A dinuclear ruthenium(II) phototherapeutic that targets duplex and quadruplex DNA

With the aim of developing a sensitizer for photodynamic therapy, a previously reported luminescent dinuclear complex that functions as a DNA probe in live cells was modified to produce a new iso-structural derivative containing RuII(TAP)2 fragments (TAP = 1,4,5,8-tetraazaphenanthrene). The structure of the new complex has been confirmed by a variety of techniques including single crystal X-ray analysis. Unlike its parent, the new complex displays Ru → L-based 3MLCT emission in both MeCN and water. Results from electrochemical studies and emission quenching experiments involving guanosine monophosphate are consistent with an excited state located on a TAP moiety. This hypothesis is further supported by detailed DFT calculations, which take into account solvent effects on excited state dynamics. Cell-free steady-state and time-resolved optical studies on the interaction of the new complex with duplex and quadruplex DNA show that the complex binds with high affinity to both structures and indicate that its photoexcited state is also quenched by DNA, a process that is accompanied by the generation of the guanine radical cation sites as photo-oxidization products. Like the parent complex, this new compound is taken up by live cells where it primarily localizes within the nucleus and displays low cytotoxicity in the absence of light. However, in complete contrast to [{RuII(phen)2}2(tpphz)]4+, the new complex is therapeutically activated by light to become highly phototoxic toward malignant human melanoma cell lines showing that it is a promising lead for the treatment of this recalcitrant cancer

Insight into the origin of trapping in polymer/fullerene blends with a systematic alteration of the fullerene to higher adducts

The bimolecular recombination characteristics of conjugated polymer poly[(4,4′-bis(2-ethylhexyl)dithieno[3,2-b:2′,3′-d]silole)-2,6-diyl-alt-(2,5-bis 3-tetradecylthiophen-2-yl thiazolo 5,4-d thiazole)-2,5diyl] (PDTSiTTz) blended with the fullerene series PC60BM, ICMA, ICBA, and ICTA have been investigated using microsecond and femtosecond transient absorption spectroscopy, in conjunction with electroluminescence measurements and ambient photoemission spectroscopy. The non-Langevin polymer PDTSiTTz allows an inspection of intrinsic bimolecular recombination rates uninhibited by diffusion, while the low oscillator strengths of fullerenes allow polymer features to dominate, and we compare our results to those of the well-known polymer Si-PCPDTBT. Using μs-TAS, we have shown that the trap-limited decay dynamics of the PDTSiTTz polaron becomes progressively slower across the fullerene series, while those of Si-PCPDTBT are invariant. Electroluminescence measurements showed an unusual double peak in pristine PDTSiTTz, attributed to a low energy intragap charge transfer state, likely interchain in nature. Furthermore, while the pristine PDTSiTTz showed a broad, low-intensity density of states, the ICBA and ICTA blends presented a virtually identical DOS to Si-PCPDTBT and its blends. This has been attributed to a shift from a delocalized, interchain highest occupied molecular orbital (HOMO) in the pristine material to a dithienosilole-centered HOMO in the blends, likely a result of the bulky fullerenes increasing interchain separation. This HOMO localization had a side effect of progressively shifting the polymer HOMO to shallower energies, which was correlated with the observed decrease in bimolecular recombination rate and increased “trap” depth. However, since the density of tail states remained the same, this suggests that the traditional viewpoint of “trapping” being dominated by tail states may not encompass the full picture and that the breadth of the DOS may also have a strong influence on bimolecular recombination

Making the right link to theranostics : the photophysical and biological properties of dinuclear Ru^II-Re^I dppz complexes depend on their tether

The synthesis of new dinuclear complexes containing linked RuII(dppz) and ReI(dppz) moieties is reported. The photophysical and biological properties of the new complex, which incorporates a N,N′-bis(4-pyridylmethyl)-1,6-hexanediamine tether ligand, are compared to a previously reported RuII/ReI complex linked by a simple dipyridyl alkane ligand. Although both complexes bind to DNA with similar affinities, steady-state and time-resolved photophysical studies reveal that the nature of the linker affects the excited state dynamics of the complexes and their DNA photocleavage properties. Quantum-based DFT calculations on these systems offer insights into these effects. While both complexes are live cells permeant, their intracellular localizations are significantly affected by the nature of the linker. Notably, one of the complexes displayed concentration-dependent localization and possesses photophysical properties that are compatible with SIM and STED nanoscopy. This allowed the dynamics of its intracellular localization to be tracked at super resolutions

