Search

The cyclin-dependent kinase (CDK5) forms a stable complex with its activator p25, leading to the hyperphosphorylation of tau proteins and to the formation of plaques and tangles that are considered to be one of the typical causes of Alzheimer's disease (AD). Hence, the pathological CDK5-p25 complex is a promising therapeutic target for AD. Small peptides, obtained from the truncation of CDK5 physiological activator p35, have shown promise in inhibiting the pathological complex effectively while also crossing the blood-brain barrier. One such small 24-residue peptide, p5, has shown selective inhibition toward the pathological complex in vivo. Our previous research focused on the characterization of a computationally predicted CDK5-p5 binding mode and of its pharmacophore, which was consistent with competitive inhibition. In continuation of our previous work, herein, we investigate four additional binding modes to explore other possible mechanisms of interaction between CDK5 and p5. The quantitative description of the pharmacophore is consistent with both competitive and allosteric p5-induced inhibition mechanisms of CDK5-p25 pathology. The gained insights can direct further in vivo/in vitro tests and help design small peptides, linear or cyclic, or peptidomimetic compounds as adjuvants of orthosteric inhibitors or as part of a cocktail of drugs with enhanced effectiveness and lower side effects.

N-functionalization of 5,6-dihydroxyindole with a hydrophilic triethyleneglycol (TEG) chain provides access to a new class of water-soluble eumelanin-like materials with relatively high dielectric constant and polyelectrolyte behaviour, reflecting enhanced charge transport by in-depth incorporation of hydration networks.

We report on the optical and photo-physical properties of a fluorinated poly(p-phenylenevinylene) derivative, namely poly(2-methoxy-5-[(2-ethylhexyl)oxy]-1,4-phenylenedifluorovinylene) (MEH-PPDFV) and we compare them with those of the well-known non fluorinated reference system, poly(2-methoxy-5-[(2-ethylhexyl)oxy]-1,4-phenylenevinylene) (MEH-PPV) synthesized with the same procedure. Remarkable blue-shifts of absorption and emission spectra of MEH-PPDFV with respect to MEH-PPV are observed, due to the larger distortion from planarity of the fluorinated species. In addition, the blue-shift for optical transitions in absorption spectra is more pronounced than in emission ones, since the molecule conformation in the excited states is more planar than in the ground one. Microsecond photo-induced absorption spectra of MEH-PPDFV reveal three bands possessing spectral properties and/or kinetics different from those observed for MEH-PPV. The assignment of these transitions is provided in terms of free and trapped polarons as well of triplet excitons. Free-polarons have an intrinsic decay constant of 3 μs, while the trapping dynamics has a longer kinetics of 40 μs. The triplet exciton, instead, shows a monoexponetial decay behavior of constant about 10 μs.

Weak and ultraweak protein-protein association play a role in molecular recognition and can drive spontaneous self-assembly and aggregation. Such interactions are difficult to detect experimentally, and are a challenge to the force field and sampling technique. A method is proposed to identify low-population protein-protein binding modes in aqueous solution. The method is designed to identify preferential first-encounter complexes from which the final complex(es) at equilibrium evolve. A continuum model is used to represent the effects of the solvent, which accounts for short- and long-range effects of water exclusion and for liquid-structure forces at protein/liquid interfaces. These effects control the behavior of proteins in close proximity and are optimized on the basis of binding enthalpy data and simulations. An algorithm is described to construct a biasing function for self-adaptive configurational-bias Monte Carlo of a set of interacting proteins. The function allows mixing large and local changes in the spatial distribution of proteins, thereby enhancing sampling of relevant microstates. The method is applied to three binary systems. Generalization to multiprotein complexes is discussed.

