Number Of Aromatic Rings Research Articles

Introducing a Novel Approach for Oil‐Oil Correlation based on Asphaltene Structure: X‐ray Diffraction

AbstractAsphaltenes have always been an attractive subject for researchers. However, the application of this fraction of the geochemical field has only been studied in a limited way. In other words, despite many studies on asphaltene structure, the application of asphaltene structures in organic geochemistry has not so far been assessed. Oil‐oil correlation is a well‐known concept in geochemical studies and plays a vital role in basin modeling and the reconstruction of the burial history of basin sediments, as well as accurate characterization of the relevant petroleum system. This study aims to propose the X‐ray diffraction (XRD) technique as a novel method for oil‐oil correlation and investigate its reliability and accuracy for different crude oils. To this end, 13 crude oil samples from the Iranian sector of the Persian Gulf region, which had previously been correlated by traditional geochemical tools such as biomarker ratios and isotope values, in four distinct genetic groups, were selected and their asphaltene fractions analyzed by two prevalent methods of XRD and Fourier‐transform infrared spectroscopy (FTIR). For oil‐oil correlation assessment, various cross‐plots, as well as principal component analysis (PCA), were conducted, based on the structural parameters of the studied asphaltenes. The results indicate that asphaltene structural parameters can also be used for oil‐oil correlation purposes, their results being completely in accord with the previous classifications. The average values of distance between saturated portions (dr) and the distance between two aromatic layers (dm) of asphaltene molecules belonging to the studied oil samples are 4.69Å and 3.54Å, respectively. Furthermore, the average diameter of the aromatic sheets (La), the height of the clusters (Lc), the number of carbons per aromatic unit (Cau), the number of aromatic rings per layer (Ra), the number of sheets in the cluster (Me) and aromaticity (fa) values of these asphaltene samples are 10.09Å, 34.04Å, 17.42Å, 3.78Å, 10.61Å and 0.26Å, respectively. The results of XRD parameters indicate that plots of dr vs. dm, dr vs. Me, dr vs. fa, dm vs. Lc, Lc vs. La, and fa vs. La perform appropriately for distinguishing genetic groups. A comparison between XRD and FTIR results indicated that the XRD method is more accurate for this purpose. In addition, decision tree classification, one of the most efficacious approaches of machine learning, was employed for the geochemical groups of this study for the first time. This tree, which was constructed using XRD data, can distinguish genetic groups accurately and can also determine the characteristics of each geochemical group. In conclusion, the obtaining of structural parameters for asphaltene by the XRD technique is a novel, precise and inexpensive method, which can be deployed as a new approach for oil‐oil correlation goals. The findings of this study can help in the prompt determination of genetic groups as a screening method and can also be useful for assessing oil samples affected by secondary processes.

Chemical Structure Transformations in Kerogen from Longmaxi Shales in Response to Tectonic Stress as Investigated by HRTEM, FTIR, and 13C NMR

Kerogen molecular structure controls the micropore (<2 nm diameter) evolution in shale and exerts a significant impact on shale gas adsorption, desorption, and diffusion. However, the influence of tectonic deformation on kerogen structure and organic micropores needs intensive study. Our study mainly focuses on the transformations in the extracted kerogen structure and organic micropores of Longmaxi shale during tectonic deformation. Vitrinite reflectance measurement (VRM) and Raman spectroscopy (RS) were utilized to determine the maturity of organic matter. Organic pore network attributes of kerogen samples were estimated using CO2 adsorption experiments. High-resolution transmission electron microscopy (HRTEM), Fourier transform infrared spectroscopy (FTIR), and 13C nuclear magnetic resonance (13C NMR) were utilized to interpret the kerogen molecular structures of these samples. VRM and RS results show that Longmaxi shale has reached the wet gas window. Adsorption analyses of CO2 indicate that kerogen samples in shale with strong deformation have larger micropore volume and surface area (<2 nm). 13C NMR and FTIR results reveal that the tectonic stress may promote the shedding of aliphatic carbon. HRTEM images exhibit that aromatic rings with a size of 3 × 3 account for the largest proportion in all kerogen samples, which indicates that the kerogen samples have reached a high thermal evolution level, consistent with the Raman experiment. For weakly deformed shale samples, 66.5 and 88.8% of the total number of aromatic rings in LZ-1 and LZ-4 kerogen belong to the major direction (within a 45° range). In the most strongly deformed sample, LZ-2, distribution orientations of aromatic fringes are dispersed and primarily concentrated at 15–105°. Such disorientation of nanometer-sized polyaromatic layers in the strongly deformed sample creates a nanopore network in organic matter (OM) that increases the micropore volume and surface area. These findings from integrated approaches can provide a new perspective of adsorbed gas enrichment in the complex tectonic areas.

