Visualizing functional group distribution in solid-support beads by using optical analysis

Chemistry - A European Journal

Volumn 5, Issue 12, 1999, Pages 3528-3532

  McAlpine, Shelli R ^a   Schreiber, Stuart L ^a  

^a HARVARD UNIVERSITY   (United States)

Author keywords

Combinatorial chemistry; Fluorescence; Optical analysis; Polystyrene; Solid phase synthesis

Indexed keywords

GLASS; POLYSTYRENE;

ARTICLE; CHEMICAL REACTION; FLUORESCENCE; POLARIMETRY; POLYMERIZATION; SYNTHESIS;

EID: 0032785099     PISSN: 09476539     EISSN: None     Source Type: Journal    
DOI: 10.1002/(SICI)1521-3765(19991203)5:12<3528::AID-CHEM3528>3.0.CO;2-4     Document Type: Article

References (51)

1. For a review see: S. Booth, P. H. H. Hermkens, H. C. J. Ottenheijm, D. C. Rees, Tetrahedron 1998, 54, 15385-15443.
2. a) J. Labadie, Curr. Opin. Chem. Bio. 1998, 2, 346-352;
3. b) M. E. Wilson, K. Paech, W.-J. Zhou, M. J. Kurth, J. Org. Chem. 1998, 63, 5094-5099;
4. c) W. Li, B. Yan, J. Org. Chem. 1998, 63, 4092-4097;
5. d) M. Adinolfi, G. Barone, L. D. Napoli, A. Iadonisi, G. Piccialli, Tetrahedron Lett. 1998, 39, 1953-1956;
6. e) R. M. Cook, J. H. Adams, D. Hudson, Tetrahedron Lett. 1994, 35, 6777-6780.
7. ArgoPore is a new macroporous polystyrene for solid phase organic synthesis. Argonaut Technical Bulletin, San Carlos (USA).
8. Trisoperl is a trademark of Schuller, D-97865 Wertheim (Germany).
9. M. F. Songster, G. Barany, Methods Enzymol. 1997, 289, 126-174.
10. Tentagel is a trademark of Rapp. Polymere, D-72072 Tubingen (Germany).
11. F. Albericio, N. Kneib-Cordonier, S. Biancalana, L. Gera, R. I. Masada, D. Hudson, G. Barany, J. Org. Chem. 1990, 55, 3730-3743, and references therein.
12. a) A. R. Mitchell, S. B. H. Kent, M. Engelhard, R. B. Merrifield, J. Org. Chem. 1978, 43, 2845-2852;
13. b) J. H. Adams, R. M. Cook, D. Hudson, V. Jammalamadaka, M. H. Lyttle, M. F. Songster, J. Org. Chem. 1998, 63, 3706-3716;
14. c) C. C. Zikos, N. G. Ferderigos, Tetrahedron Lett. 1995, 36, 3741-3744;
15. d) A. R. Mitchell, S. B. Kent, B. W. Erickson, R. B. Merrifield, Tetrahedron Lett. 1976, 42, 3795-3798.
16. a) A. Guyot, Pure Appl. Chem. 1988, 60, 365-376;
17. b) S. Mohanraj, W. T. Ford, Macromolecules 1986, 19, 2470-2472.
18. a) For review see: D. C. Sherrington, Chem. Commun. 1998, 2275-2286;
19. b) K. J. Shea, G. T. Stoddard, Macromolecules 1991, 24, 1207-1209.
20. a) H. Morawetz, J. Macromol. Sci. Chem. A 1979, 13, 311-320;
21. b) B. Yan, P. C. Martin, J. Lee, J. Comb. Chem. 1999, 7, 78-81;
22. c) B. J. Egner, S. Rana, H. Smith, N. Bouloc, J. G. Frey, W. S. Brocklesby, M. Bradley, Chem. Commun. 1997, 735-736;
23. d) B. Yan, Comb. Chem. High Throughput Screen. 1998, 1, 215-229.
24. L. Kallal, A. W. Gagnon, R. B. Penn, J. L. Benovic, J. Biol. Chem. 1998, 273, 322-328.
25. S. B. Roscoe, J. M. J. Fréchet, J. F. Walzer, A. J. Dias, Science 1998, 280, 270-273.
26. V. K. Sarin, S. B. H. Kent, R. B. Merrifield, J. Am. Chem. Soc. 1980, 102, 5463-5470.
27. a) F. Svec, J. M. J. Fréchet, Science 1996, 273, 205-210;
28. b) E. Bayer, Angew. Chem. 1991, 103, 117-133; Angew. Chem. Int. Ed. Engl. 1991, 30, 113-216;
29. b) E. Bayer, Angew. Chem. 1991, 103, 117-133; Angew. Chem. Int. Ed. Engl. 1991, 30, 113-216;
30. c) K Setinek, V. Blazek, J. Hradil, F. Svec, J. Kalal, J. Catal. 1983, 80, 123-129.
31. a) H. Köster, A. Stumpe, A. Wolter, Tetrahedron Lett. 1983, 24, 747-750;
32. b) S. P. Adams, K. S. Kauka, E. J. Wykes, S. B. Holder, G. R. Galluppi, J. Am. Chem. Soc. 1983, 105, 661-663.
33. a) E. Bayer, B. Hemmasi, K. Albert, W. Rapp, M. Dengler, Peptides: Structure and Function, Pierce Chem. Comput., Rockford, IL 1983;
