Aromatic Lactones Research Articles

Achieving stable organic solar cells with 19.2 % efficiency via fine interpenetrating network with fused-ring aromatic lactone donor

The ternary strategy has enhanced the power conversion efficiency (PCE) of organic solar cells. However, long-term stability remains a challenge due to heat-induced molecular interactions and excessive self-aggregation. The fused-ring aromatic lactone (FAL) unit, with its extended molecular plane and electron-withdrawing ability, acts as an ideal building block in our newly designed donor P35. By introducing P35 into PM6:L8-BO systems, it optimizes film morphology and enhances π-π stacking, facilitating phase separation and balancing charge transport channels. The electron-withdrawing capability of P35 lowers the HOMO levels, thereby decreasing non-radiative recombination. Additionally, the extended molecular plane of P35 provides structural support to prevent the collapse of fiber-like PM6 and crosslinks with PM6 to form a thermodynamically stable interpenetrating network. This effectively limits the formation of isolated SMA islands, thereby minimizing the degeneration of the active layer. Consequently, an optimized PCE of 19.2 % (certified 18.55 %) is achieved in the PM6:P35:L8-BO devices, which still retains 80 % initial PCE under 600 h of AM 1.5 G illumination and 90 % PCE after 950 h storage in darkness. This research emphasizes the importance of electron-withdrawing capabilities and extended molecular planes in achieving long-term stability and high efficiency.

Flavouring Group Evaluation 80, Revision 2 (FGE.80Rev2): Consideration of alicyclic, alicyclic-fused and aromatic-fused ring lactones evaluated by the JECFA (61st and 82nd meetings) structurally related to an aromatic lactone evaluated in FGE.27.

The EFSA Panel on Food Additives and Flavourings was requested to evaluate 14 flavouring substances assigned to the Flavouring Group Evaluation 80 (FGE.80), using the Procedure as outlined in the Commission Regulation (EC) No 1565/2000. Thirteen substances have already been considered in FGE.80 and its revision and in FGE.96 [FL-no: 10.005, 10.024, 10.025, 10.050, 10.061, 10.069, 10.070, 10.072, 10.169, 13.009, 13.012, 13.161 and 16.055]. The remaining flavouring substance 3a,4,5,7a-tetrahydro-3,6-dimethylbenzofuran-2(3H)-one [FL-no: 10.057] has been cleared with respect to genotoxicity in FGE.217Rev3 and it is considered in this revision 2 of FGE.80. The substance [FL-no: 10.057] was evaluated through a stepwise approach that integrates information on the structure-activity relationships, intake from current uses, threshold of toxicological concern (TTC) and available data on metabolism and toxicity. The Panel concluded that [FL-no: 10.057] does not give rise to safety concerns at its levels of dietary intake, when estimated on the basis of the 'Maximised Survey-derived Daily Intake' (MSDI) approach. Besides the safety assessment of the flavouring substance, the specifications for the material of commerce have also been considered and the information provided was complete for [FL-no: 10.057]. However, for the flavouring substance [FL-no: 10.057] in the present revision and for eight substances evaluated in previous revisions, the 'modified Theoretical Added Maximum Daily Intakes' (mTAMDIs) values are above the TTC for their structural class (III). For four substances previously evaluated in FGE.80Rev1 and in FGE.96, use levels are still needed to calculate the mTAMDI estimates. Therefore, in total for 13 flavouring substances, data on uses and use levels should be provided to finalise their safety evaluations. For [FL-no: 10.050, 10.069 and 13.161], information on the composition of stereoisomeric mixtures is needed.

A broad specificity β-propeller enzyme from Rhodopseudomonas palustris that hydrolyzes many lactones including γ-valerolactone

Lactones are prevalent in biological and industrial settings, yet there is a lack of information regarding enzymes used to metabolize these compounds. One compound, γ-valerolactone (GVL), is used as a solvent to dissolve plant cell walls into sugars and aromatic molecules for subsequent microbial conversion to fuels and chemicals. Despite the promise of GVL as a renewable solvent for biomass deconstruction, residual GVL can be toxic to microbial fermentation. Here, we identified a Ca2+-dependent enzyme from Rhodopseudomonas palustris (Rpa3624) and showed that it can hydrolyze aliphatic and aromatic lactones and esters, including GVL. Maximum-likelihood phylogenetic analysis of other related lactonases with experimentally determined substrate preferences shows that Rpa3624 separates by sequence motifs into a subclade with preference for hydrophobic substrates. Additionally, we solved crystal structures of this β-propeller enzyme separately with either phosphate, an inhibitor, or a mixture of GVL and products to define an active site where calcium-bound water and calcium-bound aspartic and glutamic acid residues make close contact with substrate and product. Our kinetic characterization of WT and mutant enzymes combined with structural insights inform a reaction mechanism that centers around activation of a calcium-bound water molecule promoted by general base catalysis and close contacts with substrate and a potential intermediate. Similarity of Rpa3624 with other β-propeller lactonases suggests this mechanism may be relevant for other members of this emerging class of versatile catalysts.

