Aromatic Probes Research Articles

Alkylaromatic mass transport – acidity properties correlation for commercial and mesostructured Y zeolites with the catalytic behavior of cracking reactions

A strategy to mitigate diffusion restrictions associated with heavy crude oil conversions is using mesostructured Y zeolite. In recent years, multiple routes have been proposed for obtaining materials with improved catalytic performance versus catalysts with higher molecular transport restrictions. Typically, after the implementation of these treatments, improvement in catalytic activity is correlated either with changes in textural properties (area and porous volume) or the modification of physicochemical properties (Si/Al ratio and acid strength); however, the correlation with diffusional mass transport characteristics is not typical. In this study, alkylaromatic molecules of different kinetic diameters, such as benzene, toluene, p–xylene, and m–xylene, were used as molecule probes to determine the effective diffusion through a pulse experiment under conditions of no adsorption or reaction. The studied solids include five commercial zeolites from the Zeolyst CBV series and four top–down mesostructured Y zeolites. The obtained concentration curves were fitted to an exponential decay model, a solution of the second Fick's law under defined experimental conditions, and correlation values between 0.9996 > R2 > 0.9896 were found. Furthermore, the implementation of the descriptors “Transport ratio (TRMR)” and “Corrected transport ratio (TRMRc)” was proposed, which allowed the combined representation of the change in the mass transport of aromatic probes and the changes in the acidity of the zeolite, after the application of top–down treatments. These descriptors proved simple and effective tools to correlate the changes after mesopore insertion with the catalytic performance in the 1,3,5–Triisopropylbenzene (TIPB) cracking reaction. Our approach is an integral method of screening mesostructured zeolites with an adequate balance of acidity and transport properties.

Bioanalytical method optimization for simultaneous quantification of structurally related probe drugs in a phenotyping cocktail using liquid chromatography‐tandem mass spectrometry

AbstractThe physicochemical diversity of the structurally related aromatic probe drugs, used together in a drug cocktail to assess metabolic and transport phenotypes, require optimized analytical procedures for simultaneous quantification. The analytical conditions can greatly influence the analyte selectivity, retention, stability, and ultimately the robustness of the method. The aim of this study was to assess the selectivity of the structurally related ionizable analytes between the commonly used C18 column chemistry and an alternative biphenyl column chemistry as well as the influence of changes in the analytical conditions on method robustness using liquid chromatography‐tandem mass spectrometry. A repeated measure two‐factor analysis of variance with Geisser‐Greenhouse correction was used to determine statistical significance. The results showed that a biphenyl stationary phase in combination with methanol as the organic eluent, could provide improved resolution and analyte selectivity. Changes in analytical conditions caused statistically significant variation in the retention behavior, selectivity, column efficiency, and sensitivity of the analytes of interest The robustness experiment confirmed the importance of controlling analytical conditions to ensure the reproducibility and reliability of the quantitative method.

Challenges Relating to the Quantification of Ferryl(IV) Ion and Hydroxyl Radical Generation Rates Using Methyl Phenyl Sulfoxide (PMSO), Phthalhydrazide, and Benzoic Acid as Probe Compounds in the Homogeneous Fenton Reaction.

Ferryl ion ([FeIVO]2+) has often been suggested to play a role in iron-based advanced oxidation processes (AOPs) with its presence commonly determined using the unique oxidation pathway from methyl phenyl sulfoxide (PMSO) to methyl phenyl sulfone (PMSO2). However, we show here that the oxidation products of PMSO, formed on reaction with hydroxyl radical, enhance PMSO2 formation as a result of their complexation with Fe(III) leading to the changes in the reactivity of Fe(III) species in the homogeneous Fenton reaction. As such, PMSO should be used with caution to investigate the role of [FeIVO]2+ in iron-based AOPs with these insights suggesting the need to reassess the findings of many previous studies in which this reagent was used. The other common target compounds, phthalhydrazide and hydroxybenzoic acids, were also found to modify the rate and extent of iron cycling as a result of complexation and/or redox reactions, either by the probe compound itself and/or oxidation products formed. Overall, this study highlights that these confounding effects of the aromatic probe compounds on the reactivity of iron species should be recognized if reliable mechanistic insights into iron-based AOPs are to be obtained.

Computational Study of Tetrahedral Fullerenes Containing Fused Pentagon-Triples.

