Packing Incubation and Addition of Rot Fungi Extracts Improve BTEX Elimination from Air in Biotrickling Filters.

The removal of benzene, toluene, ethylbenzene, and xylene (BTEX) from air was investigated in two similar biotrickling filters (BTFs) packed with polyurethane (PU) foam, differing in terms of inoculation procedure (BTF A was packed with pre-incubated PU discs, and BTF B was inoculated via the continuous recirculation of a liquid inoculum). The effects of white rot fungi enzyme extract addition and system responses to variable VOC loading, liquid trickling patterns, and pH were studied. Positive effects of both packing incubation and enzyme addition on biotrickling filtration performance were identified. BFF A exhibited a shorter start-up period (approximately 20 days) and lower pressure drop (75 ± 6 mm H2O) than BTF B (30 days; 86 ± 5 mm H2O), indicating the superior effects of packing incubation over inoculum circulation during the biotrickling filter start-up. The novel approach of using white rot fungi extracts resulted in fast system recovery and enhanced process performance after the BTF acidification episode. Average BTEX elimination capacities of 28.8 ± 0.4 g/(m3 h) and 23.1 ± 0.4 g/(m3 h) were reached for BTF A and BTF B, respectively. This study presents new strategies for controlling and improving the abatement of BTEX in biotrickling filters.

Revisiting the Most Stable Structures of the Benzene Dimer.

The benzene dimer (BD) is an archetypal model of π∙∙∙π and C-H∙∙∙π noncovalent interactions as they occur in its cofacial and perpendicular arrangements, respectively. The enthalpic stabilization of the related BD structures has been debated for a long time and is revisited here. The revisit is based on results of computations that apply the coupled-cluster theory with singles, doubles and perturbative triples [CCSD(T)] together with large basis sets and extrapolate results to the complete basis set (CBS) limit in order to accurately characterize the three most important stationary points of the intermolecular interaction energy (ΔE) surface of the BD, which correspond to the tilted T-shaped (TT), fully symmetric T-shaped (FT) and slipped-parallel (SP) structures. In the optimal geometries obtained by searching extensive sets of the CCSD(T)/CBS ΔE data of the TT, FT and SP arrangements, the resulting ΔE values were -11.84, -11.34 and -11.21 kJ/mol, respectively. The intrinsic strength of the intermolecular bonding in these configurations was evaluated by analyzing the distance dependence of the CCSD(T)/CBS ΔE data over wide ranges of intermonomer separations. In this way, regions of the relative distances that favor BD structures with either π∙∙∙π or C-H∙∙∙π interactions were found and discussed in a broader context.

Development of a fluorescent ligand that specifically binds to the c-MYC G-quadruplex by migrating the benzene group on a carbazole-benzothiazolium scaffold.

c-MYC is one of the most important oncogenes, which is overexpressed in many cancers, and is highly related to development, metastasis, and drug resistance of cancers. The G4 structure in the promoter of c-MYC oncogene contributes a lot to the gene transcriptional mechanism. Small-molecule ligands binding to the c-MYC G4 appear to be a new class of anticancer agents. However, selective ligands for the c-MYC G4 over other G4s have been rarely reported. In this study, we reported a novel fluorescent ligand by migrating the benzene group on a carbazole-benzothiazolium scaffold, which was demonstrated to exhibit considerable specificity to the c-MYC G4, which was distinguished from other small-molecule ligands. The further cellular experiments suggested that this ligand may indeed target the promoter G4 and cause apparent transcriptional inhibition of the c-MYC oncogene instead of other G4-mediated oncogenes, which thereby resulted in cancer cell growth inhibition. Collectively, this study provided a good example for developing specific c-MYC G4 ligands, which may further develop into an effective anticancer agent that inhibit the c-MYC expression.

An Insight Into Risk Assessment and Reformulation of Drug Products Manufactured Using Benzene Grade Carbomer: A Regulatory Perspective.

