Synthesis of Platinum(II) N-Heterocyclic Carbenes Based on Adenosine
Organometallic derivatization of nucleosides is a highly promising strategy for the improvement of the therapeutic profile of nucleosides. Herein, a methodology for the synthesis of metalated adenosine with a deprotected ribose moiety is described. Platinum(II) N-heterocyclic carbene complexes based...
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MDPI AG
2021-09-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/26/17/5384 |
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| author | Maria Inês P. S. Leitão Giulia Francescato Clara S. B. Gomes Ana Petronilho |
| author_facet | Maria Inês P. S. Leitão Giulia Francescato Clara S. B. Gomes Ana Petronilho |
| author_sort | Maria Inês P. S. Leitão |
| collection | DOAJ |
| description | Organometallic derivatization of nucleosides is a highly promising strategy for the improvement of the therapeutic profile of nucleosides. Herein, a methodology for the synthesis of metalated adenosine with a deprotected ribose moiety is described. Platinum(II) N-heterocyclic carbene complexes based on adenosine were synthesized, namely N-heterocyclic carbenes bearing a protected and unprotected ribose ring. Reaction of the 8-bromo-2′,3′,5′-tri-<i>O</i>-acetyladenosine with Pt(PPh<sub>3</sub>)<sub>4</sub> by C8−Br oxidative addition yielded complex <b>1</b>, with a Pt<sup>II</sup> centre bonded to C-8 and an unprotonated N7. Complex <b>1</b> reacted at N7 with HBF<sub>4</sub> or methyl iodide, yielding protic carbene <b>2</b> or methyl carbene <b>3</b>, respectively. Deprotection of <b>1</b> to yield <b>4</b> was achieved with NH<sub>4</sub>OH. Deprotected compound <b>4</b> reacted at N7 with HCl solutions to yield protic NHC <b>5</b> or with methyl iodide yielding methyl carbene <b>6</b>. Protic N-heterocyclic carbene <b>5</b> is not stable in DMSO solutions leading to the formation of compound <b>7</b>, in which a bromide was replaced by chloride. The cis-influence of complexes <b>1</b>–<b>7</b> was examined by <sup>31</sup>P{<sup>1</sup>H} and <sup>195</sup>Pt NMR. Complexes <b>2</b>, <b>3</b>, <b>5</b>, <b>6</b> and <b>7</b> induce a decrease of <sup>1</sup><i>J</i><sub>Pt,P</sub> of more than 300 Hz, as result of the higher cis-influence of the N-heterocyclic carbene when compared to the azolato ligand in <b>1</b> and <b>4</b>. |
| first_indexed | 2024-03-10T08:05:46Z |
| format | Article |
| id | doaj.art-45f64b9e62e9476a9f06c5a43b955ecd |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T08:05:46Z |
| publishDate | 2021-09-01 |
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| spelling | doaj.art-45f64b9e62e9476a9f06c5a43b955ecd2023-11-22T11:03:20ZengMDPI AGMolecules1420-30492021-09-012617538410.3390/molecules26175384Synthesis of Platinum(II) N-Heterocyclic Carbenes Based on AdenosineMaria Inês P. S. Leitão0Giulia Francescato1Clara S. B. Gomes2Ana Petronilho3ITQB-NOVA—Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Avd da Republica, 2780-157 Oeiras, PortugalITQB-NOVA—Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Avd da Republica, 2780-157 Oeiras, PortugalLAQV-REQUIMTE, Department of Chemistry, NOVA School of Science and Technology, Universidade Nova de Lisboa, 2829-516 Caparica, PortugalITQB-NOVA—Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Avd da Republica, 2780-157 Oeiras, PortugalOrganometallic derivatization of nucleosides is a highly promising strategy for the improvement of the therapeutic profile of nucleosides. Herein, a methodology for the synthesis of metalated adenosine with a deprotected ribose moiety is described. Platinum(II) N-heterocyclic carbene complexes based on adenosine were synthesized, namely N-heterocyclic carbenes bearing a protected and unprotected ribose ring. Reaction of the 8-bromo-2′,3′,5′-tri-<i>O</i>-acetyladenosine with Pt(PPh<sub>3</sub>)<sub>4</sub> by C8−Br oxidative addition yielded complex <b>1</b>, with a Pt<sup>II</sup> centre bonded to C-8 and an unprotonated N7. Complex <b>1</b> reacted at N7 with HBF<sub>4</sub> or methyl iodide, yielding protic carbene <b>2</b> or methyl carbene <b>3</b>, respectively. Deprotection of <b>1</b> to yield <b>4</b> was achieved with NH<sub>4</sub>OH. Deprotected compound <b>4</b> reacted at N7 with HCl solutions to yield protic NHC <b>5</b> or with methyl iodide yielding methyl carbene <b>6</b>. Protic N-heterocyclic carbene <b>5</b> is not stable in DMSO solutions leading to the formation of compound <b>7</b>, in which a bromide was replaced by chloride. The cis-influence of complexes <b>1</b>–<b>7</b> was examined by <sup>31</sup>P{<sup>1</sup>H} and <sup>195</sup>Pt NMR. Complexes <b>2</b>, <b>3</b>, <b>5</b>, <b>6</b> and <b>7</b> induce a decrease of <sup>1</sup><i>J</i><sub>Pt,P</sub> of more than 300 Hz, as result of the higher cis-influence of the N-heterocyclic carbene when compared to the azolato ligand in <b>1</b> and <b>4</b>.https://www.mdpi.com/1420-3049/26/17/5384N-heterocyclic carbenesadenosineplatinum complexesorganometallic nucleosides<sup>195</sup>Pt NMRcis-influence |
| spellingShingle | Maria Inês P. S. Leitão Giulia Francescato Clara S. B. Gomes Ana Petronilho Synthesis of Platinum(II) N-Heterocyclic Carbenes Based on Adenosine Molecules N-heterocyclic carbenes adenosine platinum complexes organometallic nucleosides <sup>195</sup>Pt NMR cis-influence |
| title | Synthesis of Platinum(II) N-Heterocyclic Carbenes Based on Adenosine |
| title_full | Synthesis of Platinum(II) N-Heterocyclic Carbenes Based on Adenosine |
| title_fullStr | Synthesis of Platinum(II) N-Heterocyclic Carbenes Based on Adenosine |
| title_full_unstemmed | Synthesis of Platinum(II) N-Heterocyclic Carbenes Based on Adenosine |
| title_short | Synthesis of Platinum(II) N-Heterocyclic Carbenes Based on Adenosine |
| title_sort | synthesis of platinum ii n heterocyclic carbenes based on adenosine |
| topic | N-heterocyclic carbenes adenosine platinum complexes organometallic nucleosides <sup>195</sup>Pt NMR cis-influence |
| url | https://www.mdpi.com/1420-3049/26/17/5384 |
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