Pyrene-Based Self-Assembling Peptide for Ratiometric Detection of Heparin.

Heparin is a commonly used anticoagulant in clinical practice; however, excessive heparin can cause serious adverse reactions. Convenient and accurate detection of heparin levels is thus very important. In this research, a pyrene-based self-assembling fluorescent peptide PyFFRRR was designed for simple, selective, and efficient heparin detection. The guanidine groups in the arginine residues of PyFFRRR bind tightly with heparin, which is highly sulfated, through electrostatic interactions. Charge neutralization facilitated the self-assembly of PyFFRRR, resulting in its spectral response changing from deep blue monomer fluorescence to green excimer fluorescence. PyFFRRR exhibited excellent sensitivity and selectivity for ratiometric detection of heparin. The binding mechanism was investigated by using spectral and simulation tools, and structural observation. Finally, PyFFRRR was employed in human serum samples for ratiometric detection of heparin.

Non-covalent π-π functionalized Gii-senseⓇ graphene foam for interleukin 10 impedimetric detection.

Monitoring Interleukin 10 (IL-10) is essential for understanding the vast responses of T-cells in cancer, autoimmunity, and internal homeostasis after physical stress. However, current diagnostic methods are complex and more focused on medical screening rather than point-of-care monitoring. Biosensors based on graphene's conductivity and flexibility are attractive to offer simple single-use and reduced handling. However, oxidation of its carbon lattice to develop functional moieties for biomolecule immobilization cuts down its electronic conductivity potential. In this work, the authors present a microfluidic lab-on-chip device for simple impedimetric monitoring of IL-10 based on graphene foam (GF) flexible electrodes. Graphene's structure was maintained by employing π-π non-covalent functionalization with pyrene carboxylic acid (PCA). Impedimetric measurements could be performed in low ionic strength phosphate-buffered saline (LI-PBS). The PCA-antibody modification showed to endure the incubation, measurement, and washing processes performed in the microfluidic device. Electrode modification and measurements were characterized by, electrochemical impedance spectroscopy (EIS), contact angle, and scanning electron microscopy. From the contact angle results, we found that the wettability of the graphene surface increased gradually after each modification step. Detection measurements performed in the 3D-printed microfluidic device showed a linear response between 10 fg/mL to 100 fg/mL with a limit of detection (LOD) of 7.89 fg/mL in artificial saliva. With these features, the device was used to quantify IL-10 samples by the standard addition method for 10 fg and 50 fg with recoveries between 82% and 99%. Specificity was evaluated towards interleukin 6, TNF-⍺ and bovine serum albumin.

Synthesis and Optoelectronic Properties of a Quinoxalino-Phenanthrophenazine (QPP) Extended Tribenzotriquinacene (TBTQ).

A six-step synthesis towards a tribenzotriquinacene (TBTQ) bearing three quinoxalinophenanthrophenazine (QPP) units is presented. The optoelectronic properties are investigated and the effect of the three-dimensional arrangement of the individual QPP planes is examined using optical spectroscopy, electrochemical analysis and quantum-chemical calculations.

Pyrene Tags for the Detection of Carbohydrates by Label-Assisted Laser Desorption/Ionisation Mass Spectrometry*.

Matrix-assisted laser desorption/ionisation mass spectrometry (MALDI-MS) is widely used for the analysis of biomolecules. Label-assisted laser desorption/ionisation mass spectrometry (LALDI-MS) is a matrix-free variant of MALDI-MS, in which only analytes covalently attached to a laser desorption/ionisation (LDI) enhancer are detected. LALDI-MS has shown promise in overcoming the limitations of MALDI-MS in terms of sample preparation and MS analysis. In this work, we have developed a series of pyrene-based LDI reagents (LALDI tags) that can be used for labelling and LALDI-MS analysis of reducing carbohydrates from complex (biological) samples without the need for additional chemical derivatisation or purification. We have systematically explored the suitability of four pyrene-based LDI enhancers and three aldehyde-reactive handles, optimised sample preparation, and demonstrated the use of LALDI tags for the detection of lactose. We have also exemplified the potential of LALDI tags for labelling carbohydrates in biological samples by direct detection of lactose in cow's milk. These results demonstrate that LALDI-MS is a promising technique for the analysis of reducing carbohydrates in biological samples, and pave the way for the development of LALDI-MS for glycomics and diagnostics.