Ultrafast transient absorption spectroscopy of inkjet-printed graphene and aerosol gel graphene films : effect of oxygen and morphology on carrier relaxation dynamics

The tunable electronic properties of nanostructured graphene make it one of the most sought alternatives to metals for novel technological applications. In particular, the ability to prepare inks out of these nanostructures allows for printable and thus scalable graphene-based electronics. Here, we investigate the electronic properties of novel inkjet-printed aerosol gel graphene (AG) films and compare them to those of inkjet-printed graphene (G) films. More specifically, we report on the photoinduced carrier dynamics of these materials via ultrafast transient absorption spectroscopy. In comparison to graphene, AG films have a higher oxygen content as well as a complex 3D morphology. While G and AG both differ in composition and structure, the similitude in their carrier–optical phonon scatter rates (in 74–140 fs range) indicates a comparable lattice defect density. It is therefore not the number of defects but the type of defect that is electronically relevant. Indeed, in comparison to G films, which exhibit complete recovery of the transient signal, the AG films exhibit only partial recovery within our 400 ps experimental time window. The persisting signal is assigned to trapped electronic states. These long-lived electronic states are most probably due to the presence of oxygen rather than due to the films’ unique 3D morphology

From chemotherapy to phototherapy – changing the therapeutic action of a metallo-intercalating RuII-ReI luminescent system by switching its sub-cellular location

The synthesis of a new heterodinuclear ReIRuII metallointercalator containing RuII(dppz) and ReI(dppn) moieties is reported. Cell-free studies reveal that the complex has similar photophysical properties to its homoleptic M(dppz) analogue and it also binds to DNA with a similar affinity. However, the newly reported complex has very different in-cell properties to its parent. In complete contrast to the homoleptic system, the RuII(dppz)/ReI(dppn) complex is not intrinsically cytotoxic but displays appreciable phototoxic, despite both complexes displaying very similar quantum yields for singlet oxygen sensitization. Optical microscopy suggests that the reason for these contrasting biological effects is that whereas the homoleptic complex localises in the nuclei of cells, the RuII(dppz)/ReI(dppn) complex preferentially accumulates in mitochondria. These observations illustrate how even small structural changes in metal based therapeutic leads can modulate their mechanism of action

Sudden stratospheric warmings seen in MINOS deep underground muon data

The rate of high energy cosmic ray muons as measured underground is shown to be strongly correlated with upper-air temperatures during short-term atmospheric (10-day) events. The effects are seen by correlating data from the MINOS underground detector and temperatures from the European Centre for Medium Range Weather Forecasts during the winter periods from 2003-2007. This effect provides an independent technique for the measurement of meteorological conditions and presents a unique opportunity to measure both short and long-term changes in this important part of the atmosphere. Copyright 2009 by the American Geophysical Union

Search for active neutrino disappearance using neutral-current interactions in the MINOS long-baseline experiment

We report the first detailed comparisons of the rates and spectra of neutral-current neutrino interactions at two widely separated locations. A depletion in the rate at the far site would indicate mixing between νμ and a sterile particle. No anomalous depletion in the reconstructed energy spectrum is observed. Assuming oscillations occur at a single mass-squared splitting, a fit to the neutral- and charged-current energy spectra limits the fraction of νμ oscillating to a sterile neutrino to be below 0.68 at 90% confidence level. A less stringent limit due to a possible contribution to the measured neutral-current event rate at the far site from νe appearance at the current experimental limit is also presented. © 2008 The American Physical Society

Search for muon-Neutrino to electron-Neutrino transitions in MINOS

This Letter reports on a search for νμ→νe transitions by the MINOS experiment based on a 3.14×1020 protons-on-target exposure in the Fermilab NuMI beam. We observe 35 events in the Far Detector with a background of 27±5(stat)±2(syst) events predicted by the measurements in the Near Detector. If interpreted in terms of νμ→νe oscillations, this 1.5σ excess of events is consistent with sin 2(2θ13) comparable to the CHOOZ limit when |Δm2|=2.43×10-3eV2 and sin 2(2θ23)=1.0 are assumed. © 2009 The American Physical Society