The present study underlines that the gas-phasereactivity of IBAP with •OH is faster, comparedto the likely kinetics of volatilization from aqueous systems. Therefore,it might prove very difficult to detect gas-phase IBAP. Nevertheless,up to 60% of IBAP occurring in a deep and dissolved organic carbon-richwater body might be eliminated via volatilizationand subsequent reaction with gas-phase •OH. Thepresent study suggests that the gas-phase chemistry of semi-volatileorganic compounds which, like IBAP, initially occur in natural waterbodies in contact with the atmosphere is potentially very importantin some environmental conditions.Partitioning betweensurface waters and the atmosphere is an importantprocess, influencing the fate and transport of semi-volatile contaminants.In this work, a simple methodology that combines experimental dataand modeling was used to investigate the degradation of a semi-volatilepollutant in a two-phase system (surface water + atmosphere). 4-Isobutylacetophenone(IBAP) was chosen as a model contaminant; IBAP is a toxic transformationproduct of the non-steroidal, anti-inflammatory drug ibuprofen. Here,we show that the atmospheric behavior of IBAP would mainly be characterizedby reaction with  Thispaper addresses the environmental fate of semi-volatileand toxic 4-isobutylacetophenone in a coupled water−atmospheresystem, showing that volatilization followed by gas-phase degradationcannot be neglected. The self-cleaning abilityof the atmosphere can be largely explained by physico-chemical processes,including the chemical degradation of pollutants by oxidative reactivespecies  were measured, relative to three different referencecompounds: DME, with kg(DME + •OH) = 2.83 × 10–12 cm3 molecule–1 s–1;34 cyclohexane (CyHex), with kg(CyHex + •OH) = 6.38 × 10–12 cm3 molecule–1 s–1;35 and p-Bq, with kg(p-Bq + •OH) = 4.60 ×10–12 cm3 molecule–1 s–1.36 During kineticinvestigations, gas-phase processes inside the reaction vessel wereas followst–t0, one gets kg(IBAP + •OH)/kg(ref + •OH) and, because kg(ref + •OH) is known, one also getsthe second-order rate constant for the reaction between IBAP and •OH, kg(IBAP + •OH).Gas-phase reaction rate constants of IBAP with kg(WL) = (3.1 ± 0.4) × 10–4 s–1 (uncertainties here represent ±2σ).Over an irradiation time of 15 min, photolysis at 365 nm was not observedfor IBAP or the reference compounds. At 254 nm, significant photolysiswas observed for IBAP in ESC-Q-UAIC, with an estimated first-orderrate constant of (7.5 ± 0.4) × 10–4 s–1. The photolysis rate constant was obtained from theIBAP decay, after correction for the wall-loss process as shown inFigure S1 of the Supporting Information. Because of important IBAP photolysis at 254 nm, 254 nm H2O2 photolysis could not be used as an in situ•OH radical source. Therefore, ozonolysis of TMEin the dark was a good alternative to generate •OH radicals in the reactor under NOx-freeconditions.Preliminary tests performed in theESC-Q-UAICchamber showed thatIBAP exhibited wall loss, with a first-order rate constant 3 and •NO3. None of theperformed tests indicated contributions from other processes, apartfrom wall loss, which excludes significant reactivity between IBAPand •NO3 or O3.Test experiments were also performed in the ESC-Q-UAICsmog chamberto preliminarily check for the gas-phase behavior of IBAP in the presenceof O•OH radicals.37 TME is known as an important •OH precursor, with a yield (Y) closeto unity.38 By considering the amount of ozone occurringin the reactor, the •OH radical concentration canbe estimated as follows39Thereaction of ozone with alkenes produces 8 radicals cm–3 can be estimated forthe •OH radicals,taking into account the recommended values of the reaction rate constantsof TME + •OH, kg(TME+ •OH) = 1.1 × 10–10 cm3 molecule–1 s–1; TME +O3, kg(TME + O3)= 1.1 × 10–15 cm3 molecule–1 s–1;34 and the ozoneconcentration range of (2.46–4.92) × 1013 moleculecm–3.Concentrations as high as 4 ×1045 A significant fraction of photodegraded IBPis accounted for by IBAP,41 which is initiallyformed in aqueous solution (IBAPw). IBAP can then undergoeither water-phase photodegradation or partitioning to the gas phase,where it is mostly degraded by •OH(g) as mentioned before.The overall two-phasereaction pathways involving IBP and IBAP are depicted in w, IBAPw, and IBAPg,where [IBPw]o is the initial concentration ofIBP in aqueous solution42kd is thefirst-order degradation rate constant of IBP in water, kd′ thatof IBAP, kf the formation rate constantof IBAP from IBP, and kvol the volatilizationrate constant of IBAP. The quantity f = kfkd–1 is the fraction of IBPw that is transformed into IBAPw, and From the reactions given in kf, kd, and kd′ weremodeled with the APEX software.43 APEXcan model the direct and indirect photochemistryof pollutants in well-mixed surface waters, such as the whole watercolumn of lakes during overturn, the lake epilimnion during summerstratification, and even shallow systems like flooded rice fields.44 APEX modeling requires knowledge of key environmentalfeatures of the water body and of photoreactivity parameters of the pollutant(s) under consideration.The latter include direct photolysis quantum yields, second-orderrate constants for the reactions with the different PPRIs , and, for IBAPas an intermediate, formation yields from IBP in the different reactionpathways.The values of 45 and are summarizedin These parameters have been measured experimentallyin previouswork, for each photoreaction pathway,•OH (kg) wasderived from experimental reactivity data (see previous section) asthe second-order reaction rate constant between IBAP(g) and •OH(g) [kg(IBAP + •OH)] times the typical, 24 h averagedvalues of [•OH(g)]. In particular,The pseudo-first-order reaction rate constant betweenIBAP andgas-phase kvol) was determined with EPISuite46 using a quantitative structure–activityrelationship (SAR) approach. The volatilization model followed themethod described by Thomas (1990),47 assumingrelatively calm wind conditions (0.5 m s–1 velocity).The volatilization rate constant ofIBAP from aqueous environments(Supporting Information) suggeststhat this approach works better than one based on gas–waterpartitioning equilibrium (Henry’s law), which holds only ifvolatilization is much faster than degradation in water. In the caseof IBAP, the two processes have comparable kinetics (videsupra), and the present approach based on first-order kinetics,without partitioning equilibrium, is to be preferred.Text S1 ,while in the absence of NOx, only tworeference compounds (DME and CyHex) were used. The slopes of the experimentallines provide the ratios of IBAP reaction rate constant versus referencerate constant  showsthe relative kinetic plots obtained for the •OHreactions with CyHex and p-BQ, with DME as the referencecompound. This control test showed that the ratios between the rateconstants for the reactions between CyHex and •OHand p-Bq and •OH, measured relativeto DME, are 1.95 ± 0.23 and 1.73 ± 0.12, respectively, ingood agreement  with literaturedata .36constant 4.In bot•OH-initiated degradationof IBAP in the gas phase, are presented in Supporting Information. Figure S3 (Supporting Information) shows a typical time evolution profile of the IBAP concentrationand of the concentration (in terms of mass and particle