Eumelanin-type biopolymers have attracted growing interest in the quest for soft bioinspired functional materials for application in organoelectronics. Recently, a metal-insulator-semiconductor device with a good quality interface was produced by spin coating of a commercial synthetic eumelanin-like material on a dry plasma-modified silicon surface. As a proof-of-concept step toward the design and implementation of next-generation eumelanin-inspired devices, we report herein an expedient chemical strategy to bestow n-type performance to polydopamine, a highly popular eumelanin-related biopolymer with intrinsic semiconductor behaviour, and to tune its electrical properties. The strategy relies on aerial co-oxidation of dopamine with suitable aromatic amines, e.g. 3-aminotyrosine or p- phenylenediamine, leading to good quality black polymeric films. Capacitance-voltage experiments on poly(dopamine/3-aminotyrosine) and poly(dopamine/p-phenylenediamine)-based metal insulator semiconductor devices on p-Si indicated a significant increase in flat band voltage with respect to polydopamine and previous synthetic eumelanin-based diodes. Variations of the flat band voltage under vacuum were observed for each device. These results point to polydopamine as a versatile eumelanin-type water-dependent semiconductor platform amenable to fine tuning of its electronic properties through incorporation of p-conjugating aromatic amines to tailor functionality.

Conjugated polymers with strongly twisted backbones, such as MEHPPV with fluorinated vinylene units (F-MEHPPV), demand a redefinition of the all-important ‘effective conjugation length’ ECL, which we extract here by a facile graphical method. In MEHPPV (being essentially planar), the ECL coincides with the ‘maximum conducive chain length’ MCC and extends over about n ≈ 9 repetition units (RU). In F-MEHPPV, the MCC is similarly long with n ≈ 8, but the ECL localizes on just one RU. The strong twist in F-MEHPPV persists in the excited state, broadening the emission spectrum and quenching the fluorescence with reduced radiative and enhanced non-radiative rates.

Fully fluorinated arylenevinylene polymers have been synthesized via a methodology based on the Stille cross-coupling reaction and characterized by FTIR spectroscopy and MALDI-TOF mass spectrometry. Investigation of thin film properties by cyclic voltammetry and ellipsometry shows that complete substitution of hydrogen atoms with fluorine atoms on the conjugated backbone of the poly(arylenevinylene)s results in a strong increase of the band gap.

Poly(2′,5′-dioctyloxy-4,4′,4″-terphenylenevinylene) with ( E ) configuration of the vinylene double bonds was prepared by Suzuki–Miyaura polymerization of ( E )-4,4′-dibromostilbene and 2,5-dioctyloxy-1,4-benzenediboronic acid. Attempts to extend this simple procedure to the synthesis of the polymer with ( Z ) configuration, starting from ( Z )-4,4′-dibromostilbene, were unsuccessful. However, the use of ( Z )-4,4′-diiodostilbene and a careful choice of Pd catalyst and experimental conditions, lead to a material with a >95/ Z )/( E ) ratio of vinylene units. The investigation of optical properties of both the ( E ) and ( Z ) polymers evidenced that ( Z ) linkages act as defects which reduce the effective conjugation length in the polymer backbone.

Over the past decade synthetic melanins, melanin-like polymers and melanin-based copolymers have been the focus of growing attention as soft biocompatible functional materials for engineering high performance, low cost optoelectronic devices, such as memory devices, light emitting diodes and field effect transistors. The unique combination of physicochemical properties of melanins, such as broad band absorption in the UV-visible range, intrinsic free radical character, water-dependent hybrid ionic-electronic conductor behaviour and excellent biocompatibility, have inspired use of melanic polymers as valuable functional materials for organic bioelectronics. However, several gaps and issues still hinder rapid progress of melanin-based organic electronics and bioelectronics, including in particular the limited contribution of electronic conductivity and current decay with time under biasing. The aim of this paper is to provide an overview of the structural and optoelectronic properties of melanins and to bring to focus current gaps and challenges in the development of melanin-based materials for bioelectronics. Starting from commercial samples, the paper surveys different melanin-type materials with special emphasis on the potential of polydopamine (pDA), a highly adhesive mussel-inspired melanin-type platform, for incorporation in optoelectronic devices. Simple chemical tailoring procedures for engineering pDA-based n-type polymers and photoresponsive materials for photocapacitive sensors are eventually illustrated.

