Design of Luminescent, Heteroleptic, Cyclometalated PtII and PtIV Complexes: Photophysics and Effects of the Cyclometalated Ligands.

Neutral pentafluorophenyl benzoquinolinyl PtII [Pt(bzq)(HC^N-κN)(C6 F5 )] (1 a-g) complexes, bearing nonmetalated N-heterocyclic HC^N ligands [HC^N=2,5-diphenyl-1,3,4-oxadiazole (Hoxd) a, 2-(2,4-difluorophenyl)pyridine (dfppy) b, 2-phenylbenzo[d]thiazole (pbt) c, 2-(4-bromophenyl)benzo[d]thiazole (Br-pbt) d, 2-phenylquinoline (pq) e, 2-thienylpyridine (thpy) f, 1-(2-pyridyl)pyrene (pypy) g], and heteroleptic bis(cyclometalated) PtIV fac-[Pt(bzq)(C^N)(C6 F5 )Cl] (2 b-g, bzq: benzo[h]quinolinyl) derivatives, generated by oxidation of 1 b-g with PhICl2 , are reported. The oxidation reaction of 1 a evolved with formation of the bimetallic PtIV complex syn-[Pt(bzq)(C6 F5 )Cl(µ-OH)]2 3. The crystal structures of 1 a,d,f, 2 b,d,e and 3 were corroborated by X-ray crystallography. A comparative study of the absorption and photoluminescence properties of the two series of complexes PtII (1) and PtIV (2), supported by time-dependent DFT calculations (TD-DFT), is presented. The low-lying transitions (absorption and emission) of PtII complexes 1 a-e [solution and polystyrene (PS) films] were assigned to the IL/MLCT mixture located on the cyclometalated Pt(bzq) unit, with minor IL'/ML'CT/LL'CT contributions involving the non-metalated ligand. Complex 1 g, bearing the more delocalized pyridyl pyrene (Hpypy) as an ancillary ligand, shows dual 1 ππ* and 3 ππ* (Hpypy) emission in fluid CH2 Cl2 and dual 3 IL/3 MLCT [Pt(bzq)] and [3 ππ*, Hpypy] phosphorescence at 77 K. Upon oxidation, PtIV complexes 2 b-f display (solution, PS) ligand-based phosphorescence that arises from the bzq in 2 b (3 LC) or from the second C^N ligand in 2 c-f (3 L'C) with some 3 LL'CT in 2 f. Despite metalation of the pyrenyl group, 2 g exhibits dual emission 1 ππ*/3 ππ* located on the pypy chromophore.

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

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 (14) )] 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-1 H-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.

Facile Approaches to Phosphorescent Bis(cyclometalated) Pentafluorophenyl PtIV Complexes: Photophysics and Computational Studies.

A convenient and general strategy for the synthesis of stable bis(cyclometalated) pentafluorophenyl PtIV complexes fac-[Pt(C^N)2 (C6 F5 )Cl] (3 a-f) and mer-[Pt(C^N)2 (C6 F5 )(CN)] (4 c,d) has been developed. Complexes 3 were selectively generated by low-temperature oxidation of the cyclometalated PtII complexes [Pt(C^N)(HC^N)(C6 F5 )] 2 [prepared from cis-[Pt(C6 F5 )2 (HC^N)2 ] (1) intermediates] with PhICl2 and subsequent metalation of the pendant HC^N ligand. Complexes 3 a,b were also alternatively generated by irradiation (Hg lamp, 400 W) of complexes 2 a,b, respectively, in CH2 Cl2 . This latter reaction proceeds via the hydride PtIV species cis-[Pt(C^N)2 (C6 F5 )H], detected as the only intermediate species. The molecular structures of 1 a,d, 2 a, and 3 a,b,d,e were confirmed by X-ray diffraction. The substitution of Cl- by CN- in fac-[Pt(C^N)2 (C6 F5 )Cl] [C^N=2-phenylbenzothiazole (3 c), 2-(4-bromophenyl)benzothiazole (3 d)] evolved with isomerization to give rise to the isomers (OC-6-42)-[Pt(C^N)2 (C6 F5 )(CN)] (4 c, 4 d) having a mer disposition of the cyclometalated and C6 F5 groups (X-ray, 4 c). All the complexes are luminescent and their electronic spectra have been compared and interpreted with the aid of time-dependent DFT calculations.

