Efficient transport of aromatic amino acids by sapphyrin-lasalocid conjugates

Chemistry - A European Journal

Volumn 4, Issue 1, 1998, Pages 159-167

  Sessler, Jonathan L ^a   Andrievsky, Andrei ^a  

^a UNIVERSITY OF TEXAS AT AUSTIN   (United States)

Author keywords

Amino acid transport; Amino acids; Ionophores; Molecular recognition; Sapphyrin

Indexed keywords

EID: 0031910517     PISSN: 09476539     EISSN: None     Source Type: Journal    
DOI: 10.1002/(sici)1521-3765(199801)4:1<159::aid-chem159>3.0.co;2-n     Document Type: Article

References (126)

1. a) D. Voet, J. G. Voet, Biochemistry, 2nd ed., Wiley, New York, 1995;
2. b) C. Branden, J. Tooze, Introduction to Protein Structure, Garland, New York, 1991;
3. c) A. Fersht, Enzyme Structure and Mechanism, 2nd ed., Freeman, New York, 1985.
4. Excitatory Amino Acid Receptors (Eds.: P. Krogsgaard-Larsen, J. J. Hansen), Ellis Horwood, Chichester, 1992.
5. a) For an excellent collection of reviews on molecular recognition, see: Comprehensive Supramolecular Chemistry (Eds.: J. L. Atwood, J. E. D. Davies, D. D. Macnicol, F. Vögtle), Elsevier, Exeter, 1996. Also see:
6. b) J.-M. Lehn, Supramolecular Chemistry, VCH, Weinheim, 1995;
7. c) F. Vögtle. Supramolecular Chemistry, Wiley, Chichester, 1991.
8. For a recent review see: a) C. Seel. A. Galán, J. de Mendoza, Top. Curr. Chem. 1995, 175, 101-132, and references therein. For zwitterionic α-amino acid recognition, see:
9. b) J. Rebek, Jr., B. Askew, D. Nemeth, K. Parris, J. Am. Chem. Soc. 1987, 109, 2432-2434;
10. c) A. Galán, D. Andreu, A. M. Echavarren, P. Prados, J. de Mendoza, ibid. 1992, 114, 1511-1512;
11. d) A. Metzger, K. Gloe, H. Stephan, F. P. Schmidtchen. J. Org. Chem. 1996, 61, 2051-2055:
12. e) I. Tabushi, Y. Kuroda, T. Mizutani, J. Am. Chem. Soc. 1986, 108, 4514-4518;
13. f) Y. Aoyama, M. Asakawa, A. Yamagishi, H. Toi, H. Ogoshi, ibid. 1990, 112, 3145-3151;
14. g) J. Sunamoto, K. Iwamoto, Y. Mohri, T. Kominato, ibid. 1982, 104, 5502-5504;
15. h) S. Marx-Tibbon, I. Willner, J. Chem. Soc. Chem. Commun. 1994, 1261-1262;
16. i) R. P. Bonomo, V. Cucinotta, F. D'Allessandro, G. Impellizzeri, G. Maccarrone, E. Rizzarelli, G. Vecchio, J. Inclusion Phenom. Mol. Recognit. Chem. 1993, 15, 167-180;
17. j) R. Corradini, A. Dossena, G. Impellizzeri, G. Maccarrone, R. Marchelli, E. Rizzarelli, G. Sartor, G. Vecchio, J. Am. Chem. Soc. 1994, 116, 10267-10274:
18. k) P. Scrimin, P. Tecilla, U. Tonellato, Tetrahedron 1995, 51, 217-230;
19. l) L. K. Mohler, A. W. Czarnik, J. Am. Chem. Soc. 1993, 115, 7037-7038;
20. m) M. T. Reetz, J. Huff, J. Rudolph, K. Töllner, A. Deege, R. Goddard, ibid. 1994, 116, 11588-11589;
21. n) H. C. Chen, S. Ogo, R. H. Fish. ibid. 1996, 118, 4993-5001;
22. o) H. Tsukube, J. Uenishi, T. Kanatani, H. Itoh, O. Yonemitsu, Chem. Commun.. 1996, 477-478;
23. p) N. Higashi, M. Saitou, T. Mihara, M. Niwa, ibid. 1995, 2119-2120;
24. q) K. B. Lipkowitz, S. Raghothama, J. Yang, J. Am. Chem. Soc. 1992, 114, 1554-1562.
25. For efforts directed at the recognition of amino acids in their cationic form and of cationic amino acid esters, see: a) M. Newcomb, J. L. Toner, R. C. Helgeson, D. J. Cram, J. Am. Chem. Soc. 1979, 101, 4941-4947; b) G. D. Y. Sogah, D. J. Cram, J. Am. Chem. Soc. 1979, 101, 3035-3042; c) J.-P. Behr, J.-M. Lehn, P. Vierling, Helv. Chim. Acta 1982, 65, 1853-1867; d) M. Sawada, Y. Takai, H. Yamada, T. Kaneda, K. Kamada, T. Mizooku, K. Hirose, Y. Tobe, K. Naemura, J. Chem. Soc. Chem. Commun. 1994, 2497-2498; e) S.-K. Chang, H.-S. Hwang, H. Son, J. Youk, Y. S. Kang, ibid. 1991, 217-218; f) K. Maruyama, H. Sohmiya, H. Tsukube, ibid. 1989, 864-865; g) H. Miyake, T. Yamashita, Y. Kojima, H. Tsukube, Tetrahedron Lett. 1995, 36, 7669-7672. For work on the recognition of neutral amino acid esters, see: h) Y. Kuroda, Y. Kato, T. Higashioji, J. Hasegawa, S. Kawanami, M. Takahashi, N. Shiraishi, K. Tanabe, H. Ogoshi, J. Am. Chem. Soc. 1995, 117, 10950-10958, and references therein; i) M. J. Crossley, L. G. Mackay, A. C. Try, J. Chem. Soc. Chem. Commun. 1995, 1925-1927.