Intermediates formed during natural attenuation of C9 aromatics under simulated marine conditions: Identification, transformation pathway, and toxicity to microalgae

C9 aromatics — benzene hydrocarbon containing nine carbon atoms among — leakage accident has caused serious damage to the marine ecology near Quangang District, Fujian Province, China. The ecological restoration of the accident sea area is basically realized through natural attenuation. To determine whether the natural attenuation of C9 aromatics in the marine environment will generate highly toxic intermediates, and thus cause more serious harm to marine ecology, the intermediates of C9 aromatics (n-propylbenzene, isopropylbenzene, 2-ethyltoluene, 3-ethyltoluene, 4-ethyltoluene, 1,2,3-trimethylbenzene, 1,2,4-trimethylbenzene, 1,3,5-trimethylbenzene, and indene) in the process of natural attenuation were studied under the marine conditions simulated by a microcosm. The acute toxic effects of 12 intermediates with longer residual time on Phaeodactylum tricornutum were also ascertained. Twenty natural attenuation intermediates of C9 aromatics were identified. These products primarily include the derivatives of phenols, aromatic alcohols, aromatic aldehydes, aromatic ketones, and aromatic acids, as well as an aromatic lactone compound. No intermediates of 1,3,5-trimethylbenzene and indene during the attenuation process were determined. The indirect photooxidation initiated by hydroxyl radical might play an essential role in the formation of intermediates of C9 aromatic. Based on the 96-h EC50 values for P. tricornutum, the toxicity of the 12 intermediates, in descending order, was: 4-ethylphenol, 2-methylacetophenone, 2,3-dimethylbenzyl alcohol, 4-methylacetophenone, 3-methylacetophenone, 1-phenyl-1-propanol, 1-(2-methylphenyl) ethanol, 2-phenyl-2-propanol, 3,4-dimethylbenzoic acid, 2,4-dimethylbenzoic acid, 2,5-dimethylbenzoic acid, then 4-tolylacetic acid. The 96-h EC50 values of the intermediates of C9 aromatics to P. tricornutum ranged from 8.4 to 199.1 mg/L, which were lower than that of their corresponding parent compound. The findings provided essential fundamental insights for the assessment of marine environmental risk of C9 aromatics leakage accidents, and subsequent emergency disposal countermeasures.

Muriolide, a novel antioxidant lactone from Ranunculus muricatus

Muriolide (1), a new aromatic lactone, has been isolated from the ethyl acetate fraction of Ranunculus muricatus. The compound was structurally characterized with the help of UV, IR, mass, 1D- and 2D-NMR data. It was tested in vitro for antioxidant and lipoxygenase inhibitory potential. Compound 1 showed good DPPH radical scavenging activity (IC50=56.9 μM), however it was moderately active against lipoxygenase enzyme (IC50=68.3 μM).

Nucleophilic Addition Reaction with Dearomatization of Naphthalene Ring.

Various aromatic lactones have been synthesized and their regioselectivity (1,2-addition vs. 1,4- or 1,6-addition) investigated in reactions with organolithium species, particularly n-BuLi and sec-BuLi. The regioselectivity varied greatly depending on various factors, such as the bulkiness of both substrates and organolithium species, and types of solvent and cosolvent. In particular, 1,4-addition with dearomatization occurred preferentially using sec-BuLi as the nucleophile in tetrahydrofuran (THF) with hexamethylphosphoramide (HMPA) or N,N'-dimethylpropyleneurea (DMPU) as cosolvent. For sec-BuLi, the reaction was estimated to proceed through a single-electron transfer mechanism.

A New Dichlorinated Aromatic Lactone from the Tin Mine Tailings-Derived Fungus Torula sp. YIM DT 10072

One rare dichlorinated aromatic lactone was isolated from the tin mine tailings-derived fungus Torula sp. YIM DT 10072. Its structure was determined by detailed analysis of spectroscopic data including 1H NMR, 13C NMR, 2D NMR, and HR-FAB-MS. The compound showed antibacterial activity against Staphylococcus aureus with MIC value of 64 μg/mL.

