Abstract
5-Fluorouracil is a widely used anti-cancer drug which exhibits diverse polymorphic and co-crystalline behavior. Here we report two new solvent-free co-crystals of 5-fluorouracil with model co-formers nicotinamide and isonicotinamide, along with the redetermination of their hydrated analogues. Selected co-formers are categorized as safe and therefore suitable for pharmaceutical applications. Differences and similarities in supramolecular topology of the given structures are discussed. A special emphasis is set on the influence of fluorine moieties on the overall packing and synthetic accessibility of the presented multi-component systems.
Funding source: Deutsche Forschungsgemeinschaft
Award Identifier / Grant number: 440366605
About the authors
Tobias Heinen was born and raised in Wesel, NRW, Germany. In 2011 he started his academic training at the Ruhr-University Bochum. He specialized in the field of Crystal Engineering and wrote his master thesis about the (co-)crystallization of ROY-derivatives. In November 2019 he started his PhD at the Heinrich-Heine University Düsseldorf. He is an ambiguous crystallographer focusing on the co-crystallization of pharmaceuticals to improve their properties.
Vera Vasylyeva studied chemistry at Ruhr-University Bochum in Germany and finished her Ph.D. in the group of Dr. Klaus Merz on aggregation phenomena of small organic molecules and in-situ crystallization of low melting compounds. Afterwards she joined several research groups in Duesseldorf (Prof. Christoph Janiak), Milan (Prof. Pierangelo Metrangolo and Prof. Giuseppe Resnati) and Aachen (Prof. Georg Roth) for her post-doctoral stays to deepen into the field of Crystal Engineering. Since 2018 Vera is a research group leader at Heinrich-Heine University Düsseldorf with a main focus on structural investigations and rational design of pharmaceutical and luminescent multi-component materials.
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Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
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Research funding: Funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) – 440366605.
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Conflict of interest statement: The authors declare no conflicts of interest regarding this article.
References
1. Vincent, M., Labianca, R., Harper, P. Anti Cancer Drugs 1999, 10, 337–354; https://doi.org/10.1097/00001813-199904000-00001.Search in Google Scholar PubMed
2. Peled, Y., Levavi, H., Krissi, H., Weill, Y., Sabah, G., Eitan, R. Am. J. Clin. Oncol. 2013, 36, 472–474; https://doi.org/10.1097/coc.0b013e3182549399.Search in Google Scholar PubMed
3. Shapiro, L. Q., Sherman, E. J., Riaz, N., Setton, J., Koutcher, L., Zhang, Z., Shi, W., Fury, M. G., Wolden, S. L., Pfister, D. G., Morris, L., Lee, N. Oral Oncol. 2014, 50, 947–955; https://doi.org/10.1016/j.oraloncology.2014.07.001.Search in Google Scholar PubMed PubMed Central
4. Qu, C.-Y., Zhou, M., Chen, Y.-W., Chen, M.-M., Shen, F., Xu, L.-M. Int. J. Nanomed. 2015, 10, 3911–3920.10.2147/IJN.S83211Search in Google Scholar PubMed PubMed Central
5. Diasio, R. B., Harris, B. E. Clin. Pharmacokinet. 1989, 16, 215–237; https://doi.org/10.2165/00003088-198916040-00002.Search in Google Scholar PubMed
6. Blagden, N., de Matas, M., Gavan, P. T., York, P. Adv. Drug Deliv. Rev. 2007, 59, 617–630; https://doi.org/10.1016/j.addr.2007.05.011.Search in Google Scholar PubMed