26. For efforts directed at the recognition of amino acids in their cationic form and of cationic amino acid esters, see: a) M. Newcomb, J. L. Toner, R. C. Helgeson, D. J. Cram, J. Am. Chem. Soc. 1979, 101, 4941-4947; b) G. D. Y. Sogah, D. J. Cram, J. Am. Chem. Soc. 1979, 101, 3035-3042; c) J.-P. Behr, J.-M. Lehn, P. Vierling, Helv. Chim. Acta 1982, 65, 1853-1867; d) M. Sawada, Y. Takai, H. Yamada, T. Kaneda, K. Kamada, T. Mizooku, K. Hirose, Y. Tobe, K. Naemura, J. Chem. Soc. Chem. Commun. 1994, 2497-2498; e) S.-K. Chang, H.-S. Hwang, H. Son, J. Youk, Y. S. Kang, ibid. 1991, 217-218; f) K. Maruyama, H. Sohmiya, H. Tsukube, ibid. 1989, 864-865; g) H. Miyake, T. Yamashita, Y. Kojima, H. Tsukube, Tetrahedron Lett. 1995, 36, 7669-7672. For work on the recognition of neutral amino acid esters, see: h) Y. Kuroda, Y. Kato, T. Higashioji, J. Hasegawa, S. Kawanami, M. Takahashi, N. Shiraishi, K. Tanabe, H. Ogoshi, J. Am. Chem. Soc. 1995, 117, 10950-10958, and references therein; i) M. J. Crossley, L. G. Mackay, A. C. Try, J. Chem. Soc. Chem. Commun. 1995, 1925-1927.
27. For efforts directed at the recognition of amino acids in their cationic form and of cationic amino acid esters, see: a) M. Newcomb, J. L. Toner, R. C. Helgeson, D. J. Cram, J. Am. Chem. Soc. 1979, 101, 4941-4947; b) G. D. Y. Sogah, D. J. Cram, J. Am. Chem. Soc. 1979, 101, 3035-3042; c) J.-P. Behr, J.-M. Lehn, P. Vierling, Helv. Chim. Acta 1982, 65, 1853-1867; d) M. Sawada, Y. Takai, H. Yamada, T. Kaneda, K. Kamada, T. Mizooku, K. Hirose, Y. Tobe, K. Naemura, J. Chem. Soc. Chem. Commun. 1994, 2497-2498; e) S.-K. Chang, H.-S. Hwang, H. Son, J. Youk, Y. S. Kang, ibid. 1991, 217-218; f) K. Maruyama, H. Sohmiya, H. Tsukube, ibid. 1989, 864-865; g) H. Miyake, T. Yamashita, Y. Kojima, H. Tsukube, Tetrahedron Lett. 1995, 36, 7669-7672. For work on the recognition of neutral amino acid esters, see: h) Y. Kuroda, Y. Kato, T. Higashioji, J. Hasegawa, S. Kawanami, M. Takahashi, N. Shiraishi, K. Tanabe, H. Ogoshi, J. Am. Chem. Soc. 1995, 117, 10950-10958, and references therein; i) M. J. Crossley, L. G. Mackay, A. C. Try, J. Chem. Soc. Chem. Commun. 1995, 1925-1927.
28. For efforts directed at the recognition of amino acids in their cationic form and of cationic amino acid esters, see: a) M. Newcomb, J. L. Toner, R. C. Helgeson, D. J. Cram, J. Am. Chem. Soc. 1979, 101, 4941-4947; b) G. D. Y. Sogah, D. J. Cram, J. Am. Chem. Soc. 1979, 101, 3035-3042; c) J.-P. Behr, J.-M. Lehn, P. Vierling, Helv. Chim. Acta 1982, 65, 1853-1867; d) M. Sawada, Y. Takai, H. Yamada, T. Kaneda, K. Kamada, T. Mizooku, K. Hirose, Y. Tobe, K. Naemura, J. Chem. Soc. Chem. Commun. 1994, 2497-2498; e) S.-K. Chang, H.-S. Hwang, H. Son, J. Youk, Y. S. Kang, ibid. 1991, 217-218; f) K. Maruyama, H. Sohmiya, H. Tsukube, ibid. 1989, 864-865; g) H. Miyake, T. Yamashita, Y. Kojima, H. Tsukube, Tetrahedron Lett. 1995, 36, 7669-7672. For work on the recognition of neutral amino acid esters, see: h) Y. Kuroda, Y. Kato, T. Higashioji, J. Hasegawa, S. Kawanami, M. Takahashi, N. Shiraishi, K. Tanabe, H. Ogoshi, J. Am. Chem. Soc. 1995, 117, 10950-10958, and references therein; i) M. J. Crossley, L. G. Mackay, A. C. Try, J. Chem. Soc. Chem. Commun. 1995, 1925-1927.
29. For efforts directed at the recognition of amino acids in their cationic form and of cationic amino acid esters, see: a) M. Newcomb, J. L. Toner, R. C. Helgeson, D. J. Cram, J. Am. Chem. Soc. 1979, 101, 4941-4947; b) G. D. Y. Sogah, D. J. Cram, J. Am. Chem. Soc. 1979, 101, 3035-3042; c) J.-P. Behr, J.-M. Lehn, P. Vierling, Helv. Chim. Acta 1982, 65, 1853-1867; d) M. Sawada, Y. Takai, H. Yamada, T. Kaneda, K. Kamada, T. Mizooku, K. Hirose, Y. Tobe, K. Naemura, J. Chem. Soc. Chem. Commun. 1994, 2497-2498; e) S.-K. Chang, H.-S. Hwang, H. Son, J. Youk, Y. S. Kang, ibid. 1991, 217-218; f) K. Maruyama, H. Sohmiya, H. Tsukube, ibid. 1989, 864-865; g) H. Miyake, T. Yamashita, Y. Kojima, H. Tsukube, Tetrahedron Lett. 1995, 36, 7669-7672. For work on the recognition of neutral amino acid esters, see: h) Y. Kuroda, Y. Kato, T. Higashioji, J. Hasegawa, S. Kawanami, M. Takahashi, N. Shiraishi, K. Tanabe, H. Ogoshi, J. Am. Chem. Soc. 1995, 117, 10950-10958, and references therein; i) M. J. Crossley, L. G. Mackay, A. C. Try, J. Chem. Soc. Chem. Commun. 1995, 1925-1927.