Analysis and assessment of respirable particles in asphalt pavement recycling from perspectives of workers’ health

Different groups of people are exposed to respirable particles in recycling asphalt pavement materials. In evaluating the health issues of such particles posed to construction workers, existing studies mainly focus on respirable crystalline silica but rarely address the organic fractions. In this study, respirable particles in reclaimed asphalt pavement (RAP) materials were collected from different sources and analyzed to determine their morphology, elemental composition, organic content, and the content and type of polycyclic aromatic hydrocarbons (PAHs). Focus is placed on the analysis of PAHs in the particles, for which the hazards are assessed using benzo[a]pyrene toxic equivalent concentration. The respirable particles are found to contain much richer asphalt content than RAP mixtures. A variety of PAHs can be found in the particles, especially those with a large number of aromatic rings (>3). Moreover, very old RAP materials contain more PAHs, due to the oxidation reaction of the hydrocarbons in asphalt binder. Based on the analysis data and reported exposure levels to such particles in milling asphalt pavements, it is concluded that the health risks posed by such particles cannot be neglected. Mitigation measures and personal protective equipment are recommended to be used in producing and handling RAP materials.

Pyrolysis behaviors of model compounds with representative oxygen-containing functional groups in coal over calcium

Calcium has great catalytic potentials to regulate volatiles from low-rank coal pyrolysis to form high-valued products. Due to the complexity of coal structure, it's still no consensus on the catalytic mechanism over calcium catalyst. In this paper, coal-related model compounds with representative O-containing functional groups [1,4-naphthalenedicarboxylic acid, poly (4-vinylphenol) and poly (2,6-dimethyl-1,4-phenylene oxide)] were chosen to study the primary pyrolysis product distribution and composition over calcium components by FTIR, TGA and in-situ pyrolysis vacuum ultraviolet photoionization time-of-flight mass spectrometry. The results show that calcium could be ion-exchanged with the O-containing acidic groups (carboxyl functional group or phenolic hydroxyl group) presented in the model compounds to significantly improve the thermal stability, and the pyrolysis of carboxylic and phenolic compounds in the presence of calcium will not only promote a complex cross-linking reaction for the formation of polymers, but also lead to the formation of ketone compounds. The addition of calcium has no effect on the decomposition modes of ether bond connecting two aromatic rings. In addition, the interaction mode and thermal conversion mechanism between carboxyl groups and calcium component were studied. The benzoic acid, 2-naphthoic acid, anthracene-9-carboxylic acid, and 1-pyrenecarboxylic acid were used to investigate the effect of aromatic ring number on the transformation of carboxyl functional groups under the action of calcium. The results showed that the difference of substitution positions may have a certain effect on the formation of products, but the effect of calcium on the main transformation mechanism of carboxyl functional groups in different aromatic structures is universal.

Revealing the role of hydrogen bonding interactions and supramolecular complexes in lignin dissolution by deep eutectic solvents

