Molecular recognition of amidines in water

Organic Letters

Volumn 5, Issue 10, 2003, Pages 1641-1644

  Grawe, Thomas ^a   Schäfer, Gerhard ^a   Schrader, Thomas ^a  

^a PHILIPPS UNIVERSITY MARBURG   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

4',6 DIAMIDINO 2 PHENYLINDOLE; AMIDINE; CATION; PENTAMIDINE; PHOSPHONIC ACID DERIVATIVE; WATER;

ARTICLE; BIOMIMETICS; CHEMICAL ANALYSIS; CHEMICAL STRUCTURE; DRUG BINDING; STRUCTURE ANALYSIS;

EID: 0141629383     PISSN: 15237060     EISSN: None     Source Type: Journal    
DOI: 10.1021/ol0343055     Document Type: Article

References (23)

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2. Selected examples for thrombine inhibitors: (a) Bode, W.; Turk, D.; Stürzebecher, J. Eur. J. Biochem. 1990, 193, 175-182. (b) Hilpert, K.; Ackermann, J.; Banner, D. W.; Gast, A.; Gubernator, K.; Hadvary, P.; Labler, L. ; Müller, K.; Schmid, G.; Tschopp, T. B.; van de Waterbeemd, H. J. Med. Chem. 1994, 37, 3889-3901. RGD mimetics: Stilz, H. U.; Guba, W.; Jablonka, B.; Just, M.; Klingler, O.; König, W.; Wehner, V.; Zoller, G. J. Med. Chem. 2001, 44, 1158-1167.
3. Selected examples for thrombine inhibitors: (a) Bode, W.; Turk, D.; Stürzebecher, J. Eur. J. Biochem. 1990, 193, 175-182. (b) Hilpert, K.; Ackermann, J.; Banner, D. W.; Gast, A.; Gubernator, K.; Hadvary, P.; Labler, L. ; Müller, K.; Schmid, G.; Tschopp, T. B.; van de Waterbeemd, H. J. Med. Chem. 1994, 37, 3889-3901. RGD mimetics: Stilz, H. U.; Guba, W.; Jablonka, B.; Just, M.; Klingler, O.; König, W.; Wehner, V.; Zoller, G. J. Med. Chem. 2001, 44, 1158-1167.
4. Bell, T. W.; Santora, V. J. J. Am. Chem. Soc. 1992, 114, 8300-8302. An imprinted polymer and a dendrimer capable of amidinium recognition have been described: Sellergren, B. Anal. Chem. 1994, 66, 1578-1582. Zimmerman, S. C.; Wang, Y.; Bharathi, P.; Moore, J. S. J. Am. Chem. Soc. 1998, 120, 2172-2173.
5. Bell, T. W.; Santora, V. J. J. Am. Chem. Soc. 1992, 114, 8300-8302. An imprinted polymer and a dendrimer capable of amidinium recognition have been described: Sellergren, B. Anal. Chem. 1994, 66, 1578-1582. Zimmerman, S. C.; Wang, Y.; Bharathi, P.; Moore, J. S. J. Am. Chem. Soc. 1998, 120, 2172-2173.
6. Bell, T. W.; Santora, V. J. J. Am. Chem. Soc. 1992, 114, 8300-8302. An imprinted polymer and a dendrimer capable of amidinium recognition have been described: Sellergren, B. Anal. Chem. 1994, 66, 1578-1582. Zimmerman, S. C.; Wang, Y.; Bharathi, P.; Moore, J. S. J. Am. Chem. Soc. 1998, 120, 2172-2173.
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8. Schrader, T. Chem. Eur. J. 1997, 3, 1537. Schrader, T. Tetrahedron Lett. 1998, 39, 517-520.
9. The classical amidinium phosphonate binding pattern uses only the two inner protons of the cationic guest and never gives any shifts of the outer NH protons.
10. Wilcox, C. S. In Frontiers in Supramolecular Chemistry and Photochemistry; Schneider, H.-J., Dürr, H., Eds.; VCH: Weinheim, Germany, 1991; p 123.
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15. Higher aggregates or mixed alternating arrays are highly unlikely, because the Job plots showed maxima close to X = 0.33, and sharp signals were always found in the NMR spectra.
16. -1.
17. Table 4 demonstrates the effectiveness of this second step: Usually it equals the first one in free binding enthalpy, only in the case of 6a@pentamidine and 9a@DAPI is the first complexation step considerably more exergonic than the second one.
18. Water solvates the polar headgroups, while DMSO interacts with the nonpolar centerpieces.
19. Large upfield shifts of aromatic and aliphatic host and guest proton signals of up to 0.4 ppm are produced, especially in water, indicative of dispersive interactions from π-stacking and related processes.
20. Both drugs are moderately AT-selective, rendering their binding constants higher for AT-rich sequences: Cory, M.; Tidwell, R. R.; Fairley, T. A. J. Med. Chem. 1992, 35, 431-438.
21. -2 ∼ 12 kcal/mol.
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23. Eblinger, F.; Schneider, H.-J. Angew. Chem., Int. Ed. 1998, 37, 826-829. Hossain, M. A. S.; Schneider, H.-J. Chem. Eur. J. 1999, 5, 1284-1290.