Cancer has been an enormous pain point for patients and regulatory bodies across the globe. In Dec. 2023, the US FDA released guidance on benzene-grade carbomer formulations, which triggered pharmaceutical manufacturers to assess risk, test finished products, and reformulate drug products with benzene-grade carbomer. The immediate implementation of the stoppage of finished products with benzene-grade carbomers has threatened pharmaceutical excipients and finished product manufacturers. The gravity of this situation prompted the US Pharmacopeia to extend the deadline for discontinuation from August 1, 2025, to August 1, 2026, allowing manufacturers ample time for reformulation and regulatory compliance.There is an immediate need to understand the guidance and to learn how manufacturers should do the risk assessment and approach reformulation. This review provides an in-depth analysis of the risk assessment and reformulation processes involved in various dosage forms utilizing benzene-grade carbomer, supported by specific case studies.This review offers insights into navigating the USFDA guidelines to ensure formulation safety and compliance, thus enabling pharmaceutical practitioners to uphold the highest standards of patient care and tackle life cycle management challenges.The decision of the USFDA to restrict the usage of high benzene content of carbomer in the formulation is a welcome move. This article has shown a way for researchers to see opportunities in the path and provide best-in-class medicines to patients with a better formulation safety profile.

Prediction of BTEX volatilization in polluted soil based on the sorption potential energy theory.

Initial volatile concentration (Cs0) is a crucial parameter for the migration and diffusion of volatile organic pollutants (VOCs) from the soil to the atmosphere. The acquisition of Cs0 is, however, time-consuming and labor-intensive. This study developed a prediction model for Cs0 based on theoretical analysis and experimental simulations. The model was established by correlating the molecular kinetic and sorption potential energy. The pore structure and pore size distribution of the soil were analyzed based on the fractal theory of porous media, followed by calculating the sorption potential energy corresponding to each pore size. It was observed that the pore size distribution of soil influenced BTEX (benzene, toluene, ethylbenzene, and xylene) volatilization by impacting sorption potential energy. The soil parameters, such as organic matter and soil moisture content, and the initial concentration and physical properties of BTEX were coupled to the prediction model to ensure its practicability. Red soil was finally used to verify the accuracy and applicability of the model. The experimental and predicted values' maximum relative and root-mean-square errors were determined to be 24.2% and 11.7%, respectively. The model provides a simple, rapid, and accurate assessment of soil vapor emission content due to BTEX contamination. This study offers an economical and practical method for quantifying the amount of volatile BTEX in contaminated sites, providing a reference for its monitoring, control, and subsequent remediation.

Oxygen Vacancy Enabled Electronic Structure Engineering of Pt-WO3 Nanosheets toward Highly Efficient BTEX Sensing.

A Pt nanoparticle-immobilized WO3 material is a promising candidate for catalytic reactions, and the surface and electronic structure can strongly affect the performance. However, the effect of the intrinsic oxygen vacancy of WO3 on the d-band structure of Pt and the synergistic effect of Pt and the WO3 matrix on reaction performance are still ambiguous, which greatly hinders the design of advanced materials. Herein, Pt-decorated WO3 nanosheets with different electronic metal-support interactions are successfully prepared by finely tuning the oxygen vacancy structure of WO3 nanosheets. Notably, Pt-modified WO3 nanosheets annealed at 400 °C exhibit excellent benzene series (BTEX) sensing performance (S = 377.33, 365.21, 348.45, and 319.23 for 50 ppm ethylbenzene, benzene, toluene, and xylene, respectively, at 140 °C), fast response and recovery dynamics (10/7 s), excellent reliability (σ = 0.14), and sensing stability (φ = 0.08%). Detailed structural characterization and DFT results reveal that interfacial Ptδ+-Ov-W5+ sites are recognized as the active sites, and the oxygen vacancies of the WO3 matrix can significantly affect the d-band structure of Pt nanoparticles. Notably, Pt/WO3-400 with improved surface oxygen mobility and medium electronic metal-support interaction facilitates the activation and desorption of BTEX, which contributes to the highly efficient BTEX sensing performance. Our work provides a new insight for the design of high-performance surface reaction materials for advanced applications.

Sorption and attenuation of petroleum VOCs in five unsaturated soils: Microcosms and column experiments.