Electrochemical C-O Bond Formation: Facile Access to Aromatic Lactones.

An efficient and robust methodology based on electrochemical techniques for the direct synthesis of aromatic lactones through dehydrogenative C-O cyclization is described. This new and useful electrochemical reaction can tolerate a variety of functional groups, and is scalable to 100 g under mild conditions. Remarkably, heterocycle-containing substrates can be employed, thus expanding the scope of radical C-O cyclization reactions.

New aromatic lactone derivatives with inhibitory activities on nitric oxide production from Homalium stenophyllum

Two new aromatic lactone derivatives, homastenones A (1) and B (2), together with six known compounds (3–8), were isolated from the stems of Homalium stenophyllum. Their structures were established on the basis of extensive spectroscopic analyses. Among them, homastenones A (1) and B (2) are two novel aromatic lactone derivatives containing 12 carbon atoms on the carbon skeleton, and the known compounds (3–8) were isolated from this plant for the first time. All new compounds were evaluated for their inhibitory activities on nitric oxide (NO) production induced by lipopolysaccharide in mouse macrophage RAW 264.7 cells in vitro. Compounds 1 and 2 exhibited inhibitory activities with IC50 values of 12.25 ± 0.45 and 25.36 ± 1.65 μM, respectively.

Decarboxylation of α,β-unsaturated aromatic lactones: synthesis ofE-ortho-hydroxystilbenes from 3-arylcoumarins or isoaurones

A simple and eco-friendly strategy for the synthesis ofE-ortho-hydroxystilbenes from two kinds of α,β-unsaturated aromatic lactones is described.

Recent Advances on Bioactive Constituents in Ferula.

Preclinical Research The genus Ferula (Umbelliferea) is widely distributed across Central Asia and the Mediterranean. Some plants of the genus Ferula have been used as sources of pharmaceuticals for centuries. Ferula is a rich source of biologically active compounds, including coumarin derivatives, sesquiterpene-substituted compounds, daucane esters, humulane, and germacrane compounds, aromatic lactones and disulfide compounds. Therefore, utilizing these bioactive constituents with antimicrobial and insecticidal effects not only can provide a new strategy for developing drug and green pesticide, but also protect endangered plant resources. In the present review, research advances on the bioactive constituents of the genus Ferula the plant sources. Drug Dev Res 78 : 321-331, 2017. © 2017 Wiley Periodicals, Inc.

Volatile and key odourant compounds of Turkish Berberis crataegina fruit using GC-MS-Olfactometry

This research was conducted to identify the aroma and aroma-active compounds of Berberis crataegina for the first time. Volatile profile of B. crataegina was obtained using the purge and trap extraction method with dichloromethane. Gas chromatography was coupled to mass spectrometry (GC–MS) allowed the quantitative and qualitative detection of 22 compounds in the sample. Aldehydes were the main chemical group in the sample and followed by aromatic alcohols and lactone. Aroma extract dilution analysis was implemented for the specification of key odourants of B. crataegina. In total, eight key odourants were detected in the extract of the sample, using GC–MS–Olfactometry and aldehydes were the leading chemical group. The key odourants, found to be contributing to the overall aroma in B. crataegina, were nonanal (FD = 1024; green, flowery), hexanal (FD = 512; green) and linalool (FD = 256; flowery, rose) because of high FD factors.

In vitro inhibition effect of some coumarin compounds on purified human serum paraoxonase 1 (PON1)

Human serum paraoxonase 1 (PON1; EC 3.1.8.1) is a high-density lipoprotein associated, calcium-dependent enzyme that hydrolyses aromatic esters, organophosphates and lactones and can protect the low-density lipoprotein against oxidation. In this study, in vitro effect of some hydroxy and dihydroxy ionic coumarin derivatives (1–20) on purified PON1 activity was investigated. Among these compounds, derivatives 11–20 are water soluble. In investigated compounds, compounds 6 and 13 were found the most active (IC50 = 35 and 34 µM) for PON1, respectively. The present study has demonstrated that PON1 activity is very highly sensitive to studied coumarin derivatives.

