- Email: [email protected]
Synthesis of a cradle cyclodextrin
TetrahedronLctm. Vol. 34. No. 22. pp. 3531-3X34.1993 Rimed in Cheat Britain
ocm-4039/93 $6.00+ .oo
PegcmonRwr~
Synthesis of a Cradle Cyclodextrln Zoe Pikramenou, Kermit M. Johnson, and Daniel G. Nocesa*
Departmentof Chemistryand the Centerfor FundamentalMaterialsResearch,MkhiganState University,East Lansing,Ml 48824,USA
Key Words:cyclodextrin:am crown ether: supramolectdar; cradle assembly; 2D TOCSY Abstract: Attachment of an aza crown ether at the (A,D) positions on the primary side of /3cyclodextrin (CD) has been achieved to provide a mtdti@tctional assembly whereby a metal receptor site is cradled at the bottom of the hydrophobic receptor site of the CD cup.
The synthesis of new supramolecular architectures bearing multiple recognition sites for substrate binding represents a central challenge to the study of photoinduced energy and electron transfer processes.’ Of the diverse molecular templates available for supramolecule desigu2 cyclodextrins (CD) are well suited for functionalixation with organic ligandsj and macropolycyclic receptors.4 The ability of the CD’s hydrophobic cavity to molecularly recognize substrates provides the opportunity to design multicomponent systems where structure specific interactions can perturb photochemical and photophysical processes. 5*6 In our efforts to design assemblies in which luminescence is triggered by molecular recognition, we have synthesized a cyclodextrin derivatixed with an europium aza crown (1,4,10.13-tetraoxa-7.16diazacyc1ooctadecane) at the primary side of the CD cavity.5 Red emission from the Et? center occurs when an absorption-energy transfer-emission process is established by inclusion of a light-harvesting substrate in the CD cup. Tethered at only one nitrogen, the aza crown prefers to assume a conformation that is swung away from the hydrophobic cup. Yet our energy transfer studies show that the most efficient luminescence will occur for a supramolecular assembly featuring the aza receptor site rigidly situated at the base of the CD cup, and not as a swing.’ We now report the synthesis and characterization of a double-strapped (or cradled) CD where the aza crown ether is tethered to the primary side of the CD cup via its two nitrogens. Scheme I summarizes the strategy employed in the synthesis of the cradle CD with the axa attached to the (AP) positions of the P-CD cup. Energy minimixed calculations using a Dreiding fame field as implemented by BioGraph software reveal that this attachment is least sterically constrained. As elaborated by Tabushi, reaction of the B-CD with biphenyl-4,4’-disulfonyl chloride yields a cyclodextrin rigidly capped with the biphenyl sulfonate spanning the (AD) glucosyl subunits8 Subsequent reaction with KI produces the diiodo-substituted CD, which was isolated from the
3531
3533
F2/ppm 3.0
3.5
4.0
4.5
5.0
5.5 5.5
5.0
4.5
4.0
3.5
3.0
Fl /ppm
Figure 1. The 500 MHz ‘H TOCSY spectrum of BCDU’aza at 30 ‘C. The mixing time was 120 ms.
moiety. These anomeric protons show relevant cross peaks with the remaining glucosyl protons at 3.8-4.0 ppm (H,,,,e) and at 3.5 -3.7 ppm (H&. The islands at 3.8 and 3.7 ppm. which we attribute to the aza crown methylenes adjacent to oxygen, correlate to the 3.2 and 3.5 resonances respectively. The 3.2 and 3.5 ppm peaks are consistent with assignment to aza methylene protons next to nitrogen and the CD’s Ce protons of the substituted glucose residues. It is noteworthy that the 3.5 ppm peak correlates with the remaining protons of the glucosyl subunit. In addition, the peak at 4.1 ppm correlates to the (H3,5,e) at 4.0 ppm as well as to the island at 3.7 ppm. This peak at 4.1 ppm appears to be, as in other cases,% attributed to the H4 proton of the substituted glucose rings. The correlations between carbons and protons are identified from heteronuclear multiplequantum coherence measurements. The CD proton resonances correlate to the relevant carbons as follows: Hz.4 at 3.5 -3.7 to C2 at 68 ppm and to C4 at 79 ppm; H3.5.6at 3.8-4.0 to C3,s.e at 67, 68 ppm; and Ht at 5.1 to Cl at 102 ppm. The protons on the methylenes adjacent to nitrogen, as well as the Ce protons of the glucosyl units where aza substitution occurs, cannot be assigned because of the
3534
spectral congestion. However, the axa methylenes adjacent to oxygen show proton resonances at 3.7 ppm, which correlate to the carbon signal at 64 ppm. The insertion of europium ion into the axa cradle of &C!DU 2aza was accomplished as previously described.’ Red luminescence is observed from acetonitrile solutions of p-CDU2azaDEu3+ when excited at wavelengths coincident with the ‘Le t ‘Fu transition (Xc,, = 394 nm). Steady-state luminescence spectra reveal the characteristic 5Du + ‘FJ pattern of Eu3+ ion resulting from transitions from the lowest energy 5Du excited state to the ‘FJ spin orbit manifold of the ground ~tate.~ The lifetime of the %u excited state of bCDU2axa=Eu3+ is 835 ps. Investigations of the energy transfer from guests included in the cup to the luminescent Eu” ion in the cradle am underway. Acknowledgments.The FABMS spectra were obtained in the NIH/MSU Mass Spectrometry Facility
(NIH grant DRR-00480). Financial support of this work from Ford Motor Company and the Center for Fundamentals Materials Research at Michigan State University is gratefully acknowledged. Referencesand Notes
1.