number) ofthe secondary organic aerosol (SOA) formed under •OH/NOx photo-oxidation. Additional results, from the Supporting Information) underlinesthe secondary nature of the detected particles. From these experiments,we concluded that 5% of the total consumed carbon from gas-phase IBAPcould be found in the form of SOA. These results show that IBAP haspotential as a possible SOA precursor, upon reaction with •OH in the gas phase. However, this datum should be considered withcaution, and other experiments are needed to completely elucidatethe connection between IBAP degradation in the gas phase and SOA formation.Figure S4 /kg(ref), represent ±σ,obtained from linear regression analysis. The errors for the individual kg(IBAP) rate constants include an additionaluncertainty of 10%, propagated from the recommended kg(ref + •OH) values.The list of the kinetic values determined within the present studyfor the IBAP reaction with x, the rate constantvalue for the reaction between IBAP and •OH is (4.67± 0.36) × 10–12 cm3 molecule–1 s–1, if estimated as the weightedaverage of kg(IBAP + •OH) . Thelower rate coefficient value of (2.91 ± 0.28) × 10–12 cm3 molecule–1 s–1 was estimated for the reaction of IBAP with •OHin the absence of NOx. No literature datumis available for comparison unfortunately. As a reference for comparison, kg(IBAP + •OH), together with the mean lifetime of IBAP in the atmosphere, dueto •OH reactions. The SAR estimates were calculatedby using the approach exploited in EPISuite–AOPWIN software,as proposed in Calvert et al.,48 as well as in Jenkin et al. .In the presence of NOin et al. The EPISOH(IBAP), wasdetermined using •OH]= 1.13 × 106 radicals cm–3.51 From this •OH concentrationvalue, one gets that 2–3 days would be required to decreasethe atmospheric concentration of IBAP by an exponential factor . Due to quite fast reactionkinetics in the gas phase, IBAP can be considered as a local pollutant,the availability of which is spatially bounded to its main sources.The atmospheric lifetime of IBAP,τx. Although the rateconstants are similar, the value measured in the absence of NOx is significantly lower. On the one hand,in the presence of NOx, the experimentalconditions inside the smog chamber are such that IBAP reactivity mightbe enhanced by reaction with peroxy radicals, formed from the hydrogenabstraction channel from alkylic carbon, followed by reaction withO2.52 On the other hand, concerningthe NOx-free conditions, only very fewstudies report on the use of the reaction of TME with ozone as the •OH radical source.53 TMEhas high reactivity toward •OH, which introducesa limitation to the use of this •OH source in reactionswith rate constants higher than 10–12 cm3 molecule–1 s–1. For furtherdiscussion, we consider the rate coefficient obtained with the highestNOx concentrations, which could representa lower limit for the gas-phase persistence of IBAP.A difference of about 37% was observedbetween the IBAP rate constantswith and without NO•OH. In theliterature, gas-phase rate constants can be found for a similar compound,4-methylacetophenone (MAP).54 MAP has arate constant of about (4.50 ± 0.43) × 10–12 cm3 molecule–1 s–1,54 which almost overlaps with the rateconstants determined here for IBAP. MAP has been studied with a relativerate method, in the presence of NOx, usingthe 365 nm photolysis of a CH3ONO/NO mixture as the •OH radical source. This similar rate constant can berelated to the structural similarity of MAP and IBAP, which both havea deactivated aromatic ring due to the presence of the keto group.To ourbest knowledge, this is the first study that evaluates thegas-phase rate constant of IBAP with kg(toluene+ •OH) = (5.6 ± 1.46) × 10–12 cm3 molecule–1 s–1, and cumene, with kg(cumene + •OH) = (6.3 ± 1.89) × 10–12 cm3 molecule–1 s–1.34 These compounds have slightly higher rate constants comparedwith IBAP and MAP, probably because their respective para positionsare available for possible •OH attack. Furthermore,hydrogen abstraction from different aliphatic substituents may bethe cause of further reactivity differences between IBAP and MAP.As a comparison with the IBAP–MAP pair, we could also comparethe reactivity of toluene, with et al.,48 EPISuite–AOPWIN,34 and Jenkin et al. orienting in a meta position,which should have a positive value and decrease Σ(σ+) in the expression of the addition channel: log(k) = −11.71 – 1.34 × Σ(σ+).48 Moreover, these two estimated SARvalues predict that both •OH-addition and H-atomabstraction channels have similar contributions (∼50–50%).The third estimate was obtained by applying the model developed byJenkin et al.. By using the experimentallymeasured kg(IBAP + •OH) = 4.7 × 10–12 cm3 molecules–1 s–1 and assuming a 24 h averaged[•OH(g)] = 1.13 × 106 molecules cm–3,46 we got kg = 5.3 × 10–6 s–1 = 0.46 day–1. The photoreactionparameters for natural waters were obtained by photochemical modelingwith the APEX software, which were (see kd); (ii) the formationrate constant of IBAP from IBP (kf), aswell as (iii) the overall photodegradation rate constant of IBAP (kd′). APEX has been able to correctly predict the attenuation kineticsof IBP in natural waters.45The volatilizationrate constant of IBAPfrom an aqueous environment to the gas phase was assessed as were see 1 as follkf, kd, and kd′ as a functionof environmental parameters such as, most notably, water depth, DOC,and the concentration values of nitrate and nitrite.WithAPEX, we computed the reaction rate constants (i)d = 1 m) with high nitrate (10–4 M) and nitrite(10–6 M) (“fast kinetics” scenario),for which low-DOC conditions were additionally considered (1 mgC L–1);shallow waters ((ii)d =10 m) with low nitrate (10–6 M) and nitrite (10–8 M) (“slow kinetics” scenario), plushigh-DOC conditions (10 mgC L–1).deep waters . Moreover, Figure S6 reports IBAP yield from IBP [y(IBP → IBAP)]. Depending on conditions, y(IBP → IBAP) = kf(kd)−1 = 0.18–0.26.In addition to these extreme cases 4, there In the “fast kinetics” scenario 4c,d, fas•OH scavenging and induces quenching ofthe direct photolysisof IBP, IBAP, nitrate, and nitrite (the latter two as •OH sources), which all compete with CDOM for sunlight irradiance.Moreover, high DOC (and high CDOM as a consequence)enhances •OH and 3CDOM*. Furthermore,direct photolysis and 3CDOM* are also involved in the formationof IBAP from IBP. Although •OH is important in bothIBP and IBAP degradation, it plays a minor role in IBAP formationdue to the low value of •OH(w)] is generally detrimental tothe occurrence of IBAP: in such conditions,IBP degrades fast but with relatively low IBAP production, and IBAPis degraded fast as well. Relatively high [•OH(w)] can, for instance, be attained in the presence of high-concentrationvalues of nitrate and nitrite , which are both photochemical •OH sources.56 At high DOC, where [•OH(w)] is generally low, the 3CDOM* processdominates both IBAP formation and degradation (see IBP and IBAP are mainly degraded by direct photolysis (d.p.) andby reactions with alue of  1. Thereftion see 4. Finallkf would vary from 0.005 day–1  to 0.05 day–1 . Under the same conditions, kd′ would vary from 0.03 to 0.4 day–1, respectively,and kd from 0.02 to 0.3 day–1.Overall, in the different conditions, we foundthat kd = 0.3 day–1, kf = 0.05 day–1, and kd′ = 0.4 day–1 ; (ii) “slow” kinetics, with