2- and 2,7-Substituted para-N-Methylpyridinium Pyrenes: Syntheses, Molecular and Electronic Structures, Photophysical, Electrochemical, and Spectroelectrochemical Properties and Binding to Double-Stranded (ds) DNA.

Two N-methylpyridinium compounds and analogous N-protonated salts of 2- and 2,7-substituted 4-pyridyl-pyrene compounds were synthesised and their crystal structures, photophysical properties both in solution and in the solid state, electrochemical and spectroelectrochemical properties were studied. Upon methylation or protonation, the emission maxima are significantly bathochromically shifted compared to the neutral compounds, although the absorption maxima remain almost unchanged. As a result, the cationic compounds show very large apparent Stokes shifts of up to 7200 cm-1 . The N-methylpyridinium compounds have a single reduction at ca. -1.5 V vs. Fc/Fc+ in MeCN. While the reduction process was reversible for the 2,7-disubstituted compound, it was irreversible for the mono-substituted one. Experimental findings are complemented by DFT and TD-DFT calculations. Furthermore, the N-methylpyridinium compounds show strong interactions with calf thymus (ct)-DNA, presumably by intercalation, which paves the way for further applications of these multi-functional compounds as potential DNA-bioactive agents.

Highly Emissive Water-Soluble Polysulfurated Pyrene-Based Chromophores as Dual Mode Sensors of Metal Ions.

Pyrene-based materials have gained considerable attention as stimuli-responsive chemical sensors. We designed a polysulfurated arene system based on a tetra(phenylthio)pyrene core decorated with four carboxylic acid units. Three different regioisomers, ortho, meta and para were studied in organic and aqueous solution. These systems are soluble in water at pH≥8 due to the deprotonation of carboxylic acids. The addition of metal ions cannot only quench the fluorescence of the central pyrene core, but also control the formation of three-dimensional nanoscopic objects in a dual mode function. Several divalent metal ions were tested and compared. Addition of ethylenediaminetetraacetic acid (EDTA) disassembles the non-emissive supramolecular system and restores the initial fluorescence of the pyrene core.

Phenalenannulations: Three-Point Double Annulation Reactions that Convert Benzenes into Pyrenes.

3-Point annulations, or phenalenannulations, transform a benzene ring directly into a substituted pyrene by "wrapping" two new cycles around the perimeter of the central ring at three consecutive carbon atoms. This efficient, modular, and general method for π-extension opens access to non-symmetric pyrenes and their expanded analogues. Potentially, this approach can convert any aromatic ring bearing a -CH2 Br or a -CHO group into a pyrene moiety. Depending upon the workup choices, the process can be directed towards either tin- or iodo-substituted product formation, giving complementary choices for further various cross-coupling reactions. The two-directional bis-double annulation adds two new polyaromatic extensions with a total of six new aromatic rings at a central core.

Crystalline Diradical Dianions of Pyrene-Fused Azaacenes.

Although diradicals and azaacenes have been greatly attractive in fundamental chemistry and functional materials, the isolable diradical dianions of azaacenes are still unknown. Herein, we describe the first isolation of pyrene-fused azaacene diradical dianion salts [(18-c-6)K(THF)2 ]+ [(18-c-6)K]+ ⋅12-.. and [(18-c-6)K(THF)]2+ ⋅22-.. by reduction of the neutral pyrene-fused azaacene derivatives 1 and 2 with excess potassium graphite in THF in the presence of 18-crown-6. Their electronic structures were investigated by various experiments, in conjunction with theoretical calculations. It was found that both dianions are open-shell singlets in the ground state and their triplet states are thermally readily accessible owing to the small singlet-triplet energy gap. This work provides the first examples of crystalline diradical dianions of azaacenes with considerable diradical character.

Direct High-Throughput Screening Assay for mRNA Cap Guanine-N7 Methyltransferase Activity.