The fate of volatile organic compounds (VOC) vapors in the unsaturated zone is the basis for evaluating the natural attenuation potential and vapor intrusion risk. Microcosm and column experiments were conducted to study the effects chemical speciation and soil types/properties on the fate of petroleum VOCs in unsaturated zone. The biodegradation and total attenuation rates of the seven VOCs obtained by microcosm experiments in black soil and yellow earth were also generally higher than those in floodplain soil, lateritic red earth, and quartz sand. The VOC vapors in floodplain soil, lateritic red earth, and quartz sand showed slow total attenuation rates (<0.3 d-1). N-pentane, methylcyclopentane, and methylcyclohexane showed lower biodegradation rates than octane and three monoaromatic hydrocarbons. Volatilization into the atmosphere and biodegradation are two important natural attenuation paths for VOCs in unsaturated soil columns. The volatilization loss fractions of different volatile hydrocarbons in all five unsaturated soils were generally in the order: n-pentane (93.5%-97.8%) > methylcyclopentane (77.2%-85.5%) > methylcyclohexane (53.5%-69.2%) > benzene (17.1%-73.3%) > toluene (0-45.7%) > octane (1.9%-34.2%) > m-xylene (0-5.7%). The fractions by volatilization into the atmosphere of all seven hydrocarbons in quartz sand, lateritic red earth, and floodplain soil were close and higher compared to the yellow earth and black soil. Overall, this study illustrated the important roles chemical speciation and soil properties in determining the vapor-phase transport and natural attenuation of VOCs in the unsaturated zone.

High-performance activation of ozone by sonocavitation for BTEX degradation in water.

This work presents a novel advanced oxidation process (AOP) for degradation of emerging organic pollutants - benzene, toluene, ethylbenzene and xylenes (BTEXs) in water. A comparative study was performed for sonocavitation assisted ozonation under 40-120 kHz and 80-200 kHz dual frequency ultrasounds (DFUS). Based on the obtained results, the combination of 40-120 kHz i.e., low-frequency US (LFDUS) with O3 exhibited excellent oxidation capacity degrading 99.37-99.69% of BTEXs in 40 min, while 86.09-91.76% of BTEX degradation was achieved after 60 min in 80-200 kHz i.e., high-frequency US (HFDUS) combined with O3. The synergistic indexes determined using degradation rate constants were found as 7.86 and 2.9 for LFDUS/O3 and HFDUS/O3 processes, respectively. The higher extend of BTEX degradation in both processes was observed at pH 6.5 and 10. Among the reactive oxygen species (ROSs), hydroxyl radicals (HO•) were found predominant according to scavenging tests, singlet oxygen also importantly contributed in degradation, while O2•- radicals had a minor contribution. Sulfate (SO42-) ions demonstrated higher inhibitory effect compared to chloride (Cl-) and carbonate (CO32-) ions in both processes. Degradation pathways of BTEX was proposed based on the intermediates identified using GC-MS technique.

A cellulose nanocrystal-based dual response of photonic colors and fluorescence for sensitive benzene gas detection.

Benzene, as a common volatile organic compound, represents serious risk to human health and environment even at low level concentration. There is an urgent concern on visualized, sensitive and real time detection of benzene gases. Herein, by doping Fe3+ and graphene quantum dots (GQDs), a cellulose nanocrystal (CNC) chiral nematic film was designed with dual response of photonic colors and fluorescence to benzene gas. The chiral nematic CNC/Fe/GQDs film could respond to benzene gas changes by reversible motion. Moreover, chiral nematic film also displays reversible responsive to humidity changes. The resulting CNC/Fe/GQDs chiral nematic film showed excellent response performance at benzene gas concentrations of 0-250 mg/m3. The maximal reflection wavelength film red shifted from 576 to 625 nm. Furthermore, structural color of CNC/Fe/GQDs chiral nematic film change at 44 %, 54 %, 76 %, 87 %, and 99 % relative humidity. Interestingly, due to the stability of GQDs to water molecules, CNC/Fe/GQDs chiral nematic film exhibit fluorescence response to benzene gas even in high humidity (RH = 99 %) environment. Besides, we further developed a smartphone-based response network system for quantitively determinization and signal transformation. This work provides a promising routine to realize a new benzene gas response regime and promotes the development of real-time benzene gas detection.

Fostering a Holistic Understanding of the Full Volatility Spectrum of Organic Compounds from Benzene Series Precursors through Mechanistic Modeling.

