High Risk α-HPV E6 Impairs Translesion Synthesis by Blocking POLη Induction.

High risk genus α human papillomaviruses (α-HPVs) express two versatile oncogenes (α-HPV E6 and E7) that cause cervical cancer (CaCx) by degrading tumor suppressor proteins (p53 and RB). α-HPV E7 also promotes replication stress and alters DNA damage responses (DDR). The translesion synthesis pathway (TLS) mitigates DNA damage by preventing replication stress from causing replication fork collapse. Computational analysis of gene expression in CaCx transcriptomic datasets identified a frequent increased expression of TLS genes. However, the essential TLS polymerases did not follow this pattern. These data were confirmed with in vitro and ex vivo systems. Further interrogation of TLS, using POLη as a representative TLS polymerase, demonstrated that α-HPV16 E6 blocks TLS polymerase induction by degrading p53. This doomed the pathway, leading to increased replication fork collapse and sensitivity to treatments that cause replication stress (e.g., UV and Cisplatin). This sensitivity could be overcome by the addition of exogenous POLη.

Correlated rotational switching in two-dimensional self-assembled molecular rotor arrays.

Molecular devices are capable of performing a number of functions from mechanical motion to simple computation. Their utility is somewhat limited, however, by difficulties associated with coupling them with either each other or with interfaces such as electrodes. Self-assembly of coupled molecular devices provides an option for the construction of larger entities that can more easily integrate with existing technologies. Here we demonstrate that ordered organometallic arrays can be formed spontaneously by reaction of precursor molecular rotor molecules with a metal surface. Scanning tunnelling microscopy enables individual rotors in the arrays to be switched and the resultant switches in neighbouring rotors imaged. The structure and dimensions of the ordered molecular rotor arrays dictate the correlated switching properties of the internal submolecular rotor units. Our results indicate that self-assembly of two-dimensional rotor crystals produces systems with correlated dynamics that would not have been predicted a priori.

Ullmann coupling mediated assembly of an electrically driven altitudinal molecular rotor.

Surface-bound molecular rotation can occur with the rotational axis either perpendicular (azimuthal) or parallel (altitudinal) to the surface. The majority of molecular rotor studies involve azimuthal rotors, whereas very few altitudinal rotors have been reported. In this work, altitudinal rotors are formed by means of coupling aryl halides through a surface-mediated Ullmann coupling reaction, producing a reaction state-dependent altitudinal molecular rotor/stator. All steps in the reaction on a Cu(111) surface are visualized by low-temperature scanning tunneling microscopy. The intermediate stage of the coupling reaction is a metal-organic complex consisting of two aryl groups attached to a single copper atom with the aryl rings angled away from the surface. This conformation leads to nearly unhindered rotational motion of ethyl groups at the para positions of the aryl rings. Rotational events of the ethyl group are both induced and quantified by electron tunneling current versus time measurements and are only observed for the intermediate structure of the Ullmann coupling reaction, not the starting material or finished product in which the ethyl groups are static. We perform an extensive set of inelastic electron tunneling driven rotation experiments that reveal that torsional motion around the ethyl group is stimulated by tunneling electrons in a one-electron process with an excitation energy threshold of 45 meV. This chemically tunable system offers an ideal platform for examining many fundamental aspects of the dynamics of chemically tunable molecular rotor and motors.

Two-dimensional bricklayer arrangements of tolans using halogen bonding interactions.

Diphenylacetylene (tolan) derivatives with self-complementary aryl halides and halogen bond-accepting nitriles form 2D bricklayer packing motifs when halogen bonding occurs. When halogen bonding is absent, as occurred with fluorinated aryl bromides, the molecules adopt other packing motifs. These results suggest halogen bonding is potentially useful for producing rarely observed 2D bricklayer motifs in organic semiconductors.

Electronic effects of ring fusion and alkyne substitution on acene properties and reactivity.

This paper describes the synthesis and systematic study of substituted acenes that have differences in conjugation both along their long axes (by the number of fused benzene or thiophene rings) and along their short axes (by the number of arylethynyl substituents). These acenes include what we believe to be the first reported examples of five new subclasses of substituted acenes. Systematic analyses of data obtained using absorbance and fluorescence spectroscopies, cyclic voltammetry, and DFT calculations reveal clear correlations between these common structural perturbations to acene structure and the key parameters, such as HOMO-LUMO gap, frontier molecular orbital energies, and reactivity with singlet oxygen.

Photoinduced Aggregation of Polythiophenes.

This letter describes thiophene-based materials that undergo photoinduced aggregation or precipitation upon irradiation with UV light. The only solubilizing side chains on these materials are photocleavable by connection through photolabile nitrobenzyl esters. While quaterthiophene oligomers yield diacids that remain soluble in dichloromethane at micromolar concentrations upon exposure to ultraviolet light, the polymeric analog shows both red-shifted absorbance and heavily quenched fluorescence, consistent with aggregation due to photochemical cleavage of solubilizing alkyl chains. Thin films of this polymer also resisted dissolution in organic solvent upon irradiation, suggesting applicability in the construction of multilayer solid-state devices.