{"id":1685,"date":"2026-05-06T07:24:33","date_gmt":"2026-05-06T05:24:33","guid":{"rendered":"https:\/\/sites.unica.it\/pe2026\/?p=1685"},"modified":"2026-05-06T13:19:13","modified_gmt":"2026-05-06T11:19:13","slug":"sara-damiani","status":"publish","type":"post","link":"https:\/\/sites.unica.it\/pe2026\/2026\/05\/06\/sara-damiani\/","title":{"rendered":"Sara Damiani"},"content":{"rendered":"\n
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OC3 – Sara Damiani<\/strong><\/p>\n\n\n\n

University of Ljubljana, Faculty of Pharmacy, Ljubljana, Slovenia<\/p>\n\n\n\n

e-mail<\/a> – LinkedIn<\/a><\/strong><\/p>\n<\/div><\/div>\n\n\n\n

Synthesis and Investigation of Fluorinated Scaffolds Exhibiting<\/strong> Through-Space Scalar 19<\/sup>F \u201319<\/sup>F NMR Coupling<\/strong><\/strong><\/td><\/tr>
Damiani Sara1<\/sup>, O\u0161trek Andra\u017e 1<\/sup>, Lozin\u0161ek Matic 2<\/sup>, Zupan\u010di\u010d \u0160pela 1<\/sup>, Per\u0161olja Peter 1<\/sup>, Satta Giuseppe 3<\/sup>, Plavec Janez 3<\/sup> and Cotman Andrej Emanuel 1<\/sup>
<\/em>
1 <\/sup>University of Ljubljana, Faculty of Pharmacy, A\u0161ker\u010deva cesta 7, 1000 Ljubljana, Slovenia;
2<\/sup> Jo\u017eef Stefan Institute, Jamova cesta 39, 1000 Ljubljana, Slovenia;
3<\/sup> Kemijski in\u0161titut, Hajdrihova 19,1000 Ljubljana, Slovenia<\/td><\/tr>
Abstract<\/strong>
Fluorinated functional groups play a central role in modern medicinal and chemical research due to their strong influence on molecular conformation, physicochemical properties, and intermolecular interactions [1]. Among them, the trifluoromethyl (CF3<\/sub>) group is particularly important [2]. In this work we report design, synthesis and characterization of \u03b1-phthalimido-trifluoromethyl carbinols as precursors of homochiral J<\/em>FF<\/sub>-detected H-bond sensors.  Following a modified literature procedure on phenylalaninol [3], preliminary studies on the corresponding \u03b1-phthalimido-aldehydes revealed a selective mono-trifluoromethylation only at -78 \u00b0C, while double addition with Rupert\u2013Prakash reagent occurs only at higher temperature. The obtained hit compound was prepared on a gram scale with a diastereomeric ratio of 44:39:7:10. One of the diastereomers displayed a peculiar pattern in the 19<\/sup>F NMR spectrum, characterized by a pentet and a quartet corresponding to the tertiary and quaternary carbon-bound CF3<\/sub> group. Single-crystal X-Ray diffraction analysis confirmed close proximity of the two CF3<\/sub> groups and the relative (R*<\/sup>,R*<\/sup>,S*<\/sup><\/em>) configuration revealing a hydrogen-bond-gated 19<\/sup>F\u201319<\/sup>F through-space scalar coupling [4]. Understanding the structural origin of this phenomenon could enable the rational design of fluorinated molecular systems acting as NMR-responsive probes. Therefore, motived by the use of CF3<\/sub> as promising probe for 19<\/sup>F NMR [4], we started to explore \u03b2-carboxamido trifluoromethyl carbinols as potential systems in which hydrogen-bond modulation controls the presence or absence of through-space 19<\/sup>F \u201319<\/sup>F scalar coupling. Namely, solvent-dependent 19<\/sup>F NMR experiments were performed, revealing a disruption of this hydrogen bond in DMSO-d<\/em>6<\/sub>\/buffer mixtures and the consequent disappearance of the scalar coupling pattern, confirming the dynamic and solvent-sensitive nature of the system. Moreover, to explore potential pharmaceutical application, the hit compound was incorporated into lipid-based delivery systems to evaluate whether the characteristic 19<\/sup>F \u201319<\/sup>F coupling could still be observed in a biomimetic lipophilic environment through 19<\/sup>F 2D NMR experiments. The results are expected to contribute to the broader understanding of fluorine-based molecular reporters and to support the development of responsive fluorinated systems for chemical and biochemical applications.<\/td><\/tr>
References  <\/strong>
[1] M\u00fcller, K.; Faeh, C.; Diederich, F., Fluorine in Pharmaceuticals: Looking Beyond Intuition, Science<\/em>, 2007<\/strong>, 317<\/em>, 1881 1886. https:\/\/doi.org\/10.1126\/science.1131943<\/a>.
[2] Nov\u00e1s, M.; Matos, M.J. The Role of Trifluoromethyl and Trifluoromethoxy Groups in Medicinal Chemistry: Implications for Drug Design. Molecules<\/em> 2025<\/strong>, 30<\/em>, 3009. https:\/\/doi.org\/10.3390\/molecules30143009<\/a>
[3] Eeda, V.; Selvaraju, M.; Altman, R. A., Synthesis of Leu-enkephalin peptidomimetics containing trifluoromethylalkenes as amide isopolar mimics, J. Fluor. Chem.<\/em> 2019<\/strong>, 218<\/em>, 90\u201398. https:\/\/doi.org\/10.1016\/j.jfluchem.2018.12.005<\/a>.
[4] Orton, H. W.; Qianzhu, H.; Abdelkader, E. H.; Habel, E. I.; Tan, Y. J.; Frkic, R. L.; Jackson, C. J.; Huber, T.; Otting, G., Through-Space Scalar 19F-19F Couplings between Fluorinated Noncanonical Amino Acids for the Detection of Specific Contacts in Proteins, J. Am. Chem. Soc<\/em>. 2021<\/strong>, 143 (46)<\/em>, 19587\u201319598. https:\/\/doi.org\/10.1021\/jacs.1c10104<\/a>.<\/td><\/tr><\/tbody><\/table><\/div><\/figure>\n\n\n\n

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OC3 – Sara Damiani University of Ljubljana, Faculty of Pharmacy, Ljubljana, Slovenia e-mail – LinkedIn Synthesis and Investigation of Fluorinated Scaffolds Exhibiting Through-Space Scalar 19F \u201319F NMR Coupling Damiani Sara1, O\u0161trek Andra\u017e 1, Lozin\u0161ek Matic 2, […]<\/p>\n","protected":false},"author":9643,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[1],"tags":[],"class_list":["post-1685","post","type-post","status-publish","format-standard","hentry","category-senza-categoria"],"_links":{"self":[{"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/posts\/1685","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/users\/9643"}],"replies":[{"embeddable":true,"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/comments?post=1685"}],"version-history":[{"count":4,"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/posts\/1685\/revisions"}],"predecessor-version":[{"id":1777,"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/posts\/1685\/revisions\/1777"}],"wp:attachment":[{"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/media?parent=1685"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/categories?post=1685"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/tags?post=1685"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}