In eukaryotes, mature mRNA is formed through modifications of precursor mRNA, one of which is 5' cap biosynthesis, involving RNA cap guanine-N7 methyltransferase (N7-MTase). N7-MTases are also encoded by some eukaryotic viruses and facilitate their replication. N7-MTase inhibitors have therapeutic potential, but their discovery is difficult because long RNA substrates are usually required for activity. Herein, we report a universal N7-MTase activity assay based on small-molecule fluorescent probes. We synthesized 12 fluorescent substrate analogues (GpppA and GpppG derivatives) varying in the dye type, dye attachment site, and linker length. GpppA labeled with pyrene at the 3'-O position of adenosine acted as an artificial substrate with the properties of a turn-off probe for all three tested N7-MTases (human, parasite, and viral). Using this compound, a N7-MTase inhibitor assay adaptable to high-throughput screening was developed and used to screen synthetic substrate analogues and a commercial library. Several inhibitors with nanomolar activities were identified.

Sulfonated Pyrene as a Photoregulator for Single-Stranded DNA Looping.

Controlling the conformation and function of biomolecules through photoregulators holds great promise as a spatiotemporally controllable tool for disease control. In addition, introducing photoregulators into biomolecules has also found applications in constructing smart nanomaterials. In spite of the astonishing advances that have been made in the past few years, realizing highly controllable and efficient regulation over the conformation and function of biomolecules under physiological conditions is still challenging. Herein, sulfonated pyrene SPy was synthesized and used as a photoregulator to control the looping of single-stranded DNAs (ssDNAs) in aqueous solution. Due to its water solubility, SPy merits use in the study of biomolecules in aqueous solution. The looping of the doubly SPy-modified ssDNAs is stimulated by irradiation and regulated by SPy. Photoionization generates the radical cation of SPy (SPy.+ ). The association of SPy.+ with its neutral counterpart, SPy, gives rise to the dimer radical cation of SPy (SPy2 .+ ). During the association process, the stabilization energy released to form SPy2 .+ provides a driving force for the looping of ssDNAs. Conversely, the formed loop conformations were trapped by the formation of SPy2 .+ , and this allowed the looping dynamics to be investigated. The results reported herein suggest potential of SPy as a photoregulator for controlling the conformation and function of biomolecules under physiological conditions.

Effect of Alkyl Groups in Pyrene Chromophore on the Mechanical Response of Pyrene-Octafluoronaphthalene Co-Crystals.

Changes in the photophysical properties of pyrene (Py)-octafluoronaphthalene (OFN) co-crystals (Py⋅OFN) upon mechanical stimuli are described herein. The Py⋅OFN co-crystal showed a mechano-induced bathochromic shift in emission, and a similar tendency was observed for the 1,3,6,8-tetramethylpyrene-OFN co-crystal. These shifts are due to disruption of the microscopic molecular orientation in the co-crystal, which allows for excimer formation. In sharp contrast to the parent Py⋅OFN and methyl-substituted Py-OFN co-crystals, no mechano-induced bathochromic shift was observed when longer alkyl chains were introduced to the 1-, 3-, 6-, and 8-positions of the Py chromophore. This photophysical opposability against mechanical stimuli could be explained by the orthogonally oriented alkyl groups on the Py ring, which existed between two Py cores like pillars. This fixed OFN to maintain the face-to-face alternatively stacked structure of the co-crystal and thus prevented the formation of the Py excimer. The pillar effect demonstrated herein provides a rational design for co-crystalline systems that are photophysically stable against mechanical stresses.

Data on GC/MS elution profile, 1H and 13C NMR spectra of 1-, 3-, and 6-Nitrobenzo[a]pyrenes.

The data presented in this article is related to the research article entitled, "13C NMR Chemical Shift Assignments of Nitrated Benzo[a]pyrenes based on Two-dimensional Techniques and DFT/GIAO Calculations", Kefa K. Onchoke, J. Chem. Sci. (2020) [1]. The NMR spectral profiles of nitrated benzo[a]pyrenes is presented. Further, the article describes elution profiles of 1-, 3- and 6-NBaP, the acquisition of 1H and 13C NMR data and the J-Coupling constants (which are useful for the assignment of peaks via 2D HMQC and HMBC techniques). The data presented is useful for developing structure-activity relationships for other nitrated polycyclic aromatic hydrocarbons (NPAHs).

