Influence of Ligand and Nuclearity on the Cytotoxicity of Cyclometallated C^N^C Platinum(II) Complexes

Abstract

As eries of cyclometallated mono-and di-nuclear platinum(II) complexes and the parento rganicl igand, 2,6-diphenylpyridine 1 (HC^N^CH), have been synthesized and characterized. This library of compounds includes [(C^N^C)Pt II (L)] (L = dimethylsulfoxide (DMSO) 2 and triphenylphosphine(PPh 3) 3)a nd [((C^N^C)Pt II) 2 (L')] (where L' = Nheterocycles (pyrazine (pyr) 4,4 ,4'-bipyridine (4,4'-bipy) 5 or diphosphine (1,4-bis(diphenylphosphino)butane (dppb) 6). Their cytotoxicity was assessed against four cancerous cell lines and one normalc ell line, with resultsh ighlighting significantly increaseda ntiproliferative activity for the dinuclear complexes (4-6), when compared to the mononucleated species (2 and 3). Complex 6 is the most promisingc andidate, displaying very high selectivity towards cancerous cells, with selectivity index (SI) values > 29.5 (A2780) and > 11.2 (A2780cisR), ando utperforming cisplatin by > 4-fold and > 18-fold, respectively.

Enhanced luminescence properties through heavy ancillary ligands in [Pt(C^N^C)(L)] complexes, L = AsPh3 and SbPh3

“…The new complexes [Pt(C^N^C)(AsPh 3 )] and [Pt(C^N^C)(SbPh 3 )] were synthesised in the same way as the previously reported lighter congeners [Pt(C^N^C)(PPh 3 )] 50,51 via a facile ligand exchange reaction from the corresponding [Pt(C^N^C)(dmso)] precursors as shown in Scheme 1 in good yields ranging from 64% to 84% (more information in the ESI†). The new complexes were characterised by nuclear magnetic resonance (NMR) spectroscopy (see Fig.…”

“…Details on data collection, structure solution and refinement as well as selected structural parameters are listed in Tables S1–S3 (ESI†) alongside with the data for the previously reported [Pt(dpp)(PPh 3 )] and [Pt(dba)(PPh 3 )]. 50,51 The crystal structures feature long Pt⋯Pt distances ranging from about 7 to 10 Å (far beyond a significant interaction between the Pt atoms, typically below 3.5 Å); thus, no significant Pt⋯Pt interactions nor π-stacking interactions were found. 52,53 In contrast, the dba containing structures show pronounced π-stacking of the acridine moieties with centroid distances between 3.5 and 3.6 Å.…”

“…Herein, we report two series of double cyclometalated Pt( ii ) complexes [Pt(C^N^C)(PnPh 3 )] (Pn = P, As, Sb) based on the two established C^N^C ligand systems dpp (H 2 dpp = 2,6-diphenyl-pyridine) 31,50 and dba (H 2 dba = dibenzo[ c , h ]acridine) 31,51 which showed an enhancement of the phosphorescence quantum yields for their heavier congeners. The role of radiative and radiationless deactivation rates was studied by combining extensive photoluminescence (PL) and transient absorption spectroscopy (TAS) with density functional theory (DFT) calculations.…”

“…After a first study on a series of Pt(II) complexes [Pt(N^N^N)(PnPh 3 )] (Pn = P, As, Sb) containing the tridentate N^N^N = 2,6-bis(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)pyridine and 2,6-bis(3-(tert-butyl)-1H-1,2,4-triazol-5-yl)pyridine ligands found little systematic variation between the PnPh 3 homologues due to a saturation effect from Pt on the emission efficiency in this N^N^N system, 30 we moved on to cyclometalated C^N^C ligand systems. 31 Herein, we report two series of double cyclometalated Pt(II) complexes [Pt(C^N^C)(PnPh 3 )] (Pn = P, As, Sb) based on the two established C^N^C ligand systems dpp (H 2 dpp = 2,6diphenyl-pyridine) 31,50 and dba (H 2 dba = dibenzo[c,h] acridine) 31,51 which showed an enhancement of the phosphorescence quantum yields for their heavier congeners. The role of radiative and radiationless deactivation rates was studied by combining extensive photoluminescence (PL) and transient absorption spectroscopy (TAS) with density functional theory (DFT) calculations.…”

C–H Metalation of Terpyridine Stereoisomers with Ni(II), Pd(II), and Pt(II)

“…Double NˆCˆC cyclometalation with dianionic NˆCˆC 2− ligands based on diphenyl-2-pyridine (Hdphpy) was never observed for Pt(II), while for Pd(II) and Ni(II), the complexes [M(dphpy)(PPh 3 )] (M = Pd and Ni) were recently reported [56]. In contrast to this, − CˆNˆC − coordination with the prototypical 2,6-diphenylpyridine system (Hdpp) to Pt(II) is quite frequent [57][58][59][60][61][62], while for Pd(II) the first example was only very recently reported [Pd(dpp)(PPh 3 )] [63], and no Ni(II) derivatives have been found. Triple CˆCˆC cyclometalation is not known for any of these metals.…”