Covalently Platinated DNA Oligonucleotides as Ratiometric Dioxygen Sensors.

Phosphorescent Pt(II) complexes, composed of a tridentate N^N^C donor ligand and a monodentate ancillary ligand, were covalently attached to DNA oligonucleotides. Three modes of attachment were investigated: positioning the tridentate ligand as an artificial nucleobase via a 2′-deoxyribose or a propane-1,2-diol moiety and orienting it towards the major groove by appending it to a uridine C5 position. The photophysical properties of the complexes depend on the mode of attachment and on the identity of the monodentate ligand (iodido vs. cyanido ligand). Significant duplex stabilization was observed for all cyanido complexes when they are attached to the DNA backbone. The luminescence strongly depends on whether a single or two adjacent complexes are introduced, with the latter showing an additional emission band indicative of excimer formation. The doubly platinated oligonucleotides could be useful as ratiometric or lifetime-based oxygen sensors, as the green photoluminescence intensities and average lifetimes of the monomeric species are drastically boosted upon deoxygenation, whereas the red-shifted excimer phosphorescence is nearly insensitive to the presence of triplet dioxygen in solution.

The solution structure of an antisense DNA.RNA hybrid duplex, d(CGCGTT-MMI-TTGCGC).r(GCGCAAAACGCG) (designated R4), containing an MMI backbone linker [3'-CH(2)N(CH(3))-O5'], is elucidated. The structural details of the MMI linker, its structural effects on the neighboring residues, and the molecular basis of the MMI effects are examined. The lipophilic N-methyl group of MMI is peripheral to the helix, assuming a conformation that is most stable with regard to the N-O torsion angle. The MMI linker promotes a 3'-endo conformation for the sugar moieties at both 3'- and 5'-adjacent positions and a backbone kink involving distant residues along the 3'-direction. Comparison of R4 with other analogous hybrid duplexes previously studied in this laboratory reveals a new family of low-energy helical conformations that can be accommodated in stable duplexes and a common feature of C3'-modified sugars for adopting a C3'-endo pucker. The results of these studies emphasize the interplay of several factors that govern the formation of stable hybrid duplexes and provide a basis for the understanding of the biological role of the MMI modifications, which are important building blocks for a family of promising chimeric antisense oligonucleotides.

The synthesis and evaluation of a series of novel nucleobases based on substituted 1,8-naphthyridin-2(1H)-ones are reported. The nucleobases were designed to meet the requirements for incorporation into peptide nucleic acids (PNAs) and were evaluated as part of PNA duplex and triplex nucleic acid recognition systems. Of the various nucleobases tested, only the 7-chloro-1,8-naphthyridin-2(1H)-one (7-Cl-bT) nucleobase led to consistently increased affinity in all recognition systems, duplex (Watson-Crick) as well as triplex (Hoogsteen). For multiply modified systems, the increase in thermal stability per modification was dependent on the sequence context, ranging from 2.0 degrees C (in separate positions) to 3.5 degrees C (in adjacent positions) in PNA-DNA duplexes and from 1.2 degrees C (in separate positions) to 3.2 degrees C (in adjacent positions) in PNA-RNA duplexes. Singly mismatched oligonucleotide targets were employed to demonstrate uncompromised sequence discrimination. When part of multiply modified triplex (Hoogsteen) recognition systems, the 7-Cl-bT unit gave rise to increases in the thermal stability ranging from 2.7 to 3.5 degrees C when incorporated into separated and adjacent positions, respectively. Our results furthermore indicate that the duplex stabilization is predominantly enthalpic and therefore most likely not a consequence of single-strand preorganization. Finally, and most surprisingly, we find no direct correlation between the end-stacking efficiency of this type of nucleobase and its helix stabilization when involved in Watson-Crick base pairing within a helix.