Fullerenes that violate the isolated pentagon rule are too reactive and were obtained only as endoor exohedral derivatives. Density functional theory using the B3LYP hybrid density functional was applied to investigate the electronic and structural properties of the ten smallest tetrahedral (Td or T point group) fullerenes containing four directly fused pentagon-triples. The influence of nitrogen doping and exohedral hydrogenation of the four reactive sites was also analyzed. Nucleus independent chemical shifts values computed using B3LYP/6-31G(d) are used as global and local aromaticity probe. The global strain energy is evaluated in terms of the pyramidalization (POAV) angle. The results show that the stability increases with the elimination of the energetically unfavorable strain.

Investigation of sorption and diffusion of hydrocarbons into polydimethylsiloxane in the headspace-solid phase microextraction sampling process via inverse gas chromatography

Inverse gas chromatography was employed to investigate the sorption and diffusion of hydrocarbons into polydimethylsiloxane (PDMS) in the headspace-solid phase microextraction (HS-SPME) sampling process. Six hydrocarbons as molecular probes and two types of non-cross-linked PDMS with different average molecular weights as stationary phases were used in this study. Experimental measurements with columns containing a PDMS stationary phase were carried out to obtain specific retention volumes, molar enthalpies of sorption, interaction parameters, diffusion coefficients, and activation energies of diffusion of hydrocarbon probes over temperatures ranging from 60 to 90°C. The primary driving force of the hydrocarbon sorption into the PDMS SPME fibers was found to be the molar enthalpy of sorption, which depended on the molecular size of the hydrocarbons. As the molecular size of the hydrocarbon increased, the molar enthalpies of sorption became more exothermic. Interaction parameters and diffusion coefficients indicated that both n-heptane and n-octane were diffused into the PDMS matrix and localized to form clusters or aggregates, which were responsible for more negative molar entropies of sorption. However, the diffusivities of n-nonane and aromatic probes were limited due to their large molecular size and lack in the structural flexibility, respectively. The molar enthalpies of hydrocarbon sorption were independent of the average molecular weight of PDMS. However, specific retention volumes, interaction parameters, diffusion coefficients, and activation energies of diffusion of the hydrocarbons depended on the molecular weight of PDMS as well as the molecular weights and structures of hydrocarbons, as shown by the results of the Wilcoxon signed-rank test.

Click Preparation of Triazole-Bridged Aggregation-Induced Emission Aromatic Acid Probe for the Selective Determination of Aluminium Ion

A novel aggregation induced emission (AIE) aromatic acid probe tetraphenylethene (TPE) – triazole-COOH (TTC) was synthesized via click chemistry bridging the (TPE) with ethynylpropionate followed with hydrolysis in alkaline conditions. The novel probe shows a highly specific turn-on fluorescence response toward Al3+ by the synergistic effects of triazole and the carboxyl group. Here is proposed a novel synergistic recognition mechanism. The TTC probe shows excellent aggregation induced emission aqueous dimethyl sulfoxide and may be induced to aggregate by Al3+ in this solution. A linear response between the fluorescence intensity and the concentration of Al3+ was obtained across the range from 1 µM to 6 µM with a low limit of detection equal to 1 µM.

New Route to Toxic Nitro and Nitroso Products upon Irradiation of Micropollutant Mixtures Containing Imidacloprid: Role of NOx and Effect of Natural Organic Matter.

In this study, we reveal the capacity of imidacloprid (a neonicotinoid insecticide) to photoinduce the nitration and nitrosation of three aromatic probes (phenol, resorcinol, and tryptophan) in water. Using a gas-flow reactor and a NOx analyzer, the production of gaseous NO/NO2 was demonstrated during irradiation (300-450 nm) of imidacloprid (10-4 M). Quantum calculations showed that the formation of NOx proceeds via homolytic cleavage of the RN-NO2 bond in the triplet state. In addition to gaseous NO/NO2, nitrite and nitrate were also detected in water, with the following mass balance: 40 ± 8% for NO2, 2 ± 0.5% for NO, 52 ± 5% for NO3-, and 16 ± 2% for NO2-. The formation of nitro/nitroso probe derivatives was evidenced by high-resolution mass spectrometry, and their yields were found to range between 0.08 and 5.1%. The contribution of NO3-/NO2- to the nitration and nitrosation processes was found to be minor under our experimental conditions. In contrast, the addition of natural organic matter (NOM) significantly enhanced the yields of nitro/nitroso derivatives, likely via the production of triplet excited states (3NOM*) and HO•. These findings reveal the importance of investigating the photochemical reactivity of water contaminants in a mixture to better understand the cocktail effects on their fate and toxicity.

Targeting pharmacophore with probe-reactivity-guided fractionation to precisely identify electrophilic sesquiterpenes and its activity of anti-TNBC.

