Ir al menú de navegación principal Ir al contenido principal Ir al pie de página del sitio

Estudio de nuevos complejos metálicos derivados de un ligando flexible polidentado para aplicaciones biológicas y biomédicas

Resumen

El presente estudio muestra la obtención de 4 nuevos complejos lantánidos con iones Gd(III), Eu(III), Dy(III) y Yb(III), con dos ligandos polidentados F y L para evaluar su potencial aplicación en el contraste de imágenes para microscopía de fluorescencia (MF), resonancia magnética de imágenes (RMI) y como agentes antibacterianos. Se propone que los complejos poseen una estructura molecular en donde los ligandos quelan al centro metálico a través de los grupos -OH, -N- y -COO-, exhibiendo un aparente número de coordinación de 7. La relajatividad molar r1 muestra que los 4 complejos son capaces de acelerar el tiempo de relajación longitudinal T1 del agua, obteniéndose un r1 de 6.45 mmol-1·L-1·s-1 para el compuesto 1, el cual fue mayor que el valor 2.25 mmol-1·L-1·s-1 para el Dotarem® usado como medicamento de referencia en RMI. Los rendimientos cuánticos en referencia a la fluoresceína fueron menores al 1%, exhibiendo baja eficiencia en los procesos de emisión de radiación visible. Para los complejos se obtuvieron constantes de estabilidad aparente (-log[kap]) entre 21-18, siendo incluso mejores que algunos agentes de contraste. Finalmente, se confirmó que los complejos obtenidos logran unirse a las hebras del ADN a través de un posible mecanismo de intercalación.

Palabras clave

Ligando polidentado, agente de contraste, resonancia magnética nuclear, iones lantánidos, microscopía de fluorescencia

PDF

Archivo(s) complementario(s)

