Synthesis and Exciton Dynamics of Triplet Sensitized Conjugated Polymers

We report the synthesis of a novel polythiophene-based host-guest copolymer incorporating a Pt-porphyrin complex (TTP-Pt) into the backbone for efficient singlet to triplet polymer exciton sensitization. We elucidated the exciton dynamics in thin films of the material by means of Transient Absorption Spectrosopcy (TAS) on multiple time scales and investigated the mechanism of triplet exciton formation. During sensitization, singlet exciton diffusion is followed by exciton transfer from the polymer backbone to the complex where it undergoes intersystem crossing to the triplet state of the complex. We directly monitored the triplet exciton back transfer from the Pt-porphyrin to the polymer and found that 60% of the complex triplet excitons were transferred with a time constant of 1087 ps. We propose an equilibrium between polymer and porphyrin triplet states as a result of the low triplet diffusion length in the polymer backbone and hence an increased local triplet population resulting in increased triplet-triplet annihilation. This novel system has significant implications for the design of novel materials for triplet sensitized solar cells and upconversion layers

High-efficiency and air-stable P3HT-based polymer solar cells with a new non-fullerene acceptor

We thank BASF for partial financial support, as well as EPSRC Projects EP/G037515/1 and EP/M023532/1, EC FP7 Project SC2 (610115), EC FP7 Project ArtESun (604397), EC FP7 Project POLYMED (612538), Project Synthetic carbon allotropes project SFB 953 and the King Abdullah University of Science and Technology (KAUST)

Structure and mechanism of human DNA polymerase η

The variant form of the human syndrome xeroderma pigmentosum (XPV) is caused by a deficiency in DNA polymerase eta (Pol eta), a DNA polymerase that enables replication through ultraviolet-induced pyrimidine dimers. Here we report high-resolution crystal structures of human Pol eta at four consecutive steps during DNA synthesis through cis-syn cyclobutane thymine dimers. Pol eta acts like a 'molecular splint' to stabilize damaged DNA in a normal B-form conformation. An enlarged active site accommodates the thymine dimer with excellent stereochemistry for two-metal ion catalysis. Two residues conserved among Pol eta orthologues form specific hydrogen bonds with the lesion and the incoming nucleotide to assist translesion synthesis. On the basis of the structures, eight Pol eta missense mutations causing XPV can be rationalized as undermining the molecular splint or perturbing the active-site alignment. The structures also provide an insight into the role of Pol eta in replicating through D loop and DNA fragile sites

Simultaneous disruption of two DNA polymerases, Polη and Polζ, in Avian DT40 cells unmasks the role of Polη in cellular response to various DNA lesions

Replicative DNA polymerases are frequently stalled by DNA lesions. The resulting replication blockage is released by homologous recombination (HR) and translesion DNA synthesis (TLS). TLS employs specialized TLS polymerases to bypass DNA lesions. We provide striking in vivo evidence of the cooperation between DNA polymerase η, which is mutated in the variant form of the cancer predisposition disorder xeroderma pigmentosum (XP-V), and DNA polymerase ζ by generating POLη−/−/POLζ−/− cells from the chicken DT40 cell line. POLζ−/− cells are hypersensitive to a very wide range of DNA damaging agents, whereas XP-V cells exhibit moderate sensitivity to ultraviolet light (UV) only in the presence of caffeine treatment and exhibit no significant sensitivity to any other damaging agents. It is therefore widely believed that Polη plays a very specific role in cellular tolerance to UV-induced DNA damage. The evidence we present challenges this assumption. The phenotypic analysis of POLη−/−/POLζ−/− cells shows that, unexpectedly, the loss of Polη significantly rescued all mutant phenotypes of POLζ−/− cells and results in the restoration of the DNA damage tolerance by a backup pathway including HR. Taken together, Polη contributes to a much wide range of TLS events than had been predicted by the phenotype of XP-V cells