Target-Catalyzed Assembly of Pyrene-Labeled Hairpins for Exponentially Amplified Biosensing.

Rapid and sensitive detection of nucleic acids is vital for disease diagnosis. This work designed an enzyme-free isothermal strategy for rapid exponential signal amplification through target-triggered catalytic hairpin assembly (CHA) to induce the spatially sensitive fluorescent signal of the pyrene excimer. Functionally, this system consisted of three pyrene labelled hairpins (H1, H2, and H3) and one catalyst DNA C. In the presence of C, the CHA was activated to generate intermediate I, which contained a single-stranded region identical to the C sequence for initiating the second cycle of CHA to obtain 2I and thus achieved the exponential formation of I along with the switching of pyrene excimer. The fluorescent signal of the pyrene excimer could be further enhanced via the inclusion of γ-cyclodextrin and showed a linear increase upon increasing logarithm of C concentration. Through the introduction of a helping hairpin H4-containing C sequence and a region specific to the target, this strategy could be extended to realize the quick and sensitive detection of different analytes. Using dengue virus RNA as an analyte model, the proposed fluorescent method showed a linear range from 0.1 to 50 nM with a limit of detection of 0.048 nM at 3σ and good selectivity. The excellent performance and convenient operation demonstrated its promising application in clinical disease diagnosis.

Molecular Packing and Solid-State Photophysical Properties of 1,3,6,8-Tetraalkylpyrenes.

The relationship between the photophysical properties and molecular orientation of 1,3,6,8-tetraalkylpyrenes in the solid state is described herein. The introduction of alkyl groups with different chain structures (in terms of length and branching) did not affect the photophysical properties in solution, but significantly shifted the emission wavelengths and fluorescence quantum yields in the solid state for some samples. Pyrenes bearing ethyl, isobutyl, or neopentyl groups at the 1-, 3-, 6-, and 8-positions showed similar emission profiles in both the solution and solid states. In contrast, pyrenes bearing other alkyl groups exhibited an excimer emission in the solid state, similar to that of the parent pyrene. On studying the photophysical properties in the solid state with respect to the obtained crystal structures, the observed solid-state photophysical properties were found to depend on the relative position of the pyrene chromophores. The solid-state photophysical properties can be controlled by the alkyl groups, which provide changing crystal packing. Among the pyrenes tested, 1,3,6,8-tetraethylpyrene showed the highest fluorescence quantum yield of 0.88 in the solid state.

An Organic Molecular Photocatalyst Releasing Oxygen from Water.

Artificial photosynthesis employing solar energy is one of the best means of reaching a sustainable energy cycle, in which water is oxidized to oxygen and supplies electrons for fuel generation. The development of suitable oxygen evolution materials driven by sunlight is hence the most challenging research topic in the field of photocatalysis. Herein, photocatalytic O2 production from water at a rate of 22.6 µmol h-1 was performed by using a pyrene-based organic molecule constructed through the Ullmann coupling reaction. Its significantly improved light-harvesting ability and notably accelerated separation and transfer of photogenerated charges enhanced the O2 evolution efficiency. This study highlights the structural design of organic molecules applied to photocatalytic water splitting.

Multiple Photoluminescent Processes from Pyrene Derivatives with Aggregation- and Mechano-Induced Excimer Emission.

Two novel pyrene-based isocyanide gold(I) complexes have been designed and synthesized. The different structures lead to distinct and diverse photophysical properties both in solution and in the aggregate state. Multiple photoluminescence, involving monomer emission, locally excited emission and excimer emission, are observed. Notably, an excimer is formed by aggregation in solution and external mechanical stimulation in the solid state, showing aggregation- and mechano-induced excimer emission.

Controlling Pyrene Association in DNA Duplexes by B- to Z-DNA Transitions.

