Synthesis and Physicochemical Properties of Cryptophazane—A Soluble and Functionalizable C1-Symmetrical Cryptophane
Clément Vigier
Normandie Univ, UNICAEN, Centre d'Etudes et de Recherche sur le Médicament de Normandie (CERMN), 14000 Caen, France
Institut Blood and Brain @ Caen Normandie (BB@C), Boulevard Henri Becquerel, 14000 Caen, France
These authors contributed equally to this work.
Search for more papers by this authorDimitri Fayolle
Normandie Univ, UNICAEN, Centre d'Etudes et de Recherche sur le Médicament de Normandie (CERMN), 14000 Caen, France
Institut Blood and Brain @ Caen Normandie (BB@C), Boulevard Henri Becquerel, 14000 Caen, France
UMR−S U1237, Normandie Univ, Physiopathology and Imaging of Neurological Disorders (PhIND), 14000 Caen, France
These authors contributed equally to this work.
Search for more papers by this authorHussein El Siblani
Normandie Univ, ENSICAEN, UNICAEN, CNRS, Laboratoire Catalyse et Spectrochimie (LCS), 14000 Caen, France
Search for more papers by this authorJana Sopkova - de Oliveira Santos
Normandie Univ, UNICAEN, Centre d'Etudes et de Recherche sur le Médicament de Normandie (CERMN), 14000 Caen, France
Search for more papers by this authorFrederic Fabis
Normandie Univ, UNICAEN, Centre d'Etudes et de Recherche sur le Médicament de Normandie (CERMN), 14000 Caen, France
Institut Blood and Brain @ Caen Normandie (BB@C), Boulevard Henri Becquerel, 14000 Caen, France
Search for more papers by this authorCorresponding Author
Thomas Cailly
Normandie Univ, UNICAEN, Centre d'Etudes et de Recherche sur le Médicament de Normandie (CERMN), 14000 Caen, France
Institut Blood and Brain @ Caen Normandie (BB@C), Boulevard Henri Becquerel, 14000 Caen, France
Normandie Univ, UNICAEN, IMOGERE, 14000 Caen, France
CHU Côte de Nacre, Department of Nuclear Medicine, 14000 Caen, France
Search for more papers by this authorCorresponding Author
Emmanuelle Dubost
Normandie Univ, UNICAEN, Centre d'Etudes et de Recherche sur le Médicament de Normandie (CERMN), 14000 Caen, France
Institut Blood and Brain @ Caen Normandie (BB@C), Boulevard Henri Becquerel, 14000 Caen, France
UMR−S U1237, Normandie Univ, Physiopathology and Imaging of Neurological Disorders (PhIND), 14000 Caen, France
Search for more papers by this authorClément Vigier
Normandie Univ, UNICAEN, Centre d'Etudes et de Recherche sur le Médicament de Normandie (CERMN), 14000 Caen, France
Institut Blood and Brain @ Caen Normandie (BB@C), Boulevard Henri Becquerel, 14000 Caen, France
These authors contributed equally to this work.
Search for more papers by this authorDimitri Fayolle
Normandie Univ, UNICAEN, Centre d'Etudes et de Recherche sur le Médicament de Normandie (CERMN), 14000 Caen, France
Institut Blood and Brain @ Caen Normandie (BB@C), Boulevard Henri Becquerel, 14000 Caen, France
UMR−S U1237, Normandie Univ, Physiopathology and Imaging of Neurological Disorders (PhIND), 14000 Caen, France
These authors contributed equally to this work.