An Extended Chain and Trinuclear Complexes Based on Pt(II)-M (M = Tl(I), Pb(II)) Bonds: Contrasting Photophysical Behavior.

The syntheses and structural characterizations of a Pt-Tl chain [{Pt(bzq)(C6F5)2}Tl(Me2CO)]n 1 and two trinuclear Pt2M clusters (NBu4)[{Pt(bzq)(C6F5)2}2Tl] 2 and [{Pt(bzq)(C6F5)2}2Pb] 3 (bzq = 7,8-benzoquinolinyl), stabilized by donor-acceptor Pt → M bonds, are reported. The one-dimensional heterometallic chain 1 is formed by alternate "Pt(bzq)(C6F5)2" and "Tl(Me2CO)" fragments, with Pt-Tl bond separations in the range of 2.961(1)-3.067(1) Å. The isoelectronic trinuclear complexes 2 (which crystallizes in three forms, namely, 2a, 2b, and 2c) and 3 present a sandwich structure in which the Tl(I) or Pb(II) is located between two "Pt(bzq)(C6F5)2" subunits. NMR studies suggest equilibria in solution implying cleavage and reformation of Pt-M bonds. The lowest-lying absorption band in the UV-vis spectra in CH2Cl2 and tetrahydrofuran (THF) of 1, associated with (1)MLCT/(1)L'LCT (1)[5dπ(Pt) → π*(bzq)]/(1)[(C6F5) → bzq], displays a blue shift in relation to the precursor, suggesting the cleavage of the chain maintaining bimetallic Pt-Tl fragments in solution, also supported by NMR spectroscopy. In 2 and 3, it shows a blue shift in THF and a red shift in CH2Cl2, supporting a more extensive cleavage of the Pt-M bonds in THF solutions than in CH2Cl2, where the trinuclear entities are predominant. The Pt-Tl chain 1 displays in solid state a bright orange-red emission ascribed to (3)MM'CT (M' = Tl). It exhibits remarkable and fast reversible vapochromic and vapoluminescent response to donor vapors (THF and Et2O), related to the coordination/decoordination of the guest molecule to the Tl(I) ion, and mechanochromic behavior, associated with the shortening of the intermetallic Pt-Tl separations in the chain induced by grinding. In frozen solutions (THF, acetone, and CH2Cl2) 1 shows interesting luminescence thermochromism with emissions strongly dependent on the solvent, concentration, and excitation wavelengths. The Pt2Tl complex 2 shows an emission close to 1, ascribed to charge transfer from the platinum fragment to the thallium [(3)(L+L')MM'CT]. 2 also shows vapoluminescent behavior in the presence of vapors of Me2CO, THF, and Et2O, although smaller and slower than those of 1. The trinuclear neutral complex Pt2Pb 3 displays a blue-shift emission band, tentatively assigned to admixture of (3)MM'CT (3)[Pt(d) → Pb(sp)] with some metal-mediated intraligand ((3)ππ/(3)ILCT) contribution. In contrast to 1 and 2, 3 does not show vapoluminescent behavior.

A new family of luminescent [Pt(pbt)2(C6F5)L]n+ (n = 1, 0) complexes: synthesis, optical and cytotoxic studies.