A copolymer of 2,3,5,6-tetrafluoro-1,4-phenylenevinylene and 2,5-dioctyloxy-1,4-phenylenevinylene [co(TFPV-DOPV)], containing more than 60% of tetrafluorophenylenevinylene monomeric units, was synthesized by the Stille cross-coupling reaction. Its linear and nonlinear optical properties were investigated. Linear absorption and photoluminescence measurements performed on thin films and solution indicate interchain migration upon excitation. A copolymer of 2,3,5,6-tetrafluoro-1,4-phenylenevinylene and 2,5-dioctyloxy-1,4-phenylenevinylene [co(TFPV-DOPV)], containing more than 60% of tetrafluorophenylenevinylene monomeric units, was synthesized by the Stille cross-coupling reaction. Its linear and nonlinear optical properties were investigated. Linear absorption and photoluminescence measurements performed on thin films and solution indicate interchain migration upon excitation. The Z-scan technique was used to evaluate the third-order nonlinear susceptibility. A very high refractive nonlinearity was measured with a value one order of magnitude larger than that of the corresponding dialkoxy-substituted homopolymer.

Colloidal white emitting nanostructures were successfully fabricated by covalently binding a blue emitting oligofluorene at the surface of silica beads, that incorporate orange luminescent colloidal CdSe@ZnS quantum dots (QDs). White light was achieved by carefully tuning the size of the QDs to complementarily match the emission color of the blue fluorophore and taking into account the delicate balance between the emission of the QDs in the core of the silica beads and the amount of the organic dye bound to the silica surface. The proposed approach is highly versatile as it can be extended to the fabrication of a variety of luminescent hybrid nano-objects, playing with the complementarity of the emission color of the inorganic and organic fluorophores at the nanoscale. This journal is © the Partner Organisations 2014.

A white emitting copolymer with the polyphenylenevinylene (PPV) structure is obtained via the Stille cross-coupling reaction. Substitution of hydrogen atoms with fluorine atoms on the vinylene units of poly(1,4-dialkoxyphenylenevinylene) shifts the emission from orange-red to blue. White emission is obtained by combining dialkoxyphenylenedifluorovinylene and dialkoxyphenylenevinylene units in proper ratio. The two complementary emitters are obtained separately by Stille polymerization reaction. Then, the two reaction mixtures are combined without purification in different ratios and further reacted in similar experimental conditions. A white luminescent material is obtained using 99/1 mixing ratio. OLED devices fabricated with this copolymer shows near-white emission with CIE (0.30, 0.40) and excellent stability in the range 10–200 cd/m 2 .

The electrical transport across a biomimetic interface made up of spin coated melanin layers on nanotextured silicon surfaces with different texturing features and wetting properties is discussed. Nanotexturing allows, under certain conditions, the melanin to anchor better on a hydrophobic silicon surface, overcoming the hydrophilic melanin–hydrophobic silicon interface issue. The feature of the electrical signal transduction across such a structure was studied by impedance spectroscopy and found to be influenced by the nano-texturing chemistry and surface morphology. The effects of a voltage pulse, as external stimulus modifying the electrical transport mechanisms, and retention of the subsequently achieved carrier transport conditions have been elucidated. The results suggest a possible exploiting of this circuit element for bio and environmental molecules’ sensing.

Nowadays considerable efforts are devoted to the synthesis of low bandgap conjugated polymers for application in organic polymer solar cells. A large variety of low bandgap polymers are prepared by alternating copolymerization of electron-donating donor and electron-withdrawing acceptor units. The interaction between these two units can reduce the polymer bandgap, increasing the sunlight absorption. Benzothiadiazole is commonly used as acceptor block unit in low bandgap polymers. In this contribution we investigate the supramolecular organization and optical properties of thin films of conjugated polymers consisting of benzothiadiazole and thiophene with electron-withdrawing difluorovinylene, and electron-donating vinylene substituents. Atomic force microscopy and spectroscopic ellipsometry are exploited for the analysis of the morphology and optical transitions, respectively. It is found that F-atoms in the vinylene unit yield a blue-shift of the absorption peaks of 0.2 eV respect to the hydrogenated polymer and an increase in the absorption coefficient of fluorinated polymers, which indicates their potential application as photovoltaic material. The morphology evolution of the conjugated polymers blended with a fullerene derivate ([6,6]-phenyl C61-butyric acid methyl ester, PCBM) is also investigated by atomic force microscopy.