Discovery of a series of aromatic lactones as ALDH1/2-directed inhibitors

In humans, the aldehyde dehydrogenase superfamily consists of 19 isoenzymes which mostly catalyze the NAD(P)+-dependent oxidation of aldehydes. Many of these isoenzymes have overlapping substrate specificities and therefore their potential physiological functions may overlap. Thus the development of new isoenzyme-selective probes would be able to better delineate the function of a single isoenzyme and its individual contribution to the metabolism of a particular substrate. This specific study was designed to find a novel modulator of ALDH2, a mitochondrial ALDH isoenzyme most well-known for its role in acetaldehyde oxidation. 53 compounds were initially identified to modulate the activity of ALDH2 by a high-throughput esterase screen from a library of 63,000 compounds. Of these initial 53 compounds, 12 were found to also modulate the oxidation of propionaldehyde by ALDH2. Single concentration measurements at 10μM compound were performed using ALDH1A1, ALDH1A2, ALDH1A3, ALDH2, ALDH1B1, ALDH3A1, ALDH4A1, and/or ALDH5A1 to determine the selectivity of these 12 compounds toward ALDH2. Four of the twelve compounds shared an aromatic lactone structure and were found to be potent inhibitors of the ALDH1/2 isoenzymes, but have no inhibitory effect on ALDH3A1, ALDH4A1 or ALDH5A1. Two of the aromatic lactones show selectivity within the ALDH1/2 class, and one appears to be selective for ALDH2 compared to all other isoenzymes tested.

Isolation and Identification of Two Novel Condensed Aromatic Lactones from Zhundong Subbituminous Coal

Zhundong subbituminous coal was extracted with isometric carbon disulfide (CDS) and acetone mixed solvent (IMCDSAMS) to obtain the extract (EM). EM was fractionated with petroleum ether (PE), CDS, methanol, acetone, IMCDSAMS, and tetrahydrofuran to obtain the sub-extracts 1–6 (ES1–ES6), respectively. ES2 was sequentially eluted with PE and 30, 50, and 70% CDS/PE mixed solvents through a silica-gel-packed column to obtain eluted fractions 1–4 (EF1–EF4). A series of condensed aromatic lactones (CALs) were detected in EF4. Among them, 5H-phenanthro[1,10,9-cde]chromen-5-one and 4H-benzo[5,10]anthra[1,9,8-cdef]chromen-4-one were further isolated as nearly pure compounds by gelatin column chromatography and identified by gas chromatography/mass spectrometry, atmospheric solid analysis probe/time-of-flight mass spectrometry, Fourier transform infrared spectrometry, 1H nuclear magnetic resonance spectrometry, and 1H–1H correlation spectrometry. Main fragmental ions in the mass spectrum of each CAL are formed by successive losses of m/z 28 (CO) and 29 (−CHO) from the molecular ion. An effective way to isolate CALs from low-rank coals was provided in this paper.

Intramolecular hydrogen bond in biologically active o-carbonyl hydroquinones.

Intramolecular hydrogen bonds (IHBs) play a central role in the molecular structure, chemical reactivity and interactions of biologically active molecules. Here, we study the IHBs of seven related o-carbonyl hydroquinones and one structurally-related aromatic lactone, some of which have shown anticancer and antioxidant activity. Experimental NMR data were correlated with theoretical calculations at the DFT and ab initio levels. Natural bond orbital (NBO) and molecular electrostatic potential (MEP) calculations were used to study the electronic characteristics of these IHB. As expected, our results show that NBO calculations are better than MEP to describe the strength of the IHBs. NBO energies (∆Eij(2)) show that the main contributions to energy stabilization correspond to LP→σ* interactions for IHBs, O1…O2-H2 and the delocalization LP→π* for O2-C2 = Cα(β). For the O1…O2-H2 interaction, the values of ∆Eij(2) can be attributed to the difference in the overlap ability between orbitals i and j (Fij), instead of the energy difference between them. The large energy for the LP O2→π* C2 = Cα(β) interaction in the compounds 9-Hydroxy-5-oxo-4,8, 8-trimethyl-l,9(8H)-anthracenecarbolactone (VIII) and 9,10-dihydroxy-4,4-dimethylanthracen-1(4H)-one (VII) (55.49 and 60.70 kcal/mol, respectively) when compared with the remaining molecules (all less than 50 kcal/mol), suggests that the IHBs in VIII and VII are strongly resonance assisted.