Material Suplementario

Citas

  1. J. Ye, J. Wang, Q. Li, X. Dong, W. Ge, Y. Chen, X. Jiang, H. Liu, H. Jiang and X. Wang, "Rapid and accurate tumor-target bio-imaging through specific in vivo biosynthesis of a fluorescent europium complex", Biomater. Sci., vol. 4, pp. 652–660, 2016. DOI: 10.1039/C5BM00528K. DOI: https://doi.org/10.1039/C5BM00528K
  2. A. King, "Seeking a better contrast", Chemistry World, 2016. [Online]. Available: https://www.chemistryworld.com/feature/new-mri-contrast-agents/1017395.article. [Accessed: 09-Dec-2021].
  3. V. C. Pierre, M. J. Allen, and P. Caravan, "Contrast agents for MRI: 30+ years and where are we going? Topical issue on metal-based MRI contrast agents", J. Biol. Inorg. Chem., vol. 19, no. 2, pp. 127–131, 2014. DOI: 10.1007/s00775-013-1074-5. DOI: https://doi.org/10.1007/s00775-013-1074-5
  4. J. Lohrke, T. Frenzel, J. Endrikat, F. C. Alves, T. M. Grist, M. Law, J. M. Lee, T. Leiner, K.-C. Li, K. Nikolaou, M. R. Prince, H. H. Schild, J. C. Weinreb, K. Yoshikawa and H. Pietsch, "25 Years of Contrast-Enhanced MRI: Developments, Current Challenges and Future Perspectives", Adv. Ther., vol. 33, no. 1, pp. 1–28, 2016. DOI: 10.1007/s12325-015-0275-4. DOI: https://doi.org/10.1007/s12325-015-0275-4
  5. A. Bianchi, L. Calabi, F. Corana, S. Fontana, P. Losi, A. Maiocchi, L. Paleari and B. Valtancoli, "Thermodynamic and structural properties of Gd ( III ) complexes with polyamino-polycarboxylic ligands : basic compounds for the development of MRI contrast agents", Coord. Chem. Rev., vol. 204, pp. 309–393, 2000. DOI: 10.1016/S0010-8545(99)00237-4. DOI: https://doi.org/10.1016/S0010-8545(99)00237-4
  6. J. Wahsner, E. M. Gale, A. Rodríguez-Rodríguez, and P. Caravan, "Chemistry of MRI contrast agents: Current challenges and new frontiers", Chem. Rev., vol. 119, no. 2, pp. 957–1057, 2019. DOI: 10.1021/acs.chemrev.8b00363. DOI: https://doi.org/10.1021/acs.chemrev.8b00363
  7. A. Barge, G. Cravotto, E. Gianolio, and F. Fedeli, "How to determine free Gd and free ligand in solution of Gd chelates. A technical note", Contrast. Media. Mol. Imaging, vol. 1, no. 5, pp. 184–188, 2006. DOI: 10.1002/cmmi.110. DOI: https://doi.org/10.1002/cmmi.110
  8. H. Wang, M. Zhao, J. L. Ackerman, and Y. Song, "Saturation-inversion-recovery: A method for T1 measurement", J. Magn. Reson., vol. 274, no. November, pp. 137–143, 2017. DOI: 10.1016/j.jmr.2016.11.015. DOI: https://doi.org/10.1016/j.jmr.2016.11.015
  9. M. Grabolle, M. Spieles, V. Lesnyak, N. Gaponik, A. Eychmüller, and U. Resch-Genger, "Determination of the fluorescence quantum yield of quantum dots: Suitable procedures and achievable uncertainties", Anal. Chem., vol. 81, no. 15, pp. 6285–6294, 2009. DOI: 10.1021/ac900308v. DOI: https://doi.org/10.1021/ac900308v
  10. J. M. Andrews, "Determination of minimum inhibitory concentrations", J. Antimicrob. Chemother., vol. 49, no. 6, p. 1049, 2002. DOI: 10.1093/jac/dkf083. DOI: https://doi.org/10.1093/jac/dkf083
  11. J. D. Londoño-Mosquera, A. Aragón-Muriel, and D. Polo-Cerón, "Synthesis, antibacterial activity and DNA interactions of lanthanide(III) complexes of N(4)-substituted thiosemicarbazones", Univ. Sci., vol. 23, no. 2, pp. 141–169, 2018. DOI: 10.11144/Javeriana.SC23-2.saaa. DOI: https://doi.org/10.11144/Javeriana.SC23-2.saaa
  12. G. B. Deacon and R. J. Philibs, "Relationships Between The Carbon-Oxygen Stretching Frecuencies of Carboxilato Complexes and The Type of Carboxylate Coordination", Coord. Chem. Rev., vol. 33, pp. 227–250, 1980. DOI: 10.1016/S0010-8545(00)80455-5. DOI: https://doi.org/10.1016/S0010-8545(00)80455-5