Deep eutectic solvents (DESs) have great potential for lignocellulose valorization, especially in terms of lignin extraction and upgrading. It is important to understand the mechanisms involved in lignin dissolution in DESs in order to design solvents for biomass fractionation and extraction of property-tailorable lignin. Here, we use molecular dynamics simulations to gain mechanistic insights into lignin dissolution in DESs. Three DESs based on choline chloride with different hydrogen bond donors (HBDs) (i.e., ethylene glycol, formic acid, and lactic acid) are examined. The main intermolecular interactions in each DES as well as their interactions with lignin are identified. The association between lignin and cellulose in each DES is also investigated. The simulation results reveal that both the functional groups (i.e., hydroxyl group and carboxyl group) and the number of oxygen atoms in the HBD of a DES determine the characteristics of its hydrogen bonding network and the strength of its hydrogen bonding interactions with lignin. Ethylene glycol tends to form H-bonds with α-OH in lignin and both lactic acid and formic acid prefer γ-OH in lignin. The average interaction energy between chloride ion and lignin is comparable to that between the HBD and lignin, indicating that the role of the anion in lignin dissolution is similar to that of the HBD in terms of thermodynamics. Molecular interactions between lignin and a DES are found to play a key role in dissociating lignin from cellulose. The number of aromatic rings of lignin on the cellulose in CCFA and CCLA are only 77% and 56% of that in CCEG. The insights gained in this study advance the understanding of lignin dissolution at the molecular level in DESs and provide guidance to design effective DESs for lignin extraction and valorization.

Hydrolysable tannins change physicochemical parameters of lipid nano-vesicles and reduce DPPH radical - Experimental studies and quantum chemical analysis

Tannins belong to plant secondary metabolites exhibiting a wide range of biological activity. One of the important aspects of the realization of the biological effects of tannins is the interaction with lipids of cell membranes. In this work we studied the interaction of two hydrolysable tannins: 1,2,3,4,6-penta-O-galloyl-β-d-glucose (PGG) and 1,2-di-O-galloyl-4,6-valoneoyl-β-d-glucose (T1) which had the same number of both aromatic rings (5) and hydroxyl groups (15) but differing in flexibility due to the presence of valoneoyl group in the T1 molecule with DMPC (dimyristoylphosphatidylcholine) lipid nano-vesicles (liposomes). Tannins-liposomes interactions were investigated using fluorescence spectroscopy, differential scanning calorimetry, laser Doppler velocimetry, dynamic light scattering and Fourier Transform Infra-Red spectroscopy. It was shown that more flexible PGG molecules stronger decreased the microviscosity of the liposomal membranes and increased the values of negative zeta potential in comparison with the more rigid T1. Both compounds diminished the phase transition temperature of DMPC membranes, interacted with liposomes via PO groups of head of phospholipids and their hydrophobic regions. These tannins neutralized DPPH free radicals with the stoichiometry of the reaction equal 1:1.The effects of the studied compounds on liposomes were discussed in relation to tannin quantum chemical parameters calculated by molecular modeling.

Evaluating anti-coronavirus activity of some phosphoramides and their influencing inhibitory factors using molecular docking, DFT, QSAR, and NCI-RDG studies

The recent prevalence of coronavirus disease in 2019 (COVID-19) has triggered widespread global health concerns.Antiviral drugs based on phosphoramides have significant inhibitory activity against the main protease (Mpro) of the virus and prevent transcription and viral replication. Hence, in order to design and introduce a group of inhibitors affecting the coronavirus, 35 phosphoramide compounds based on phospho-guanine and phospho-pyrazine derivatives were selected for molecular docking study. The results showed that most phosphoguanides containing the amino benzimidazole have a high interaction tendency with COVID-19. Among them, compound 19 was identified as the strongest inhibitor with the -9.570 kcal/mol binding energy whereas, the binding energy of Remdesivir is -6.75 kcal/mol. The quantitative structure-activity relationship (QSAR) results demonstrated that the number of aromatic rings, amide's nitrogens and their ability in π-staking, and hydrogen interactions with Mpro active sites are major factors contributing to the inhibitory activity of these compounds.Also, the NCI-RDG and DFT results were in good accordance with those of QSAR and molecular docking. The findings of this investigation can be underlying the synthesis of effective and efficient drugs against COVID-19.

