Photoluminescent DNA binding and cytotoxic activity of a platinum(II) complex bearing a tetradentate β-diketiminate ligand

Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. .
Dalton Transactions (Impact Factor: 4.2). 11/2012; 42(9). DOI: 10.1039/c2dt32462h
Source: PubMed


A platinum(ii) complex of a monoanionic, tetradentate β-diketiminate (BDI) ligand with pendant quinoline arms, BDI(QQ)H, is reported. The complex, [Pt(BDI(QQ))]Cl, is emissive in DMSO, but non-emissive in aqueous buffer. Upon binding DNA in buffer, however, a 150-fold turn-on in emission intensity occurs. Dynamic light scattering and (1)H NMR spectroscopy indicate that [Pt(BDI(QQ))]Cl forms non-emissive aggregates in aqueous solution; DNA-binding disperses the aggregates leading to the large emission turn-on response. The cytotoxic activity of the complex, measured in two cancer cell lines, is comparable to or better than that of the established anticancer drug cisplatin.

Full-text preview

Available from:
  • [Show abstract] [Hide abstract]
    ABSTRACT: A dinuclear alkynylplatinum(II) terpyridine complex containing an amphiphilic binaphthol bridge was designed and synthesized, and was shown to display cylindrical columnar assemblies in aqueous acetonitrile solutions, presumably mediated by the PtPt and π-π stacking interactions. The length of the binaphthol bridge was found to have a profound effect on the degree of helicity for hierarchical helices of helices and serves as a critical determinant in the formation of tertiary structures for foldamers. Interestingly, the reciprocal association of multiple helices has led to luminescence enhancement behavior, which provides a luminescence turn-on switch for the reporting of the hierarchical assembly of foldamers into higher-order structures, distinct from that of the pure organic systems. Such a transverse aggregation of multiple helices driven by metallophilic interactions has been studied by electronic absorption, circular dichroism, emission spectroscopy and electron microscopy.
    Chemical Science 11/2013; 4(11):4228. DOI:10.1039/c3sc51534f · 9.21 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: A detailed examination was performed on photophysical properties of phosphorescent cyclometalated (C(∧)N)Pt(O(∧)O) complexes (ppy)Pt(dpm) (1), (ppy)Pt(acac) (1'), and (bzq)Pt(dpm) (2) and newly synthesized (dbq)Pt(dpm) (3) (C(∧)N = 2-phenylpyridine (ppy), benzo[h]quinoline (bzq), dibenzo[f,h]quinoline (dbq); O(∧)O = dipivolylmethanoate (dpm), acetylacetonate (acac)). Compounds 1, 1', 2, and 3 were further characterized by single crystal X-ray diffraction. Structural changes brought about by cyclometalation were determined by comparison with X-ray data from model C(∧)N ligand precursors. The compounds emit from strongly metal-perturbed, ligand-centered triplet states (E0-0 = 479 nm, 1; E0-0 = 495 nm, 2; E0-0 = 470 nm, 3) with disparate radiative rate constants (kr = 1.4 × 10(5) s(-1), 1; kr = 0.10 × 10(5) s(-1), 2; kr = 2.6 × 10(5) s(-1), 3). Zero-field splittings of the triplet states (ΔEIII-I = 11.5 cm(-1), 1'; ΔEIII-I < 2 cm(-1), 2; ΔEIII-I = 46.5 cm(-1), 3) were determined using high resolution spectra recorded in Shpol'skii matrices. The fact that the E0-0 energies do not correspond to the extent of π-conjugation in the aromatic C(∧)N ligand is rationalized on the basis of structural distortions that occur upon cyclometalation using data from single crystal X-ray analyses of the complexes and ligand precursors along with the triplet state properties evaluated using theoretical calculations. The wide variation in the radiative rate constants and zero-field splittings is also explained on the basis of how changes in the electronic spin density in the C(∧)N ligands in the triplet state alter the spin-orbit coupling in the complexes.
    Inorganic Chemistry 10/2013; 52(21). DOI:10.1021/ic4011532 · 4.76 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Ferrocenyl platinum(ii) complexes (), viz. [Pt(Fc-tpy)Cl]Cl (), [Pt(Fc-tpy)(NPC)]Cl (, HNPC = N-propargyl carbazole) and [Pt(Fc-bpa)Cl]Cl (), were prepared, characterized and their anti-proliferative properties in visible light in human keratinocyte (HaCaT) cell lines have been studied. [Pt(Ph-tpy)Cl]Cl () was prepared and used as a control. Complexes and , structurally characterized by X-ray crystallography, show distorted square-planar geometry for the platinum(ii) centre. Complexes and having the Fc-tpy ligand showed an intense absorption band at ∼590 nm. The ferrocenyl complexes are redox active showing the Fc(+)-Fc couple near 0.6 V vs. SCE in DMF-0.1 M tetrabutylammonium perchlorate (TBAP). Complexes showed external binding to calf thymus DNA. Both and showed remarkable photocytotoxicity in HaCaT cell lines giving respective IC50 values of 9.8 and 12.0 μM in visible light of 400-700 nm with low dark toxicity (IC50 >60 μM). Fluorescent imaging studies showed the spread of the complexes throughout the cell localising both in cytoplasm and the nucleus. The ferrocenyl complexes triggered apoptosis on light exposure as evidenced from the Annexin V-FITC/PI and DNA ladder formation assays. Spectral studies revealed the formation of ferrocenium ions upon photo-irradiation generating cytotoxic hydroxyl radicals via a Fenton type mechanism. The results are rationalized from a TDDFT study that shows involvement of ferrocene and the platinum coordinated terpyridine moiety as respective HOMO and LUMO.
    Dalton Transactions 10/2013; 43(2). DOI:10.1039/c3dt51922h · 4.20 Impact Factor
Show more