Innovative strategy is urgently needed to precisely discover novel natural products as lead compounds for development of new drugs against orphan diseases such as triple-negative breast cancer (TNBC). Herein, we describe a targeting pharmacophore with probe-reactivity-guided strategy for the discovery of electrophilic sesquiterpene (ES), a class of bioactive natural product. This study aimed to identify pharmacophore, based on pharmacophore with probe-reactivity-guided strategy for precisely discovering ESs from ethyl acetate extract of Eupatorium chinense L. (EEEChL) METHODOLOGY: MTT assay combined with ultra-performance liquid chromatography (UPLC) analysis was used to identify pharmacophore. UPLC-mass spectrometry (MS) was applied to carefully compare the intrinsic reactivity characteristics of two chemoselective nucleophilic probes: glutathione (GSH) and 4-bromothiophenol (BTP) reaction with ESs. ESs was isolated and identified from EEEChL by phytochemical methods. Furthermore, stoichiometric ratio and binding site of one typical ES 8β-[4'-hydroxytigloyloxy]-5-desoxy-8-desacyleuparotin (HDDE) reaction with BTP were studied by UPLC-quadrupole time-of-flight (Q-TOF)-MS and two-dimensional nuclear magnetic resonance (NMR). Eleven ESs were identified from EEEChL, MTT assay illustrated that all of the 11 ESs possess fairly good anti-TNBC activity CONCLUSIONS: Electrophilic groups were confirmed as pharmacophore of bioactive compounds contained in EEEChL. An optimised halogenated aromatic probe BTP furnishes ES-BTP conjugates that are highly conspicuous via MS by virtue of a unique isotopic bromine signature, conjugates also have a considerable separation on C18 column. The new probe-reactivity-guided strategy can effectively improve the traditional bioassay-guided approaches, and significantly increase the probability of obtaining designated bioactive compounds.

Особенности применения ароматических молекул-зондов для ЭПР -спектроскопии в исследовании кислотных свойств поверхности модифицированных алюмооксидных каталитических систем

В обзоре систематизированы работы, посвящённые применению метода спектроскопии ЭПР в варианте ароматических молекул-зондов для исследования гетерогенных алюмооксидных катализаторов, а также дополнены новыми результатами исследований, проведённых в ИППУ СО РАН. Рассмотрены перспективы метода и представления о механизме взаимодействия молекул-зондов с активными центрами поверхности и их природе. Отмечено наличие противоречий во взглядах на механизмы, а также что современная точка зрения склоняется к участию БКЦ в ионизации ароматических молекул-зондов.

Metal-free photochemical hydrogen storage in aromatic compounds

Based on Baird́s rule, which states that the excited state of an aromatic compound is antiaromatic, a new method for hydrogenating aromatic molecules by metal-free photochemical reaction employing 1,4-cyclohexadiene (1,4-CHD) as hydrogen source is proposed. Here only light and 1,4-CHD are required to hydrogenate aromatic compounds without metal catalysts or temperature. The proposed mechanism is related to the reduction potential of the aromatic probes on their first triplet excited state. In such methodology, besides the non-aromatic character of the excited state, the aromatization of the hydrogen donor turns this reaction feasible as a hydrogen storage procedure at low cost, expanding the chemical interest for materials like graphene.

Dihydropyrene as an Aromaticity Probe for Partially Quinoid Push-Pull Systems.

Although aromaticity is a key concept in chemistry that is frequently used to explain the structure and reactivity of organic compounds, it remains challenging to actually measure this property. Proper probes allow for an experimental quantification of aromaticity using nuclear magnetic resonance (NMR) spectroscopy and in this study 15,16-dimethyl-15,16-dihydropyrene (DHP) is demonstrated to be particularly well suited for this purpose. DHP has two internal methyl groups, which are positioned within the π cloud of this bridged, planar, and rigid [14]annulene, and are therefore shifted to higher field in proton NMR spectra owing to ring-current effects. A specific DHP derivative bearing strongly electron-donating dimethylamino and strongly electron-accepting nitro groups in a relative pseudo-para orientation has been synthesized and characterized with respect to its quinoid character. Solvatochromism as well as a reduced ring current show that the partial quinoid character in this push-pull DHP derivative is about 12 %. This study extends the scope of DHP as an aromaticity probe and aids in the better understanding of the phenomenon of aromaticity.