(a) Balzani, V.; Scandola F. Supramoleculur Photochemistry; Balzani, V. Ed. In Ellis Honwod Series in Physical Chemistry: West Sussex, England, 1991. (b) Lehn, J. M. Angew. Chem., Int. Ed Engl. 1988.27.89.(c) Bissell, R. A.; De Silva, P.; Gunaratne, H. Q. N.; Lynch,P.LM.; Maguim, GEM.; Sandanayake, K. R. A. S. Chem. Sot. Rev. 1992,187. 2. (a) See& C.; Vagtle, F. Angew. Chem., Int. Ed Engl. 1992.31,528. (b) An, H.; Bradshaw, J. S.; Izatt, R. M. Chem Rev. 1992,92,543.(c) Gutsche, C. D. Calixurenes; Stoddart, J. F. Ed. In Series in Monographs in Supramolecular Chemistry; Royal Society of Chemistry: Cambridge, England, 1989. (d) Gokel, G. Crown Ethers und Cryptunds; Stoddart, J. F. Ed. In Series in Monographs in Supramolecular Chemistry; Royal Society of Chemistry: Cambridge, England, 1989. 3. For reviews see : (a) Croft, A. P.; Bartsch, R. A. Tetrahedron l!W3,39,1417. (b) Tabushi, I. Tetrahedron l!M4,40, 269. 4. Willner, I.; C&en, Z. J. Chem. Sot., Chem. Commun. M3.1469. 5. Pikraaznou,Z.; Nocera,D. G. Inorg. C&m. 1992,31.532. 6. (a) Johnson M. D.; Reinsborough, V. C., Ward, S. Inorg. Chem. 1992.31, 1085. (b) Brugger, N.; Deschenaux, R.; Ruth, T.; Ziessel, R. Tetrahedron L&t. 1992.33.3871. 7. Pikramenou, Z.; Nocera, D. G. In Proceedings of the Sixth International Symposium on Cyclodextrins; Editions de Santi Paris, France, 1992. 8. (a) Tab&i, I. Acc.Chem Res. 1982,15,66.(b) Tab&i, I.; Yamamura, K.; Nabeshima. T. J. Am. Chem Sot. 1984. IW, 5267. (c) Tabushi, I.; Kuroda, Y. J. Am. Chem. Sot. 1984,106, 4580. (d) Tabushi, I.; Kuroda, Y.; Yokota, K.; Yuan, L. C. J. Am. Chem. Sue. 1981,103,711. 9. (a) Cucinotta, V.; D’Alesssandro, F.; Impellizzeri, G.; Vecchio, G. Curbohydr. Res. 1992, 224,95. (b) Tabushi, I.; Kuroda, Y.; Mochizuki, A. J. Am. Chem. Sot. 1980,102, 1152. (c) Breslow. R. Isr. .I. Chem. 1979.18.187. 10. Ernst. R. R. Angew. Chem, Int. Ed Engl. 1992,31,805. 11. As expected, we observe only a single island in the anomeric proton region in the COSY and TOCSY spectra of the monosubstituted swing compound. 12. Parrot-Lopez, H.; Galons, H.; Coleman, A. W.; Mahuteau, J.; Miocque, M. Tetrahedron Lett. 1992.33,209.
