Monofunctional platinum(ii) anticancer complexes based on multidentate phenanthridine-containing ligand frameworks

Abstract

Pt(ii) complexes supported by chelating, multidentate ligands containing phenanthridine heterocycles are reported and shown to exhibit a superior in vitro therapeutic index compared with phenanthriplatin and cisplatin.

Brightly Luminescent Platinum Complexes of N∧C–∧N Ligands Forming Six-Membered Chelate Rings: Offsetting Deleterious Ring Size Effects Using Site-Selective Benzannulation

“…1 H NMR spectroscopy confirmed the coordination of the ligand to platinum through three distinct features, as highlighted for t Bu L PtCl: (1) the disappearance of the central aryl proton resonance (C 16 H ; triplet at 8.11 ppm in t Bu LH ); (2) a downfield shift of the phenanthridinyl H CN resonances (9.34 ppm in t Bu LH to 10.17 ppm); and (3) the appearance of 195 Pt satellites for this signal ( 3 J PtH = 46.2 Hz). The downfield shift of the H CN proton resonance upon binding to an electrophilic transition metal center is a consistent feature of square-planar group 10 coordination complexes of phenanthridinyl-based pincer-type ligand frameworks. , …”

“…The downfield shift of the HCN proton resonance upon binding to an electrophilic transition metal center is a consistent feature of square-planar group 10 coordination complexes of phenanthridinyl-based pincer-type ligand frameworks. 22,23 Interestingly, while the complexes were judged to be generally stable to ambient air and moisture, diffusion of hexanes vapor into a chloroform solution of CF3 LPtCl over 3 months 24 deposited crystals of an oxidized trichlorido Pt(IV) species ( CF3 LPtCl 3 ) indicating that CF3 LPtCl is unstable toward oxidation via reaction with chloroform over longer time periods. Indeed, refluxing CF3 LH with K 2 PtCl 4 in glacial acetic acid under an aerobic atmosphere led to the appearance of a new resonance in the 19 F NMR spectrum (δ −62.0 ppm) just downfield of the peak assigned to CF3 LPtCl.…”

P–C Bond Activation and Transfer of a Diphenylphosphino Unit from 1,1′-Bis(diphenylphosphino)ferrocene: Unexpected Templated Synthesis of an N∧N–∧P Pincer Ligand Palladium Complex

“…As part of our work developing routes to incorporating benzannulated N -heterocycles into multidentate ligand platforms, we became interested in pincer-type scaffolds which combine amido donors with strongly π-accepting groups such as phenanthridine (3,4-benzoquinoline). These sorts of architectures have allowed construction of unusually deep-red-emitting phosphorescent materials, , coordination complexes with promising anticancer activity, and iron­(II) compounds with panchromatic absorption and exceptionally long-lived charge-transfer excited states . In order to expand our library of synthetically available analogs, we targeted the formation of secondary N , N -(2-bromophenyl)­(phenanthridinyl)­amines that might be further elaborated into tridentate, pincer-like scaffolds via functionalization of the aryl bromide, as has been demonstrated for related P ∧ N ∧ N-diarylamido ligands .…”

Synthesis, characterization, and coordination chemistry of a phenanthridine-containing N-heterocyclic carbene ligand

“…The solid-state structure confirms the installation of the 1-mesitylimidazole at the 6-position of the phenanthridine unit, along the presence of a bromide counterion (Figure 2). A slightly shorter C=N distance is observed in the phenanthridinyl unit [C(13)-N(1) 1.286(4) Å] when compared to other reported phenanthridine-based proligands 37,38 in which the 6-position of remains unsubstituted To explore the coordinating ability of tethered phenanthridinyl-carbenes derived from 1•HX, we first prepared a Ag(I) complex (Scheme 2). Linear Ag(I)-NHC complexes are capable of transmetalation reactions and thus are useful sources of carbene ligands.…”