Author(s): Leitão, Maria Inês P. S. ; Francescato, Giulia ; Gomes, Clara S. B. ; Petronilho, Ana
Date: 2021
Persistent ID: http://hdl.handle.net/10362/131339
Origin: Repositório Institucional da UNL
Subject(s): Pt NMR; Adenosine; Cis-influence; N-heterocyclic carbenes; Organometallic nucleosides; Platinum complexes; Analytical Chemistry; Chemistry (miscellaneous); Molecular Medicine; Pharmaceutical Science; Drug Discovery; Physical and Theoretical Chemistry; Organic Chemistry
Funding Information: This research was funded by national funds through FCT?Funda??o para a Ci?ncia e a Tecnologia, I.P., Project MOSTMICRO-ITQB (refs. UIDB/04612/2020 and UIDP/04612/2020), and IF/00109/2014/CP1244/CT0007. This work was also supported by FCT fellowships number PD/BD/135483/2018 (M.I.P.S.L.) and SFRH/BD/1444412019 (G.F.). Clara S. B. Gomes acknowledges the Associate Laboratory for Green Chemistry?LAQV and the Applied Molecular Biosciences Unit?UCIBIO, which are financed by national funds from Funda??o para a Ci?ncia e a Tecnologia (UIDB/50006/2020, UIDP/50006/2020, UIDB/04378/2020, UIDP/04378/2020, respectively).The NMR spectra were acquired at CERMAX?ITQB, integrated in the National NMR Network and are partially supported by Infrastructure Project No. 022161 (co-financed by FEDER through COMPETE 2020, POCI, PORL and FCT through PIDDAC). Mass spectroscopy measurements were obtained by the UniMass Laboratory at ITQB-NOVA, Portugal. Clara S. B. Gomes acknowledges the XTAL?Macromolecular Crystallography group for granting access to the X-ray diffractometer. X-ray infrastructure financed by FCT-MCTES through project RECI/BBB-BEP/0124/2012. Funding Information: Funding: This research was funded by national funds through FCT—Fundação para a Ciência e a Tecnologia, I.P., Project MOSTMICRO-ITQB (refs. UIDB/04612/2020 and UIDP/04612/2020), and IF/00109/2014/CP1244/CT0007. This work was also supported by FCT fellowships number PD/BD/135483/2018 (M.I.P.S.L.) and SFRH/BD/1444412019 (G.F.). Clara S. B. Gomes acknowledges the Associate Laboratory for Green Chemistry—LAQV and the Applied Molecular Biosciences Unit—UCIBIO, which are financed by national funds from Fundação para a Ciência e a Tecnologia (UIDB/50006/2020, UIDP/50006/2020, UIDB/04378/2020, UIDP/04378/2020, respectively). Funding Information: Acknowledgments: The NMR spectra were acquired at CERMAX—ITQB, integrated in the National NMR Network and are partially supported by Infrastructure Project No. 022161 (co-financed by FEDER through COMPETE 2020, POCI, PORL and FCT through PIDDAC). Mass spectroscopy measurements were obtained by the UniMass Laboratory at ITQB-NOVA, Portugal. Clara S. B. Gomes acknowledges the XTAL—Macromolecular Crystallography group for granting access to the X-ray diffractometer. X-ray infrastructure financed by FCT-MCTES through project RECI/BBB-BEP/0124/2012. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
Organometallic derivatization of nucleosides is a highly promising strategy for the im-provement 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-O-acetyladenosine with Pt (PPh3)4 by C8−Br oxidative addition yielded complex 1, with a PtII centre bonded to C-8 and an unprotonated N7. Complex 1 reacted at N7 with HBF4 or methyl iodide, yielding protic carbene 2 or methyl carbene 3, respectively. Deprotection of 1 to yield 4 was achieved with NH4OH. Deprotected compound 4 reacted at N7 with HCl solutions to yield protic NHC 5 or with methyl iodide yielding methyl carbene 6. Protic N-heterocyclic carbene 5 is not stable in DMSO solutions leading to the formation of compound 7, in which a bromide was replaced by chloride. The cis-influence of complexes 1–7 was examined by31P{1H} and195Pt NMR. Complexes 2, 3, 5, 6 and 7 induce a decrease of1 JPt,P of more than 300 Hz, as result of the higher cis-influence of the N-heterocyclic carbene when compared to the azolato ligand in 1 and 4.
