Luminescent Cycloplatinated Complexes with Biologically Relevant Phosphine Ligands: Optical and Cytotoxic Properties

Abstract

Two series of neutral luminescent pentafluorophenyl cycloplatinated­(II) complexes [Pt­(C^N)­(C6F5)­L] [C^N = C-deprotonated 2-phenylpyridine (ppy; a), 2-(2,4-difluorophenylpyridine (dfppy; b)] incorporating dimethyl sulfoxide [L = DMSO for 1 (1a reported by us in ref )] or biocompatible phosphine [L = PPh2C6H4COOH (dpbH; 2), PPh2C6H4CONHCH2COOMe (dpbGlyOMe; 3), P­(C6H4SO3Na)3 (TPPTS; 4)] ligands have been prepared and characterized and their optical properties studied. Their cytotoxic activities against tumor A549 (lung carcinoma), HeLa (cervix carcinoma), and nontumor NL-20 (lung epithelium) cell lines, as well as the ability to interact with DNA (plasmid pBR322), were evaluated. Complexes 2 exhibit higher cytotoxicity (IC50 3.89–20.29 μM) than compounds 1 (9.03–20.50 μM), whereas the activities of complexes 3 and 4 are negligible. All cytotoxic complexes show low selective toxicities toward cancer cells. Interestingly, except 1a, these complexes do not show evidence of DNA intercalation. Along the same lines, fluorescence costaining with Hoechst (2,5′-bi-1H-benzimidazole, 2′-(4-ethoxyphenyl)-5-(4-methyl-1-piperazinyl), a nuclear DNA stain) reveals that all complexes easily internalize, being mainly localized in the cytoplasm. In order to deepen the mechanism of biological action, the effect of the most cytotoxic complex 2b toward the dynamics of tubulin was explored. This complex displays tubulin depolymerization activity, exhibiting more potent inhibition of microtubule formation in A549 than in HeLa cells, in accordance with its higher antiproliferative activity (IC50 6.98 vs 12.45 μM), placing this complex as a potential antitubulin agent.

Synthesis, structural characterization, and luminescence properties of mono- and di-nuclear platinum(II) complexes containing 2-(2-pyridyl)-benzimidazole

“…In the case of complex 3, there is a clear 3 IL pbz transition from the benzimidazole ring to pyridine ring, with some contributions of metal to ligand charge transfer 3 MLCT (see Table 5). Upon cooling of the solid samples to 77 K, the emission for both complexes 8 27 A cComparative HOMO-LUMO gap diagram for the complexes 1-4 is shown in Fig. 8.…”

“…Additionally, cycloplatinated(II) complexes bearing the rollover 2,2′-bipyridinate (bpy) ligand can also be emissive in solution or solid state [24][25][26]. Among the reported emissive Pt(II) compounds, those with the [Pt(C^N)R] moiety (C^N= cyclometalated ligand and R= alkyl, aryl or halide) are very attractive due to their ease of preparation [22,25,27,28]. These cyclometalated Pt(II) complexes have been synthesized through a C-H activation of ligands C^N (such as ppy, bpy and bhq) with a suitable Pt(II) precursor complex [19,[29][30][31].…”

Luminescent PtII and PtIV Platinacycles with Anticancer Activity Against Multiplatinum‐Resistant Metastatic CRC and CRPC Cell Models

“…2a' [17] 277 (7524) Pt II cyclometallated compounds show severala bsorption bands in the UV/Visible range ( Figure S8, Supporting Information). [18][19][20] Pt IV compoundso nly show absorption bands in the high energy range, except for compound 3b' which also displays lower energy absorptionbands. An additional high energy absorption band, observed in the range 275-301 nm with higher e values, can be attributed to p!p*i ntraligand transitions, as it matches the absorption recorded for the free ligand ( Figure S9, Supporting Information).…”

“…The new compounds 2b', 3a' and 3b' werecharacterised by elemental analyses, mass spectra,a nd 1 Ha nd 19 FNMR spectra and the molecular structures of these compounds and the previously reported compound 2a' wered etermined by XRD analysis of suitable crystals (see Figure 1, S1-S7, Supporting Infor-mation). In compounds 2a' and 2b' the Pt II centrala tom adopts as quare-planar coordination completed with at ridentate (C,N,N')l igand and an halido (Cl for 2a or Br for 2a') ligand trans to the imine.…”

“…An additional high energy absorption band, observed in the range 275-301 nm with higher e values, can be attributed to p!p*i ntraligand transitions, as it matches the absorption recorded for the free ligand ( Figure S9, Supporting Information). [18][19][20] Pt IV compoundso nly show absorption bands in the high energy range, except for compound 3b' which also displays lower energy absorptionbands.…”