Effect-directed identification of novel aryl hydrocarbon receptor-active aromatic compounds in coastal sediments collected from a highly industrialized area

In this study, we identified major aryl hydrocarbon receptor (AhR) agonists in the sediments from Yeongil Bay (n = 6) using effect-directed analysis. Using the H4IIE-luc bioassays, great AhR-mediated potencies were found in aromatic fractions (F2) of sediment organic extracts from silica gel column chromatography and sub-fractions (F2.6–F2.8) from reverse phase-HPLC. Full-scan mass spectrometric analysis using GC-QTOFMS was conducted to identify novel AhR agonists in highly potent fractions, such as F2.6–F2.8 of S1 (Gumu Creek). Selection criteria for AhR-active compounds consisted of three steps, including matching factor of NIST library (≥70), aromatic structures, and the number of aromatic rings (≥4). Fifty-nine compounds were selected as tentative AhR agonist candidates, with the AhR-mediated activity being assessed for six compounds for which standard materials were available commercially. Of these compounds, 20-methylcholanthrene, 7-methylbenz[a]anthracene, 10-methylbenz[a]pyrene, and 7,12-dimethylbenz[a]anthracene exhibited significant AhR-mediated potency. Relative potency values of these compounds were determined relative to benzo[a]pyrene to be 3.2, 1.4, 1.2, and 0.2, respectively. EPA positive matrix factorization modeling indicated that the sedimentary AhR-active aromatic compounds primarily originated from coal combustion and vehicle emissions. Potency balance analysis indicated that four novel AhR agonists explained 0.007% to 1.7% of bioassay-derived AhR-mediated potencies in samples.

Size exclusion chromatography of aromatic compounds in high-boiling petroleum samples

Knowledge of aromatic compounds in petroleum samples is of paramount interest from processing and environmental viewpoints. Considering the complexity of such samples, a selective analytical strategy viz. aromatic specific size exclusion chromatographic methodology using amino-bonded silica phase, was adopted to obtain the average molecular weights of distilled cuts, residue and the corresponding crude oil. The method was found to be suitable from middle distillates up to the residue. It was found that the increase in boiling temperature of distilled cuts was reflected in an increase in high molecular weight aromatic species. The increase in the molecular weight of aromatic species is linked to the increase in alkylation as verified by studying the elution pattern of alkylated aromatic compounds. The accuracy of the molecular weights obtained from the size exclusion chromatographic method depends on the elution profile of aromatic species in petroleum samples. It was found that the size and shape of the parent aromatic compounds negatively influence the size exclusion elution profile. However, such influence can be assumed to be negligible as all the aromatic species of each distilled cut, residue, and crude oil eluted in the permeation zone of the chromatogram. This method has the potential to be used in the second dimension of a 2D-LC method where the aromatic compounds are separated based on the size (or alkylation). The first dimension will separate compounds based on the number of aromatic rings, thereby eliminating the interference of parent aromatic compounds of different sizes in the total elution profile.

The Multifarious Medical Applications of Carbon Curvatures: A Cohort review

Carbon curvatures are novel therapeutic bio-material that are being studied due to its multifarious applications in a variety of research aspects. All the carbon allotropes were grouped mathematically into three types based upon surface Gaussian curvatures: zero curvature (graphene), negative curvature (schwarzites), and positive curvature (fullerenes, CNTs), because they have physiochemical activities, such as optoelectrical, chemical, thermal and magnetic properties. All these allotropes consist of sp2 hybridization with delocalized π bond electrons. Based on the types and number of aromatic carbon rings, all ofthese have unique geometric structural characteristics, chirality, and solubility, which offers them as a potential candidate for biomedical and therapeutic applications. In this short review, we highlight the basic structural and physicochemical characteristics of carbon allotropes and their biomedical and therapeutic applications recentlystudied by researchers and describe the therapeutic applications of graphene and its derivatives in drug delivery, gene delivery, bio-imaging, biosensors, therapeutic diagnosis, and photo-stimulation therapies.