  13. M. M. Hincapié-Otero, A. Joaqui-Joaqui, and D. Polo-Cerón, "Synthesis and characterization of four N-acylhydrazones as potential O,N,O donors for Cu2+: An experimental and theoretical study", Univ. Sci., vol. 26, no. 2, pp. 193–215, 2021. DOI: 10.11144/JAVERIANA.SC26-2.SACO. DOI: https://doi.org/10.11144/Javeriana.SC26-2.saco
  14. X. C. Su and J. L. Chen, "Site-Specific Tagging of Proteins with Paramagnetic Ions for Determination of Protein Structures in Solution and in Cells", Acc. Chem. Res., vol. 52, no. 6, pp. 1675–1686, 2019. DOI: 10.1021/acs.accounts.9b00132. DOI: https://doi.org/10.1021/acs.accounts.9b00132
  15. I. Płowaś, J. Świergiel, and J. Jadżyn, "Electrical conductivity in dimethyl sulfoxide + potassium iodide solutions at different concentrations and temperatures", J. Chem. Eng. Data, vol. 59, no. 8, pp. 2360–2366, 2014. DOI: 10.1021/je4010678. DOI: https://doi.org/10.1021/je4010678
  16. D. Polo-Cerón, "Cu(II) and Ni(II) complexes with new tridentate NNS thiosemicarbazones: Synthesis, characterisation, DNA interaction, and antibacterial activity", Bioinorg. Chem. Appl., vol. 2019, 2019. DOI: 10.1155/2019/3520837. DOI: https://doi.org/10.1155/2019/3520837
  17. P. Caravan, "Strategies for increasing the sensitivity of gadolinium based MRI contrast agents", Chem. Soc. Rev., vol. 35, no. 6, p. 512, 2006. DOI: 10.1039/b510982. DOI: https://doi.org/10.1039/b510982p
  18. L. J. Xu, G. T. Xu, and Z. N. Chen, "Recent advances in lanthanide luminescence with metal-organic chromophores as sensitizers", Coord. Chem. Rev., vol. 273–274, pp. 47–62, 2014. DOI: 10.1016/j.ccr.2013.11.021. DOI: https://doi.org/10.1016/j.ccr.2013.11.021
  19. B. N. Siriwardena-Mahanama and M. J. Allen, "Strategies for optimizing water-exchange rates of lanthanide-based contrast agents for magnetic resonance imaging", Molecules, vol. 18, no. 8, pp. 9352–9381, 2013. DOI: 10.3390/molecules18089352. DOI: https://doi.org/10.3390/molecules18089352
  20. M. Rohrer, H. Bauer, J. Mintorovitch, M. Requardt, and H. J. Weinmann, "Comparison of magnetic properties of MRI contrast media solutions at different magnetic field strengths", Invest. Radiol., vol. 40, no. 11, pp. 715–724, 2005. DOI: 10.1097/01.rli.0000184756.66360.d3. DOI: https://doi.org/10.1097/01.rli.0000184756.66360.d3
  21. Y. Shen, F. L. Goerner, C. Snyder, J. N. Morelli, D. Hao, D. Hu, X. Li and V. M. Runge, "T1 relaxivities of gadolinium-based magnetic resonance contrast agents in human whole blood at 1.5, 3, and 7T", Invest. Radiol., vol. 50, no. 5, pp. 330–338, 2015. DOI: 10.1097/RLI.0000000000000132. DOI: https://doi.org/10.1097/RLI.0000000000000132
  22. P. Caravan, D. Esteban-Gómez, A. Rodríguez-Rodríguez, and C. Platas-Iglesias, "Water exchange in lanthanide complexes for MRI applications. Lessons learned over the last 25 years", Dalt. Trans., vol. 48, no. 30, pp. 11161–11180, 2019. DOI: 10.1039/c9dt01948k. DOI: https://doi.org/10.1039/C9DT01948K
  23. M. C. Heffern, L. M. Matosziuk, and T. J. Meade, "Lanthanide probes for bioresponsive imaging", Chem. Rev., vol. 114, no. 8, pp. 4496–4539, 2014. DOI: 10.1021/cr400477t. DOI: https://doi.org/10.1021/cr400477t
  24. H. Scientific, "Assessing the Need and Identifying the Response", in A guide to recording Fluorecence Quantum Yileds, 2017, pp. 1–6.
