Pyrazolyl-diamine ligands that bear anthracenyl moieties and their rhenium(I) tricarbonyl complexes: synthesis, characterisation and DNA-binding properties.
Two novel families of pyrazolyl-diamine ligands that bear an anthracen-9-yl group as a DNA-binding fragment, pz*(CH2)2NH(CH2)2NHCH2-9-anthryl (pz*=pz (L(1)), 3,5-Me2pz (L2)) and pz*(CH2)2NH(CH2)2NH(2 (pz*=4-(9-anthrylmethyl)pz (L3), 3,5-Me2-4-(9-anthrylmethyl)pz (L4)), have been prepared and fully characterised. In the case of L2-L4, the evaluation of their coordination capability towards the fac-[Re(CO)3]+ core led to the synthesis of the organometallic complexes fac-[Re(CO)(3){3,5-Me(2)pz(CH2)2NH(CH2)2NHCH2-9-anthryl}]Br (7) and fac-[Re(CO)3{4-(9-anthrylmethyl)pz*(CH2)2NH(CH2)2NH2}]Br (pz*=pz (8), 3,5-Me2pz 9). The interaction of the novel pyrazole-diamine ligands and the rhenium(I) complexes with calf thymus (CT) DNA has been investigated with a variety of spectroscopic techniques (UV-visible, fluorescence, circular dichroism (CD) and linear dichroism (LD)). All of the evaluated compounds have a moderate affinity to CT DNA (3.46x10(3)<K(b)<1.95x10(4)), but the binding mode depends on the position of the chromophore in the framework of the pyrazolyl-diamine ligands. LD measurements have shown that L1 and L2 act as DNA intercalators, but complex 7 intercalates only partially. By contrast, the compounds with the anthracenyl group at the 4-position of the azolyl ring (L(3), L4 and 9) do not intercalate, and behave more like DNA groove binders. Fluorescence microscopy studies have demonstrated that complexes 7 and 9 can target the nucleus of murine B16-F1 melanoma cells, and appear to be promising platforms for the further design of radiopharmaceuticals for targeted radiotherapy.
Departamento de Química, ITN, Estrada Nacional 10, 2686-953 Sacavém Codex, Portugal.
Rute F
RF
Vitor
Isabel
I
Correia
Margarida
M
Videira
Fernanda
F
Marques
António
A
Paulo
João
J
Costa Pessoa
Giampietro
G
Viola
Gabriel G
GG
Martins
Isabel
I
Santos
D000818:Animals; D000873:Anthracenes / Q000737:chemistry*; D002414:Cations, Monovalent / Q000737:chemistry*; D002417:Cattle; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D002614:Chelating Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D002942:Circular Dichroism; D004247:DNA / Q000378:metabolism*; D003959:Diamines / Q000737:chemistry*; D008024:Ligands; D051379:Mice; D008860:Microscopy, Ultraviolet; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D011720:Pyrazoles / Q000737:chemistry*; D012211:Rhenium / Q000737:chemistry*; D013050:Spectrometry, Fluorescence
D000873:Anthracenes; D002414:Cations, Monovalent; D002614:Chelating Agents; D003959:Diamines; D008024:Ligands; D009942:Organometallic Compounds; D011720:Pyrazoles; C031280:pyrazole; D012211:Rhenium; D004247:DNA; C427203:calf thymus DNA