medium, and whether a templating anion was employed.4,10 While perhaps not uniformly true, in the case of 9 the RRββ and RRRβ configurational isomers could be isolated cleanly using chromatographic methods and in the case of 10 the RRββ, RRRβ, and RRRR isomers could be likewise isolated,10,11 a set of findings that reflects presumably the marked differences in overall molecular polarity present in these various systems. In both cases, the purified products, affectionately referred to as “deepdish” calix[4]pyrroles, were found to possess high walls and/or well-defined binding cavities, as judged from both
Ind. Eng. Chem. Res., Vol. 39, No. 10, 2000 3473
Figure 1. Side views of the RRββ, RRRβ, and RRRR isomers (parts A-C, respectively) of meso-tetraarylcalix[4]pyrroles 9 (B) and 10 (A and C) showing the well-defined walls and deep cavities formed by the aryl substituents. Substrate binding within these cavities is also illustrated by these structures. Table 2. Stability Constants (Ka) for Complexes Formed between Compounds 9-11 (M-1) with Chloride and Fluoride Anions (Studied in the Form of Their Tetrabutylammonium Salts) as Recorded in Acetonitrile-d3 (0.5% v/v D2O) at 22 °Ca compound 9 F-
ClH2PO4-
compound 10
compound 11
RRββ
RRRβ
RRRR
RRββ
RRRβ
RRRR
RRββ
RRRβ
RRRR
>10 000 2 000 890
>10 000 2 100 900
NDb
>10 000 1 400 520
5 000 260 230
>10 000 320 500
4 600 10 000 430 1 200 c
a Errors