kd = 0.02 day–1, kf = 0.005 day–1, and kd′ =0.03 day–1 . In all the cases, kvol = 0.052 day–1 and kg = 0.47 day–1. The corresponding time trendsof IBPw, IBAPw, and IBAPg . Therefore, IBP degradationwould also entail disappearance of its toxic transformation intermediateby both volatilization and photodegradation.To transfer these results into the two-phase model depictedin nd IBAPg 6–8 are sv of IBAP that undergoesvolatilizationto the gas phase is inversely proportional to the transformation kineticsof IBAP in aqueous solution: indeed, the longer the IBAPw persists, the more chances it has to volatilize. In particular, v would range from 10% in the “fast kinetics”scenario (•OH(g). Because the reactionIBAP + •OH(g) is fast, the gas-phaselevels of IBAP would always be extremely low, irrespective of the v value.The fraction scenario 5ato 60%scenario 5b. In thFj ofIBAP that is degraded by a given process j  can be expressedas followski = k•OH, k3CDOM*, kd.p., or kvol represents the first-orderrate constants of IBAP removal by the processes that were taken intoaccount here. Overall, the photodegradation routes of IBAP in thetwo scenarios would be the following :(i)x– and low DOC): 45% IBAP would be degraded by direct photolysis inwater, 40% by reaction with •OH(w), 5%by 3CDOM(w)*, and 10% by •OH(g).Fast aqueous-phase kinetics x– andhigh DOC): 60% IBAP would be degraded by reaction with •OH(g), 30% by 3CDOM(w)*, and 5% each by •OH(w) and direct photolysis in water.Slow aqueous-phase kinetics(deepwater with low NOThe fraction •OH(g), cannotbe ignored, especially in the case of deep water bodies with highDOC. Note that d = 10 m could well be the epilimniondepth of a deep lake during the summer season.57 In such a scenario, IBAP volatilization (followed by gas-phasedegradation) is expected to contribute much to IBAP removal from water.Still, gas-phase IBAP degradation is so fast compared to volatilizationthat it would be very unlikely to detect IBAP in the atmosphere.These data suggest that IBAP volatilization to the gasphase, andsubsequent degradation by 3CDOM* (31% IBAP yield), direct photolysis (25%yield) and, with lower importance, •OH reaction(2.3% yield). Once photoproduced, IBAP can undergo photodegradationin water, as well as partition to the gas phase. Interestingly, IBAPwould quickly react with gas-phase •OH, showinghalf-life times of 1.5–2 days that are faster/much faster thanthose in sunlit surface waters. The latter amount to 2–30 daysdepending on conditions such as depth and water chemistry . The combination of relatively slow volatilizationwith quite fast transformation kinetics could hamper detection ofIBAP in the gas phase. Actually, v = kvol/(kvol + k′d).IBAP is formed in sunlitsurfacewaters upon photodegradation ofIBP by v for some European rivers,located in the latitude belt between 40 and 50°N. Details aboutthe modeling procedure are reported in Text S2. It was considered a reasonable 2 m deep water column, while DOCranged from <1 to ∼10 mgC L–1 .58 It is suggested that IBAPvolatilization from surface-water environments to the gas phase ispotentially quite significant as it may approach up to 25% for theconsidered scenarios. Higher values of v were foundin rivers with a relatively high content of (C)DOM (DOC ≥ 7mgC L–1), where IBAP direct photolysiswould be inhibited by CDOM (which absorbs sunlight) and only partiallyoffset by the prevailing 3CDOM* degradation. For lowerDOC values (<5 mgC L–1), faster IBAPphotodegradation would decrease the relative role of volatilization.Interestingly, direct photolysis and 3CDOM* reaction wouldbe comparable for 5 mgC L–1 < DOC< 7 mgC L–1 and, in these conditions,reaction with •OH(w) would account for∼10% IBAP degradation. Variation of the water depth, in therange of 1–3 m, would affect the IBAP fraction undergoing partitioningto the gas phase .•OH and 3CDOM*; ofdiclofenac into 2,6-dichloroaniline by 3CDOM*,59 and of gemfibrozil into 2,5-dimethylphenol bydirect photolysis.60The photochemical transformationof ionizable IBP into semivolatileIBAP might not be a general finding for all contaminants. In severalinstances, the phototransformation products of pollutants are hydroxylatedcompounds and/or molecules bearing a carboxylic function that makesthem less volatile than their parent pollutant. However, there arealso several cases in which a pollutant yields more volatile phototransformationproducts: some examples are the transformation of clofibric acid into4-chlorophenol by


The concise construction of diene scaffolds is quite useful in the synthesis of polyenes. Many diene building blocks have been developed based on Suzuki, Still and Hiyama couplings. Herein, the commercially available and environmentally friendly compound dienedioic acid is used as a diene building block. Broad substrate scope, good functional group tolerance, and late-stage derivatization of complex drug molecules are achieved. Different moieties can be conveniently introduced to both sides. Piperine and the methyl ester of azoxymycin C are each prepared in three steps. Additionally, one product shows promising anticancer activities in leukemia K562 and MV-4-11 cells. Mechanistic studies indicate that the reaction proceeds through a Heck-decarboxylate coupling procedure, and the carboxylic group acts as a directing group to promote the reaction and control regioselectivity. Our research suggests that dienedioic acid can serve as a good alternative for diene preparation via a directed Heck-decarboxylate coupling. E/Z isomerism. Here configurationally stable divinyldicarboxylic acid is used as a coupling reagent in which the carboxylates direct the Heck reaction prior to decarboxylation.Dienes are useful reagents for cross-couplings in the synthesis of unsaturated natural products, but decarboxylative Heck reactions of dienes are limited by facile  Cyclobutenes have also been used to introduce diene scaffolds in a ring-opening fashion8. Albeit such significant progress has been achieved, there is still room for improvement, particularly considering that these well-established building blocks suffer from either being not commercially available or requiring multiple steps to prepare or being toxic. Therefore, additional efforts are worthy to develop novel, economically available, and environment-friendly diene-building blocks , can serve as good complementary diene-building blocks by decarboxylative coupling, particularly considering that it is a commercially available, cost friendly, and bench-stable white solid  the β-selectivity product might dominate the reaction under carboxylate-directed Heck-coupling mechanism; (2) the innate steric and electronic properties of dienedioic acid also favored the β- or γ-selectivity.Although vinyl carboxylic acid has been investigated in decarboxylative couplinga28 Fig. . In addie31 Fig. . AccordiHerein we report that the dienedioic acid can serve as a good complementary building block in diene synthesis, through the directed Pd-catalyzed decarboxylative coupling mechanism. Broad substrate scope, good functional group tolerance, and late-stage functionalization of complex drug molecules are achieved in this reaction Fig. .1–2 and 2–1 were selected as model substrates for condition optimization. Initially, P(tol)3 was selected as ligand according to Heck’s30 and Goossen’s reports25, and luckily the desired product 3–1 was isolated in unsatisfactorily 14% yield . Significant improvements were achieved with bidentate ligands, like dppf and dppe (Table R)-BINAP and XantPhos /methylthio (3–3)/alkyl /aryl /cyclopropyl group (3–5), aldehyde (3–9), nitrone (3–10), as well as ketone . Aryl bromide, chloride, iodide, and trifluoromethanesulfonate worked well in this reaction, affording comparable yields based on the substrates . Generally, the aryl bromides bearing electronically neutral or rich groups afforded better yields compared with those bearing electronically deficient ones. Notably, selective coupling with aryl bromide in the presence of aryl chloride was achieved with dppf as ligand . Steric hindrance was also well tolerated. For example, 2-bromo-1,1’-biphenyl even gave better yield than bromobenzene (3–11 vs. 3–6). 