B- to Z-DNA transitions play a crucial role in biological systems and have attracted the interest of researchers for their applications in DNA nanotechnology. DNA and DNA analogues have also been used as templates to construct helical chromophore associations with π interactions. In this work, the B- to Z-DNA transition-induced switching of pyrene in an association manner was evaluated using DNA duplexes with non-nucleosidic pyrene residues in the middle of d(CG) repeat sequences. One of the pyrene-labeled DNAs was shown to exhibit inverted exciton coupled circular dichroism signals upon pyrene association through a B- to Z-DNA transition. This observation indicates that pyrene association switches the DNA conformation from right- to left-handed. Interestingly, the fluorescence of the pyrene-labeled DNA duplex also dynamically changed upon switching of the pyrene in an association-based manner. Taken together, these studies demonstrate that pyrene-labeled DNA shows promise as a chiroptical molecular switch.

Controlling the Optoelectronic Properties of Pyrene by Regioselective Lewis Base-Directed Electrophilic Aromatic Borylation.

Given that pyrene represents one of the most versatile chromophores, the development of new selective routes for its functionalization and tuning of its emission properties is highly desirable. Pyrene-based BN Lewis pair (LP)-functionalized polycyclic aromatic hydrocarbons (PAHs) were prepared by regioselective Lewis base-directed electrophilic aromatic substitution. The requisite 1,6-dipyridylpyrene ligands were accessed by Suzuki-Miyaura cross-coupling of 1,6-bis(pinacolatoboryl)pyrenes with 2-bromopyridine derivatives. Subsequent electrophilic borylation with BCl3 in the presence of AlCl3 and 2,6-di-tert-butylpyridine as a hindered base produced the dichloroborane complexes, which were then in situ reacted with diphenyl or diethyl zinc. The presence or absence of alkyl chains in the 3,8-positions of the pyrene moiety determined the position of the B-C bond formation (2,7 in the non-K region versus 5,10 in the K region) and thereby also the size of the BN heterocycle (five- versus six-membered). The impact of the regioisomeric borylation on the electrochemical, photophysical and structural properties was investigated and the conclusions supported by theoretical calculations. The rapid synthesis of derivatives that are borylated in the K region also suggests strong potential for the development of pyrene derivatives that are otherwise difficult to access.

Presence and Spatial Distribution of Polynuclear Aromatic Hydrocarbons (PAHs) in Groundwater of Merida City, Yucatan, Mexico.

The karstic aquifer of Yucatan features a high permeability, therefore, all contaminants placed in the soil surface, can reach it through infiltration along with the rain water. The purpose of the present study is to determine the spatial distribution of the aromatic hydrocarbons in the underground water of Merida City. Fifty wells inside the city were sampled. The sampling took place during the dry season, from October 2007 to March 2008. Liquid-liquid Hydrocarbon extraction was performed using hexane and purification was made by previously packed chromatography columns. Regarding the occurrence of polynuclear aromatic hydrocarbon (PAHs) traces, 28 water samples (56%) contained residues of these compounds. The following PAHs presented the highest concentrations: benzo(a)anthracene y benzo(k)fluoranthene 13.26 and 7.88 µg L-1 respectively. Only three of the sampled wells showed levels above those allowed by EPA and WHO norms. The origin of these compounds is mainly pyrogenic.

π-Stacking Interactions of Graphene-Coated Cobalt Magnetic Nanoparticles with Pyrene-Tagged Dendritic Poly(Vinylidene Fluoride).

This study investigates the non-covalent coating of cobalt magnetic nanoparticles (MNPs) involving a graphene surface with pyrene-tagged dendritic poly(vinylidene fluoride) (PVDF). Dendrimers bearing a pyrene moiety were selected to play the role of spacers between the graphene surface of the MNPs and the PVDF chains, the pyrene unit being expected to interact with the surface of the MNPs. The pyrene-tagged dendritic spacer 11 decorated with ten acetylenic units was prepared and fully characterized. Azido-functionalized PVDF chains were then grafted onto each branch of the dendrimer using Huisgen's [3+2] cycloaddition reaction. Next, the association of the resulting pyrene-tagged dendritic PVDF 13 with commercially available Co/C MNPs by π-stacking interactions was studied by fluorescence spectroscopy. Evaluated were the stability of the π-stacking interactions when the temperature increased and the reversibility of the process when the temperature decreased. Also, hybrid MNPs were prepared from pyrene-tagged dendrimers decorated either with acetylenic functions (11) or with PVDF branches (13), and they were characterized by transmission electron microscopy and comparative elemental analysis was carried out with naked MNPs.