Toward high-level theoretical studies on the reaction kinetics of PAHs growth based on HACA pathway: An ONIOM[G3(MP2,CC)//B3LYP:DFT] method developed

Polycyclic aromatic hydrocarbons (PAHs) as precursors of soot, have been one of intensive concerns of human health and environmental contamination. G3(MP2,CC)//B3LYP theory has been widely used for prediction of PAHs growth. It is, however, a computational challenge for studying fairly large PAHs formation using this method. Herein, an ONIOM[G3(MP2,CC)//B3LYP:DFT] method, a two-layer composite ab inito molecular-orbital theory, was developed where the high layer of the real reaction systems is treated with G3(MP2,CC)//B3LYP and low layer is dealt with hybrid density functional B3LYP method. To evaluate the performance of the ONIOM method on PAHs growth, the potential energy surfaces (PESs) of naphthalene growth obtained from ONIOM method were compared with that from G3(MP2,CC)//B3LYP based on hydrogen-abstraction/C2H2-addition (HACA) mechanism. It is found that the results of ONIOM method are in good agreement with the results from G3(MP2,CC)//B3LYP method with mean energy error of −0.24 kcal/mol. After calculating the PESs of anthracene, phenanthrene, pyrene, and coronene growth based on HACA mechanism by ONIOM method, it is found that the computational costs of ONIOM method decrease significantly compared with G3(MP2,CC)//B3LYP method as the numbers of aromatic rings in PAHs increases. At the same time, ONIOM method maintains accurate prediction of PAHs growth. At last, time-dependent RRKM-based master equations using the obtained energy from ONIOM method were solved to calculate the pressure- and temperature-dependent rate coefficients of PAHs formations. Armed with this developed ONIOM method, more kinetics studies of PAHs growth may be carried out.

Insight into molecular interactions between condensed aromatics in high-temperature coal tar and organic solvents by combining experimental, density functional theory, and molecular dynamics

Kilogram-level extraction, modified high-pressure preparative chromatography (MHPPC), and flash preparative chromatography (FPC) were applied to separate condensed arenes (CAs) and heteroatom-containing aromatics (HACAs) from a high-temperature coal tar and its petroleum ether-extractable portion (PEEP). A series of CAs and HACAs were enriched from PEEP via MHPPC. Naphthalene and other 8 arenes were purified with purities of 99.9% and higher than 75%, respectively, by recrystallization and FPC. Density functional theory and molecular dynamics were used to calculate the solvation free energies (SFEs) and the complex intermolecular interactions (IMIAs), respectively, between solvent and solute at the molecular level. The difference in SFE is positively correlated with the number of aromatic rings of each compound. The IMIAs related to the separations include hydrogen bonds, such as >CH2···X (X denotes NH<, –N<, or HO-AR), >CO···X, and –O–H···X bonds, >CH2···π, >CO···π, –O–H···π bonds, π···π stacking, and van der Waals forces.

In-situ characterization of volatiles from pyrolysis of Fengfeng coal by a double ionization time-of-flight mass spectrometer

Coal from Fengfeng (FF) colliery, Hebei, China, was pyrolyzed in a self-developed pyrolysis reactor coupled with double ionization sources (viz., electron impact ionization (EI) and photoionization (PI))and time-of-flight mass spectrometer (Py-EI/PI-TOFMS), to characterizein-situ the primary products from pyrolysis (heteroatom-containing compounds in particular). The relative contents of various pyrolysis products were obtained by semi-quantitative analysis and the temperature-evolved profile of each product was obtained by scanning the signal of the distinguished peak with the lapse of time; in addition, the evolution of five small molecule gaseous products (viz., H2O, CO, CO2, H2 and CH4) was analyzed by EI-TOFMS. The results indicatethat the Py-PI-TOFMS system is able to detect and characterize the primary productsin-situ during coal pyrolysis. In the pyrolysis products with a mass-to-charge ratio (m/z) less than 240, which accountfor about 70% of detected volatiles,hydrocarbons consist of mainly aromatics of 1–3 rings, whereas the phenolic compounds are dominated by phenols containing 1–3 benzene rings (especially the 3-ringphenols). The peak temperature with maximum evolution of phenols containing the same alkyl substituents shifts to lower temperature with the increase of the number of aromatic rings. In addition, the relative contents of nitrogen/sulfur-containing compounds are all less than 1.0%, where the content of sulfur-containing heterocyclic compounds is higher than that of nitrogen-containing heterocyclic compounds.