9H-fluorene could afford the desired product 3–16 as well, albeit that possible Michael addition might be involved32. Heteroarenes are frequently encountered in medicinal chemistry, and it is important to develop novel access to their functionalization. Therefore, several heteroaryl bromides were selected and tested in this reaction, including benzofuran (3–20), benzothiophene (3–21), pyridine (3–22), carbazole (3–23), and quinoline (3–24), all of which afforded the desired products as expected. Of note, pyridine (3–19) and isoquinoline (3–24) bearing Lewis basic nitrogen can be well tolerated, although they could coordinate to palladium. However, 2-bromopyridine failed to afford the desired coupling product (3–20).Within the optimized condition at hand, the scope of aryl electrophiles was investigated as summarized in Fig. 3–25) in a two-step sequence. Anti-inflammation drugs tolfenamic acid (3–26) and indomethacin (3–32) also gave coupling products in moderate yield, albeit that they contained an aryl and alkyl carboxylic acid moiety, respectively, demonstrating the high selectivity among vinyl, aryl, and alkyl carboxylate in our approach. Pesticide dimethomorph (3–29) and antihistamine drug loratadine (3–30) bearing alkene motifs, successfully afforded the products as well. The installation of diene moiety on aggregation-induced emission (AIE) material was also proved successful (3–28). Remarkably, even amodiaquine, a drug to cure malaria, containing phenol and amine moieties, worked smoothly in this reaction (3–31).The late-stage functionalization of complex molecules is quite useful in drug discovery and complex molecule synthesis. Given the good functional group tolerance obtained previously, it is reasonable to hypothesize that late-stage installing diene motif via our method should work as well. Indeed, estrone can smoothly afford the desired product , L-valine t-butyl ester (3–36), and β-citronellol (3–35) in the following decarboxylative coupling. Simple benzo ester and amide also afford the desired products . The dienedioic acid 1–2 and bromobenzene can also provide compound 3–6 via first decarboxylative coupling, followed by hydrolysis (3–38). From compound 3–38, various transformations can take place based on the second decarboxylative coupling, like protodecarboxylation (5–1)33, introducing a vinyl moiety (5–2)26, and installing a (hetero)arene motif (5–3). The two (hetero)aryl scaffolds can be installed via a dual coupling as well, affording the 1,4-di(hetero)aryl-buta-1,3-diene .In theory, various coupling partners can be installed on both sides of dienedioic acid either by a two-step sequential or one-step dual-coupling procedure as summarized in Fig. 3–39, particularly taking into account that many possible side reactions can be involved  study, the B ring in DMU-212 can be replaced by a vinyl carboxylate, as shown in compound 3–47 prepared from 3,4,5-trimethoxylbenzyl bromide by this decarboxylative coupling. In all the tested cancer cell lines , compound 3–47 showed comparable inhibition rates as those of DMU-212, except HT29 and HepG2 cells. By contrast, a control compound 3–19 bearing a pyridine motif in the A ring and vinyl ester in the B ring, failed to show any cytotoxicity. Such evident different performances excluded the possibility that they worked only as a Michael acceptor that led to cytotoxicity. Thus, compound 3–47 can be a starting point for anticancer drug discovery, indicating the good potential of our methods in medicinal chemistry try Fig. .Three possible reaction pathways could be involved in this reaction: (1) “Suzuki type”, in which decarboxylation occurred first to form C–M  bond followed by transmetallation and reductive elimination similar to Suzuki coupling Fig. , path a;39, facilitating decarboxylation to form C–Cu/Ag bonds. In our reaction, adding either CuBr or AgOAc failed to promote the reaction, but instead inhibited the reaction. In addition, both substrates 1–1740 and 1–13, in theory, can also afford the desired coupling products, if the reaction followed the “Suzuki type” mechanism. The possible Pd intermediates II-2 and II-3 should be formed similarly as II-1, leading to comparable yields of products. However, significant erosion of efficiency was observed with only 8% and 25% yield of products, respectively  with significantly electronically and sterically different ɑ-/β-positions, bearing one carboxylic group on one side and a methyl group on the other side, was selected as control substrate. To our surprise, the ɑ-selective product 5–10 still dominated the reaction. Sterically and electronically favored β-/δ-selective products  from conventional Heck coupling were not observed. In contrast, under normal Heck-coupling condition, the δ-selective coupling product from sorbic acid was obtained31  bearing similar steric and electronic properties as those of sorbic acid, afforded no ɑ- and β-selective products . Instead, the δ-selective product 5–15 was observed by H-NMR, in consistent with Heck’s discovery42 , no deuteration product was observed when adding D2O, and no intermediate 9–2 was observed from the background experiment; the “Decarboxylation-Heck type” mechanism is less favored, but might be involved in a complex fashion.Since compound  5–11, 5– from con 5–11, 5– from conoducts 5–, 5–14. Id33 Fig. . Taking 1–3 and 2–39 for 6 h, followed by adding MeI to trap possible intermediate 10–125. However, no corresponding product 5–18 derived from 10–2 was detected by H-NMR of crude reaction mixture, except 60% yield of product 3–47  took place to afford catalyst intermediate (VI), followed by ligand coordination from dienedioic acid 2 to afford intermediate VII. The carboxylic acid then directed the insertion step to afford intermediate III, of which both carboxylic acid and another alkene moiety could help stabilize the Pd catalyst by providing the addition coordination effect. The desired diene-containing product 3 was generated after the β-decarboxylative elimination and releasing Pd-catalyst (IV). Meanwhile, the β–H elimination might also be involved to afford intermediate 10 followed by decarboxylation to yield product 3  promote the reaction and (2) control the ɑ-regioselectivity albeit the substrates’ innate electronic and steric properties. Besides, the diene motif also played an important role to promote the reaction. Thus, having identified the importance of both carboxylic acid and diene moieties, the reaction mechanism was proposed as the following. The oxidative insertion of aryl halides of Pd-catalyst  promoting the reaction; (2) controlling the regioselectivity. Further work to utilize the method to application in quick access of biologically important polyenes is under progress in our lab.See Supplementary Methods and Supplementary Figs. See Supplementary Figs. See Supplementary Methods.See Supplementary Methods, Supplementary Figs. Supplementary InformationDescription of Additional Supplementary FilesSupplementary Data 1