A series of novel phosphorescent platinum (II) complexes bearing phosphine ligands were synthesized. Photoluminescence of platinum (II) complexes in solid state are influenced by substituents on phosphine ligands, but the energy gap between HOMO and LUMO isn’t. Tri-(4-flourophenyl) phosphine has the best steric effect for preventing Pt-Pt interaction and π-π interaction to make red shift in photoluminescence. DFT-calculation was measured on several of platinum (II) complexes to discuss the reaction mechanism and the effect of different types of anions. According to DFT-calculation, PtdfppyCNPPh3 has the biggest energy gap between HOMO and LUMO, so I tried to synthesize PtdfppyCNPPh3 which can be a deep blue phosphorescent material in OLED. The synthesis of PtdfppyCNPPh3 was unsuccessful, but fortunately, aggregate complex with high luminescence was obtained. We changed reaction condition to promote the yield of aggregate complexes by self-assembly reaction. These two aggregate complexes have unique parellelogramal structure with Pt-CN-Ag unit, which was the first example of Pt-CN-Ag aggregate complex. In other hand, platinum (IV) complexes were synthesized by oxidative-addition process. While platinum (II) complexes were oxidized to platinum (IV) complexes, MLCT gap will be induced to larger. Hence, photoluminescence of platinum (IV) complexes are blue-shifted than that of platinum (II) complexes. Especially, for PtdfppyacacCH3CN, the complex can emit deep blue phosphorescence at 77 K with wavelength of 437 nm, 465 nm, 497nm in which 437 nm was the shortest wavelength of emission with 2,4-diflourophenyl pyridyl ligand.

8.17 - Luminescent Coordination and Organometallic Complexes for OLEDs

The applications of phosphorescent platinum(II) complexes in white organic light-emitting diode (WOLED) are discussed. White electroluminescence formed by complementary colors mixing has been achieved by employing phosphorescent platinum(II) complexes as dopants. The approach is to mix triplet monomer emissions of the platinum(II) dopant complexes at orange-red region with a blue-emitting component or, alternatively, to mix the emissions from both monomer and aggregate states of the same platinum(II) complex in the blue-green (λ max~480nm) and orange-red (λ max~600nm) regions. Platinum(II) material-based WOLEDs could be fabricated from both thermal deposition and solution process, since polymeric WOLED materials could be prepared by incorporating platinum(II) complexes in polymer backbone. The WOLEDs fabricated from platinum(II) complexes exhibit good Commission Internationale de l’Eclairage, color-rendering index, and device efficiency, which may find potential applications for solid-state lighting.KeywordsInternal Quantum EfficiencyEmissive LayerLuminous EfficiencyTriplet ExcitonExcimer EmissionThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Three new ligands of the general formula [RNHCH(py)(2)] (py = pyridine; R = tosyl, Ts-dpm; R = dansyl, Ds-dpm; R = 7-nitro-1,2,3-benzoxadiazole, NBD-dpm) have been synthesized and characterized. Reactions of these ligands with cis-[Pt(DMSO)(2)Cl(2)] (DMSO = dimethyl sulfoxide) in methanol affords [Pt(Ts-dpm)Cl(2)] (1), [Pt(Ds-dpm)Cl(2)] (2), and [Pt(NBD-dpm)Cl(2)] (3). The crystal structures of these complexes reveal bidentate coordination of the ligands to the Pt center with nonplanar chelate rings. Because of inequivalent substituents on the methine carbon atom of the ligands, distinct exo and endo isomers exist in the three complexes. X-ray analyses indicate that 1 crystallizes in the endo conformation, 2 in the exo conformation, and 3 as a mixture of the two conformers. The (1)H NMR and (195)Pt NMR spectra of the complexes display two sets of independent signals corresponding to the chemically inequivalent exo and endo conformers. The exo conformer was determined by 2D NMR spectroscopy to be thermodynamically favored for all three complexes. Density functional theory (DFT), time-dependent DFT, and atoms in molecules calculations were carried out for both conformers of 3 to investigate differences in their electronic structures and to explore intramolecular interactions. In the presence of dioxygen, 1 thermally decomposes at 60 degrees C to form several unidentified products. Compound 2 is thermally stable even in the presence of dioxygen and water but upon light exposure decomposes to form a new platinum(II) species with a (195)Pt NMR shift of -2177 ppm. Compound 3 reacts both thermally and photochemically in the presence of dioxygen and trace amounts of water to form both 4-amino-7-nitro-2,1,3-benzoxadiazole and [Pt(dpk)Cl(2)] (dpk = di-2-pyridyl ketone). Oxidation of 1 and 3 with H(2)O(2) in acetic acid affords a mixture of compounds, two of which contain dpm ligands bound in a tridentate manner to platinum.

