Synthetic hosts by monomolecular imprinting inside dendrimers

Abstract

Synthetic host systems capable of selectively binding guest molecules are of interest for applications ranging from separations and chemical or biological sensing to the development of biomedical materials. Such host systems can be efficiently prepared by ‘imprinting’ polymers or inorganic materials with template molecules, which, upon removal, leave behind spatially arranged functional groups that act as recognition sites1,2,3,4. However, molecularly imprinted polymers have limitations, including incomplete template removal, broad guest affinities and selectivities, and slow mass transfer5,6,7,8. An alternative strategy for moulding desired recognition sites uses combinatorial libraries of assemblies that are made of a relatively small number of molecules, interconverting in dynamic equilibrium; upon addition of a target molecule, the library equilibrium shifts towards the best hosts9,10,11. Here we describe the dynamic imprinting of dendritic macromolecules with porphyrin templates to yield synthetic host molecules containing one binding site each. The process is based on our general strategy to prepare cored dendrimers12,13, and involves covalent attachment of dendrons to a porphyrin core, cross-linking of the end-groups of the dendrons, and removal of the porphyrin template by hydrolysis. In contrast to more traditional polymer imprinting, our approach ensures nearly homogeneous binding sites and quantitative template removal. Moreover, the hosts are soluble in common organic solvents and amenable to the incorporation of other functional groups, which should facilitate further development of this system for novel applications.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Figure 1: Scheme illustrating the preparation of imprinted dendrimer 6.
Figure 2: Structural drawing illustrating structural changes that occur upon hydrolysis of the cross-linked dendrimer 5.
Figure 3: Porphyrins used to study binding properties of imprinted dendrimer 6.
Figure 4: Calculated structure of imprinted dendrimer 6 built by iterative attachment of dendrons to the core porphyrin, minimization and cross-linking of neighbouring double bonds.

References

  1. 1

    Wulff, G. & Sarhan, A. The use of polymers with enzyme-analogous structures for the resolution of racemates. Angew. Chem. Int. Edn Engl. 11, 341–343 (1972)

    CAS  Google Scholar 

  2. 2

    Shea, K. J. Molecular imprinting of synthetic network polymers: the de novo synthesis of macromolecular binding and catalytic sites. Trends Polym. Sci. 2, 166–173 (1994)

    CAS  Google Scholar 

  3. 3

    Andersson, L., Sellergren, B. & Mosbach, K. Imprinting of amino acid derivatives in macroporous polymers. Tetrahedr. Lett. 25, 5211–5214 (1984)

    CAS  Article  Google Scholar 

  4. 4

    Katz, A. & Davis, M. E. Molecular imprinting of bulk, microporous silica. Nature 403, 286–289 (2000)

    ADS  CAS  Article  Google Scholar 

  5. 5

    Wulff, G. Molecular imprinting in cross-linked materials with the aid of molecular templates—a way towards artificial antibodies. Angew. Chem. Int. Edn Engl. 34, 1812–1832 (1995)

    CAS  Article  Google Scholar 

  6. 6

    Katz, A. & Davis, M. Investigations into the mechanisms of molecular recognition with imprinted polymers. Macromolecules 32, 4113–4121 (1999)

    ADS  CAS  Article  Google Scholar 

  7. 7

    Sellergren, B. & Shea, K. J. Influence of polymer morphology on the ability of imprinted network polymers to resolve enantiomers. J. Chromatogr. 635, 39–41 (1993)

    Article  Google Scholar 

  8. 8

    Vlatakis, G., Andersson, L. I., Muller, R. & Mosbach, K. Drug assay using antibody mimics made by molecular imprinting. Nature 361, 645–647 (1993)

    ADS  CAS  Article  Google Scholar 

  9. 9

    Lehn, J.-M. & Eliseev, A. V. Dynamic combinatorial chemistry. Science 291, 2331–2332 (2001)

    CAS  Article  Google Scholar 

  10. 10

    Cousins, G. R. L., Poulsen, S.-A. & Sanders, J. K. M. Molecular evolution: dynamic combinatorial libraries, autocatalytic networks and the quest for molecular function. Curr. Opin. Chem. Biol. 4, 270–279 (2000)

    CAS  Article  Google Scholar 

  11. 11

    Klekota, B. & Miller, B. L. Dynamic diversity and small-molecule evolution: a new paradigm for ligand identification. Trends Biotechnol. 17, 205–209 (1999)

    CAS  Article  Google Scholar 

  12. 12

    Wendland, M. S. & Zimmerman, S. C. Synthesis of cored dendrimers. J. Am. Chem. Soc. 121, 1389–1390 (1999)