7. Bolla, G., Nangia, A. Chem. Commun. 2016, 52, 8342–8360; https://doi.org/10.1039/c6cc02943d.Search in Google Scholar PubMed
8. Fallon, L. Acta Crystallogr. 1973, B29, 2549–2556; https://doi.org/10.1107/s0567740873006989.Search in Google Scholar
9. Jarzembska, K. N., Kubsik, M., Kaminski, R., Wozniak, K., Dominiak, P. M. Cryst. Growth Des. 2012, 12, 2508–2524; https://doi.org/10.1021/cg300129z.Search in Google Scholar
10. Hulme, A. T., Price, S. L., Tocher, D. A. J. Am. Chem. Soc. 2005, 127, 1116–1117; https://doi.org/10.1021/ja044336a.Search in Google Scholar PubMed
11. Vasylyeva, V., Shishkin, O. V., Maleev, A. V., Merz, K. Cryst. Growth Des. 2012, 12, 1032–1039; https://doi.org/10.1021/cg201623e.Search in Google Scholar
12. Vangala, V. R., Nangia, A., Lynch, V. M. Chem. Commun. 2002, 1304–1305; https://doi.org/10.1039/b202181a.Search in Google Scholar PubMed
13. Result of a CCDC web search. https://www.ccdc.cam.ac.uk/structures/WebCSD/StructureSearch with 75 results, excluding all repeatedly mentioned structures (accessed Aug 28, 2021).Search in Google Scholar
14. Castro, R. A. E., Ribeiro, J. D. B., Maria, T. M. R., Silva, M. R., Yuste-Vivas, C., Canotilho, J., Eusébio, M. E. S. Cryst. Growth Des. 2011, 11, 5396–5404; https://doi.org/10.1021/cg2009946.Search in Google Scholar
15. Bommaka, M. K., Mannava, M. K. C., Suresh, K., Gunnam, A., Nangia, A. Cryst. Growth Des. 2018, 18, 6061–6069; https://doi.org/10.1021/acs.cgd.8b00921.Search in Google Scholar
16. Sanphui, P., Kumar, S. S., Nangia, A. Cryst. Growth Des. 2012, 12, 4588–4599; https://doi.org/10.1021/cg300784v.Search in Google Scholar
17. Fengxian, L., Naiqin, L., Yan, Z. A kind of preparation method of 5-fluorouracil-isonicotinamide-water and application, 2017. CN 107445906 A.Search in Google Scholar
18. Zhang, Z., Yu, N., Xue, C., Gao, S., Deng, Z., Li, M., Liu, C., Castellot, J., Han, S. ACS Omega 2020, 5, 15777–15782; https://doi.org/10.1021/acsomega.9b03574.Search in Google Scholar PubMed PubMed Central
19. Apex2, Data Collection Program for the CCD Area-Detector System; Saint, Data Reduction and Frame Integration Program for the CCD Area-Detector System; Bruker Analytical X-ray Systems: Madison, Wisconsin, USA, 1997–2006.Search in Google Scholar
20. Sheldrick, G. M. Acta Crystallogr. A 2008, 64, 112–122; https://doi.org/10.1107/s0108767307043930.Search in Google Scholar PubMed
21. Macrae, C. F., Sovago, I., Cottrell, S. J., Galek, P. T. A., McCabe, P., Pidcock, E., Platings, M., Shields, G. P., Stevens, J. S., Towler, M., Wood, P. A. J. Appl. Crystallogr. 2020, 53, 226–235; https://doi.org/10.1107/s1600576719014092.Search in Google Scholar
22. Agilent; Agilent Technologies Ltd, Yarnton, Oxfordshire, England, 2014.Search in Google Scholar
23. Dolomanov, O. V., Bourhis, L. J., Gildea, R. J., Howard, J. A. K., Puschmann, H. J. Appl. Crystallogr. 2009, 42, 339–341; https://doi.org/10.1107/s0021889808042726.Search in Google Scholar
24. Kitajgorodsky, A. I. Molecular Crystals and Molecules; Academic Press: New York, 1973.Search in Google Scholar
25. Tyler, A. R., Ragbirsingh, R., McMonagle, C. J., Waddell, P. G., Heaps, S. E., Steed, J. W., Thaw, P., Hall, M. J., Probert, M. R. Inside Chem. 2020, 6, 1755–1765; https://doi.org/10.1016/j.chempr.2020.04.009.Search in Google Scholar PubMed PubMed Central
Supplementary Material
The online version of this article offers supplementary material (https://doi.org/10.1515/zkri-2021-2052).
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