Non-covalent interactions between poly(N-isopropylacrylamide) and small aromatic probe molecules studied by NMR spectroscopy

One of the most important goals in drug delivery is to carry drug molecules to their target as selectively and efficiently as possible. To accomplish this goal it is crucial to understand the interactions of carriers and their loading. The interactions between a thermoresponsive potential drug carrier polymer, poly(N-isopropylacrylamide) (PNIPA) and small aromatic probe molecules: phenol, dopamine and indole derivatives including tryptophan were studied by using solution-state NMR spectroscopy. These substances represent structural elements often found in pharmaceutically relevant compounds. The indole ring is an important part of biologically active natural products, it can be found in several plants and animals. To investigate the effect of temperature on binding and the significance of coil-to-globule transition, 1H T1 and T2 relaxation times, 1H one- and two-dimensional nuclear Overhauser effect spectroscopy (NOESY) and diffusion ordered spectroscopy (DOSY) measurements were carried out in D2O and organic solvents. In the case of phenol and indole derivatives a strong interaction was observed above the lower critical solution temperature (LCST), for it to be much weaker below. According to relaxation measurements only the aromatic ring of tryptophan is bound to the polymer. No interaction was observed between dopamine and the polymer.

Direct Observation, Molecular Structure, and Location of Oxidation Debris on Graphene Oxide Nanosheets.

The presence of oxidation debris (OD) complicates the structures and properties of graphene oxide (GO) nanosheets, thereby impacting their potential applications. However, the origin of OD is still in dispute. Moreover, characterizing the structure and location of supposed OD on nanosheets of GO produced during the oxidation process is difficult. Herein, the attached state and size of OD on graphene oxide nanosheets were directly observed using HRTEM, the molecular structure of OD was initially proposed based on the spectroscopic characterization and Q-TOF mass spectrometry, and the locations of OD on the GO nanosheets were detected through the adsorption of probe molecules onto as-prepared GO (a-GO) and base-washed GO (bw-GO). The results indicated that OD possesses a highly crystalline structure and can be defined as several nanometre-sized polyaromatic molecules with a considerable number of oxygen-containing functional groups attached on the edges. The dark nanodot seated on a-GO was clearly observed in the HRTEM images, whereas it appeared as a clean nanosheet in the image of bw-GO, indicating that OD is removed by base-washing treatment. Following the base-washing treatment, the contents of carboxyl groups on bw-GO unexpectedly increased and subsequently contributed to the desorption of OD from a-GO due to the electrostatic repulsion being stronger than primary π-π interactions. Compared with a-GO, the adsorption of phenanthrene, as an aromatic probe, onto bw-GO increased by 6-fold via π-π stacking interactions, whereas the increase in the adsorption of m-dinitrobenzene, as a defect probe, was not as remarkable as that of phenanthrene. Reasonably, the OD nanoparticles were primarily located at the sp(2) structures on the GO nanosheets through π-π interactions rather than attached on defects/edges. The insights regarding the existence, molecular structures and attached sites of OD nanoparticles on GO nanosheets provide a theoretical basis for preparing OD-free GO for optimizing the potential applications of GO nanosheets.

Interactions in aromatic probe molecule loaded poly(N-isopropylacrylamide) hydrogels and implications for drug delivery

Small aromatic molecules are known to interact with poly(N-isopropylacrylamide) (PNIPA) based hydrogels, one of the most frequently employed polymers in temperature induced drug delivery systems. These interactions are poorly understood at the molecular level. In this article we investigate PNIPA both at the macroscopic and at the molecular level using measurements of swelling, differential scanning microcalorimetry (DSC), X-ray powder diffraction (XRD) and solid state 1H NMR methods. The nature and the strength of the interactions affect the efficiency and kinetics of drug delivery. Phenols exert a major influence on PNIPA by reducing its phase transition temperature. The effect depends linearly on the phenol concentration, and is influenced also by the number of phenolic OH groups, as well as their relative positions. The strong interaction between phenol and the polymer that is detected by NMR hinders the crystallisation of phenol when the water is gradually evaporated. The aminoethyl phenol derivative dopamine has a much more limited effect, but in the opposite direction – the transition temperature increases slightly. The strong interaction observed among the dopamine molecules disables the polymer–dopamine interaction and favours crystallization of the dopamine when water is removed. These results reveal that embedding the drugs into polymer matrices for controlled delivery can alter the crystallinity of the stored molecules. As morphology is one of the crucial factors in delivery, this may compromise the rate and the efficiency of release.

Exploring Graphene Nanocolloids as Potential Substrates for the Enhancement of Raman Scattering

Graphene, especially few-layer graphene solid film, has been found to strongly suppress fluorescence and enhance Raman signals of probe molecules. In this paper, we attempt to explore the possibility of using graphene nanocolloids as potential substrates for the enhancement of Raman scattering. Graphene nanocolloids chemically produced from the reduction of graphene oxide by sodium citrate are nearly all monolayers in solution and are also found to exhibit certain surface-enhanced Raman scattering (SERS) activity to common aromatic probe molecules. Interestingly, largely different from few-layer graphene solid film, graphene nanocolloids show maximal SERS activity only when the probe molecules are at resonant laser excitation. According to our analysis, this phenomenon should arise from a combined effect of fluorescence quenching of graphene and a photoinduced charge transfer mechanism, in which the strong charge transfer accounts for the main contribution from close coupling between graphenes and probe molecules photoinduced by resonant excitation as well as the desolvation of graphene sheets and probe molecules.