Procedure-related life-threatening bleeding occurred in 9 (18%) patients in the “Surgical” group and none in the “Catheter” group, p = 0.018. Nine (18%) patients died in 30 days in the “Surgical” group, and none died in the “Catheter” group, p = 0.039. A mean follow-up was 3.3 years. No difference was found between the groups by the degree of residual paravalvular regurgitation either at discharge or at follow-up. During the follow-up, 19 (39%) patients died in the “Surgical” group and 2 (7%) among the “Catheter” patients. Conclusions: Transapical catheter-based closure of mitral paravalvular leak seems to be a safer treatment procedure than conventional re-do surgery, and the effectiveness of these procedures does not differ.Background: There is a lack of studies where the outcomes of mitral paravalvular leak treatment were compared between surgery and catheter-based closure. The aim of this study was to compare the outcomes of re-do surgery with transapical catheter-based paravalvular leak closure. Methods: This is a retrospective observational study at a single institution; 76 patients were included. According to the treatment, two groups were formed: the “Surgical” group (49 patients after re-do surgery) and the “Catheter” group . Results: In-hospital myocardial infarction occurred in 9 (18%) cases in the “Surgical” group and none in the “Catheter” group,  Repeat surgery with cardiopulmonary bypass has been the only available effective therapy for the treatment of clinically significant PVL, despite high mortality rates associated with perioperative morbidity ,2. The dVilnius Regional Biomedical Research Ethics Committee and State Data Protection Inspectorate have granted approval for this study (protocol number MVPVF2017). The study received no funding. We retrospectively reviewed all patients who underwent conventional redo surgery or transapical catheter-based procedures for mitral PVL treatment from January 2005 until January 2019. An automatic search of the hospital electronic database for the key word “mitral paravalvular leak” was conducted. Eighty-nine patients were identified in this primary search. We excluded patients with active infective prosthetic endocarditis, dehiscence of prosthesis more than one-third of the annulus perimeter and patients who underwent catheter-based closure with an “off label” device from the formal analysis. Following this refined selection, we remained with a cohort of 76 patients. The group of patients who underwent transapical catheter-based closure of mitral PVL was named “Catheter” and consisted of 27 patients, while the other group of patients who underwent conventional re-do surgery for mitral PVL, named “Surgical,” had 49 patients.p < 0.05). Quantitative data, distributed as normal, presented as a mean ± standard deviation. The quantitative continuous data distributed outside the normal distribution are presented as the median and quartile intervals. The categorical data are expressed as percentages. Freedom from moderate or severe residual paravalvular regurgitation, new or worsening hemolysis requiring transfusion, new or worsening prosthesis dysfunction and conversion to open surgery, mortality, stroke, readmission for heart failure or treatment of hemolytic anemia were estimated using the Kaplan–Meier method. The censored data included patients who had follow-up terminated. We considered differences statistically significant when the p value was lower than 0.05.A comparison of the effectiveness and safety of treatment modalities was performed within the framework of “Clinical Trial Principles and Endpoint Definitions for Paravalvular Leaks in Surgical Prosthesis” . PreoperThe procedure was performed in a hybrid operating room (described previously in detail) . In all p = 0.027. The mean perioperative mortality risk according to the European System for Cardiac Operative Risk Evaluation was 6% (4–10%) for the “Catheter” group of patients and 8% (6–11%) for the “Surgical” group. Otherwise, no other differences were found.A detailed description is presented in p = 0.01. Life-threatening or disabling bleeding occurred in 9 (18%) patients in the “Surgical” group, and none among the “Catheter” group (p = 0.01). The “Surgical” patients statistically significantly lost more blood in the first 24 h after surgery. Due to higher postoperative morbidity, patients in the “Surgical” group spent more time in the intensive therapy unit and in hospital. This high early postoperative morbidity among “Surgical” patients led to higher immediate and in-hospital mortality; none of the patients died in the “Catheter” group at early follow-up.Early postoperative data and complications in detail are described in Forty patients (82%) out of 49 were discharged alive from the hospital in the “Surgical” group, while all patients went home from the “Catheter” group. With regard to residual paravalvular regurgitation, we found no difference between the groups; data in detail is presented in p = 0.001). Mortality at follow-up in the “Catheter” group was 8%, and 39% among the “Surgical” cases (p = 0.001). The recurrence of significant paravalvular regurgitation of higher than mild degree did not show any statistical significance. Data in detail are shown in p = 0.636, shown in the central image).Overall, follow-up was available in all discharged patients; the median duration for the “Catheter” group of patients was 2.45 (0.96–3.15) years, while the “Surgical” ones were followed a longer period, 6.3 (2.87–9.3) years  cases.No occluder migration, detachment, fracture, embolization due to thrombosis or endocarditis occurred. Device success was achieved in 23 (85%) patients due to failure to treat severe PVL in one patient, worsening anemia developed in two patients, and one patient had excessive postoperative bleeding requiring surgical revision.p = 0.02) at 30 days after the procedure.All patients were discharged from the hospital. A complete closure of mitral PVL intraoperatively and at discharge  was achieved in 22 (81%) patients, reduction to mild in four (15%) patients; in one patient (4%), the reduction of paravalvular regurgitation was not achieved. The reduction of paravalvular regurgitation to a mild or lesser degree was achieved in 26 (96%) patients. A six-minute walk increased from 264 ± 108 m on admission to 313 ± 120 m   patients treated. Individual patient success at the one-year follow-up was not achieved in five patients. First is the patient in whom we failed to reduce mitral paravalvular regurgitation . Another patient died due to uncontrolled sepsis caused by a hemodialysis catheter . Two patients had worsened anemia. Fifth, a patient suffered severe bleeding from a fractured rib.Access to mitral PVL during catheter-based closure varies