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Ligand-Tuning of the Stability of Pd(II) Conjugates with Cyanocobalamin

Besides the well-known functions performed by vitamin B(12) (CblCN) in biochemical processes of the human body, an increasing interest has been raised by the possibility of its use as a transmembrane drug carrier, capable, among others, of enhancing the accumulation of inorganic cytostatics in cance...

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Detalles Bibliográficos
Autores principales: Porębska, Dominika, Orzeł, Łukasz, Rutkowska-Zbik, Dorota, Stochel, Grażyna, van Eldik, Rudi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8347314/
https://www.ncbi.nlm.nih.gov/pubmed/34360738
http://dx.doi.org/10.3390/ijms22157973
Descripción
Sumario:Besides the well-known functions performed by vitamin B(12) (CblCN) in biochemical processes of the human body, an increasing interest has been raised by the possibility of its use as a transmembrane drug carrier, capable, among others, of enhancing the accumulation of inorganic cytostatics in cancer cells. The present study was aimed at determining the possibility of the formation of CblCN conjugates with Pd(II) complexes. A key aspect was their stability, which we attempted to tune by appropriate choice of ligands. Syntheses, spectroscopic analysis of postreaction systems and kinetic investigations of conjugate formation reactions, have been complemented by DFT modelling. The obtained results showed that ligand charge, geometry and electron affinity may have a significant impact on carrier binding and release leading to the activation of the Pd(II) complex. This provides a rationale to expect that with appropriate composition of the coordination sphere, it will be possible to extend the spectrum of less toxic inorganic chemotherapeutics.