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Title: Tricarbonyl M(I) (M = Re, 99mTc) complexes bearing acridine fluorophores : synthesis, characterization, DNA interaction studies and nuclear targeting
Authors: Esteves, Teresa
Xavier, Catarina
Gama, Sofia
Mendes, Filipa
Raposinho, Paula D.
Marques, Fernanda
Paulo, António
Pessoa, João Costa
Rino, José
Viola, Giampietro
Santos, Isabel
Keywords: Acridine
Fluorescence spectroscopy
Cell nucleus
Issue Date: 2010
Publisher: Royal Society of Chemistry
Citation: Org. Biomol. Chem., 2010, 8, 4104-4116
Abstract: 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.
Description: © The Royal Society of Chemistry 2010
Peer review: yes
ISSN: 1477-0520
Appears in Collections:IMM - Artigos em Revistas Internacionais

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