Search for more papers by this authorHussein El Siblani
Normandie Univ, ENSICAEN, UNICAEN, CNRS, Laboratoire Catalyse et Spectrochimie (LCS), 14000 Caen, France
Search for more papers by this authorJana Sopkova - de Oliveira Santos
Normandie Univ, UNICAEN, Centre d'Etudes et de Recherche sur le Médicament de Normandie (CERMN), 14000 Caen, France
Search for more papers by this authorFrederic Fabis
Normandie Univ, UNICAEN, Centre d'Etudes et de Recherche sur le Médicament de Normandie (CERMN), 14000 Caen, France
Institut Blood and Brain @ Caen Normandie (BB@C), Boulevard Henri Becquerel, 14000 Caen, France
Search for more papers by this authorCorresponding Author
Thomas Cailly
Normandie Univ, UNICAEN, Centre d'Etudes et de Recherche sur le Médicament de Normandie (CERMN), 14000 Caen, France
Institut Blood and Brain @ Caen Normandie (BB@C), Boulevard Henri Becquerel, 14000 Caen, France
Normandie Univ, UNICAEN, IMOGERE, 14000 Caen, France
CHU Côte de Nacre, Department of Nuclear Medicine, 14000 Caen, France
Search for more papers by this authorCorresponding Author
Emmanuelle Dubost
Normandie Univ, UNICAEN, Centre d'Etudes et de Recherche sur le Médicament de Normandie (CERMN), 14000 Caen, France
Institut Blood and Brain @ Caen Normandie (BB@C), Boulevard Henri Becquerel, 14000 Caen, France
UMR−S U1237, Normandie Univ, Physiopathology and Imaging of Neurological Disorders (PhIND), 14000 Caen, France
Search for more papers by this authorGraphical Abstract
Cryptophanes are molecular hosts of particular interest for the development of biosensors based on xenon magnetic resonance imaging as they bind xenon reversibly. To prepare such a biosensor, a reactive site on the cryptophane core, which is desirable for such applications but synthetically challenging, has now been introduced by replacing a crown methylene bridge by a nitrogen atom to form a cryptophazane.
Abstract
The first example of a cryptophazane, a cryptophane functionalized with a nitrogen atom replacing one of the methylene bridges, is obtained with a 28 % overall yield over 8 steps, through the preparation of a C1-symmetrical aza-cyclotriveratrylene (aza-CTV). Herein, we demonstrate that the introduction of a nitrogen atom on this part of the cryptophane core enhances the solubility in organic media of both the cryptophane and the synthetic intermediates, while presenting the same conformation as known cryptophanes. Cryptophazane was prepared on a multigram scale and easily functionalized. We also investigated its ability to encapsulate xenon atoms using hyperpolarized 129Xe (HP 129Xe) NMR spectroscopy. We found that both its affinity and exchange kinetics were in the appropriate range for applications in 129Xe magnetic resonance imaging (MRI). Combined with the wide range of possible functionalization, this makes cryptophazane an excellent candidate for targeted HP 129Xe MRI.
Conflict of interest
The authors declare no conflict of interest.
Open Research
Data Availability Statement
The data that support the findings of this study are available in the supplementary material of this article.
Supporting Information
As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors.
| Filename | Description |
|---|---|
| anie202208580-sup-0001-misc_information.pdf6.3 MB | Supporting Information |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
References
- 1J. Gabard, A. Collet, J. Chem. Soc. Chem. Commun. 1981, 1137.
- 2A. Collet, Tetrahedron 1987, 43, 5725–5759.
- 3L. Garel, B. Lozach, J. P. Dutasta, A. Collet, J. Am. Chem. Soc. 1993, 115, 11652–11653.
- 4S. Akabori, M. Miura, M. Takeda, S. Yuzawa, Y. Habata, T. Ishii, Supramol. Chem. 1996, 7, 187–193.
- 5M. A. Little, J. Donkin, J. Fisher, M. A. Halcrow, J. Loder, M. J. Hardie, Angew. Chem. Int. Ed. 2012, 51, 764–766; Angew. Chem. 2012, 124, 788–790.
- 6T. Brotin, P. Berthault, D. Pitrat, J.-C. Mulatier, J. Org. Chem. 2020, 85, 9622–9630.
- 7D. K. Eggers, S. Fu, D. V. Ngo, E. H. Vuong, T. Brotin, J. Phys. Chem. B 2020, 124, 6585–6591.