LC8, a ubiquitous and highly conserved hub protein, binds over 100 proteins involved in numerous cellular functions, including cell death, signaling, tumor suppression, and viral infection. LC8 binds intrinsically disordered proteins (IDPs), and although several of these contain multiple LC8 binding motifs, the effects of multivalency on complex formation are unclear. Drosophila ASCIZ has seven motifs that vary in sequence and inter-motif linker lengths, especially within subdomain QT2-4 containing the second, third, and fourth LC8 motifs. Using isothermal-titration calorimetry, analytical-ultracentrifugation, and native mass-spectrometry of QT2-4 variants, with methodically deactivated motifs, we show that inter-motif spacing and specific motif sequences combine to control binding affinity and compositional heterogeneity of multivalent duplexes. A short linker separating strong and weak motifs results in stable duplexes but forms off-register structures at high LC8 concentrations. Contrastingly, long linkers engender lower cooperativity and heterogeneous complexation at low LC8 concentrations. Accordingly, two-mers, rather than the expected three-mers, dominate negative-stain electron-microscopy images of QT2-4. Comparing variants containing weak-strong and strong-strong motif combinations demonstrates sequence also regulates IDP/LC8 assembly. The observed trends persist for trivalent ASCIZ subdomains: QT2-4, with long and short linkers, forms heterogeneous complexes, whereas QT4-6, with similar mid-length linkers, forms homogeneous complexes. Implications of linker length variations for function are discussed.

Photophysical properties of the new phosphorescent platinum(II) and palladium(II) complexes of benzoporphyrins and chlorins

A series of 2-vinylpyridine-type platinum(II) complexes bearing different main-group blocks (B(Mes)2, SiPh3, GePh3, NPh2, POPh2, OPh, SPh, and SO2Ph, where Mes = 2-morpholinoethanesulfonic acid) were successfully prepared. As indicated by the X-ray single-crystal diffraction, the concerned phosphorescent platinum(II) complexes exhibit distinct molecular packing patterns in the solid state to bring forth different interactions between individual molecules. The photophysical characterizations showed that the emission maxima together with phosphorescent quantum yield of these complexes can also be affected by introducing distinct main-group moieties with electron-donating or electron-withdrawing characters. Furthermore, these 2-vinylpyridine-type platinum(II) complexes exhibit markedly different photophysical and electrochemical properties compared with their 2-phenylpyridine-type analogues, such as higher-lying highest occupied molecular orbital levels and lower-energy phosphorescent emissions. Importantly, these complexes can show good potential as deep red phosphorescent emitters to bring attractive electroluminescent performances with Commission Internationale de L'Eclairage (CIE) coordinates very close to the standard red CIE coordinates of (0.67, 0.33) recommended by the National Television Standards Committee. Hence, these results successfully established structure-property relationship concerning photophysics, electrochemistry, and electroluminescence, which will not only provide important information about the optoelectronic features of these novel complexes but also give valuable clues for developing novel platinum(II) phosphorescent complexes.