Short-Lived Trace Gases in the Surface Ocean and the Atmosphere

The two-way exchange of trace gases between the ocean and the atmosphere is important for both the chemistry and physics of the atmosphere and the biogeochemistry of the oceans, including the global cycling of elements. Here we review these exchanges and their importance for a range of gases whose lifetimes are generally short compared to the main greenhouse gases and which are, in most cases, more reactive than them. Gases considered include sulphur and related compounds, organohalogens, non-methane hydrocarbons, ozone, ammonia and related compounds, hydrogen and carbon monoxide. Finally, we stress the interactivity of the system, the importance of process understanding for modeling, the need for more extensive field measurements and their better seasonal coverage, the importance of inter-calibration exercises and finally the need to show the importance of air-sea exchanges for global cycling and how the field fits into the broader context of Earth System Science

Charge Separation in Intermixed Polymer:PC70BM Photovoltaic Blends: Correlating Structural and Photophysical Length Scales as a Function of Blend Composition

A key challenge in achieving control over photocurrent generation by bulk-heterojunction organic solar cells is understanding how the morphology of the active layer impacts charge separation and in particu-lar the separation dynamics within molecularly-intermixed donor-acceptor domains versus the dynamics between phase-segregated domains. This paper addresses this issue by studying blends and devic-es of the amorphous silicon-indacenodithiophene polymer SiIDT-DTBT and the acceptor PC70BM. By changing the blend composition, we modulate the size and density of the pure and intermixed domains on the nanometre lengthscale. Laser spectroscopic studies show that these changes in morphology cor-relate quantitatively with the changes in charge separation dynamics on the nanosecond timescale, and with device photocurrent densities. At low fullerene compositions, where only a single, molecularly in-termixed polymer-fullerene phase is observed, photoexcitation results in a ~30% charge loss from gem-inate polaron pair recombination, which is further studied via light intensity experiments showing that the radius of the polaron pairs in the intermixed phase is 3-5 nm. At high fullerene compositions (≥ 67%), where the intermixed domains are 1-3 nm and the pure fullerene phases reach ~4 nm, the geminate recombination is suppressed by the reduction of the intermixed phase making the fullerene domains accessible for electron escape

Spectroscopic Investigation of the Effect of Microstructure and Energetic Offset on the Nature of Interfacial Charge Transfer States in Polymer: Fullerene Blends

Despite performance improvements of organic photovoltaics, the mechanism of photoinduced electron-hole separation at organic donor-acceptor interfaces remains poorly understood. Inconclusive experimental and theoretical results have produced contradictory models for electron-hole separation in which the role of interfacial charge-transfer (CT) states is unclear, with one model identifying them as limiting separation and another as readily dissociating. Here, polymer-fullerene blends with contrasting photocurrent properties and enthalpic offsets driving separation were studied. By modifying composition, film structures were varied from consisting of molecularly mixed polymer-fullerene domains to consisting of both molecularly mixed and fullerene domains. Transient absorption spectroscopy revealed that CT state dissociation generating separated electron-hole pairs is only efficient in the high energy offset blend with fullerene domains. In all other blends (with low offset or predominantly molecularly mixed domains), nanosecond geminate electron-hole recombination is observed revealing the importance of spatially localized electron-hole pairs (bound CT states) in the electron-hole dynamics. A two-dimensional lattice exciton model was used to simulate the excited state spectrum of a model system as a function of microstructure and energy offset. The results could reproduce the main features of experimental electroluminescence spectra indicating that electron-hole pairs become less bound and more spatially separated upon increasing energy offset and fullerene domain density. Differences between electroluminescence and photoluminescence spectra could be explained by CT photoluminescence being dominated by more-bound states, reflecting geminate recombination processes, while CT electroluminescence preferentially probes less-bound CT states that escape geminate recombination. These results suggest that apparently contradictory studies on electron-hole separation can be explained by the presence of both bound and unbound CT states in the same film, as a result of a range of interface structures