depending on the location of the leak or more often on the institution’s chosen preference. A transapical approach in the literature is limited either to case reports or single-center experiences . The eviTo date, only a few papers exist where “Surgical” treatment has been compared to the “Catheter” modality and included 848 patients . UnfortuAlkhouli et al. published a comparison of 195 patients who underwent catheter-based treatment for mitral PVL and 186 cases that had redo surgery . In contTechnical success differs between our and Alkhouli et al. groups of the surgical cohorts 90% versus 95.5%, respectively. Comparison of technical success between our catheter-based patients and the Alkhouli et al. group was higher in our group—96% versus 70.1%. Hospital mortality among patients treated surgically was lower among patients in the Alkhouli et al. group compared to our surgically treated patients, 7.7% versus 18%, respectively. In our catheter-based group of patients had a hospital mortality rate of 0%, while it was 3.1% in Alkhouli et al.Wells et al. compared 58 “Surgical” and 56 “Catheter” patients. Hospital mortality in their “Surgical” arm was 6.9% and in the “Catheter” group—7.1%. Wells et al.’s patients in the catheter-based group stayed shorter at hospital compared to our treated cohort. However, at one year, they found no difference in mortality, readmission or repeat intervention between patients in the “Surgical” and “Catheter” groups [Millán et al. presented outcomes of 163 patients who underwent treatment for mitral PVL surgically or in a catheter-based fashion. In their patients, “Surgical” treatment was applied to 98 patients, and the “Catheter” procedure was performed in 65 cases . In contThis research has several limitations. Firstly, this is a retrospective study of a single center practice, where prospectively enrolled patients for mitral PVL treatment in the “Catheter” group compared with a “historical” group of patients who had redo surgery for mitral PVL, when catheter-based treatment for PVL was not available at our institution, this explains the shortness of the follow-up period. Second, the groups compared were not as homogeneous as they could be in a prospective randomized study. Patients who underwent classic cardiac surgery had more invasive and higher-risk procedures. This could be an explanation for the poorer outcomes. Third, the small number of patients aggravates the comparison of the treatment modalities for mitral PVL. Thus, further inclusion of the patients is needed to prove or deny the superiority or inferiority of both methods. In addition, due to the changes in the definitions of the periprocedural myocardial infarction over the time span of inclusion of our patients (2005–2019), we considered the periprocedural myocardial infarction to be significant when the blood serum troponin T was 10 times greater than the normal laboratory values with ischemic ECG changes, hemodynamic compromise necessitating inotropic support and necessity for coronary intervention. Similar issues occurred with the definition of sepsis. It was defined as clinically significant if this diagnosis was present in the patients’ documentation, prolonged intravenous antibiotics usage and the presence of significantly elevated inflammatory blood markers.The transapical catheter-based closure of mitral paravalvular leak seems to be a safer treatment procedure than a conventional re-do surgery, and the effectiveness of these procedures does not differ. To definitively support or deny this statement, a randomized controlled trial would be beneficial.


Two experimental Syrah red wines with different polyphenol contents were used to study the impact of acetaldehyde addition on olfactory perception. Free acetaldehyde levels were measured in red wine by Head Space-Gas Chromatography-Mass Spectrometry (HS-GC-MS) to determine the acetaldehyde combination levels for those wines. Significant differences were observed for both sensory threshold and acetaldehyde combination for the wines. A descriptive sensory analysis of the wines was then performed by using a trained panel and a Hierarchical-Check-All-That-Apply (HCATA) analysis of the wines with or without acetaldehyde addition. The results show that classical cited sensory descriptors for acetaldehyde (overripe apple and oxidized apple) varied significantly between the control wines and those with acetaldehyde addition. Non-acetaldehyde related descriptors  were also significantly impacted in the samples with increasing acetaldehyde additions. This suggests possible interactions between acetaldehyde and other volatile compounds that can create antagonistic or synergistic effects between the molecules or at the olfactory receptor level. Acetaldehyde is a volatile molecule and one of the most abundant carbonyl compounds in many fermented foods ,2. Gener2), a major wine antioxidant and antimicrobial molecule to form non-volatile adducts known as hydroxysulfonates [Acetaldehyde is a very reactive carbonyl compound and can combine quickly and strongly with sulfur dioxide  analysis.The objectives of this article are:Acetaldehyde (≥99%), methyl-2-methylbutyrate (99%), sodium chloride, phloroglucinol (≥99%), catechin (≥98%), and ascorbic acid were purchased from Sigma-Aldrich ; acetaldehyde  and ammonium sulfate were obtained from Merck . Oenin chloride was obtained from Extrasynthèse .Syrah 1 (S1): TPI of 41.Syrah 2 (S2): TPI of 80.Two 100% Syrah red wines with different Total Polyphenol Index (TPI)  were obtDifferent amounts of acetaldehyde were spiked into the red wine samples. The acetaldehyde additions to the wine samples were performed the day before in a cold room (+6 °C) to prevent acetaldehyde evaporation during the sample preparation. After the addition, the samples were stored with the minimum head-space at 17 °C in a cellar for at least 8 h before sensory and chemical analysis, to reach free acetaldehyde equilibrium as reported by Arias-Pèrez et al. .Classical oenological parameters methods were measured following International Organisation of Vine and Wine (OIV) reference methods. Alcoholic percentage was determined by Fourier transformed infrared spectroscopy—FTIR  (OIV-MA-BS-08) , free anm/z used for quantification were 29 for acetaldehyde and 88 for methyl-2-methylbutyrate.Free acetaldehyde was determined by head-space gas chromatography coupled to a quadrupole mass spectrometer detector (HS-GC-MS) following the method described in Carrascon et al.  with sliExternal calibration curves in model wine  containing known amounts of acetaldehyde were prepared.v/v) aqueous trifluoroacetic acid and mobile phase B containing acetonitrile. The column temperature was set at 50 °C. The 40 min elution method at flow of 0.25 mL/min was 1% B (0 min), 1–8.8% (0–5 min) B, 8.8–20.6% (5–30 min) B, 20.6–96% (30–30.5 min) B, isocratic with 96% B (30.5–34 min), 96–1% (34–34.1 min) B, and isocratic with 1% B (34.1–40 min). The detection was monitored at 520 nm. The quantification of monomeric anthocyanins was performed as described previously with slight modifications . The winAn external malvidin-3-O-glucoside calibration curve was used. The results are expressed as mg malvidin-3-O-glucoside equivalent (M3G eq.)