Hysteresis behaviour of the current–voltage characteristics collected on spin coated synthetic eumelanin layer embedded in the Au/eumelanin/ITO/glass structure is shown. The effect has been observed under dark both in air and vacuum environment and its magnitude has been found related to the eumelanin hydration state. Moreover, in vacuum and under white light illumination, enhancement of the hysteresis loop area respect to those collected under dark has been observed. Space charge storage and charge trapping/detrapping as possible mechanisms responsible of the observed current–voltage behaviour are discussed. Preliminary experimental results have evidenced the possible integration of eumelanin layers in electro-optical charge storage based memory devices.

This study is an investigation on the interplay between supramolecular organization and optical properties of thin films of conjugated polymers with fluorinated vinylene units such as poly[2-(2-ethylhexyloxy)-5-methoxy]-1,4-phenylenedifluorovinylene (MEH-PPDFV) and poly(2-methoxy-5-propyloxysulfonatephenylenedifluorovinylene) (MPS-PPDFV), which are both PPV polymers with fluorinated double bonds with alkoxy chains in the 2 and 5 positions. MEH-PPDFV is the fluorinated version of the widely investigated MEH-PPV, and MPS-PPDFV is characterized by the presence of ionic alkoxy side chains. This interplay is elucidated exploiting atomic force microscopy, spectroscopic ellipsometry and photoluminescence to obtain complementary information. It is demonstrated that the presence of F-atoms in the vinylene units of the MEH-PPDFV yields a blue optical band gap with the maximum of the fundamental HOMO–LUMO transition and of the room temperature photoluminescence at 3.74 eV (331 nm) and at 2.71 eV (458 nm), respectively. The blue-absorption and emission in the thin films are ascribed to the fact that fluorine atoms on the vinylene units prevent π-stacking of polymeric chains. Furthermore, the dependence of morphology, anisotropy in optical properties and photoluminescence properties of films on deposition methodology is also discussed. MEH-PPDFV also emits homogeneous blue-greenish electroluminescence at 2.46 eV (504 nm).

In situ attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroelectrochemistry during oxidation (p-doping) and reduction (n-doping) as well as photoinduced infrared spectroscopy of a random copolymer of 2,3,5,6-tetrafluoro-1,4-phenylenevinylene and 2,5-dioctyloxy-1,4-phenylenevinylene [co(TFPV-DOPV)] is presented. The infrared active vibration (IRAV) patterns obtained during electrochemical oxidation (p-doping) and reduction (n-doping) are different. The copolymer shows photoinduced IRAV bands that are similar to those obtained during electrochemical reduction (n-doping) in contrast to most of the other conjugated polymers which show similarities with oxidation (p-doping) IRAV bands. To our knowledge this is the only p- and n-dopable polymer with different IRAV patterns of charge carriers of both signs, and a similarity between n-doping and photodoping IRAV bands.

We investigated the third-order nonlinear optical (NLO) properties of three poly(2′,5′-dioctyloxy-4,4′,4″-terphenylenevinylene)s having different cis / trans -vinylene ratios. The nonlinear measurements were performed at λ =532 nm in chloroform solutions using single-beam Z-scan technique with picosecond laser pulses. All the investigated polymers exhibit a moderate two-photon resonance at this wavelength. On the contrary, the magnitude of the nonlinear refractive index is high and shows a considerable dependence on the cis / trans ratio of the double bonds. The largest third-order nonlinear optical susceptibility, | χ (3) |=(5±1)×10 −10 esu, was measured for a polymer with all monomers having vinylene unit in trans -configuration.

The dependence of the linear optical properties of some soluble poly(terphenylenevinylene)s on the relative amount of cis - and trans -vinylene units has been investigated. A regular blue-shift of the absorption spectra in solution has been observed upon the addition of cis double bonds. Luminescence spectra show a vibronic structure which accounts for the reduced inter-ring torsion in the excited state with respect to the ground state. Moreover, an increased electron–phonon coupling for cis -rich polymers has been observed.

Poly(2,3,5,6-tetrafluoro-1,4-phenylenevinylene) (PTFPV) was prepared for the first time by the Stille cross-coupling reaction and the resulting material was characterized through MALDI-TOF mass spectrometry, employing a novel sample preparation protocol suitable for insoluble compounds; preliminary optical and electrooptical measurements were performed.