Mactinin, a fragment of cytoskeletal α-actinin, is a novel inducer of heat shock protein (Hsp)-90 mediated monocyte activation

<p>Abstract</p> <p>Background</p> <p>Monocytes, their progeny such as dendritic cells and osteoclasts and products including tumor necrosis factor (TNF)-α, interleukin (IL)-1α and IL-1β play important roles in cancer, inflammation, immune response and atherosclerosis. We previously showed that mactinin, a degradative fragment of the cytoskeletal protein α-actinin, is present at sites of monocytic activation in vivo, has chemotactic activity for monocytes and promotes monocyte/macrophage maturation. We therefore sought to determine the mechanism by which mactinin stimulates monocytes.</p> <p>Results</p> <p>Radiolabeled mactinin bound to a heterocomplex on monocytes comprised of at least 3 proteins of molecular weight 88 kD, 79 kD and 68 kD. Affinity purification, mass spectroscopy and Western immunoblotting identified heat shock protein (Hsp)-90 as the 88 kD component of this complex. Hsp90 was responsible for mediating the functional effects of mactinin on monocytes, since Hsp90 inhibitors (geldanamycin and its analogues 17-allylamino-17-demethoxygeldanamycin [17-AAG] and 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin [17-DMAG]) almost completely abrogated the stimulatory activity of mactinin on monocytes (production of the pro-inflammatory cytokines IL-1α, IL-1β and TNF-α, as well as monocyte chemotaxis).</p> <p>Conclusion</p> <p>Mactinin is a novel inducer of Hsp90 activity on monocytes and may serve to perpetuate and augment monocytic activation, thereby functioning as a "matrikine." Blockage of this function of mactinin may be useful in diseases where monocyte/macrophage activation and/or Hsp90 activity are detrimental.</p

A phase I trial of antibody directed enzyme prodrug therapy (ADEPT) in patients with advanced colorectal carcinoma or other CEA producing tumours

Antibody-directed enzyme prodrug therapy is a targeted therapy in which a prodrug is activated selectively at the tumour site by an enzyme, which has been targeted to the tumour by an antibody (antibody-enzyme conjugate). Previous clinical trials have shown evidence of tumour response, however, the activated drug had a long half-life, which resulted in dose-limiting myelosuppression. Also, the targeting system, although giving high tumour to blood ratios of antibody-enzyme conjugate (10 000 : 1) required administration of a clearing antibody in addition to the antibody-enzyme conjugate. The purpose of this current study therefore was to attempt tumour targeting of the antibody-enzyme conjugate without the clearing antibody, and to investigate a new prodrug (bis-iodo phenol mustard, ZD2767P) whose activated form is highly potent and has a short half-life. Twenty-seven patients were treated with antibody-directed enzyme prodrug therapy using A5CP antibody-enzyme conjugate and ZD2767P prodrug, in a dose-escalating phase I trial. The maximum tolerated dose of ZD2767P was reached at 15.5 mg m−2×three administrations with a serum carboxypeptidase G2 level of 0.05 U ml−1. Myelosuppression limited dose escalation. Other toxicities were mild. Patients' quality of life was not adversely affected during the trial as assessed by the measures used. There were no clinical or radiological responses seen in the study, but three patients had stable disease at day 56. Human anti-mouse antibody and human anti-carboxypeptidase G2 antibody were produced in response to the antibody enzyme conjugate (A5CP). The antibody-enzyme conjugate localisation data (carboxypeptidase G2 enzyme levels by HPLC on tumour and normal tissue samples, and gamma camera analysis of I-131 radiolabelled conjugate) are consistent with inadequate tumour localisation (median tumour: normal tissue ratios of antibody-enzyme conjugate of less than 1). A clearance system is therefore desirable with this antibody-enzyme conjugate or a more efficient targeting system is required. ZD2767P was shown to clear rapidly from the circulation and activated drug was not measurable in the blood. ZD2767P has potential for use in future antibody-directed enzyme prodrug therapy systems