- 8D. R. Jacobson, N. S. Khan, R. Colle, R. Fitzgerald, L. Laureano-Perez, Y. Bai, I. J. Dmochowski, Proc. Natl. Acad. Sci. USA 2011, 108, 10969–10973.
- 9K. E. Chaffee, H. a Fogarty, T. Brotin, B. M. Goodson, J.-P. Dutasta, J. Phys. Chem. A 2009, 113, 13675–84.
- 10M. Benounis, N. Jaffrezic-Renault, J. P. Dutasta, K. Cherif, A. Abdelghani, Sens. Actuators B 2005, 107, 32–39.
- 11K. Bartik, M. Luhmer, J.-P. Dutasta, A. Collet, J. Reisse, J. Am. Chem. Soc. 1998, 120, 784–791.
- 12T. Brotin, J.-P. Dutasta, Chem. Rev. 2009, 109, 88–130.
- 13H. a Fogarty, P. Berthault, T. Brotin, G. Huber, H. Desvaux, J.-P. Dutasta, J. Am. Chem. Soc. 2007, 129, 10332–3.
- 14T. Brotin, J. P. Dutasta, Eur. J. Org. Chem. 2003, 973–984.
- 15S. D. Zemerov, I. J. Dmochowski, RSC Adv. 2021, 11, 7693–7703.
- 16S. D. Zemerov, Y. Lin, I. J. Dmochowski, Anal. Chem. 2021, 93, 1507–1514.
- 17Q. Zeng, Q. Guo, Y. Yuan, X. Zhang, W. Jiang, S. Xiao, B. Zhang, X. Lou, C. Ye, M. Liu, L.-S. Bouchard, X. Zhou, ACS Appl. Bio Mater. 2020, 3, 1779–1786.
- 18M. Schnurr, I. Volk, H. Nikolenko, L. Winkler, M. Dathe, L. Schröder, Adv. Biosyst. 2020, 4, 1900251.
- 19H. Zhang, Q. Yu, Y. Li, Z. Yang, X. Zhou, S. Chen, Z.-X. Jiang, Chem. Commun. 2020, 56, 3617–3620.
- 20E. Mari, Y. Bousmah, C. Boutin, E. Léonce, G. Milanole, T. Brotin, P. Berthault, M. Erard, ChemBioChem 2019, 20, 1450–1457.
- 21H. Zhang, S. Chen, Y. Yuan, Y. Li, Z. Jiang, X. Zhou, ACS Appl. Bio Mater. 2019, 2, 27–32.
- 22E. Mari, P. Berthault, Analyst 2017, 142, 3298–3308.
- 23Y. Wang, I. J. Dmochowski, Acc. Chem. Res. 2016, 49, 2179–2187.
- 24M. Schnurr, K. Sydow, H. M. Rose, M. Dathe, L. Schröder, Adv. Healthcare Mater. 2015, 4, 40–45.
- 25G. K. Seward, Y. Bai, N. S. Khan, I. J. Dmochowski, Chem. Sci. 2011, 2, 1103.
- 26G. K. Seward, Q. Wei, I. J. Dmochowski, Bioconjugate Chem. 2008, 19, 2129–2135.
- 27C. Boutin, A. Stopin, F. Lenda, T. Brotin, J. P. Dutasta, N. Jamin, A. Sanson, Y. Boulard, F. Leteurtre, G. Huber, A. Bogaert-Buchmann, N. Tassali, H. Desvaux, M. Carrire, P. Berthault, Bioorg. Med. Chem. 2011, 19, 4135–4143.
- 28N. Kotera, N. Tassali, E. Léonce, C. Boutin, P. Berthault, T. Brotin, J.-P. Dutasta, L. Delacour, T. Traoré, D.-A. Buisson, F. Taran, S. Coudert, B. Rousseau, Angew. Chem. Int. Ed. 2012, 51, 4100–4103; Angew. Chem. 2012, 124, 4176–4179.