30. For efforts directed at the recognition of amino acids in their cationic form and of cationic amino acid esters, see: a) M. Newcomb, J. L. Toner, R. C. Helgeson, D. J. Cram, J. Am. Chem. Soc. 1979, 101, 4941-4947; b) G. D. Y. Sogah, D. J. Cram, J. Am. Chem. Soc. 1979, 101, 3035-3042; c) J.-P. Behr, J.-M. Lehn, P. Vierling, Helv. Chim. Acta 1982, 65, 1853-1867; d) M. Sawada, Y. Takai, H. Yamada, T. Kaneda, K. Kamada, T. Mizooku, K. Hirose, Y. Tobe, K. Naemura, J. Chem. Soc. Chem. Commun. 1994, 2497-2498; e) S.-K. Chang, H.-S. Hwang, H. Son, J. Youk, Y. S. Kang, ibid. 1991, 217-218; f) K. Maruyama, H. Sohmiya, H. Tsukube, ibid. 1989, 864-865; g) H. Miyake, T. Yamashita, Y. Kojima, H. Tsukube, Tetrahedron Lett. 1995, 36, 7669-7672. For work on the recognition of neutral amino acid esters, see: h) Y. Kuroda, Y. Kato, T. Higashioji, J. Hasegawa, S. Kawanami, M. Takahashi, N. Shiraishi, K. Tanabe, H. Ogoshi, J. Am. Chem. Soc. 1995, 117, 10950-10958, and references therein; i) M. J. Crossley, L. G. Mackay, A. C. Try, J. Chem. Soc. Chem. Commun. 1995, 1925-1927.
31. For efforts directed at the recognition of amino acids in their cationic form and of cationic amino acid esters, see: a) M. Newcomb, J. L. Toner, R. C. Helgeson, D. J. Cram, J. Am. Chem. Soc. 1979, 101, 4941-4947; b) G. D. Y. Sogah, D. J. Cram, J. Am. Chem. Soc. 1979, 101, 3035-3042; c) J.-P. Behr, J.-M. Lehn, P. Vierling, Helv. Chim. Acta 1982, 65, 1853-1867; d) M. Sawada, Y. Takai, H. Yamada, T. Kaneda, K. Kamada, T. Mizooku, K. Hirose, Y. Tobe, K. Naemura, J. Chem. Soc. Chem. Commun. 1994, 2497-2498; e) S.-K. Chang, H.-S. Hwang, H. Son, J. Youk, Y. S. Kang, ibid. 1991, 217-218; f) K. Maruyama, H. Sohmiya, H. Tsukube, ibid. 1989, 864-865; g) H. Miyake, T. Yamashita, Y. Kojima, H. Tsukube, Tetrahedron Lett. 1995, 36, 7669-7672. For work on the recognition of neutral amino acid esters, see: h) Y. Kuroda, Y. Kato, T. Higashioji, J. Hasegawa, S. Kawanami, M. Takahashi, N. Shiraishi, K. Tanabe, H. Ogoshi, J. Am. Chem. Soc. 1995, 117, 10950-10958, and references therein; i) M. J. Crossley, L. G. Mackay, A. C. Try, J. Chem. Soc. Chem. Commun. 1995, 1925-1927.
32. For efforts directed at the recognition of amino acids in their cationic form and of cationic amino acid esters, see: a) M. Newcomb, J. L. Toner, R. C. Helgeson, D. J. Cram, J. Am. Chem. Soc. 1979, 101, 4941-4947; b) G. D. Y. Sogah, D. J. Cram, J. Am. Chem. Soc. 1979, 101, 3035-3042; c) J.-P. Behr, J.-M. Lehn, P. Vierling, Helv. Chim. Acta 1982, 65, 1853-1867; d) M. Sawada, Y. Takai, H. Yamada, T. Kaneda, K. Kamada, T. Mizooku, K. Hirose, Y. Tobe, K. Naemura, J. Chem. Soc. Chem. Commun. 1994, 2497-2498; e) S.-K. Chang, H.-S. Hwang, H. Son, J. Youk, Y. S. Kang, ibid. 1991, 217-218; f) K. Maruyama, H. Sohmiya, H. Tsukube, ibid. 1989, 864-865; g) H. Miyake, T. Yamashita, Y. Kojima, H. Tsukube, Tetrahedron Lett. 1995, 36, 7669-7672. For work on the recognition of neutral amino acid esters, see: h) Y. Kuroda, Y. Kato, T. Higashioji, J. Hasegawa, S. Kawanami, M. Takahashi, N. Shiraishi, K. Tanabe, H. Ogoshi, J. Am. Chem. Soc. 1995, 117, 10950-10958, and references therein; i) M. J. Crossley, L. G. Mackay, A. C. Try, J. Chem. Soc. Chem. Commun. 1995, 1925-1927.
33. For efforts directed at the recognition of amino acids in their cationic form and of cationic amino acid esters, see: a) M. Newcomb, J. L. Toner, R. C. Helgeson, D. J. Cram, J. Am. Chem. Soc. 1979, 101, 4941-4947; b) G. D. Y. Sogah, D. J. Cram, J. Am. Chem. Soc. 1979, 101, 3035-3042; c) J.-P. Behr, J.-M. Lehn, P. Vierling, Helv. Chim. Acta 1982, 65, 1853-1867; d) M. Sawada, Y. Takai, H. Yamada, T. Kaneda, K. Kamada, T. Mizooku, K. Hirose, Y. Tobe, K. Naemura, J. Chem. Soc. Chem. Commun. 1994, 2497-2498; e) S.-K. Chang, H.-S. Hwang, H. Son, J. Youk, Y. S. Kang, ibid. 1991, 217-218; f) K. Maruyama, H. Sohmiya, H. Tsukube, ibid. 1989, 864-865; g) H. Miyake, T. Yamashita, Y. Kojima, H. Tsukube, Tetrahedron Lett. 1995, 36, 7669-7672. For work on the recognition of neutral amino acid esters, see: h) Y. Kuroda, Y. Kato, T. Higashioji, J. Hasegawa, S. Kawanami, M. Takahashi, N. Shiraishi, K. Tanabe, H. Ogoshi, J. Am. Chem. Soc. 1995, 117, 10950-10958, and references therein; i) M. J. Crossley, L. G. Mackay, A. C. Try, J. Chem. Soc. Chem. Commun. 1995, 1925-1927.