Given the widely recognized bioactivity of 2-arylbenzothiazoles against tumor cells, we have designed a new family of luminescent heteroleptic pentafluorophenyl-bis(2-phenylbenzothiazolyl) PtIV derivatives, fac-[Pt(pbt)2(C6F5)L]n+ (n = 1, 0) [L = 4-Mepy 1, 4-pyridylbenzothiazole (pybt) 2, 4,4'-bipyridine (4,4'-bpy) 3, 1,2-bis-(4-pyridyl)ethylene (bpe) 4 (E/Z ratio: 90/10), 1,4-bis-(pyridyl)butadiyne (bpyb) 5, trifluoroacetate (-OCOCF3) 6] and a dinuclear complex [{Pt(pbt)2(C6F5)}2(µ-bpyb)](PF6)27, in which the trans ligand to the metalated C-(pbt) was varied to modify the optical properties and lipophilicity. Their photophysical properties were systematically studied through experimental and theoretical investigations, which were strongly dependent on the identity of the N-bonded ligand. Thus, complexes 1, 3 and 6 display, in different media, emission from the triplet excited states of primarily intraligand 3ILCT nature localized on the pbt ligand, while the emissions of 2, 5 and 7 were ascribed to a mixture of close 3IL'(N donor)/3ILCT(pbt) excited states, as supported by lifetime measurements and theoretical calculations. Irradiation of the initial E/Z mixture of 4 (15 min) led to a steady state composed of roughly 1 : 1.15 (E : Z) and this complex was not emissive at room temperature due to an enhanced intramolecular E to Z isomerization process of the 1,2-bis-(4-pyridyl)ethylene ligand. Complexes 1-3 and 6 showed excellent quantum yields for the generation of singlet oxygen in aerated MeCN solution with the values of ϕ(1O2) ranging from 0.66 to 0.86 using phenalenone as a reference. Cationic complexes 1-3 exhibited remarkable efficacy in the nanomolar range against A549 (lung carcinoma) and HeLa (cervix carcinoma) cell lines with notable selectivity relative to the non-tumorigenic BEAS-2B (bronchial epithelium) cells. In the A549 cell line, the neutral complex 6 showed low cytotoxicity (IC50: 29.40 µM) and high photocytotoxicity (IC50: 5.75) when cells were irradiated with blue light for 15 min. These complexes do not show evidence of DNA interaction.

Preparation of Titanocene-Gold Compounds Based on Highly Active Gold(I)-N-Heterocyclic Carbene Anticancer Agents: Preliminary in†vitro Studies in Renal and Prostate Cancer Cell Lines.

Heterometallic titanocene-based compounds containing gold(I)-phosphane fragments have been extremely successful against renal cancer in vitro and in vivo. The exchange of phosphane by N-heterocyclic carbene ligands to improve or modulate their pharmacological profile afforded bimetallic complexes effective against prostate cancer, but less effective against renal cancer in vitro. Herein we report the synthesis of new bimetallic Ti-Au compounds by the incorporation of two previously reported highly active gold(I)-N-heterocyclic carbene fragments derived from 4,5-diarylimidazoles. The two new compounds [(η5 -C5 H5 )2 TiMe(µ-mba)Au(NHC)] (where NHC=1,3-dibenzyl-4,5-diphenylimidazol-2-ylidene, NHC-Bn 2 a; or 1,3-diethyl-4,5-diphenylimidazol-2-ylidene, NHC-Et 2 b) with the dual linker (-OC(O)-p-C6 H4 -S-) containing both a carboxylate and a thiolate group were evaluated in vitro against renal and prostate cancer cell lines. The compounds were found to be more cytotoxic than previously described Ti-Au compounds containing non-optimized gold(I)-N-heterocyclic fragments. We present studies to evaluate their effects on cell death pathways, migration, inhibition of thioredoxin reductase (TrxR) and vascular endothelial growth factor (VEGF) in the PC3 prostate cancer cell line. The results show that the incorporation of a second metallic fragment such as titanocene into biologically active gold(I) compounds improves their pharmacological profile.

Alkynyl bridged cyclometalated Ir2M2 clusters: impact of the heterometal in the photo- and electro-luminescence properties.

We report two unprecedent alkynyl bridging cyclometalated clusters [Ir2M2(ppy)4(µ-C[triple bond, length as m-dash]CC6H4-OMe3)4] where M is Ag (2) and Cu (3), which display distinctive luminescence properties. While 2 features a green phosphorescence/electroluminescence nature located at the ppy ligands ((3)LC), 3 shows an orange emission confined to the metals and alkynyl groups having a mixed (3)L'C/(3)L'MCT/(3)MMCT (L' = alkynyl) nature.