34. b) R. B. Merrifield, J. Am. Chem. Soc. 1963, 85, 2149-2154;
35. c) R. Arshady, Collid. Polym. Sci. 1992, 270, 717-732;
36. d) D. C. Sherrington, in Polymer-Supported Reactions in Organic Synthesis (Eds. : D. C. Sherrington, P. Hodge), Wiley, New York, 1981, pp. 1-82.
37. Beads were coupled three times with three equivalents of dye each time and our experience from using qualitative analysis on similar reactions indicates this is sufficient for complete coupling. Further, the elemental analysis indicated that high loadings of dye were achieved (see Experimental Section) and therefore we conclude all available amino sites were functionalized with rhodamine dye. Experiments using a linker were examined as they were in conjunction with other experiments in our laboratory; however, the linker played no role in the optical analysis.
38. Multiple beads of each type were examined using optical analysis to ensure that a representative bead for each type was shown. Experiments were done on beads with no photolinker and a direct coupling of Rhodamine dye to the bead; they produced results indistinguishable from those with linkers.
39. Integration of the photon count yields approximate values in the outer 5-10 microns versus photons on the inner 50-90 microns of each slice. The values obtained are an average of several beads by using two slices in the approximate center of the bead.
40. The relative intensity of the beads were not compared with each other as multiple factors contribute to the fluorescence intensity for each bead, including bead size and loading.
41. This may also be a function of the amino-terminated PEG chains.
42. a) B. Sauerbrei, V. Jungmann, H. Waldmann, Angew. Chem. 1998, 110, 1187-1190; Angew. Chem. Int. Ed. 1998, 37, 1143-1146;
43. a) B. Sauerbrei, V. Jungmann, H. Waldmann, Angew. Chem. 1998, 110, 1187-1190; Angew. Chem. Int. Ed. 1998, 37, 1143-1146;
44. b) S. Leon, R. Quarrell, G. Lowe, Bioorg. Med. Chem. Lett. 1998, 8, 2997-3002;
45. c) G. L. Böhm, J. Dowden, D. C. Rice, I. Burgess, J.-F. Pilard, B. Guilbert, A. Haxton, R. C. Hunter, N. J. Turner, S. L. Flitsch, Tetrahedron Lett. 1998, 39, 3819-3822;
46. d) J. Vágner, G. Barany, K. S. Lam, V. Krchnák, N. F. Sepetov, J. A. Ostrem, P. Strop, M. Lebl, Proc. Natl. Acad. Sci. 1996, 93, 8194-8199.
47. K. S. Lam, M. Lebl, V. Krchnák, Chem. Rev. 1997, 97, 411-448.
48. We have observed differing reaction rates on a number of different resins that appear to be batch dependent (data not shown).
49. S. M. Sternson, S. L. Schreiber, Tetrahedron Lett. 1998, 39, 7451-7454.
50. A recent publication (L. D. Mayfield, D. R. Corey, Bioorg. Med. Chem. Lett. 1999, 9, 1419-1422) that describes the use of a PE biosystem Expedite 8909 Automated synthesizer demonstrated that rhodamine can noncovalently bind to poly(ethylene) glycol polystyrene beads. However, as a result of the difference between their reaction conditions and ours we propose the Tentagel beads used in our study are derivatized at least to 70% completion, as indicated by the elemental analysis. Further, noncovalently bound rhodamine does not seem to occur significantly with polystyrene, glass, or ArgoPore resins.
51. Other reaction sequences and subsequent Fmoc analysis have shown that frequently the highest loading actually achieved after a number of synthetic transformations are similar to the values seen from elemental analysis (i.e., 70-80% for all resins). Thus it appears some amines on the manufactured beads may not be accessible. Further, as these samples were stored for 8 months before the elemental analysis and decomposition may have occurred (see ref. [11d]).