34. For studies involving the recognition of amino acids in their anionic forms and of N-protected amino acids, see: a) V. Alcazar, F. Diederich, Angew. Chem. 1992, 104, 1503-1505; Angew. Chem. Int. Ed. Engl. 1992, 31, 1521-1523;
35. For studies involving the recognition of amino acids in their anionic forms and of N-protected amino acids, see: a) V. Alcazar, F. Diederich, Angew. Chem. 1992, 104, 1503-1505; Angew. Chem. Int. Ed. Engl. 1992, 31, 1521-1523;
36. b) R. J. Pieters, F. Diederich, Chem. Commun., 1996, 2255-2256;
37. c) K. Maruyama, H. Tsukube, T. Araki, J. Am. Chem. Soc. 1982, 104, 5197-5203;
38. d) H. Tsukube, Tetrahedron Lett. 1981, 22, 3981-3984;
39. e) K. Maruyama, H. Tsukube, T. Araki, ibid. 1981, 22, 2001-2004;
40. f) G. J. Pernia, J. D. Kilburn, M. Rowley, J. Chem. Soc. Chem. Commun. 1995, 305-306;
41. g) H. Kataoka, T. Katagi, Tetrahedron 1987, 43, 4519-4530;
42. h) K. Konishi, K. Yahara, H. Toshishige, T. Aida, S. Inoue, J. Am. Chem. Soc. 1994, 116, 1337-1344;
43. i) M. Zinic, L. Frkanec, V. Skaric, J. Trafton, G. W. Gokel, J. Chem. Soc. Chem. Commun. 1990, 1726-1728.
44. Issues relevant to the analytical chemistry of amino acids are discussed in Amino Acid Analysis (Ed.: J. M. Rattenbury), Ellis Horwood, Chichester, 1981.
45. a) For a short review, see: H.-J. Schneider, Angew. Chem. 1993, 105, 890-892; Angew. Chem. Int. Ed. Engl. 1993, 32, 848-850. A number of excellent peptide receptors have been prepared in the Still laboratory:
46. a) For a short review, see: H.-J. Schneider, Angew. Chem. 1993, 105, 890-892; Angew. Chem. Int. Ed. Engl. 1993, 32, 848-850. A number of excellent peptide receptors have been prepared in the Still laboratory:
47. b) G. Li, W. C. Still, J. Org. Chem. 1991, 56, 6964-6966;
48. c) J.-I. Hong, S. K. Namgoong, A. Bernardi, W. C. Still, J. Am. Chem. Soc. 1991, 113, 5111-5112;
49. d) S. S. Yoon, W. C. Still, ibid. 1993, 115, 823-824. For other peptide recognition work, see:
50. e) J. S. Albert, M.S. Goodman, A. D. Hamilton, ibid. 1995, 117, 1143-1144;
51. f) K. Konishi, S. Kimata, K. Yoshida, M. Tanaka, T. Aida, Angew. Chem. 1996, 108, 3001-3003; Angew. Chem. Int. Ed. Engl. 1996, 35, 2823-2825;
52. f) K. Konishi, S. Kimata, K. Yoshida, M. Tanaka, T. Aida, Angew. Chem. 1996, 108, 3001-3003; Angew. Chem. Int. Ed. Engl. 1996, 35, 2823-2825;
53. g) C. P. Waymark, J. D. Kilburn, I. Gillies, Teterahedron Lett. 1995, 36, 3051-3054;
54. h) J. Dowden, P. D. Edwards, J. D. Kilburn, Tetrahedron Lett. 1997, 38, 1095-1098.
55. a) H. Furuta, K. Furuta, J. L. Sessler, J. Am. Chem. Soc. 1991, 113, 4706-4707;
56. b) J. L. Sessler, D. A. Ford, M. J. Cyr, H. Furuta, J. Chem. Soc. Chem. Commun. 1991, 1733-1735;
57. c) J. L. Sessler, T. D. Mody, D. A. Ford, V. Lynch, Angew. Chem. 1992, 104, 461-464; Angew. Chem. Int. Ed. Engl. 1992, 31, 452-455;
58. c) J. L. Sessler, T. D. Mody, D. A. Ford, V. Lynch, Angew. Chem. 1992, 104, 461-464; Angew. Chem. Int. Ed. Engl. 1992, 31, 452-455;
59. d) V. Král, J. L. Sessler, H. Furuta, J. Am. Chem. Soc. 1992, 114, 8704-8705;
60. e) J. L. Sessler, H. Furuta, V. Král, Supramol. Chem. 1993, 1, 209-220;
61. f) V. Král, J. L. Sessler, Tetrahedron 1995, 51, 539-554;
62. g) V. Král, A. Andrievsky, J. L. Sessler, J. Chem. Soc. Chem. Commun. 1995, 2349-2351;
63. h) V. Král, A. Andrievsky, J. L. Sessler, Am. Chem. Soc. 1995, 117, 2953-2954.
64. For reviews of biological amino acid transport systems, see: a) Mammalian Amino Acid Transport. Mechanisms and Control (Ed.: M.S. Kilberg, D. Häussinger). Plenum. New York. 1992; b) M. S. Kilberg, B. R. Stevens, D. A. Novak, Annu. Rev. Nutr. 1993, 13, 137-165; c) K. Ring, Angew. Chem. 1970, 82, 343-355; Angew. Chem. Int. Ed. Engl. 1970, 9, 345-356.
65. For reviews of biological amino acid transport systems, see: a) Mammalian Amino Acid Transport. Mechanisms and Control (Ed.: M.S. Kilberg, D. Häussinger). Plenum. New York. 1992; b) M. S. Kilberg, B. R. Stevens, D. A. Novak, Annu. Rev. Nutr. 1993, 13, 137-165; c) K. Ring, Angew. Chem. 1970, 82, 343-355; Angew. Chem. Int. Ed. Engl. 1970, 9, 345-356.
66. For reviews of biological amino acid transport systems, see: a) Mammalian Amino Acid Transport. Mechanisms and Control (Ed.: M.S. Kilberg, D. Häussinger). Plenum. New York. 1992; b) M. S. Kilberg, B. R. Stevens, D. A. Novak, Annu. Rev. Nutr. 1993, 13, 137-165; c) K. Ring, Angew. Chem. 1970, 82, 343-355; Angew. Chem. Int. Ed. Engl. 1970, 9, 345-356.
67. For reviews of biological amino acid transport systems, see: a) Mammalian Amino Acid Transport. Mechanisms and Control (Ed.: M.S. Kilberg, D. Häussinger). Plenum. New York. 1992; b) M. S. Kilberg, B. R. Stevens, D. A. Novak, Annu. Rev. Nutr. 1993, 13, 137-165; c) K. Ring, Angew. Chem. 1970, 82, 343-355; Angew. Chem. Int. Ed. Engl. 1970, 9, 345-356.
