5-Fluorocytosine/Isocytosine Monohydrate. The First Example of Isomorphic and Isostructural Co-Crystal of Pyrimidine Nucleobases
To date, despite the crucial role played by cytosine, uracil, and thymine in the DNA/RNA replication process, no examples showing isomorphic and isostructural behavior among binary co-crystals of natural or modified pyrimidine nucleobases have been so far reported in the literature. In view of the r...
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| Format: | Article |
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MDPI AG
2020-11-01
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| Series: | Crystals |
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| Online Access: | https://www.mdpi.com/2073-4352/10/11/999 |
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| author | Gustavo Portalone |
| author_facet | Gustavo Portalone |
| author_sort | Gustavo Portalone |
| collection | DOAJ |
| description | To date, despite the crucial role played by cytosine, uracil, and thymine in the DNA/RNA replication process, no examples showing isomorphic and isostructural behavior among binary co-crystals of natural or modified pyrimidine nucleobases have been so far reported in the literature. In view of the relevance of biochemical and pharmaceutical compounds such as pyrimidine nucleobases and their 5-fluoroderivatives, co-crystals of the molecular complex formed by 5-fluorocytosine and isocytosine monohydrate, C<sub>4</sub>H<sub>4</sub>FN<sub>3</sub>O·C<sub>4</sub>H<sub>5</sub>N<sub>3</sub>O·H<sub>2</sub>O, have been synthesized by a reaction between 5-fluorocytosine and isocytosine. They represent the first example of isomorphic and isostructural binary co-crystals of pyrimidine nucleobases, as X-ray diffraction analysis shows structural similarities in the solid-state organization of molecules with that of the (1:1) 5-fluorocytosine/5-fluoroisocytosine monohydrate molecular complex, which differs solely in the H/F substitution at the C5 position of isocytosine. Molecules of 5-fluorocytosine and isocytosine are present in the crystal as 1<i>H</i> and 3<i>H</i>-ketoamino tautomers, respectively. They form almost coplanar WC base pairs through nucleobase-to-nucleobase DAA/ADD hydrogen bonding interactions, demonstrating that complementary binding enables the crystallization of specific tautomers. Additional peripheral hydrogen bonds involving all available H atom donor and acceptor sites of the water molecule give a three-dimensional polymeric structure. In the absence of H⋯F hydrogen-bonding interactions, the robustness of the supramolecular architectures based on three-point recognition synthons is responsible for the existence of isostructurality between the two molecular complexes. |
| first_indexed | 2024-03-10T15:07:23Z |
| format | Article |
| id | doaj.art-bec701c0e665489aba2e49a0079273b2 |
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| issn | 2073-4352 |
| language | English |
| last_indexed | 2024-03-10T15:07:23Z |
| publishDate | 2020-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Crystals |
| spelling | doaj.art-bec701c0e665489aba2e49a0079273b22023-11-20T19:41:10ZengMDPI AGCrystals2073-43522020-11-01101199910.3390/cryst101109995-Fluorocytosine/Isocytosine Monohydrate. The First Example of Isomorphic and Isostructural Co-Crystal of Pyrimidine NucleobasesGustavo Portalone0Department of Chemistry, ‘Sapienza’ University of Rome, 00185 Rome, ItalyTo date, despite the crucial role played by cytosine, uracil, and thymine in the DNA/RNA replication process, no examples showing isomorphic and isostructural behavior among binary co-crystals of natural or modified pyrimidine nucleobases have been so far reported in the literature. In view of the relevance of biochemical and pharmaceutical compounds such as pyrimidine nucleobases and their 5-fluoroderivatives, co-crystals of the molecular complex formed by 5-fluorocytosine and isocytosine monohydrate, C<sub>4</sub>H<sub>4</sub>FN<sub>3</sub>O·C<sub>4</sub>H<sub>5</sub>N<sub>3</sub>O·H<sub>2</sub>O, have been synthesized by a reaction between 5-fluorocytosine and isocytosine. They represent the first example of isomorphic and isostructural binary co-crystals of pyrimidine nucleobases, as X-ray diffraction analysis shows structural similarities in the solid-state organization of molecules with that of the (1:1) 5-fluorocytosine/5-fluoroisocytosine monohydrate molecular complex, which differs solely in the H/F substitution at the C5 position of isocytosine. Molecules of 5-fluorocytosine and isocytosine are present in the crystal as 1<i>H</i> and 3<i>H</i>-ketoamino tautomers, respectively. They form almost coplanar WC base pairs through nucleobase-to-nucleobase DAA/ADD hydrogen bonding interactions, demonstrating that complementary binding enables the crystallization of specific tautomers. Additional peripheral hydrogen bonds involving all available H atom donor and acceptor sites of the water molecule give a three-dimensional polymeric structure. In the absence of H⋯F hydrogen-bonding interactions, the robustness of the supramolecular architectures based on three-point recognition synthons is responsible for the existence of isostructurality between the two molecular complexes.https://www.mdpi.com/2073-4352/10/11/999nucleobases5-halonucleobasescytosine5-fluorocytosinebase pairshydrogen bond |
| spellingShingle | Gustavo Portalone 5-Fluorocytosine/Isocytosine Monohydrate. The First Example of Isomorphic and Isostructural Co-Crystal of Pyrimidine Nucleobases Crystals nucleobases 5-halonucleobases cytosine 5-fluorocytosine base pairs hydrogen bond |
| title | 5-Fluorocytosine/Isocytosine Monohydrate. The First Example of Isomorphic and Isostructural Co-Crystal of Pyrimidine Nucleobases |
| title_full | 5-Fluorocytosine/Isocytosine Monohydrate. The First Example of Isomorphic and Isostructural Co-Crystal of Pyrimidine Nucleobases |
| title_fullStr | 5-Fluorocytosine/Isocytosine Monohydrate. The First Example of Isomorphic and Isostructural Co-Crystal of Pyrimidine Nucleobases |
| title_full_unstemmed | 5-Fluorocytosine/Isocytosine Monohydrate. The First Example of Isomorphic and Isostructural Co-Crystal of Pyrimidine Nucleobases |
| title_short | 5-Fluorocytosine/Isocytosine Monohydrate. The First Example of Isomorphic and Isostructural Co-Crystal of Pyrimidine Nucleobases |
| title_sort | 5 fluorocytosine isocytosine monohydrate the first example of isomorphic and isostructural co crystal of pyrimidine nucleobases |
| topic | nucleobases 5-halonucleobases cytosine 5-fluorocytosine base pairs hydrogen bond |
| url | https://www.mdpi.com/2073-4352/10/11/999 |
| work_keys_str_mv | AT gustavoportalone 5fluorocytosineisocytosinemonohydratethefirstexampleofisomorphicandisostructuralcocrystalofpyrimidinenucleobases |