Rhenium(I) complexes and cancer: synthesis and characterisation of mono- and bi-metallic complexes
MetadataShow full item record
Organometallic compounds such as Re(I) complexes showed to be toxic to a few cancer cell lines, but lack the property of being selective towards cancer cells for the use as novel chemotherapeutic agents. Toxicity tests are preliminary tests performed on different cell lines such as HeLa, HepG2 or PT45 to determine whether the compounds could be used as potential PDT (photodynamic therapy) agents. PDT is the administration of non-toxic drugs or dyes also known as photosensitizers (PS) to patients. The main aim of this studies were to synthesize two N,Nʹ-bidentate ligands, 1,10- phenanthroline-5,6-dione (phenO2) and 1,10-phenanthroline-5,5-diamine (phen(NH2)2) and this was done successfully with a yield of 52 % and 48 % respectively, as reported in Chapter 3. Re(I) tri- and dicarbonyl complexes with different monodentate ligands: PPh3, PTA and DAPTA were synthesized for the evaluation of their luminescent properties and are reported in Chapter 5. PhenO2 and phen(NH2)2 are used as bridging ligands for the formation of two dinuclear complexes, [NEt4][Re2(CO)6(phen(NH)2)Br2] and [Re2(CO)6(phenO2)Br2]. The N,Nʹ-bidentate ligand, 1,10-phenanthroline, were coordinated to the Ru(III) metal centre which formed the precursor that was used for the synthesis of new bimetallic complexes with a combination of Pt(II) and Re(I) metals. All the compounds were successfully synthesized and characterised by NMR, IR, UV/Vis and elemental analysis as reported in Chapter 3. The crystal structures of fac-[Re(CO)3(phen)(H2O)][NO3]∙1.5H2O (3), fac- [Re(CO)3(phen)(Br)] (4) and 5-amino-6-nitro-1,10-phenanthroline (phen(NH2)(NO2)) are collected and reported in Chapter 4. 3 and 4 crystallized in the P1� space group while phen(NH2)(NO2) crystallized in the Pbca space group. The Re-CO bond distances of 3 are within the range of 1.864(15) Å to 1.914(13) Å and 4 within the range of 1.902(9) Å to 1.934(7) Å. The Re-N bond distances for 3 is 2.178(8) Å and 2.180(8) Å and for 4 the Re-N distances is 2.183(6) Å. The bite angle of 3 is 76.5(3) ° and the bite angle of 4 is 75.8(2) °. The N-H bond distances of phen(NH2)(NO2) are 0.89(3) Å and 0.93(4) Å, while the N-O bond distances are greater than the N-H distances with bond distances reported as 1.244(3) Å and 1.241(3) Å. The angles between the O-N-O and H- N-H substituents are 120.0 °. Luminescent studies was performed on the Re(I) tri- and dicarbonyl complexes for the evaluation of their luminescent properties. The Re(I) tricarbonyl complexes with monodentate phosphine ligands, fac-[Re(CO)3(phen)(PPh3)][NO3], fac-[Re(CO)3(phen)(PTA)][NO3] and fac-[Re(CO)3(phen)(DAPTA)][NO3], showed to absorb electrons from a wavelength of 265 nm to 266 nm. Their molar absorptivity coefficient ranges from 11490 to 31185 M-1 cm-1 while their emission wavelengths is at 610 nm. The Re(I) dicarbonyl complexes with bis-phosphine ligands, cis-trans-[Re(CO)2(phen)(PPh3)2][NO3], cis-trans-[Re(CO)2(phen)(PTA)2][NO3] and cis-trans-[Re(CO)2(phen)(DAPTA)2][NO3] showed luminescent properties at excitation wavelengths of 616 nm, 610 nm and 610 nm respectively. cis-trans- [Re(CO)2(phen)(PTA)2][NO3] has the largest molar absorptivity coefficient (14465 M-1 cm-1) of the three dicarbonyl complexes. cis-[Re(CO)2(phen)(PPh3)(Cl)], cis- [Re(CO)2(phen)(PTA)(Cl)] and cis-[Re(CO)2(phen)(DAPTA)(Cl)], the three dicarbonyl complexes with a monodentate phosphine ligands, have smaller molar absorptivity coefficients than all of the Re(I) compounds. These compounds also have greater emission wavelengths ranging from 620 nm to 630 nm. Three novel bimetallic complexes, [Ru(phen)2(N,Nʹ-phenO2-O,Oʹ)-Re(CO)3Br][PF6]3, [Ru(phen)2(N,Nʹ-phenO2-O,Oʹ)-PtCl2][PF6]3 and [Re(CO)3(N,Nʹ-phenO2-O,Oʹ)-PtCl2]Br with yields of 25 %, 96 % and 98 % respectively, were synthesized to evaluate their cytotoxicity against HeLa and RPE-1 cell lines. [Re(CO)3(N,Nʹ-phenO2-O,Oʹ)-PtCl2]Br is the only complex that showed cytotoxic effects against the HeLa cell line with an IC50 value of 7.31 ± 0.07 μM.