(Received in USA 9 February 1993)
ocm-4039/93 $6.00+ .oo
PegcmonRwr~
Synthesis of a Cradle Cyclodextrln Zoe Pikramenou, Kermit M. Johnson, and Daniel G. Nocesa*
Departmentof Chemistryand the Centerfor FundamentalMaterialsResearch,MkhiganState University,East Lansing,Ml 48824,USA
Key Words:cyclodextrin:am crown ether: supramolectdar; cradle assembly; 2D TOCSY Abstract: Attachment of an aza crown ether at the (A,D) positions on the primary side of /3cyclodextrin (CD) has been achieved to provide a mtdti@tctional assembly whereby a metal receptor site is cradled at the bottom of the hydrophobic receptor site of the CD cup.
The synthesis of new supramolecular architectures bearing multiple recognition sites for substrate binding represents a central challenge to the study of photoinduced energy and electron transfer processes.’ Of the diverse molecular templates available for supramolecule desigu2 cyclodextrins (CD) are well suited for functionalixation with organic ligandsj and macropolycyclic receptors.4 The ability of the CD’s hydrophobic cavity to molecularly recognize substrates provides the opportunity to design multicomponent systems where structure specific interactions can perturb photochemical and photophysical processes. 5*6 In our efforts to design assemblies in which luminescence is triggered by molecular recognition, we have synthesized a cyclodextrin derivatixed with an europium aza crown (1,4,10.13-tetraoxa-7.16diazacyc1ooctadecane) at the primary side of the CD cavity.5 Red emission from the Et? center occurs when an absorption-energy transfer-emission process is established by inclusion of a light-harvesting substrate in the CD cup. Tethered at only one nitrogen, the aza crown prefers to assume a conformation that is swung away from the hydrophobic cup. Yet our energy transfer studies show that the most efficient luminescence will occur for a supramolecular assembly featuring the aza receptor site rigidly situated at the base of the CD cup, and not as a swing.’ We now report the synthesis and characterization of a double-strapped (or cradled) CD where the aza crown ether is tethered to the primary side of the CD cup via its two nitrogens. Scheme I summarizes the strategy employed in the synthesis of the cradle CD with the axa attached to the (AP) positions of the P-CD cup. Energy minimixed calculations using a Dreiding fame field as implemented by BioGraph software reveal that this attachment is least sterically constrained. As elaborated by Tabushi, reaction of the B-CD with biphenyl-4,4’-disulfonyl chloride yields a cyclodextrin rigidly capped with the biphenyl sulfonate spanning the (AD) glucosyl subunits8 Subsequent reaction with KI produces the diiodo-substituted CD, which was isolated from the
3531
3533
F2/ppm 3.0
3.5
4.0
4.5
5.0
5.5 5.5
5.0
4.5
4.0
3.5
3.0
Fl /ppm
Figure 1. The 500 MHz ‘H TOCSY spectrum of BCDU’aza at 30 ‘C. The mixing time was 120 ms.
moiety. These anomeric protons show relevant cross peaks with the remaining glucosyl protons at 3.8-4.0 ppm (H,,,,e) and at 3.5 -3.7 ppm (H&. The islands at 3.8 and 3.7 ppm. which we attribute to the aza crown methylenes adjacent to oxygen, correlate to the 3.2 and 3.5 resonances respectively. The 3.2 and 3.5 ppm peaks are consistent with assignment to aza methylene protons next to nitrogen and the CD’s Ce protons of the substituted glucose residues. It is noteworthy that the 3.5 ppm peak correlates with the remaining protons of the glucosyl subunit. In addition, the peak at 4.1 ppm correlates to the (H3,5,e) at 4.0 ppm as well as to the island at 3.7 ppm. This peak at 4.1 ppm appears to be, as in other cases,% attributed to the H4 proton of the substituted glucose rings. The correlations between carbons and protons are identified from heteronuclear multiplequantum coherence measurements. The CD proton resonances correlate to the relevant carbons as follows: Hz.4 at 3.5 -3.7 to C2 at 68 ppm and to C4 at 79 ppm; H3.5.6at 3.8-4.0 to C3,s.e at 67, 68 ppm; and Ht at 5.1 to Cl at 102 ppm. The protons on the methylenes adjacent to nitrogen, as well as the Ce protons of the glucosyl units where aza substitution occurs, cannot be assigned because of the
3534
spectral congestion. However, the axa methylenes adjacent to oxygen show proton resonances at 3.7 ppm, which correlate to the carbon signal at 64 ppm. The insertion of europium ion into the axa cradle of &C!DU 2aza was accomplished as previously described.’ Red luminescence is observed from acetonitrile solutions of p-CDU2azaDEu3+ when excited at wavelengths coincident with the ‘Le t ‘Fu transition (Xc,, = 394 nm). Steady-state luminescence spectra reveal the characteristic 5Du + ‘FJ pattern of Eu3+ ion resulting from transitions from the lowest energy 5Du excited state to the ‘FJ spin orbit manifold of the ground ~tate.~ The lifetime of the %u excited state of bCDU2axa=Eu3+ is 835 ps. Investigations of the energy transfer from guests included in the cup to the luminescent Eu” ion in the cradle am underway. Acknowledgments.The FABMS spectra were obtained in the NIH/MSU Mass Spectrometry Facility
(NIH grant DRR-00480). Financial support of this work from Ford Motor Company and the Center for Fundamentals Materials Research at Michigan State University is gratefully acknowledged. Referencesand Notes
1.