Enrichment of oxygen-containing aromatics in an extract from Zhundong subbituminous coal

Zhundong subbituminous coal (ZSBC) was exhaustively extracted with isometric carbon disulfide (CDS)/acetone mixed solvent to afford extract 1 (E 1 ), which was sequentially extracted with petroleum ether (PE) and CDS to afford extracts 2 (E 2 ) and 3 (E 3 ). E 3 was gradiently eluted into effluent portions 1 to 5 (EPs 1 to 5) through a silica gel-packed column sequentially with PE, CDS/PE mixed solvents with volume ratio of 3:7, 1:1 and 7:3, and CDS. According to analysis with a gas chromatography/mass spectrometer, in total, 22 alkyl phenyl carbonates were enriched into EP 3 , and anthraquinone and its two derivatives, nine polycyclic aromatic ketones and two polycyclic aromatic lactones into EP 4 . Most of the oxygen-containing aromatics are value-added chemicals.

Scientific Opinion on the safety and efficacy of alicyclic and aromatic lactones (chemical group 11) when used as flavourings for all animal species

The flavour compounds 3-propylidenephthalide, 3-butylidenephthalide and 3,4-dihydrocoumarin belong to chemical group 11, defined as “alicyclic and aromatic lactones”. All three additives are currently authorised for use as flavours in food. The FEEDAP Panel was unable to perform an assessment of 3-butylidenephtalide because of the absence of data on the purity of the compound. The proposed use of 1 to 5 mg 3,4-dihydrocoumarin/kg complete feed was considered safe for all animal species with a margin of safety in the range from 5 to 18 fold. For 3-propylidenephthalide, the maximum safe level in feed would allow a use level of 1 mg/kg complete feed for all species with a margin of safety ranging from 1 to 2.5. Safe concentrations should be appropriately reduced if used in water for drinking. The narrow margin of safety would not allow the simultaneous administration of 3-propylidenephthalide in feed and water for drinking. No safety concern would arise for the consumer from the use of 3-propylidenephthalide and 3,4-dihydrocoumarin in animal nutrition. The material safety data sheets provided by the suppliers identified both compounds as irritant to skin, eye and the respiratory tract and harmful if swallowed. In addition 3,4-dihydrocoumarin has been shown to be a skin sensitizer. Based on QSAR modelling, 3,4-dihydrocoumarin and 3-propylidenephthalide at a dose of 5 and 1 mg/kg complete feed, respectively, are not expected to pose a risk to the environment. Since 3-propylidenephthalide and 3,4-dihydrocoumarin are used in food as flavourings, and their function in feed is essentially the same as that in food no further demonstration of efficacy was considered necessary.

Catalytic Versatility and Backups in Enzyme Active Sites: The Case of Serum Paraoxonase 1

The origins of enzyme specificity are well established. However, the molecular details underlying the ability of a single active site to promiscuously bind different substrates and catalyze different reactions remain largely unknown. To better understand the molecular basis of enzyme promiscuity, we studied the mammalian serum paraoxonase 1 (PON1) whose native substrates are lipophilic lactones. We describe the crystal structures of PON1 at a catalytically relevant pH and of its complex with a lactone analogue. The various PON1 structures and the analysis of active-site mutants guided the generation of docking models of the various substrates and their reaction intermediates. The models suggest that promiscuity is driven by coincidental overlaps between the reactive intermediate for the native lactonase reaction and the ground and/or intermediate states of the promiscuous reactions. This overlap is also enabled by different active-site conformations: the lactonase activity utilizes one active-site conformation whereas the promiscuous phosphotriesterase activity utilizes another. The hydrolysis of phosphotriesters, and of the aromatic lactone dihydrocoumarin, is also driven by an alternative catalytic mode that uses only a subset of the active-site residues utilized for lactone hydrolysis. Indeed, PON1's active site shows a remarkable level of networking and versatility whereby multiple residues share the same task and individual active-site residues perform multiple tasks (e.g., binding the catalytic calcium and activating the hydrolytic water). Overall, the coexistence of multiple conformations and alternative catalytic modes within the same active site underlines PON1's promiscuity and evolutionary potential.

Two Unusual Phenolic Substances and One New Xanthone from Hypericum sampsonii

AbstractSampsone A (1), a novel prenylated aromatic lactone, and sampsone B (2), an unusual dihydrodibenzodioxinone, together with sampsone C (3), a new xanthone, were isolated from the aerial parts of Hypericum sampsonii. Their structures were determined by spectroscopic methods which were mainly 1D‐ and 2D‐NMR techniques, and the structure of sampsone B (2) was also confirmed by X‐ray crystallographic analysis. All of these compounds were evaluated for in vitro antibacterial activity against methicillin‐resistant Staphylococcus aureus (MRSA). Only sampsone A showed moderate antibacterial activities at a minimum inhibitory concentration (MIC) of 32 μg/ml.