68. For a review about stereochemical aspects of molecular recognition, see: T. H. Webb, C. S. Wilcox, Chem. Soc. Rev. 1993, 383-395.
69. a) C. J. Pederson, J. Am. Chem. Soc. 1967, 89, 7017-7036.
70. b) For a discussion see also refs. [4a,b], and [5c].
71. a) J.-P. Behr, J.-M. Lehn, J. Am. Chem. Soc. 1973, 95, 6108-6110.
72. b) See also refs. [5a,e,g,6c-e,g,i]. However, several groups have succeeded in effecting the trans-membrane transport of zwitterionic amino acids under neutral conditions: see refs. [4a-d,f-h,k-m].
73. For reviews about sapphyrins and other expanded porphyrins, see: a) J. L. Sessler, A. K. Burrell. Top. Curr. Chem. 1991, 161, 176-273; b) J. L. Sessler, A. K. Burrell, H. Furuta, G. W. Hemmi, B. L. Iverson, V. Král, D. J. Magda, T. D. Mody, K. Shreder, D. Smith, S. J. Weghorn, in Transition Metals in Supramolecular Chemistry, NATO ASI Series (Eds.: L. Fabbrizzi, A. Poggi), Kluwer, Amsterdam, 1994, 391-408; J. L. Sessler, S. J. Weghorn, Expanded, Contracted, and Isomeric Porphvrins, Elsevier, London, 1997, in press; d) J. L. Sessler, M. Cyr, H. Furuta, V. Král, T. Mody, T. Morishima, M. Shionoya, S. J. Weghorn, Pure Appl. Chem. 1993, 65, 393-398; e) B. L. Iverson, K. Shreder, V. Král, D. A. Smith, J. Smith, J. L. Sessler, ibid. 1994, 66, 845-850.
74. For reviews about sapphyrins and other expanded porphyrins, see: a) J. L. Sessler, A. K. Burrell. Top. Curr. Chem. 1991, 161, 176-273; b) J. L. Sessler, A. K. Burrell, H. Furuta, G. W. Hemmi, B. L. Iverson, V. Král, D. J. Magda, T. D. Mody, K. Shreder, D. Smith, S. J. Weghorn, in Transition Metals in Supramolecular Chemistry, NATO ASI Series (Eds.: L. Fabbrizzi, A. Poggi), Kluwer, Amsterdam, 1994, 391-408; J. L. Sessler, S. J. Weghorn, Expanded, Contracted, and Isomeric Porphvrins, Elsevier, London, 1997, in press; d) J. L. Sessler, M. Cyr, H. Furuta, V. Král, T. Mody, T. Morishima, M. Shionoya, S. J. Weghorn, Pure Appl. Chem. 1993, 65, 393-398; e) B. L. Iverson, K. Shreder, V. Král, D. A. Smith, J. Smith, J. L. Sessler, ibid. 1994, 66, 845-850.
75. For reviews about sapphyrins and other expanded porphyrins, see: a) J. L. Sessler, A. K. Burrell. Top. Curr. Chem. 1991, 161, 176-273; b) J. L. Sessler, A. K. Burrell, H. Furuta, G. W. Hemmi, B. L. Iverson, V. Král, D. J. Magda, T. D. Mody, K. Shreder, D. Smith, S. J. Weghorn, in Transition Metals in Supramolecular Chemistry, NATO ASI Series (Eds.: L. Fabbrizzi, A. Poggi), Kluwer, Amsterdam, 1994, 391-408; c) J. L. Sessler, S. J. Weghorn, Expanded, Contracted, and Isomeric Porphvrins, Elsevier, London, 1997, in press; d) J. L. Sessler, M. Cyr, H. Furuta, V. Král, T. Mody, T. Morishima, M. Shionoya, S. J. Weghorn, Pure Appl. Chem. 1993, 65, 393-398; e) B. L. Iverson, K. Shreder, V. Král, D. A. Smith, J. Smith, J. L. Sessler, ibid. 1994, 66, 845-850.
76. For reviews about sapphyrins and other expanded porphyrins, see: a) J. L. Sessler, A. K. Burrell. Top. Curr. Chem. 1991, 161, 176-273; b) J. L. Sessler, A. K. Burrell, H. Furuta, G. W. Hemmi, B. L. Iverson, V. Král, D. J. Magda, T. D. Mody, K. Shreder, D. Smith, S. J. Weghorn, in Transition Metals in Supramolecular Chemistry, NATO ASI Series (Eds.: L. Fabbrizzi, A. Poggi), Kluwer, Amsterdam, 1994, 391-408; J. L. Sessler, S. J. Weghorn, Expanded, Contracted, and Isomeric Porphvrins, Elsevier, London, 1997, in press; d) J. L. Sessler, M. Cyr, H. Furuta, V. Král, T. Mody, T. Morishima, M. Shionoya, S. J. Weghorn, Pure Appl. Chem. 1993, 65, 393-398; e) B. L. Iverson, K. Shreder, V. Král, D. A. Smith, J. Smith, J. L. Sessler, ibid. 1994, 66, 845-850.
77. For reviews about sapphyrins and other expanded porphyrins, see: a) J. L. Sessler, A. K. Burrell. Top. Curr. Chem. 1991, 161, 176-273; b) J. L. Sessler, A. K. Burrell, H. Furuta, G. W. Hemmi, B. L. Iverson, V. Král, D. J. Magda, T. D. Mody, K. Shreder, D. Smith, S. J. Weghorn, in Transition Metals in Supramolecular Chemistry, NATO ASI Series (Eds.: L. Fabbrizzi, A. Poggi), Kluwer, Amsterdam, 1994, 391-408; J. L. Sessler, S. J. Weghorn, Expanded, Contracted, and Isomeric Porphvrins, Elsevier, London, 1997, in press; d) J. L. Sessler, M. Cyr, H. Furuta, V. Král, T. Mody, T. Morishima, M. Shionoya, S. J. Weghorn, Pure Appl. Chem. 1993, 65, 393-398; e) B. L. Iverson, K. Shreder, V. Král, D. A. Smith, J. Smith, J. L. Sessler, ibid. 1994, 66, 845-850.