The binding affinity of therapeutic oligonucleotides (ONs) for their cognate RNA is determined by the rates of association (ka) and dissociation (kd). Single-stranded ONs are highly flexible and can adopt multiple conformations in solution, some of which may not be conducive for hybridization. We investigated if restricting rotation around the sugar-phosphate backbone, by tethering two adjacent backbone phosphonate esters using hydrocarbon bridges, can modulate hybridization kinetics of the modified ONs for complementary RNA. Given the large number of possible analogues with different tether lengths and configurations at the phosphorus atoms, we employed molecular dynamic simulations to optimize the size of the hydrocarbon bridge to guide the synthetic efforts. The backbone-constrained nucleotide trimers with stereodefined configurations at the contiguous backbone phosphorus atoms were assembled using a ring-closing metathesis reaction, then incorporated into oligonucleotides by an in situ synthesis of the phosphoramidites followed by coupling to solid supports. Evaluation of the modified oligonucleotides revealed that 15-membered macrocyclic-constrained analogues displayed similar or slightly improved on-rates but significantly increased off-rates compared to unmodified DNA ONs, resulting in reduced duplex stability. In contrast, LNA ONs with conformationally preorganized furanose rings showed similar on-rates to DNA ONs but very slow off-rates, resulting in net improvement in duplex stability. Furthermore, the experimental data generally supported the molecular dynamics simulation results, suggesting that this strategy can be used as a predictive tool for designing the next generation of constrained backbone ON analogues with improved hybridization properties.

The DNA binding ability and binding mode of platinum complexes are crucial factors that govern their cytotoxic activity. In this work, circular dichroism spectroscopy, gel electrophoresis and MALDI-TOF MS spectrometry combined with enzymatic degradation have been used to elucidate the role of bridging ligands in DNA-binding ability and cross-linking patterns of two dinuclear antitumour active platinum(II) complexes, {[cis-Pt(NH(3))(2)Cl](2)L1}(NO(3))(2) (1, L1= 4,4'-methylenedianiline) and {[cis-Pt(NH(3))(2)Cl](2)L2}(NO(3))(2) (2, L2 = alpha,alpha'-diamino-p-xylene). Although both complexes have two cis-diammine-Pt(II) moieties (1,1/c,c), complex 1 exhibits much higher DNA-binding ability than complex 2. The former readily forms both 1,3- and 1,4-intrastrand cross-links with DNA oligonucleotides, while the latter preferentially forms 1,4- rather than 1,3-intrastrand cross-links. Cytotoxicity studies against a human non-small-cell lung cancer cell line (A549) demonstrate that complex 1 has higher activity than 2. These results show that the linker properties play a critical role in controlling the DNA-binding and cross-linking abilities and in modulating the cytotoxicity of dinuclear platinum complexes.

Excimer Formation of Perylene Bisimide Dyes within Stacking-Restrained Folda-Dimers: Insight into Anomalous Temperature Responsive Dual Fluorescence

The organic light-emitting diodes (OLEDs) using the iridium complexes of coumarin derivatives as emissive dopants were known to be highly efficient and stable. These coumarin-based Ir(III) complexes were reported to trap and transport electrons effectively in the emissive layer. In this paper, the synthesis and photophysical, electroluminescent properties of platinum (II) complexes cyclometallated with coumarin derivatives are reported. We have prepared a new series of phosphorescent platinum (II) complexes containing 3-(2-pyridinyl)coumarin (pc) as an ancillary ligand. The new heteroleptic platinum complexes, Pt(C^N)(pc) (C^N = 2-(2,4-difluorophenyl)pyridine (F2-ppy), 2-phenylpyridine (ppy) and 2-phenylquinoline (pq)) were characterized by 1H NMR and mass spectrometer. As main ligands, F2-ppy, ppy and pq were employed, which should provide the drastically different ligand molecular orbital energy levels. The platinum complexes synthesized herein showed various luminescence maxima from 551 to 596 nm with rather wide emission ranges, depending upon the relative energy levels of their main and ancillary ligands. The photoabsorption, photoluminescence and electroluminescence of the complexes were studied.

Center backbone-rigidified DNA polygonal nanostructures and bottom face-templated polyhedral pyramids with structural stability in a complex biological medium.