/L. The analyses were performed in triplicate.The flavanol composition of the wines was studied by phloroglucinolysis reaction  following the procedure described by Carrascon et al.  with sliv/v) aqueous trifluoroacetic acid and mobile phase B containing acetonitrile. The 22 min elution method at flow of 0.45 mL/min was 2% B (0 min), 2–6% B (0–10 min), 6–20% B (10–16 min), 20–99% B (16–16.1 min), isocratic with 99% B (16.1–18 min), 99–2% B (18–18.1 min), and isocratic with 2% B (18.1–18 min). The column temperature was 40 °C. Eluting peaks were monitored at 280 nm. This analysis allows us to have access to the nature and relative proportions of the terminal and extension subunits. The method used a binary gradient with mobile phase A containing 0.1% , selected on the basis of their sensory performances and interest  and traiOrthonasal thresholds for acetaldehyde were defined in S1 and S2. Six wine samples with acetaldehyde concentrations of 5, 15, 20, 25, 30, 35, and 40 mg/L were prepared. The concentration range for acetaldehyde was established around the orthonasal detection limits of acetaldehyde found in the scientific literature .The method adopted consisted of a succession of triangular tests comparing the wine without addition to the wines with acetaldehyde addition, by increasing concentrations. The analysis was repeated in a second independent session. The analysis was conducted in individual testing booths, and the temperature of the tasting room was 21 °C. Samples (4 cl) were served at 17 °C, in black wine glasses in order to avoid any potential visual influence on the participant evaluations, with three-digit random codes, different for each glass. Each glass was covered with a lid to protect the samples from aroma evaporation, particularly concerning acetaldehyde.Scores were collected by a computerized data acquisition system .A logistic regression (1) on the percentage of correct answers as a function of concentration (Re p) was used to calculate the threshold value of 50% of correct answers: Data analysis was performed using XLSTAT software  ,41. The aim of this part of the study was to characterize the olfactory perceptions of S1 and S2 according to acetaldehyde concentration. A range of 10 acetaldehyde concentrations  was analyzed using the hierarchical CATA methodology . This mePrior to this, judges attended two training sessions to exercise understanding and consistently use attributes and also to familiarize themselves with the methodology.Olfactory standards were prepared by adding compounds to red Syrah wine and were adopted to help the judges to identify and remember the sensory attributes .The analyses were conducted in individual testing booths; the temperature of the tasting room was 21 °C. The samples were evaluated in a monadic service, with the same order of presentation for all judges, in ascending order of acetaldehyde concentration. This experimental protocol was chosen to analyze the olfactory changes progressively induced by acetaldehyde addition. The evaluation was carried out in duplicate in two sessions. The samples were served at 17 °C, in black wine glass covered with a lid, identified with three-digit random codes. For each sample, the judges had to choose between 1 and 6 most pertinent attributes, from a list of 61 olfactory terms . The attScores were collected by a computerized data acquisition system .rep is the number of same terms used by the judge for each replicate, desrep1 and desrep2 are the total numbers of terms used by the judge for the first and second replicates (respectively), and n is the number of concentrations duplicated. This parameter, ranging from 0 to 1, was used in previous works [An average reproducibility index (Ri) (2) was calculated to assess the individual performance of each judge: us works .The data obtained were binary and their analysis was performed using XLSTAT software . In order to analyze the significant differences between the acetaldehyde concentrations for each attribute, a Cochran’s Q test was performed. p-value less than 0.3 were considered in order to limit noise.The correspondence analysis (on the chi2 distance) was performed on the contingency table. Only attributes with a According to 2 were different but remained low .The percentage of alcohol and pH values were very close for both samples. The values of free SODue to the high reactivity of acetaldehyde, the levels of free acetaldehyde in the wine samples used for the sensory analysis were analytically controlled by Head-Space-Gas Chromatography-Mass Spectrometry in order to calculate the real free acetaldehyde concentration in the samples after 8 h of equilibration. For the wine samples prepared for the orthonasal threshold (OT), the concentration of total acetaldehyde added to wine ranged between 0 and 40 mg/L and, for the HCATA, the spiked concentration ranged between 0 and 120 mg/L. For these concentrations, a difference of free acetaldehyde concentration was found and was different for the two wines . 2 [2 were very close for both samples. Theoretically, 30 mg/L of SO2 could bind 20 mg/L of acetaldehyde in wine [2 in the S1 wine could approximately bind only 5 mg/L of acetaldehyde and only 9 mg/L in S2. The difference in concentration of free acetaldehyde  associated with a judge allowed to evaluate the accuracy of a judge’s performance . In the The olfactory characterization of Syrah wines as a function of the amount of added acetaldehyde (5 to 120 mg/L) using the HCATA method showed that acetaldehyde increased or exacerbated various descriptors depending on its concentration for each of the two Syrah wines.Cochran’s Q tests showed that there were significant differences at a risk α of 5% for four attributes for each of the two Syrah wines and a further five and eight attributes at a risk α of 10% . The results show that the concentration of acetaldehyde in the Syrah red wines had an impact on their olfactory perception. Indeed, depending on the level of acetaldehyde, the frequency of citation of descriptors associated with Syrah wines varied significantly and in the same way that the attributes associated with the acetaldehyde molecule, such as “baked apple”, “overripe apple”, or “oxidized green apple”. A correspondence analysis (CA) was then performed  for eachFor S1, the first two axes represented 54.49% of the total variance. On the one hand, the control wine without acetaldehyde addition (TEM) was described, on axis 1, by the terms “meat juice”, “blackberry”, “burnt” as well as “spicy” and “pastry”. On the other hand, wine samples with the highest concentrations (100 and 120 mg/L) and with the concentration at 25 mg/L were characterized, on axis 2, by the descriptors “overripe fruit” and “overripe apple”. Wine samples with intermediate concentrations (55 and 70 mg/L) were described, on axis 2, by “fresh flowers” and “baked apple”.The HCATA method showed that, for S1 wine, a low concentration of spiked acetaldehyde (15 mg/L) significantly increases the apparition of “red berries” notes.Intermediate concentrations of acetaldehyde (55 and 70 mg/L) induced also the detection of the “baked apple” descriptor that is considered pleasant. whereas higher concentrations (100 and 120 mg/L) tended to be characterized by “overripe apple/overripe fruit”, corresponding to unpleasant notes. In addition to that, an increase in the number of citations