- 29J. M. Chambers, P. A. Hill, J. A. Aaron, Z. Han, D. W. Christianson, N. N. Kuzma, I. J. Dmochowski, J. Am. Chem. Soc. 2009, 131, 563–569.
- 30E. Sugawara, H. Nikaido, Antimicrob. Agents Chemother. 2014, 58, 7250–7.
- 31M. Darzac, T. Brotin, D. Bouchu, J.-P. Dutasta, Chem. Commun. 2002, 48–49.
- 32O. Baydoun, N. De Rycke, E. Léonce, C. Boutin, P. Berthault, E. Jeanneau, T. Brotin, J. Org. Chem. 2019, 84, 9127–9137.
- 33L. L. Chapellet, J. R. Cochrane, E. Mari, C. Boutin, P. Berthault, T. Brotin, J. Org. Chem. 2015, 80, 6143–6151.
- 34M. Doll, P. Berthault, E. Léonce, C. Boutin, T. Buffeteau, N. Daugey, N. Vanthuyne, M. Jean, T. Brotin, N. De Rycke, J. Org. Chem. 2021, 86, 7648–7658.
- 35C. Vigier, P. Fossé, F. Fabis, T. Cailly, E. Dubost, Adv. Synth. Catal. 2021, 363, 3756–3761.
- 36H. Hara, K. Hayashi, S. Inoue, H. Shimizu, A. Kobayashi, M. Ishizaki, Y. Matsuoka, K. Nishitani, Heterocycles 2005, 65, 1.
- 37M. R. Lutz, D. C. French, P. Rehage, D. P. Becker, Tetrahedron Lett. 2007, 48, 6368–6371.
- 38M. R. Lutz, M. Zeller, D. P. Becker, Tetrahedron Lett. 2008, 49, 5003–5005.
- 39A. M. Panagopoulos, M. Zeller, D. P. Becker, J. Org. Chem. 2010, 75, 7887–7892.
- 40Deposition number 2176118 (for 6) contains the supplementary crystallographic data for this paper. These data are provided free of charge by the joint Cambridge Crystallographic Data Centre and Fachinformationszentrum Karlsruhe Access Structures service.
- 41S. Götz, A. Schneider, A. Lützen, Beilstein J. Org. Chem. 2019, 15, 1339–1346.
- 42G. Huber, L. Beguin, H. Desvaux, T. Brotin, H. A. Fogarty, J. P. Dutasta, P. Berthault, J. Phys. Chem. A 2008, 112, 11363–11372.
- 43S. T. Mough, J. C. Goeltz, K. T. Holman, Angew. Chem. Int. Ed. 2004, 43, 5631–5635; Angew. Chem. 2004, 116, 5749–5753.
- 44A. Bouchet, T. Brotin, M. Linares, D. Cavagnat, T. Buffeteau, J. Org. Chem. 2011, 76, 7816–7825.
- 45Deposition numbers 2175850 and 2175849 (for DCM@anti-10 and DCM@syn-11) contain the supplementary crystallographic data for this paper. These data are provided free of charge by the joint Cambridge Crystallographic Data Centre and Fachinformationszentrum Karlsruhe Access Structures service.
- 46A. L. Spek, Acta Crystallogr. Sect. C 2015, 71, 9–18.
- 47A. L. Spek, Acta Crystallogr. Sect. D 2009, 65, 148–155.
- 48O. Taratula, P. A. Hill, N. S. Khan, P. J. Carroll, I. J. Dmochowski, Nat. Commun. 2010, 1, 148.
- 49F. P. Gasparro, N. H. Kolodny, J. Chem. Educ. 1977, 54, 258.
- 50J. Jayapaul, L. Schröder, Contrast Media Mol. Imaging 2019, 2019, 1–25.
- 51M. Doll, P. Berthault, E. Léonce, C. Boutin, E. Jeanneau, T. Brotin, N. De Rycke, J. Org. Chem. 2022, 87, 2912–2920.