Effect of carbon backbone on luminescence properties of Eu-organic hybrid thin films prepared by ALD/MLD

Here we show that the backbone of the organic ligand has a profound impact on the luminescence characteristics of lanthanide-organic materials. We employ the emerging atomic/molecular layer deposition (ALD/MLD) technique to deposit europium-based thin films where the organic ligands vary in terms of the number of aromatic rings in their backbone (benzene, naphthalene and anthracene). Enlarging the backbone shifts the excitation towards visible wavelengths, but it simultaneously decreases the emission intensity. Moreover, for the Eu-terephthalate films with the single benzene ring as the organic backbone, we investigate the effects of diluting the Eu3+ concentration with Y3+ to reveal that the emission intensity is optimized around 12% Eu3+ concentration. Interestingly, such a dependence of luminescence intensity on the concentration of emitting species suggests that our (Eu,Y)-organic thin films behave more like ionic phosphors than discrete metal–ligand molecules.Graphical abstract

Levels and risk assessment of polycyclic aromatic hydrocarbons in wood vinegars from pyrolysis of biomass

A method quantifying 16 polycyclic aromatic hydrocarbons (PAHs) in wood vinegars (WVs) obtained from slow pyrolysis of biomass with ultrasonic-assisted liquid-liquid extraction/gas chromatography-mass spectrometry (USALLE/GC-MS) was established. The recovery range was 83–128%, and the relative standard deviations (RSD%) were less than 15% except naphthalene, acenaphthylene and acenaphthene. Acenaphthylene, acenaphthene, fluorene, anthracene, phenanthrene, fluoranthene, and pyrene were observed in all samples and the other 9 compounds, including benzopyrene (B[a]P), were not detected. The concentration of ∑PAHs referred to the sum total of 7 PAHs mentioned above was 22.0–498.3 μg L−1. The PAHs concentration increased with the increasing pyrolysis temperature in bamboo willow WV, pinus sylvestris WV, and corncob WV, while it increased initially, and then decreased with a maximum at 550 °C in rice husk WV. The ∑PAHs concentration increased with a higher heating rate in the white pine WV, while rice husk WV and cornstalk WV showed the opposite trend. The varied condensed aromatic ring number showed that 3-ring PAHs relatively were the main component in all kind WVs. 3-ring PAHs increased with increasing temperatures, while 4-ring PAHs showed an opposite trend in sawdust WV and corncob WVs. A higher cellulose content in sawdust enhanced the reaction of lignin leading to a higher concentration of PAHs than that in straws and leaves. Calculations of the toxicity equivalents of PAHs in WVs indicated that anthracene was the most toxic among the PAHs, and the pinus sylvestris WV had the highest risk of ∑PAHs toxicity in all WVs.

Aromatic Rings as Molecular Determinants for the Molecular Recognition of Protein Kinase Inhibitors.