A comprehensive understanding of the full volatility spectrum of organic oxidation products from the benzene series precursors is important to quantify the air quality and climate effects of secondary organic aerosol (SOA) and new particle formation (NPF). However, current models fail to capture the full volatility spectrum due to the absence of important reaction pathways. Here, we develop a novel unified model framework, the integrated two-dimensional volatility basis set (I2D-VBS), to simulate the full volatility spectrum of products from benzene series precursors by simultaneously representing first-generational oxidation, multigenerational aging, autoxidation, dimerization, nitrate formation, etc. The model successfully reproduces the volatility and O/C distributions of oxygenated organic molecules (OOMs) as well as the concentrations and the O/C of SOA over wide-ranging experimental conditions. In typical urban environments, autoxidation and multigenerational oxidation are the two main pathways for the formation of OOMs and SOA with similar contributions, but autoxidation contributes more to low-volatility products. NOx can reduce about two-thirds of OOMs and SOA, and most of the extremely low-volatility products compared to clean conditions, by suppressing dimerization and autoxidation. The I2D-VBS facilitates a holistic understanding of full volatility product formation, which helps fill the large gap in the predictions of organic NPF, particle growth, and SOA formation.

Mn and Co decorated biomorphic ceria fiber catalysts for soot and benzene total oxidation.

Mn or Co supported CeO2 fiber catalysts were synthesized following a biotemplating route and evaluated in soot combustion and benzene total oxidation. The catalysts were characterized by SEM, EDX, N2 physisorption, FTIR-ATR, XRD, RAMAN and XPS. SEM results confirmed that the "twisted ribbon" morphology of the biotemplate was mostly maintained. XRD and Raman showed that Mn and Co cations partially insert into ceria lattice and also segregate at the surface of the fibers. XPS allowed to determine that both set of catalysts exhibit Ce3+ and Ce4+ species, in addition to adsorbed and lattice oxygen. Also, the average oxidation state (AOS) of surface Mn could be calculated. Compared to bare Fib Ce, the performances for both reactions were improved for the supported catalysts, except from the catalyst with lowest Mn content for soot combustion. The catalytic activity was discussed in terms of the physicochemical features of the supported catalysts.

Thermodynamically and Kinetically Enhanced Benzene Vapor Sensor Based on the Cu-TCPP-Cu MOF with Extremely Low Limit of Detection.

As a carcinogenic and highly neurotoxic hazardous gas, benzene vapor is particularly difficult to be distinguished in BTEX (benzene, toluene, ethylbenzene, xylene) atmosphere and be detected in low concentrations due to its chemical inertness. Herein, we develop a depth-related pore structure in Cu-TCPP-Cu to thermodynamically and kinetically enhance the adsorption of benzene vapor and realize the detection of ultralow-temperature benzene gas. We find that the in-plane π electronic nature and proper pore sizes in Cu-TCPP-Cu can selectively induce the adsorption and diffusion of BTEX. Interestingly, the theoretical calculations (including density functional theory (DFT) and grand canonical Monte Carlo (GCMC) simulations) exhibit that benzene molecules are preferred to adsorb and array as a consecutive arrangement mode in the Cu-TCPP-Cu pore, while the TEX (toluene, ethylbenzene, xylene) dominate the jumping arrangement model. The differences in distribution behaviors can allow adsorption and diffusion of more benzene molecules within limited room. Furthermore, the optimal pore-depth range (60-65 nm) of Cu-TCPP-Cu allows more exposure of active sites and hinders the gas-blocking process. The optimized sensor exhibits ultrahigh sensitivity to benzene vapor (155 Hz/µg@1 ppm), fast response time (less than 10 s), extremely low limit of detection (65 ppb), and excellent selectivity (83%). Our research thus provides a fundamental understanding to design and optimize two-dimensional metal-organic framework (MOF)-based gas sensors.

Improving benzene catalytic oxidation on Ag/Co3O4 by regulating the chemical states of Co and Ag.

Silver (9 wt.%) was loaded on Co3O4-nanofiber using reduction and impregnation methods, respectively. Due to the stronger electronegativity of silver, the ratios of surface Co3+/Co2+ on Ag/Co3O4 were higher than on Co3O4, which further led to more adsorbed oxygen species as a result of the charge compensation. Moreover, the introducing of silver also obviously improved the reducibility of Co3O4. Hence the Ag/Co3O4 showed better catalytic performance than Co3O4 in benzene oxidation. Compared with the Ag/Co3O4 synthesized via impregnation method, the one prepared using reduction method (named as AgCo-R) exhibited higher contents of surface Co3+ and adsorbed oxygen species, stronger reducibility, as well as more active surface lattice oxygen species. Consequently, AgCo-R showed lowest T90 value of 183°C, admirable catalytic stability, largest normalized reaction rate of 1.36 × 10-4 mol/(h·m2) (150°C), and lowest apparent activation energy (Ea) of 63.2 kJ/mol. The analyzing of in-situ DRIFTS indicated benzene molecules were successively oxidized to phenol, o-benzoquinone, small molecular intermediates, and finally to CO2 and water on the surface of AgCo-R. At last, potential reaction pathways including five detailed steps were proposed.

