Tricarbonyl M(I) (M = Re, 99mTc) complexes bearing acridine fluorophores : synt...

• Autor(es): Esteves, Teresa ; Xavier, Catarina ; Gama, Sofia ; Mendes, Filipa ; Raposinho, Paula D. ; Marques, Fernanda ; Paulo, António ; Pessoa, João Costa ; Rino, José ; Viola, Giampietro ; Santos, Isabel
• Data: 2010
• Identificador Persistente: http://hdl.handle.net/10451/7119
• Origem: Repositório da Universidade de Lisboa
• Assunto(s): Acridine; Fluorescence spectroscopy; Radiopharmaceuticals; Cell nucleus; DNA
• Tipo de Documento: Artigo
• Idioma: Inglês

Descrição

© The Royal Society of Chemistry 2010 New pyrazolyl-diamine ligands with acridine derivatives at the 4-position of the pyrazolyl ring were synthesized and characterized (L1 and L2). Coordination towards the fac-[M(CO)3]+ (M = Re, 99mTc) led to complexes fac-[M(CO)3(κ3-L)] (L = L1: M = Re1, Tc1; L = L2: M = Re2, Tc2). The interaction of the novel pyrazolyl-diamine ligands (L1 and L2) and rhenium(I) complexes (Re1 and Re2) with calf thymus DNA (CT-DNA) was investigated by a variety of techniques, namely UV-visible , fluorescence spectroscopy and circular and linear dichroism . Compounds L1 and Re1 have moderate affinity to CT-DNA and bind to DNA by intercalation, while L2 and Re2 have a poor affinity for CT-DNA. Moreover, LD measurements showed that L1 and Re1 act as perfect intercalators . By confocal fluorescence microscopy we found that L1 and Re1 internalize and localize in the nucleus of B16F1 murine melanoma cells . The congener Tc1 complex also targets the cell nucleus exhibiting a time-dependent cellular uptake and a fast and high nuclear internalization (67.2% of activity after 30 min). Plasmid DNA studies have shown that Tc1 converts supercoiled (sc) puc19 DNA to the open circular (oc) form.