Synthesis, characterization, kinetic investigation and biological evaluation of Re(i) di- and tricarbonyl complexes with tertiary phosphine ligands.

Rhenium(i) di- and tri-carbonyl complexes of the form fac-[Re(CO)(L,L'-Bid)X] and [Re(CO)(L,L'-Bid)X], where X = aqua (HO), methanol (CHOH), triphenylphosphine (PPh), 1,3,5-triaza-7-phosphaadamantane (PTA), tricyclohexylphosphine (PCy) and L,L'-Bid = O,O' bidentate ligands (tropolone = TropH and 3-hydroxyflavone = FlavH) and N,O bidentate ligands (8-hydroxyquinoline = QuinH, 5,7-chloro-8-hydroxyquinoline = diCl-QuinH and quinoline-2,4-dicarboxylic acid = QuinH), were synthesized and unambiguously characterized by H-, C-and P-NMR, IR, UV/Vis and micro-analysis. The crystal structures of four complexes, namely fac-[Re(CO)(QuinH)(HO)]·HO (5), fac-[Re(CO)(Quin)(PPh)] (11), fac-[Re(CO)(diCl-Quin)(PPh)] (12) and [Re(CO)(Trop)(PPh)]·2CHCH (20) were obtained. Re-P bonding distances for 11 and 12 are 2.4948(8) and 2.4908(8) Å, respectively, indicating the effect of the electron-withdrawing substituents of the diCl-Quin ligand. The second-order rate constants for the substitutions of methanol at 25.1 °C in fac-[Re(CO)(L,L'-Bid)(CHOH)] (L,L'-Bid = Trop, Flav and QuinH) type complexes by different entering phosphine ligands (PPh, PCy, and PTA) varied between 7.23(7) × 10 and 1.32(3) × 10 M s and were found to depend on the coordinated bidentate ligand (in general k (QuinH) < k (Trop) < k (Flav)). The toxicity of fac-[Re(CO)(QuinH)(PTA)], fac-[Re(CO)(Trop)(PTA)], fac-[Re(CO)(Trop)(PPh)] and fac-[Re(CO)(Flav)(PPh)] on the cervical cancer HeLa and epithelial RPE-1 cell lines was then evaluated. Complex fac-[Re(CO)(Flav)(PPh)] (16) and fac-[Re(CO)(Trop)(PPh)] (13) displayed the highest cytotoxicity with IC values of 12.21 ± 0.17 μM and 13.35 ± 0.94 μM, respectively in HeLa cells. Interestingly, a small selectivity towards cancer over non-cancerous cells was observed for these compounds (IC = 18.41 ± 3.16 μM and >25 μM in RPE-1 cells).