Assessing the rigidity of cubanes and bicyclo(1.1.1)pentanes as benzene bioisosteres.

Aromatic rings are critical core substructures in the majority of pharmaceutical compounds. There is much recent interest in replacing aromatic structures with saturated bioisosteres of benzene, which are generally fused or bridged ring systems. These bioisosteres often show improved solubility properties compared to benzene, and may also undergo fewer unwanted metabolic processes. One key reason why aromatic rings have proven so successful in drug design is their rigidity. This paper uses molecular dynamics simulations supported by crystallographic data to assess the rigidity of bicyclopentane and cubane ring systems as two of the most common benzene bioisosteres and compares this to benzene. Whilst a benzene ring is shown to be more flexible than these two bioisosteres in terms of its dihedral ring flexibility, substituents around the ring tend to behave in a much more similar way in both benzene and the bioisosteric systems.

Enhanced benzene vapor adsorption through microwave-assisted fabrication of activated carbon from peanut shells using ZnCl2 as an activating agent.

Herein, microwave-assisted activated carbon (MW-AC) was fabricated from peanut shells using a ZnCl2 activator and utilized for the first time to eliminate benzene vapor as a volatile organic compound (VOC). During the MW-AC production process, which involved two steps-microwave treatment and muffle furnace heating-we investigated the effects of various factors and achieved the highest iodine number of 1250 mg/g. This was achieved under optimal operating conditions, which included a 100% impregnation ratio, CO2 as the gas in the microwave environment, a microwave power set at 500 W, a microwave duration of 10 min, an activation temperature of 500 °C and an activation time of 45 min. The structural and morphological properties of the optimized MW-AC were assessed through SEM, FTIR, and BET analysis. The dynamic adsorption process of benzene on the optimized MW-AC adsorbent, which has a significant BET surface area of 1204.90 m2/g, was designed using the Box-Behnken approach within the response surface methodology. Under optimal experimental conditions, including a contact duration of 80 min, an inlet concentration of 18 ppm, and a temperature of 26 °C, the maximum adsorption capacity reached was 568.34 mg/g. The experimental data are better described by the pseudo-second-order kinetic model, while it is concluded that the equilibrium data are better described by the Langmuir isotherm model. MW-AC exhibited a reuse efficiency of 86.54% for benzene vapor after five consecutive recycling processes. The motivation of the study highlights the high adsorption capacity and superior reuse efficiency of MW-AC adsorbent with high BET surface area against benzene pollutant. According to our results, the developed MW-AC presents itself as a promising adsorbent candidate for the treatment of VOCs in various industrial applications.

Novel benzene sulfonamides with acetylcholinesterase and carbonic anhydrase inhibitory actions.

A series of benzene sulfonamides 15-26 were synthesized and determined for their in vitro and in silico inhibitory profiles toward acetylcholinesterase (AChE) and carbonic anhydrases (CAs). Commercially available 3,4-dimethoxytoluene was reacted with chlorosulfonic acid to furnish benzene sulfonyl chloride derivatives. The reaction of substituted benzene sulfonyl chloride with some amines also including (±)-α-amino acid methyl esters afforded a series of novel benzene sulfonamides. In this study, the enzyme inhibition abilities of these compounds were evaluated against AChE and CAs. They exhibited a highly potent inhibition ability on AChE and -CAs (Ki values are in the range of 28.11 ± 4.55 nM and 145.52 ± 28.68 nM for AChE, 39.20 ± 2.10 nM to 131.54 ± 12.82 nM for CA I, and 50.96 ± 9.83 nM and 147.94 ± 18.75 nM for CA II). The present newly synthesized novel benzene sulfonamides displayed efficient inhibitory profiles against AChE and CAs, and it is anticipated that they may emerge as lead molecules for some diseases including glaucoma, epilepsy, and Alzheimer's disease.

Mesoporous nanoperforators as membranolytic agents via nano- and molecular-scale multi-patterning.

