Aggregation, Photoluminescence, and Cytotoxicity of Pt(II) and Re(I) Complexes Bearing Multimodal-Coordinating Luminophores

Abstract

In this study, a polydentate ligand capable of adopting multiple coordination modes (N*N, C^N*N, and C^N*N^C) was established. Depending on the chelation conditions and the co-ligand used in the subsequent steps, nine complexes became accessible. The four Pt(II)-based species with N*N-coordination motif show tunable emission and cytotoxicity. Two Pt(II) complexes with C^N*N-type coordination were also obtained, and the exchange of the co-ligand from chlorido to cyanido led to an enhancement in the photoluminescence quantum yield from <0.02 to 0.55. These compounds exhibit distinct solid-state characteristics associated with Pt⋯Pt-interactions. Interestingly, the tetradentate C^N*N^C-coordination mode was not accessible, most likely due to kinetic reasons and insolubility-related purification hurdles. However, the use of a N*N-coordination mode for a Re(I) center yielded non-cytotoxic ³MLCT-state emitters. The multifaceted coordination modes available with the luminophoric ligand enable the design and realization of diverse metal complexes with tailored cytotoxicity and tendency towards intermolecular coupling, both in solution and in crystalline phases.

Keywords: Pt(II) complexes; Pt⋯Pt interactions; aggregation; cytotoxicity; photoluminescence.

Figure 1

Structural formulae and IC₅₀‐values (µm) for cisplatin and Pt(II)‐based triplet emitters presented by Huo and coworkers,^{[ 35 ]} along with nedaplatin,^{[ 36 ]} carboplatin and oxaliplatin.^{[ 37 ]} (a) Against NCI‐H522 lung cancer; (b) against HepG2 liver cancer; (c) averaged over four different cell lines, namely: PC‐9 and PC‐14 human luminary adenocarcinoma as well as MKN‐45 and KATO III human stomach adenocarcinoma.

Figure 2

Ligand design and different possible coordination modes.

Figure 3

N*N‐type bidentate coordination of Pt(II) with LH₂ and exchange of the chlorido ligands by L₂H₂ (GlyH₂; cbdaH₂; TsglyH₂) to yield [PtLH₂L₂ ]. (I) Bidentate coordination: [PtCl₂DMSO₂ ], DCM, room temperature, 120 h, yielding 88%. Ligand exchange: (II) AgTFA, MeOH, room temperature, 1 h; (III) L₂Na₂ (L₂H₂ , NaOMe, MeOH, room temperature, 1 h), MeOH, reflux, 4 h (yielding 68% for L₂H₂ = GlyH₂, 88% for cbdaH₂, 95% for TsglyH₂).

Figure 4

Tridentate C^N*N coordination of Pt(II) by mono‐cyclometallation with LH₂ and ligand exchange of the chlorido unit by cyanido to afford [PtLHCN]. (I) Mono‐cyclometallation: K₂[PtCl₄], ^NBu₄NCl, glacial acetic acid, 250 °C, 1 h, max. 850 W, yield: 92%. (II) Ligand exchange: AgCN, MeCN, reflux, 16 h, yield: 85%.

Figure 5

Bidentate N*N coordination of Re(I) with LH₂ and ligand exchange of the chlorido unit by cyanido to afford [ReLH₂(CO)₃CN]. (I) Bidentate coordination: [Re(CO)₅Br], MeOH, reflux, 16 h. YIELDS: 50% with X = Br; 9% with Cl. (II) Ligand exchange: AgCN, MeCN, reflux, 16 h, yielding 91%.

Figure 6

Molecular structure in the crystalline phase of 1 (left), and LH₂ (right). Displacement ellipsoids are shown at 50% probability.

Figure 7

Molecular structure in the crystalline phase of [PtLH₂Cl₂ ] (left), and [PtLH₂cbda] (right). Displacement ellipsoids are shown at 50% probability.

Figure 8

Molecular structure in the crystalline phase of [PtLHCl] (left, molecule A), and [PtLHCN] (right). Displacement ellipsoids are shown at 50% probability.

Figure 9

Depiction of the dimer formation in the single crystal of [PtLHCN] (left, yellow form; right, orange form) with the shortest Pt⋯Pt distances given in Å.

Figure 10

Molecular structure in the crystalline phase of [ReLH₂(CO)₃Br] (left), and [ReLH₂(CO)₃Cl] (right). Displacement ellipsoids are shown at 50% probability.

Figure 11

UV–vis absorption spectra in liquid DCM at 298 K (top), steady‐state photoluminescence emission spectra (bottom) in liquid DCM at 298 K (left) and in a frozen glassy matrix of DCM/MeOH (V:V = 1:1) at 77 K (right) of [PtLH₂Tsgly] (black), [PtLH₂Gly] (gray), [PtLH₂cbda] (orange), [PtLHCl] (red), [PtLHCN] (blue) and [ReLH₂(CO)₃CN] (green). Validity range of the absorption spectra: c = 5 × 10⁻⁵–2 × 10⁻⁶ m in liquid DCM at 298 K. All solutions for the emission spectra were optically diluted (A < 0.1) and normalized to the highest intensity.

Figure 12

Images of the red (round flask, left) and yellow (powders, right) solids of [PtLHCl] under ambient condition and UV irradiation (λ _Exc = 366 nm). Pure red solid of [PtLHCN] obtained from DCM (center‐left), suspended in EtOAc (yellow suspension, center), and in an EtOAc/MeOH‐mixture (center‐right) for 10 min observed under UV irradiation (λ _Exc = 366 nm).

Figure 13

Photoluminescence spectra of the complexes [PtLHCl] (left) and [PtLHCN] (right) emitting as monomeric (green) or aggregated (red) species in crystalline phases at 298 K (normalized to the highest intensity; measured using a photoluminescence spectrometer coupled to the confocal microscope). Luminescence micrographs of the crystals are shown as insets (λ _exc = 375 ± 20 nm).

Figure 14

Concentration‐dependent photoluminescence emission spectra (λ _Exc = 350 nm) in liquid Ar‐purged DCM at 298 K [PtLHCN] within the concentration range of c = 1·10⁻⁷ (blue), 1·10⁻⁶ (green), 1·10⁻⁵ (black), 1·10⁻⁴ (orange), 1·10⁻³ (red). Normalized at the highest energy maximum. Inset: Solid [PtLHCN] layered with DCM in an NMR tube yielding a concentration gradient at RT under UV irradiation (λ _Exc = 366 nm).

Figure 15

a) VT‐¹H‐NMR experiment (400 MHz, CD₂Cl₂) of a 1 mm solution of [PtCl(LH)]. (b) ¹H‐NMR spectra (400 MHz, CD₂Cl₂) of solutions of [PtCl(LH)] at different concentrations c ₀. (c) α _M (c ₀) plots of [PtCl(LH)] at 220 to 300 K (squares) and non‐linear fit based on Equation (2) (curves). (d) ln K _dim (1/T) plot of [PtCl(LH)] and linear fit following van't Hoff's relation (3).

Figure 16

Relative viability of HepG2 cells after 24 h of incubation with the tested compounds. 1% DMSO and 0.01% saponin were used as a negative and positive control, respectively. Student's one‐sample t‐test relative to 100% was used for statistical evaluation: *P = 95.0%, **P = 99.0%, ***P = 99.9%.