  25. S. Kagatikar and D. Sunil, "Aggregation-induced emission of azines: An up-to-date review", J. Mol. Liq., vol. 292, p. 111371, 2019. DOI: 10.1016/j.molliq.2019.111371. DOI: https://doi.org/10.1016/j.molliq.2019.111371
  26. W. Tang, Y. Xiang, and A. Tong, "Salicylaldehyde Azines as Fluorophores of Aggregation-Induced Emission Enhancement Characteristics A series of salicylaldehyde azine derivatives were found to exhibit interesting aggregation-induced emission enhance- ment ( AIEE ) characteristics", J. Org. Chem., pp. 2163–2166, 2009. DOI: 10.1021/jo802631m. DOI: https://doi.org/10.1021/jo802631m
  27. T. Sakurai, M. Kobayashi, H. Yoshida, and M. Shimizu, "Remarkable increase of fluorescence quantum efficiency by cyano substitution on an ESIPT molecule 2-(2-hydroxyphenyl) benzothiazole: A highly photoluminescent liquid crystal dopant", Crystals, vol. 11, no. 9, 2021. DOI: 10.3390/cryst11091105. DOI: https://doi.org/10.3390/cryst11091105
  28. A. Foucault-Collet, K. A. Gogick, K. A. White, S. Villette, A. Pallier, G. Collet, C. Kieda, T. Li, S. J. Geib, N. L. Rosi and S. Petoud, "Lanthanide near infrared imaging in living cells with Yb3+ nano metal organic frameworks", Proc. Natl. Acad. Sci. U. S. A., vol. 110, no. 43, pp. 17199–17204, 2013. DOI: 10.1073/pnas.1305910110. DOI: https://doi.org/10.1073/pnas.1305910110
  29. Z. Qu, J. Shen, Q. Li, F. Xu, F. Wang, X. Zhang, C. Fan, "Near-IR emissive rare-earth nanoparticles for guided surgery", Theranostics, vol. 10, no. 6, pp. 2631–2644, 2020. DOI: 10.7150/thno.40808. DOI: https://doi.org/10.7150/thno.40808
  30. «Ficha técnica Dotarem, Agencia española de medicamentos y productos sanitarios», pp. 5–24, 2016.
  31. CECMED, «Ficha técnica Magnevist», vol. 52, no. 1. pp. 5–24, 2003.
  32. J. Barnhart, N. Kuhnert, D. A. Bakan and R. Berk, "Biodistribution of GdCl3 and Gd-DTPA and their influence in rat tissues", Magn. Reson. Imaging, vol. 5, pp. 221–231, 1987. DOI: 10.1016/0730-725x(87)90023-3. DOI: https://doi.org/10.1016/0730-725X(87)90023-3
  33. G. Castro, M. Regueiro-Figueroa, D. Esteban-Gûmez, R. Bastida, A. Macias, P. Perez-Lourido, C. Platas-Iglesias and L. Valencia, "Exceptionally Inert Lanthanide(III) PARACEST MRI Contrast Agents Based on an 18-Membered Macrocyclic Platform", Chem. - A Eur. J., vol. 21, no. 51, pp. 18662–18670, 2015. DOI: 10.1002/chem.201502937. DOI: https://doi.org/10.1002/chem.201502937
  34. V. M. Runge, B. R. Carollo, C. R. Wolf, K. L. Nelson, and D. Y. Gelblum, "Gd DTPA: a review of clinical indications in central nervous system magnetic resonance imaging", RadioGraphics, vol. 9, no. 5, pp. 929–958, Sep. 1989. DOI: 10.1148/radiographics.9.5.2678298. DOI: https://doi.org/10.1148/radiographics.9.5.2678298
  35. V. M. Runge, "Safety of approved MR contrast media for intravenous injection", J. Magn.
  36. Reson. Imaging, vol. 12, no. 2, pp. 205–213, Aug. 2000. DOI: 10.1002/1522-2586(200008)12:2<205::AID-JMRI1>3.0.CO;2-P. DOI: https://doi.org/10.1002/1522-2586(200008)12:2<205::AID-JMRI1>3.0.CO;2-P
  37. S. Rivera, H. Agudelo-Góngora, J. Oñate-Garzón, L. Florez-Elvira, A. Correa, P. Londoño, J. Londoño-Mosquera, A. Aragón-Muriel, D. Polo-Cerón, I. Ocampo-Ibáñez, "Antibacterial Activity of a Cationic Antimicrobial Molecular Targets", Molecules, vol. 25, p. 5035, 2020. DOI: 10.3390/molecules25215035. DOI: https://doi.org/10.3390/molecules25215035

Descargas

Los datos de descargas todavía no están disponibles.

Artículos similares

1 2 > >> 

También puede {advancedSearchLink} para este artículo.