78. a) V. Král, H. Furuta, K. Shreder, V. Lynch, J. L. Sessler, J. Am. Chem. Soc. 1996, 118, 1595-1607;
79. b) B. L. Iverson, K. Shreder, V. Král, P. I. Sansom, V. Lynch, J. L. Sessler, ibid. 1996, 118, 1608-1616;
80. c) J. L. Sessler, M. J. Cyr, V. Lynch, E. McGhee, J. A. Ibers. ibid. 1990, 112, 2810-2813;
81. d) M. Shionoya, H. Furuta, V. Lynch, A. Harriman, J. L. Sessler, ibid. 1992, 114, 5714-5722;
82. e) J. L. Sessler, A. Andrievsky, Chem. Commun., 1996, 1119-1120;
83. f) J. L. Sessler, P. I. Sansom, V. Král, D. O'Connor, B. L. Iverson, J Am. Chem. Soc. 1996, 118, 12323-12330.
84. a) V. Král, S. L. Springs, J. L. Sessler, J. Am. Chem. Soc. 1995, 117, 8881-8882;
85. b) J. L. Sessler, A. Andrievsky, P. A. Gale, V. Lynch, Angew. Chem. 1996, 108, 2954-2957; Angew. Chem. Int. Ed. Engl. 1996, 35, 2782-2785.
86. b) J. L. Sessler, A. Andrievsky, P. A. Gale, V. Lynch, Angew. Chem. 1996, 108, 2954-2957; Angew. Chem. Int. Ed. Engl. 1996, 35, 2782-2785.
87. h) V. Král, A. Andrievsky, J. L. Sessler, Am. Chem. Soc. 1995, 117, 2953-2954.
88. Two different carboxylate anion complexes of protonated pentaazasapphyrin macrocycles have been structurally characterized in the solid state: firstly, the sapphyrin bisacid 3,12,13,22-tetraethyl-8,17-bis(carboxyethyl)-2,7,18,23-tetramethylsapphyrin has been found to form a supramolecular dimer in the solid state (see ref. [16b]). In this case, a carboxylate hook from one molecule is chelated to the protonated pyrrolic core of the second macrocycle. Simultaneously, this second macrocycle shares its carboxylate tail with the first sapphyrin subunit. A trifluoroacetate ion is coordinated to each of unchelated faces in the dimer and prevents these sites from being involved in further binding. The second example consists of a 2:1 complex formed between trifluoroacetic acid and the diprotonated form of 3,8,12,13,17,22-hexaethyl-2,7,18,23-tetramethylsapphyrin. In this case, the TFA carboxylate anion is chelated above the plane of the protonated sapphyrin macrocycle by a combination of electrostatic attractions and hydrogen bonding involving the ligated oxygen atom and the pyrrolic hydrogens: J. L. Sessler, A. Andrievsky, V. Lynch, unpublished results. The available solution data is consistent with this kind of binding occuring in organic media (ref. [16]).
89. a) M. Dobler, Ionophores and Their Structures, Wiley, New York. 1981;
90. b) R. Hilgenfeld, W. Saenger, Top. Curr. Chem. 1982, 101, 1-82;
91. c) G. R. Painter, B. C. Pressman, ibid. 1982, 101, 83-110.
92. For examples of metal cation complexation by lasalocid, see a) ref. [18]; b) R. Lyazghi, Y. Pointud, G. Dauphin, J. Juillard, J. Chem. Soc. Perkin Trans. 2 1993, 1681-1686, and references therein; c) H. Tsukube, K. Takagi, T. Higashiyama, T. Iwachido, N. Hayama, Inorg. Chem. 1994, 33, 2984-2987, and references therein. For examples of adducts of lasalocid with metal complexes, see: d) P. S. K. Chia, L. F. Lindoy, G. W. Walker, G. W. Everett, Pure Appl. Chem. 1993, 65, 521-526, and references therein; e) R. Ballardini, M. T. Gandolfi, M. L. Moya, L. Prodi, V. Balzani, Isr. J. Chem. 1992, 32, 47-51.
93. For examples of metal cation complexation by lasalocid, see a) ref. [18]; b) R. Lyazghi, Y. Pointud, G. Dauphin, J. Juillard, J. Chem. Soc. Perkin Trans. 2 1993, 1681-1686, and references therein; c) H. Tsukube, K. Takagi, T. Higashiyama, T. Iwachido, N. Hayama, Inorg. Chem. 1994, 33, 2984-2987, and references therein. For examples of adducts of lasalocid with metal complexes, see: d) P. S. K. Chia, L. F. Lindoy, G. W. Walker, G. W. Everett, Pure Appl. Chem. 1993, 65, 521-526, and references therein; e) R. Ballardini, M. T. Gandolfi, M. L. Moya, L. Prodi, V. Balzani, Isr. J. Chem. 1992, 32, 47-51.
94. For examples of metal cation complexation by lasalocid, see a) ref. [18]; b) R. Lyazghi, Y. Pointud, G. Dauphin, J. Juillard, J. Chem. Soc. Perkin Trans. 2 1993, 1681-1686, and references therein; c) H. Tsukube, K. Takagi, T. Higashiyama, T. Iwachido, N. Hayama, Inorg. Chem. 1994, 33, 2984-2987, and references therein. For examples of adducts of lasalocid with metal complexes, see: d) P. S. K. Chia, L. F. Lindoy, G. W. Walker, G. W. Everett, Pure Appl. Chem. 1993, 65, 521-526, and references therein; e) R. Ballardini, M. T. Gandolfi, M. L. Moya, L. Prodi, V. Balzani, Isr. J. Chem. 1992, 32, 47-51.
95. For examples of metal cation complexation by lasalocid, see a) ref. [18]; b) R. Lyazghi, Y. Pointud, G. Dauphin, J. Juillard, J. Chem. Soc. Perkin Trans. 2 1993, 1681-1686, and references therein; c) H. Tsukube, K. Takagi, T. Higashiyama, T. Iwachido, N. Hayama, Inorg. Chem. 1994, 33, 2984-2987, and references therein. For examples of adducts of lasalocid with metal complexes, see: d) P. S. K. Chia, L. F. Lindoy, G. W. Walker, G. W. Everett, Pure Appl. Chem. 1993, 65, 521-526, and references therein; e) R. Ballardini, M. T. Gandolfi, M. L. Moya, L. Prodi, V. Balzani, Isr. J. Chem. 1992, 32, 47-51.