Protein kinases are key enzymes in many signal transduction pathways, and play a crucial role in cellular proliferation, differentiation, and various cell regulatory processes. However, aberrant function of kinases has been associated with cancers and many other diseases. Consequently, competitive inhibition of the ATP binding site of protein kinases has emerged as an effective means of curing these diseases. Over the past three decades, thousands of protein kinase inhibitors (PKIs) with varying molecular frames have been developed. Large-scale data mining of the Protein Data Bank resulted in a database of 2139 non-redundant high-resolution X-ray crystal structures of PKIs bound to protein kinases. This provided us with a unique opportunity to study molecular determinants for the molecular recognition of PKIs. A chemoinformatic analysis of 2139 PKIs resulted in findings that PKIs are “flat” molecules with high aromatic ring counts and low fractions of sp3 carbon. All but one PKI possessed one or more aromatic rings. More importantly, it was found that the average weighted hydrogen bond count is inversely proportional to the number of aromatic rings. Based on this linear relationship, we put forward the exchange rule of hydrogen bonding interactions and non-bonded π-interactions. Specifically, a loss of binding affinity caused by a decrease in hydrogen bonding interactions is compensated by a gain in binding affinity acquired by an increase in aromatic ring-originated non-bonded interactions (i.e., π–π stacking interactions, CH–π interactions, cation–π interactions, etc.), and vice versa. The very existence of this inverse relationship strongly suggests that both hydrogen bonding and aromatic ring-originated non-bonded interactions are responsible for the molecular recognition of PKIs. As an illustration, two representative PKI–kinase complexes were employed to examine the relative importance of different modes of non-bonded interactions for the molecular recognition of PKIs. For this purpose, two FDA-approved PKI drugs, ibrutinib and lenvatinib, were chosen. The binding pockets of both PKIs were thoroughly examined to identify all non-bonded intermolecular interactions. Subsequently, the strengths of interaction energies between ibrutinib and its interacting residues in tyrosine kinase BTK were quantified by means of the double hybrid DFT method B2PLYP. The resulting energetics for the binding of ibrutinib in tyrosine kinase BTK showed that CH–π interactions and π–π stacking interactions between aromatic rings of the drug and hydrophobic residues in its binding pocket dominate the binding interactions. Thus, this work establishes that, in addition to hydrogen bonding, aromatic rings function as important molecular determinants for the molecular recognition of PKIs. In conclusion, our findings support the following pharmacophore model for ATP-competitive kinase inhibitors: a small molecule features a scaffold of one or more aromatic rings which is linked with one or more hydrophilic functional groups. The former has the structural role of acting as a scaffold and the functional role of participating in aromatic ring-originated non-bonded interactions with multiple hydrophobic regions in the ATP binding pocket of kinases. The latter ensure water solubility and form hydrogen bonds with the hinge region and other hydrophilic residues of the ATP binding pocket.

Preparation and Optimization of PEGylated Nano Graphene Oxide-Based Delivery System for Drugs with Different Molecular Structures Using Design of Experiment (DoE).

Graphene oxide (GO), due to its 2D planar structure and favorable physical and chemical properties, has been used in different fields including drug delivery. This study aimed to investigate the impact of different process parameters on the average size of drug-loaded PEGylated nano graphene oxide (NGO-PEG) particles using design of experiment (DoE) and the loading of drugs with different molecular structures on an NGO-PEG-based delivery system. GO was prepared from graphite, processed using a sonication method, and functionalized using PEG 6000. Acetaminophen (AMP), diclofenac (DIC), and methotrexate (MTX) were loaded onto NGO-PEG particles. Drug-loaded NGO-PEG was then characterized using dynamic light scattering (DLS), Fourier transform infrared (FTIR), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), XRD. The DLS data showed that the drug-loaded NGO-PEG suspensions were in the size range of 200 nm–1.3 µm. The sonication time and the stirring rate were found to be the major process parameters which affected the average size of the drug-loaded NGO-PEG. FTIR, DSC, XRD, and SEM demonstrated that the functionalization or coating of the NGO occurred through physical interaction using PEG 6000. Methotrexate (MTX), with the highest number of aromatic rings, showed the highest loading efficiency of 95.6% compared to drugs with fewer aromatic rings (diclofenac (DIC) 70.5% and acetaminophen (AMP) 65.5%). This study suggests that GO-based nano delivery systems can be used to deliver drugs with multiple aromatic rings with a low water solubility and targeted delivery (e.g., cancer).

An insight into the structure of 5-spiro aromatic derivatives of imidazolidine-2,4-dione, a new group of very potent inhibitors of tumor multidrug resistance in T-lymphoma cells

A series of 17 arylpiperazine derivatives of the 5-spiroimidazolidine-2,4-diones (6–22) has been explored, including variations in (i) the number of aromatic rings at position 5, (ii) the length of the linker, as well as (iii) the kind and position of the linked arylpiperazine terminal fragment. Synthesis (6–16) and X-ray crystallographic studies for representative compounds (8, 10, 14 and 18) have been performed. The ability to inhibit the tumor multidrug resistance (MDR) efflux pump P-glycoprotein (P-gp, ABCB1) overexpressed in mouse T-lymphoma cells was investigated. The cytotoxic and antiproliferative actions of the compounds on both the reference and the ABCB1-overproducing cells were also examined. The pharmacophore-based molecular modeling studies have been performed. ADMET properties in vitro of selected most active derivatives (6, 11 and 12) have been determined. All compounds, excluding 18, inhibited the cancer P-gp efflux pump with higher potency than that of reference verapamil. The spirofluorene derivatives with amine alkyl substituents at position 1, and the methyl group at position 3 (6–16), occurred the most potent P-gp inhibitors in the MDR T–lymphoma cell line. In particular, compounds 7 and 12 were 100-fold more potent than verapamil. Crystallography-supported pharmacophore-based SAR analysis has postulated specific structural properties that could explain this excellent cancer MDR-inhibitory action.