    CAS  Article  Google Scholar 

  13. 13

    Schultz, L. G., Zhao, Y. & Zimmerman, S. C. Synthesis of cored dendrimers with internal cross-links. Angew. Chem. Int. Edn Engl. 40, 1962–1966 (2001)

    CAS  Article  Google Scholar 

  14. 14

    Newkome, G. R., Moorefield, C. N. & Vögtle, F. Dendrimers and Dendrons: Concepts, Syntheses, Perspectives (Wiley-VCH, Weinheim, 2001)

    Google Scholar 

  15. 15

    Sanders, J. K. M. Templated chemistry of porphyrin oligomers. Compreh. Supramolec. Chem. 9, 131–164 (1996)

    CAS  Google Scholar 

  16. 16

    Rakow, N. A. & Suslick, K. S. A colorimetric sensor array for odour visualization. Nature 406, 710–714 (2000)

    ADS  CAS  Article  Google Scholar 

  17. 17

    Matsui, J., Higashi, M. & Takeuchi, T. Molecularly imprinted polymer as 9-ethyladenine receptor having a porphyrin-based recognition center. J. Am. Chem. Soc. 122, 5218–5219 (2000)

    CAS  Article  Google Scholar 

  18. 18

    Ogoshi, H. & Mizutani, T. Novel approaches to molecular recognition using porphyrins. Curr. Opin. Chem. Biol. 3, 736–739 (1999)

    CAS  Article  Google Scholar 

  19. 19

    Bhyrappa, P., Young, J. K., Moore, J. S. & Suslick, K. S. Dendrimer-metalloporphyrins: synthesis and catalysis. J. Am. Chem. Soc. 118, 5708–5711 (1996)

    CAS  Article  Google Scholar 

  20. 20

    Dandliker, P. J., Diederich, F., Gisselbrecht, J.-P., Louati, A. & Gross, M. Water-soluble dendritic iron porphyrins: synthetic models of globular heme proteins. Angew. Chem. Int. Edn Engl. 34, 2725–2728 (1996)

    Article  Google Scholar 

  21. 21

    Sadamoto, R., Tomioka, N. & Aida, T. Photoinduced electron transfer reactions through dendrimer architecture. J. Am. Chem. Soc. 118, 3978–3979 (1996)

    CAS  Article  Google Scholar 

  22. 22

    Balzani, V. et al. Dendrimers based on photoactive metal complexes. Recent advances. Coord. Chem. Rev. 219–221, 545–572 (2001)

    Article  Google Scholar 

  23. 23

    Hawker, C. J. & Frechet, J. M. J. A new convergent approach to monodisperse dendritic macromolecules. J. Am. Chem. Soc. 112, 7638–7647 (1990)

    CAS  Article  Google Scholar 

  24. 24

    Trnka, T. M. & Grubbs, R. H. The development of L2X2Ru = CHR olefin metathesis catalysts: an organometallic success story. Acc. Chem. Res. 34, 18–29 (2001)

    CAS  Article  Google Scholar 

  25. 25

    Coates, G. W. & Grubbs, R. H. Quantitative ring-closing metathesis of polyolefins. J. Am. Chem. Soc. 118, 229–230 (1996)

    CAS  Article  Google Scholar 

  26. 26

    Adler, A. D. et al. A simplified synthesis of meso-tetraphenylporphyrin. J. Org. Chem. 32, 476 (1967)

    CAS  Article  Google Scholar 

  27. 27

    Rho, T. & Abuh, F. One-pot synthesis of pyrimidine-5-carboxaldehyde and ethyl pyrimidine-5-carboxylate by utilizing pyrimidin-5-yl-lithium. Synth. Commun. 24, 253–256 (1994)

    CAS  Article  Google Scholar 

  28. 28

    Collman, J. P. et al. Oxygen binding to cobalt porphyrins. J. Am. Chem. Soc. 100, 2761–2766 (1978)

    CAS  Article  Google Scholar 

Download references

Acknowledgements

We thank W.A. Goddard and T. Cagin for help with dendrimer modelling. This work was funded by the NIH and the US Army Research Office. I.Z. thanks the Arnold and Mabel Beckman Foundation for a Beckman fellowship.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Steven C. Zimmerman.

Ethics declarations

Competing interests

The authors declare that they have no competing financial interests.

Supplementary information

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Zimmerman, S., Wendland, M., Rakow, N. et al. Synthetic hosts by monomolecular imprinting inside dendrimers. Nature 418, 399–403 (2002). https://doi.org/10.1038/nature00877

Download citation

Further reading

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.