96. For examples of metal cation complexation by lasalocid, see a) ref. [18]; b) R. Lyazghi, Y. Pointud, G. Dauphin, J. Juillard, J. Chem. Soc. Perkin Trans. 2 1993, 1681-1686, and references therein; c) H. Tsukube, K. Takagi, T. Higashiyama, T. Iwachido, N. Hayama, Inorg. Chem. 1994, 33, 2984-2987, and references therein. For examples of adducts of lasalocid with metal complexes, see: d) P. S. K. Chia, L. F. Lindoy, G. W. Walker, G. W. Everett, Pure Appl. Chem. 1993, 65, 521-526, and references therein; e) R. Ballardini, M. T. Gandolfi, M. L. Moya, L. Prodi, V. Balzani, Isr. J. Chem. 1992, 32, 47-51.
97. For examples of ammonium cation binding by lasalocid and its derivatives, see: a) J. W. Westley, R. H. Evans, Jr., J. F. Blount, J. Am. Chem. Soc. 1977, 99, 6057-6061; b) H. Tsukube, H. Sohmiya, J. Org. Chem. 1991, 56, 875-878; c) H. Tsukube, H. Sohmiya, Supramol. Chem. 1993, 1, 297-304, and references therein; d) R. C. R. Gueco, G. W. Everett, Tetrahedron 1985, 41, 4437-4442; e) J. F. Kinsel, E. I. Melnik, S. Lindenbaum, L. A. Sternson, Yu. A. Ovchinnikov, Biochim. Biophys. Acta 1982, 684, 233-240; f) J. F. Kinsel, E. I. Melnik, L. A. Sternson, S. Lindenbaum, Yu. A. Ovchinnikov. ibid. 1982, 692, 377-383; g) C. Shen, D. J. Patel, Proc. Natl. Acad. Sci. USA 1977, 74, 4734-4738.
98. For examples of ammonium cation binding by lasalocid and its derivatives, see: a) J. W. Westley, R. H. Evans, Jr., J. F. Blount, J. Am. Chem. Soc. 1977, 99, 6057-6061; b) H. Tsukube, H. Sohmiya, J. Org. Chem. 1991, 56, 875-878; c) H. Tsukube, H. Sohmiya, Supramol. Chem. 1993, 1, 297-304, and references therein; d) R. C. R. Gueco, G. W. Everett, Tetrahedron 1985, 41, 4437-4442; e) J. F. Kinsel, E. I. Melnik, S. Lindenbaum, L. A. Sternson, Yu. A. Ovchinnikov, Biochim. Biophys. Acta 1982, 684, 233-240; f) J. F. Kinsel, E. I. Melnik, L. A. Sternson, S. Lindenbaum, Yu. A. Ovchinnikov. ibid. 1982, 692, 377-383; g) C. Shen, D. J. Patel, Proc. Natl. Acad. Sci. USA 1977, 74, 4734-4738.
99. For examples of ammonium cation binding by lasalocid and its derivatives, see: a) J. W. Westley, R. H. Evans, Jr., J. F. Blount, J. Am. Chem. Soc. 1977, 99, 6057-6061; b) H. Tsukube, H. Sohmiya, J. Org. Chem. 1991, 56, 875-878; c) H. Tsukube, H. Sohmiya, Supramol. Chem. 1993, 1, 297-304, and references therein; d) R. C. R. Gueco, G. W. Everett, Tetrahedron 1985, 41, 4437-4442; e) J. F. Kinsel, E. I. Melnik, S. Lindenbaum, L. A. Sternson, Yu. A. Ovchinnikov, Biochim. Biophys. Acta 1982, 684, 233-240; f) J. F. Kinsel, E. I. Melnik, L. A. Sternson, S. Lindenbaum, Yu. A. Ovchinnikov. ibid. 1982, 692, 377-383; g) C. Shen, D. J. Patel, Proc. Natl. Acad. Sci. USA 1977, 74, 4734-4738.
100. For examples of ammonium cation binding by lasalocid and its derivatives, see: a) J. W. Westley, R. H. Evans, Jr., J. F. Blount, J. Am. Chem. Soc. 1977, 99, 6057-6061; b) H. Tsukube, H. Sohmiya, J. Org. Chem. 1991, 56, 875-878; c) H. Tsukube, H. Sohmiya, Supramol. Chem. 1993, 1, 297-304, and references therein; d) R. C. R. Gueco, G. W. Everett, Tetrahedron 1985, 41, 4437-4442; e) J. F. Kinsel, E. I. Melnik, S. Lindenbaum, L. A. Sternson, Yu. A. Ovchinnikov, Biochim. Biophys. Acta 1982, 684, 233-240; f) J. F. Kinsel, E. I. Melnik, L. A. Sternson, S. Lindenbaum, Yu. A. Ovchinnikov. ibid. 1982, 692, 377-383; g) C. Shen, D. J. Patel, Proc. Natl. Acad. Sci. USA 1977, 74, 4734-4738.
101. For examples of ammonium cation binding by lasalocid and its derivatives, see: a) J. W. Westley, R. H. Evans, Jr., J. F. Blount, J. Am. Chem. Soc. 1977, 99, 6057-6061; b) H. Tsukube, H. Sohmiya, J. Org. Chem. 1991, 56, 875-878; c) H. Tsukube, H. Sohmiya, Supramol. Chem. 1993, 1, 297-304, and references therein; d) R. C. R. Gueco, G. W. Everett, Tetrahedron 1985, 41, 4437-4442; e) J. F. Kinsel, E. I. Melnik, S. Lindenbaum, L. A. Sternson, Yu. A. Ovchinnikov, Biochim. Biophys. Acta 1982, 684, 233-240; f) J. F. Kinsel, E. I. Melnik, L. A. Sternson, S. Lindenbaum, Yu. A. Ovchinnikov. ibid. 1982, 692, 377-383; g) C. Shen, D. J. Patel, Proc. Natl. Acad. Sci. USA 1977, 74, 4734-4738.
102. For examples of ammonium cation binding by lasalocid and its derivatives, see: a) J. W. Westley, R. H. Evans, Jr., J. F. Blount, J. Am. Chem. Soc. 1977, 99, 6057-6061; b) H. Tsukube, H. Sohmiya, J. Org. Chem. 1991, 56, 875-878; c) H. Tsukube, H. Sohmiya, Supramol. Chem. 1993, 1, 297-304, and references therein; d) R. C. R. Gueco, G. W. Everett, Tetrahedron 1985, 41, 4437-4442; e) J. F. Kinsel, E. I. Melnik, S. Lindenbaum, L. A. Sternson, Yu. A. Ovchinnikov, Biochim. Biophys. Acta 1982, 684, 233-240; f) J. F. Kinsel, E. I. Melnik, L. A. Sternson, S. Lindenbaum, Yu. A. Ovchinnikov. ibid. 1982, 692, 377-383; g) C. Shen, D. J. Patel, Proc. Natl. Acad. Sci. USA 1977, 74, 4734-4738.