Inhalation bioacessibility and absorption of polycyclic aromatic hydrocarbons (PAHs) in indoor PM2.5 and its implication in risk assessment

Inhalation bioaccessibility of polycyclic aromatic hydrocarbons (PAHs) in PM2.5 was assessed in numerous studies, however, the lung cell uptake and penetration of PAHs was seldom taken into account in risk assessment. In the present study, eighteen indoor PM2.5 samples collected from Guangzhou, China were analyzed for the inhalation bioavailability of PAHs combining the inhalation bioaccessibility and cell absorption of PAHs. Two simulated epithelial lung fluid mimicking the healthy condition (as represented by gamble's solution (GMB), pH = 7.4) and the inflammatory condition (as represented by artificial lysosomal fluid (ALF), pH = 4.5) were employed to evaluate the inhalation bioaccessibility. The results indicated that the bioaccessibility of PAHs under the inflammatory condition (1.28%–87.7%) was higher than that under healthy condition (0.88%–87.6%). Naphthalene, phenanthrene, pyrene and benzo[a]pyrene were selected for absorption assay of lung epithelial cells (A549). The absorption rate of PAHs ranged from 64.7 to 90.7% and it was inversely proportional to the number of aromatic rings. Taken together, the inhalation bioavailability based on the bioaccessibility of PAHs and the lung cell absorption ratio ranged from 9.9 to 56.9% under the healthy state, from 12.7 to 65.6% under inflammatory condition. The correction parameter (Fc) was thus established and can be used to improve the risk assessment of human exposure to PAHs via PM2.5 inhalation in future work.

Predictive Rules of Efflux Inhibition and Avoidance in Pseudomonas aeruginosa.

Antibiotic-resistant bacteria rapidly spread in clinical and natural environments and challenge our modern lifestyle. A major component of defense against antibiotics in Gram-negative bacteria is a drug permeation barrier created by active efflux across the outer membrane. We identified molecular determinants defining the propensity of small peptidomimetic molecules to avoid and inhibit efflux pumps in Pseudomonas aeruginosa, a human pathogen notorious for its antibiotic resistance. Combining experimental and computational protocols, we mapped the fate of the compounds from structure-activity relationships through their dynamic behavior in solution, permeation across both the inner and outer membranes, and interaction with MexB, the major efflux transporter of P. aeruginosa We identified predictors of efflux avoidance and inhibition and demonstrated their power by using a library of traditional antibiotics and compound series and by generating new inhibitors of MexB. The identified predictors will enable the discovery and optimization of antibacterial agents suitable for treatment of P. aeruginosa infections.IMPORTANCE Efflux pump avoidance and inhibition are desired properties for the optimization of antibacterial activities against Gram-negative bacteria. However, molecular and physicochemical interactions defining the interface between compounds and efflux pumps remain poorly understood. We identified properties that correlate with efflux avoidance and inhibition, are predictive of similar features in structurally diverse compounds, and allow researchers to distinguish between efflux substrates, inhibitors, and avoiders in P. aeruginosa The developed predictive models are based on the descriptors representative of different clusters comprising a physically intuitive combination of properties. Molecular shape (represented by acylindricity), amphiphilicity (anisotropic polarizability), aromaticity (number of aromatic rings), and the partition coefficient (LogD) are physicochemical predictors of efflux inhibitors, whereas interactions with Pro668 and Leu674 residues of MexB distinguish between inhibitors/substrates and efflux avoiders. The predictive models and efflux rules are applicable to compounds with unrelated chemical scaffolds and pave the way for development of compounds with the desired efflux interface properties.