Plasma membrane lysis is an effective anticancer strategy, which mostly relying on soluble molecular membranolytic agents. However, nanomaterial-based membranolytic agents has been largely unexplored. Herein, we introduce a mesoporous membranolytic nanoperforators (MLNPs) via a nano- and molecular-scale multi-patterning strategy, featuring a spiky surface topography (nanoscale patterning) and molecular-level periodicity in the spikes with a benzene-bridged organosilica composition (molecular-scale patterning), which cooperatively endow an intrinsic membranolytic activity. Computational modelling reveals a nanospike-mediated multivalent perforation behaviour, i.e., multiple spikes induce nonlinearly enlarged membrane pores compared to a single spike, and that benzene groups aligned parallelly to a phospholipid molecule show considerably higher binding energy than other alignments, underpinning the importance of molecular ordering in phospholipid extraction for membranolysis. Finally, the antitumour activity of MLNPs is demonstrated in female Balb/c mouse models. This work demonstrates assembly of organosilica based bioactive nanostructures, enabling new understandings on nano-/molecular patterns co-governed nano-bio interaction.

Current trends on dry photocatalytic oxidation technology for BTX removal: Viable light sources and highly efficient photocatalysts.

One of the main gaseous pollutants released by chemical production industries are benzene, toluene and xylene (BTX). These dangerous gases require immediate technology to combat them, as they put the health of living organisms at risk. The development of heterogeneous photocatalytic oxidation technology offers several viewpoints, particularly in gaseous-phase decontamination without an additional supply of oxidants in air at atmospheric pressure. However, difficulties such as low quantum efficiency, ability to absorb visible light, affinity towards CO2 and H2O synthesis, and low stability continue to limit its practical use. This review presents recent advances in dry-phase heterogeneous photodegradation as an advanced technology for the practical removal of BTX molecules. This review also examines the impact of low-cost light sources, the roles of the active sites of photocatalysts, and the feasible concentration range of BTX molecules. Numerous studies have demonstrated a significant improvement in the efficiency of the photodegradation of volatile organic compounds by enhancing the photocatalytic reactor system and other factors, such as humidity, temperature, and flow rate. The mechanism for BTX photodegradation based on density functional theory (DFT), electron paramagnetic resonance (EPR) and diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) investigations is also discussed. Finally, the present research complications and anticipated future developments in the field of heterogeneous photocatalytic oxidation technology are discussed.

Low-temperature oxidative removal of benzene from the air using titanium carbide (MXene)-Supported platinum catalysts.

MXenes are an emerging class of two-dimensional (2D) inorganic materials with great potential for versatile applications such as adsorption and catalysis. Here, we describe the synthesis of a platinized titanium carbide MXene (Pt@Ti3C2) catalyst with varying amounts of platinum (0.1%-2 wt.%) for the low-temperature oxidation of benzene, an aromatic volatile organic compound often found in industrial flue gas. A 1% formulation of Pt@Ti3C2-R allowed near-complete (97%) oxidation of benzene to CO2 at 225 °C with a steady-state reaction rate (r) of 0.119 mol g-1·h-1. This low-temperature catalytic oxidation reaction was promoted by an increase in the lattice oxygen (O*)/Pt2+ species (active sites) of 1%Pt@Ti3C2-R from 45.3/34.6% to 71.0/61.1% through pre-thermal reduction under H2 flow, as revealed by X-ray photoelectron spectroscopy, temperature-programmed reduction, and in situ diffuse reflectance infrared Fourier transform spectroscopy analyses. The cataltyic activity of 1% Pt@Ti3C2-R against benzene was assessed under the control of the key process variables (e.g., catalyst mass, flow rate, benzene concentration, relative humidity, and time-on-stream) to help optimize the oxidation reaction process. The results provide new insights into the use of platinum-based 2D MXene catalysts for low-temperature oxidative removal of benzene from the air.

Biological Evaluation of Isosteric Applicability of 1,3-Substituted Cuneanes as m-Substituted Benzenes Enabled by Selective Isomerization of 1,4-Substituted Cubanes.

We herein evaluate a biological applicability of 1,3-substituted cuneanes as an isostere of m-substituted benzenes based on its structural similarity. An investigation of a method to obtain 1,3-substituted cuneanes by selective isomerization of 1,4-substituted cubanes enables this attempt by giving a key synthetic step to obtain a cuneane analogs of pharmaceuticals having m-substituted benzene moiety. Biological evaluation of the synthesized analogs and in silico study of the obtained result revealed a potential usage of cuneane skeleton in medicinal chemistry.