103. For examples of ammonium cation binding by lasalocid and its derivatives, see: a) J. W. Westley, R. H. Evans, Jr., J. F. Blount, J. Am. Chem. Soc. 1977, 99, 6057-6061; b) H. Tsukube, H. Sohmiya, J. Org. Chem. 1991, 56, 875-878; c) H. Tsukube, H. Sohmiya, Supramol. Chem. 1993, 1, 297-304, and references therein; d) R. C. R. Gueco, G. W. Everett, Tetrahedron 1985, 41, 4437-4442; e) J. F. Kinsel, E. I. Melnik, S. Lindenbaum, L. A. Sternson, Yu. A. Ovchinnikov, Biochim. Biophys. Acta 1982, 684, 233-240; f) J. F. Kinsel, E. I. Melnik, L. A. Sternson, S. Lindenbaum, Yu. A. Ovchinnikov. ibid. 1982, 692, 377-383; g) C. Shen, D. J. Patel, Proc. Natl. Acad. Sci. USA 1977, 74, 4734-4738.
104. Importantly, it was shown by Tsukube that chemically modified natural polyether ionophores (i.e., as their ester or amide derivatives) retain the ability to chelate ammonium cations. In most cases improved enantioselectivity is actually observed (see ref. [20b]).
105. For reviews about sapphyrins and other expanded porphyrins, see: a) J. L. Sessler, A. K. Burrell. Top. Curr. Chem. 1991, 161, 176-273
106. A. P. Krapcho, C. S. Kuell, Syrtlh. Commun. 1990, 20, 2559-2564.
107. J. L. Sessler, G. W. Genge, A. Urbach, P. I. Sansom. Synlett 1996, 187-188.
108. H. Tsukube, Liquid Membranes: Chemical Applications (Eds.: T. Araki, H. Tsukube), CRC, Boca Raton, FL, 1990.
109. In particular, increasing the pH of the receiving phase leads to deprotonation of the sapphyrin macrocycle. This, in turn should lead to weakening of the sapphyrin-amino acid carboxylate non-covalent interactions and thus result in a release of the amino acid substrate into Aq. II.
110. Compound 1b was chosen as a control because it has a large hydrophobic tail attached to the sapphyrin macrocycle. It was prepared by coupling the sapphyrin mono acid 1a with mono-tert-butyloxycarbonylethylenediamine, using 1,1′-carbonyldiimidazole as the coupling agent (see Experimental Section).
111. It appears, however, that the sapphyrin part of the conjugate plays greater role in enhancing amino acid transport than the lasalocid part.
112. -6M) concentration. Association constants and the stoichiometric compositions of the complexes were determined by Benesi-Hilde-brand plots and by standard nonlinear curve-fitting protocols: K. A. Connors, Binding Constants, Wiley, New York, 1987. For a complete discussion, see supplementary material to ref. [9h]. Also, in the case of L-Phe, 1:1 stoichiometry was confirmed by a Job plot.
113. The salicylic hydroxy group of lasalocid is acidic enough to be deprotonated by a strong base, which, in this instance, could be either sapphyrin or NaOH.
114. Charge neutralization is required for efficient carrier-mediated transport (a corollary of Fick's first law, see ref. [25]). While we favor a model wherein the net neutralization process takes place as shown in Figure 2, a referee has suggested that it could occur in part as the result of proton transfer between oppositely charged species taking place within the lipophilic medium of the model membrane (e.g., from the primary ammonium group of an amino acid zwitterion to the salicylamide moiety of the lasalocid subunit). While at present it is difficult to distinguish between these interpretive extremes of what may well be a chemical continuum, it is important to point out that functionally (i.e., in terms of experimental prediction) they are the same.
115. d) M. Shionoya, H. Furuta, V. Lynch, A. Harriman, J. L. Sessler, ibid. 1992, 114, 5714-5722;
116. Importantly, the pH increase in question is not sufficient to change the predominant form of amino acid species in Aq. I from zwitterionic to anionic.
117. Finally, in support of proposed mechanism are the results of two negative control experiments: When either a) the pH of the initial phase, Aq. I, was made basic by means of NaOH addition (pH = 13 and the other conditions as in entry 1 of Table 1) or b) the pH was lowered by adding HCl (pH = 1, with other conditions as in entry 1 of Table 1), no amino acid transport by carrier 6 was observed.
118. a) B. L. Iverson, R. E. Thomas, V. Král, J. L. Sessler, J. Am. Chem. Soc. 1994, 116, 2663-2664;
119. b) J. L. Sessler, J. W. Genge, V. Král, B. L. Iverson, Supramol. Chem. 1996, 8, 45-52.
120. Analysis of CPK space-filling models indicated that the linker between the sapphyrin core and the carboxylate group in 13 is not long enough to allow for efficient, within-monomer carboxylate-to-sapphyrin binding. This precludes internal collapse.
121. M. Berger, F. P. Schmidtchen, J. Am. Chem. Soc. 1996, 118, 8947-8948.
122. 1H NMR dilution experiments carried out in [D2]dichloromethane.
123. The deprotected, presumably zwitterionic substance 14 displayed poor transport capabilities, just as did its congener compound 13.
124. These results, not fully understood from a mechanistic point of view, somewhat resemble those of chiral amplification, a nonlinear phenomenon observed in asymmetric catalysis: R. Noyori, Asymmetric Catalysis in Organic Synthesis, Wiley, New York, 1994.
125. The W-tube was constructed in a fashion similar to Cram's Catalytic Resolving Machine (ref. [5a]). It has two organic phases (each containing competing carrier compounds) which share the same initial phase, Aq. I, (containing a mixture of the amino acids in question). Each organic phase was put in contact with its own receiving phase (Aq. II and Aq. III). The initial Aq. I phase and both of the organic phases were continuously stirred at equal rates. The increase in concentration of amino acids in phases Aq. II and Aq. III was monitored by HPLC analysis.
126. t(D-Phe) ratio for compound 12 went up from 1.6 when measured in the U-tube to 2.1 when studied by means of the W-tube. The more complex equilibria relevant to the W-tube conditions are probably responsible for this effect.