Publication:
Synthesis, chemical and biochemical characterization of TiIV and VIV complexes with anti-tumor activity

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Authors
Lamboy-Vega, José L.
Embargoed Until
Advisor
Meléndez, Enrique
College
College of Arts and Sciences - Sciences
Department
Department of Chemistry
Degree Level
M.S.
Publisher
Date
2010
Abstract
At the present time in which the metallocene dihalides have shown to possess antitumoral activity, scientists of all around the world have been working with the synthesis and structural modifications to improve their performance. This work was aimed to the synthesis and chemical/biochemical characterization of the titanium and vanadium complexes. Two complexes were synthetisized Ti(maltolato)2(OH)2 and V(maltolato)2Cl2, using as starting material titanocene and vanadocene dichlorides respectively. The characterization of both complexes was achieved using techniques as Infrared spectroscopy (IR), Nuclear Magnetic Resonance (NMR), Mass spectroscopy (MS), and Cyclic Voltammetry (CV) among others. Interaction studies between these complexes with apo-transferrin, using UV-VIS, showed that vanadium complex has the capacity to bind the biomolecule by donation of V(IV) to apo-transferrin bindin pocket. The titanium-maltol complex showed to be a robust one because does not donate the metal to apo-transferrin. Neither the titanium or vanadium complexes interact with the DNA molecule or oligonucleotide. Cytotoxic studies using HT-29 cancer cells showed that Ti(maltolato)2(OH)2 was the most active complex in comparison with other eight complexes including titanocene [1] . Ti(maltolato)2(OH)2 shows hydrolytically stability, with 120 hours of cytotoxic activity. Similar results were obtained using human epithelial adenocarcinoma cells (Caco-2 cells).

Desde el momento en que los dihaluros de metalocenos mostraron tener capacidades antitumoral, científicos de todas partes del mundo se han dado a la tarea de llevar a cabo modificaciones y nuevas síntesis con el fin de optimizar el desempeño de estos. Este trabajo esta enfocado en la síntesis y caracterización química y bioquímica de complejos de titanio y vanadio. Dos complejos fueron sintetizados Ti(maltolato)2(OH)2 y V(maltolato)2Cl2, utilizando sus respectivos dialuros como material de partida. Entre las tècnicas utilizadas para la caracterización se encuentran: Resonancia Magnetico Nuclear (RMN), Spectroscopía de infrarrojo (IR), Espectroscopía de Masa (MS/MS), Voltametria cíclica (CV), entre otras. Se llevaron a cabo estudios de interacciòn con moléculas de importancia biologica tales como: apo-transferina y ADN (calf thymus DNA), utilizando UV-VIS. El complejo de Vanadio mostró tener la capacidad de donar el metal a la apo-transferina, mientras que el complejo de titanio no dona el metal, mostrando ser un complejo mas robusto. Datos similares fueron obtenidos con la molécula de ADN, no existe interacción apreciable entre estos complejos y la molécula de ADN. Estudios de citotoxicidad en células HT-29 demuestran que el complejo de titanio es mas activo que los ocho complejos utilizados en el estudio, incluyendo a titanoceno [1] . Ti(maltolato)2(OH)2 mostró actividad hasta por 120 horas lo que demuestra la gran estabilidad hidrolítica que este posee. Resultados similares fueron obtenidos utilizando células epiteliales humanas de adenocarcinomas colorectal (células Caco-2).
Keywords
Metallocene dihalides,
Antitumoral activity,
Titanium and vanadium complexes
Cite
Lamboy-Vega, J. L. (2010). Synthesis, chemical and biochemical characterization of TiIV and VIV complexes with anti-tumor activity [Thesis]. Retrieved from https://hdl.handle.net/20.500.11801/362