(a) Balzani, V.; Scandola F. Supramoleculur Photochemistry; Balzani, V. Ed. In Ellis Honwod Series in Physical Chemistry: West Sussex, England, 1991. (b) Lehn, J. M. Angew. Chem., Int. Ed Engl. 1988.27.89.(c) Bissell, R. A.; De Silva, P.; Gunaratne, H. Q. N.; Lynch,P.LM.; Maguim, GEM.; Sandanayake, K. R. A. S. Chem. Sot. Rev. 1992,187. 2. (a) See& C.; Vagtle, F. Angew. Chem., Int. Ed Engl. 1992.31,528. (b) An, H.; Bradshaw, J. S.; Izatt, R. M. Chem Rev. 1992,92,543.(c) Gutsche, C. D. Calixurenes; Stoddart, J. F. Ed. In Series in Monographs in Supramolecular Chemistry; Royal Society of Chemistry: Cambridge, England, 1989. (d) Gokel, G. Crown Ethers und Cryptunds; Stoddart, J. F. Ed. In Series in Monographs in Supramolecular Chemistry; Royal Society of Chemistry: Cambridge, England, 1989. 3. For reviews see : (a) Croft, A. P.; Bartsch, R. A. Tetrahedron l!W3,39,1417. (b) Tabushi, I. Tetrahedron l!M4,40, 269. 4. Willner, I.; C&en, Z. J. Chem. Sot., Chem. Commun. M3.1469. 5. Pikraaznou,Z.; Nocera,D. G. Inorg. C&m. 1992,31.532. 6. (a) Johnson M. D.; Reinsborough, V. C., Ward, S. Inorg. Chem. 1992.31, 1085. (b) Brugger, N.; Deschenaux, R.; Ruth, T.; Ziessel, R. Tetrahedron L&t. 1992.33.3871. 7. Pikramenou, Z.; Nocera, D. G. In Proceedings of the Sixth International Symposium on Cyclodextrins; Editions de Santi Paris, France, 1992. 8. (a) Tab&i, I. Acc.Chem Res. 1982,15,66.(b) Tab&i, I.; Yamamura, K.; Nabeshima. T. J. Am. Chem Sot. 1984. IW, 5267. (c) Tabushi, I.; Kuroda, Y. J. Am. Chem. Sot. 1984,106, 4580. (d) Tabushi, I.; Kuroda, Y.; Yokota, K.; Yuan, L. C. J. Am. Chem. Sue. 1981,103,711. 9. (a) Cucinotta, V.; D’Alesssandro, F.; Impellizzeri, G.; Vecchio, G. Curbohydr. Res. 1992, 224,95. (b) Tabushi, I.; Kuroda, Y.; Mochizuki, A. J. Am. Chem. Sot. 1980,102, 1152. (c) Breslow. R. Isr. .I. Chem. 1979.18.187. 10. Ernst. R. R. Angew. Chem, Int. Ed Engl. 1992,31,805. 11. As expected, we observe only a single island in the anomeric proton region in the COSY and TOCSY spectra of the monosubstituted swing compound. 12. Parrot-Lopez, H.; Galons, H.; Coleman, A. W.; Mahuteau, J.; Miocque, M. Tetrahedron Lett. 1992.33,209.
(Received in USA 9 February 1993)