Esterase activity in excised and reconstructed human skin – Biotransformation of prednicarbate and the model dye fluorescein diacetate

Reconstructed human epidermis (RHE) is used in non-animal testing for hazard analysis and reconstructed human skin (RHS) gains growing interest in preclinical drug development. RHE and RHS have been characterised regarding their barrier function, but knowledge about biotransformation capacity in these constructs and in human skin remains rather poor. However, metabolising enzymes can be highly relevant for the efficacy of topical dermatics as well as genotoxicity and sensitisation. We have compared the esteratic cleavage of the prednisolone diester prednicarbate and the enzyme kinetic parameters (Vmax and S0.5) of the model substrate fluorescein diacetate (FDA) in commercially available RHS and RHE with excised human skin and monolayer cultures of normal and immortalised human keratinocytes and of fibroblasts. Formation of the main metabolite prednisolone and of fluorescein ranked as: RHS∼RHE>excised human skin and keratinocytes>fibroblasts, respectively. Because of the aromatic probe, however, Vmax of FDA cleavage did not show a linear relationship with prednicarbate metabolism. In conclusion, RHE and RHS may be useful to quantitatively address esterase activity of human skin in drug development and hazard analysis, although an increased activity compared to native human skin has to be taken into account.

A theoretical study of the parent NH-benzazoles (benzimidazoles, indazoles and benzotriazoles): geometries, energies, acidity and basicity, NMR properties and molecular electrostatic potentials

The three parent NH-benzazoles, benzimidazole, indazole and benzotriazole, have been studied theoretically at the B3LYP/6-311++G(d,p) level. Optimized geometries have been compared with those obtained by X-ray crystallography, energies with studies about tautomerism, acidbase properties with pKas, and chemical shifts with those reported in the literature. As aromaticity probe, Schleyer's Nuclear Independent Chemical Shifts (NICS) were used and represented in two 3D isosurfaces of the electron density.

Matrix-assisted laser desorption/ionisation time of flight spectrometry for the fast screening of oxosteroids using aromatic hydrated hydrazines as versatile probes

To make the use of MALDI-based mass spectrometry feasible for the fast analysis of oxosteroids, three new aromatic probes have been designed to be used simultaneously as derivatisation agents and MALDI matrices. This concept brings a number of benefits: the sample handling is reduced, the workflow is less time consuming allowing high throughput and the interferences caused by the MALDI matrix are avoided. Identification was successfully attained for all oxosteroids used in this study. As proof-of-concept, the identification of oxosteroids in urine was performed to evaluate the robustness of the new methodology. The oxosteroids 17-α-methyltestosterone, nandrolone, boldenone, 17-α-Trenbolone, fluoxymesterolone, mesterolone and bolasterone were identified in human urine at the minimum concentration level recommended by the world anti-doping agency, 2ng/mL.

A theoretical NMR study of the structure of benzynes and some of their carbocyclic and heterocyclic analogs

This work reports the theoretical study of the aromaticity of a series of carbocycles (benzene, cyclohexane, bent and planar cyclooctatetraene) and heterocycles (pyridine, furan, thiophene, pyrrole) and their didehydro forms (arynes and hetarynes). As aromaticity probe Schleyer's NICS were used and represented in two 3D isosurfaces of the electron density. The spatial 3D representation of the NICS is shown to be a powerful tool to visualize the aromaticity (or its absence) of different molecules.

Development of Three End-Capped Para-Benzoyl Calix[4,6, or 8]arene Bonded Stationary Phases for HPLC

Three end-capped para-benzoyl calixarene bonded silica gel stationary phases are prepared and characterized by elemental analysis, infrared spectroscopy, and thermal analysis. The comparison and selectivity of these phases are investigated by using PAHs, disubstituted benezene, and naphthalene positional isomers as probes. Possible separation mechanism based on the different interactions between calixarenes and analytes are discussed. The results indicate that the separation for those analytes are influenced by the supramolecular interaction including π-π interaction, π-electron transfer interactions, space steric hindrance, and hydrogen bonding interaction on the calixarene columns. Importantly, the aromatic probes with polar groups such as -OH, -NO(2), and -NH(2) could regulate the selectivity of calixarene-bonded stationary phases.