for the descriptors “vegetable” and “fresh plants” and “fresh green apples” according to acetaldehyde concentration can be noted. These observations were in agreement with those in former studies , which sOn the contrary, wine samples with higher concentrations (70 and 100 mg/L) were characterized, on axis 1, by the descriptors “strawberry”, “oxidized”, and “oxidized green apple”. The wine sample with the 25 mg/L concentration was described, on axis 2, by “pastry”, “brioche”, “malt”, and “vanilla”. The HCATA results show that the amount of acetaldehyde influenced the olfactory perception of this second wine. Nevertheless, some descriptors highlighted for some concentrations of spiked acetaldehyde were not in accordance with the literature. It must be noted that the addition of acetaldehyde at low concentrations (5 and 15 mg/L) did not differentiate the samples from the control, but a concentration of 25 mg/L in the wine exacerbated “pastry” notes, such as “cinnamon” and “brioche”. Intermediate concentrations (40 and 70 mg/L) increased the intensity of the “oxidized green apple” notes, rather associated with higher concentrations . MoreoveOverall, the results of this work confirm that acetaldehyde had an impact on the olfactory perception of Syrah red wines with different polyphenol contents. At high acetaldehyde concentrations, classical sensory descriptors, such as “overripe apple” or “oxidized apple”, were cited. At intermediate and low concentrations, other descriptors were identified, such as “vegetal”, “red berries”, “fresh flowers”, or “meat juice”. This suggests that acetaldehyde may interact with other volatile compounds to create antagonistic or synergistic effects between the molecules or at the olfactory receptor level. Its impact also differs depending on the red wine considered and the polyphenol content is an important parameter as shown by our results. Indeed, the rapid covalent or non-covalent interaction of acetaldehyde with polyphenols seemed to occur as evidenced by the very different perception threshold and free acetaldehyde measurement in our red wine samples. Further research is needed to better understand acetaldehyde–aromas interactions in red wine sensory characteristics and to understand its reactivity with polyphenol or other compounds during ageing.


Its clinical presentation varies and it may present several medical complications, namely heart defects, cleft palate, autoimmune diseases, delayed development, and psychiatric disorders. In these patients, psychiatric disorders are frequent and may include attention-deficit hyperactivity disorder, anxiety disorders, autism spectrum disorder, and schizophrenia spectrum disorders.We aim to characterize psychosis in patients diagnosed with 2q11.2 deletion syndrome, which is one of the most frequent psychiatric presentations.Pubmed database using the following expression “22q11.2 deletion syndrome”; “DiGeorge syndrome”; “velocardiofacial syndrome”; “psychosis”; “psychiatric disorders”.To introduce the topic of 22q11.2 psychiatric symptoms, we will start by presenting a clinical case. Then, a review of the related literature using the Patients diagnosed with 22q11.2 deletion syndrome are considered high-risk for psychosis. In this clinical case, we present a 19-year old man diagnosed with 22q11.2 deletion syndrome who was admitted to a psychiatric ward for psychosis. The knowledge of the increased risk for psychosis in these patients should be taken into account in the face of behavioral changes de novo to assure a timely therapeutic approach. Currently, the treatment does not differ from other patients, but this is mainly due to the lack of knowledge on the best therapeutic approach in this specific diagnosis.Genetic syndromes are often associated with psychiatric disorders. Patients diagnosed with 22q11.2 deletion syndrome are at high risk for psychosis and should deserve a multidisciplinary approach so that their diagnosis and treatment are established as early as possible.No significant relationships.


Pinaceae family have been recognized as a rich source of lignans, flavonoids, and other polyphenolics. The great common occurrence of conifers in Europe, as well as their use in the wood industry, makes both plant material and industrial waste material easily accessible and inexpensive. This is a promising prognosis for both discovery of new active compounds as well as for finding new applications for wood and its industry waste products. This study aimed to analyze and phytochemically profile 13 wood extracts of the Pinaceae family species, endemic or introduced in Polish flora, using the LC-DAD–ESI-MS/MS method and compare their respective metabolite profiles. Branch wood methanolic extracts were phytochemically profiled. Lignans, stilbenes, flavonoids, diterpenes, procyanidins, and other compounds were detected, with a considerable variety of chemical content among distinct species. Norway spruce (Picea abies (L.) H.Karst.) branch wood was the most abundant source of stilbenes, European larch (Larix decidua Mill.) mostly contained flavonoids, while silver fir  was rich in lignans. Furthermore, 10 lignans were isolated from the studied material. Our findings confirm that wood industry waste materials, such as conifer branches, can be a potent source of different phytochemicals, with the plant matrix being relatively simple, facilitating future isolation of target compounds.Many species from the  Pinaceae family encompasses 11 genera and about 230 species, making it the largest family of conifers as well as the Gymnospermae. Genera include Abies (47 spp.), Cathaya (1 sp.), Cedrus (3 spp.), Keteleeria (3 spp.), Larix (11 spp.), Nothotsuga (1 sp.), Picea (38 spp.), Pinus (113 spp.), Pseudolarix (1 sp.), Pseudotsuga (4 spp.) and Tsuga (9 spp.). The members of this family are monoecious, resinous trees distributed widely in the Northern Hemisphere, with just one equatorial crossover species − ion at m/z 577, which fragmented into m/z 559 [M−H−18]—loss of water, m/z 451 [M−H−126]− from heterocyclic ring fissure fragment, m/z 407 [M−H−170]−—product of retro-Diels–Alder reaction followed by the loss of water and m/z 289, which corresponds to (epi)catechin. Based on fragmentation patterns, they were all characterized as type B dimeric procyanidins − corresponding to the cleavage of hexose (probably glucose). Thus, compound 13 was assigned as taxifolin hexoside, which was consistent with the fragmentation pattern reported previously − corresponding to the loss of water, at m/z 193 and m/z 125. By comparing fragmentation pattern with literature data −, corresponding to the loss of CO, m/z 243 [M−H−44]−, corresponding to the loss of CO2 and m/z 181. The fragmentation pattern matched to the literature data of dihydrokaempferol (syn. aromadendrin) [33 (tr = 22.0 min) exhibited a pseudomolecular ion at m/z 271 and fragment ion at m/z 253 [M−H−18]− corresponding to the loss of water. It was tentatively identified, comparing to literature data − and UV maxima at around 225 and 280 nm. There have been previously reported three lignan isomers in conifer wood, that could give pseudomolecular ion at m/z 375: liovil, todolactol and 7-hydroxylariciresinol − and similar fragmentation patterns. Compound 32 gave a characteristic primary product ion for dibenzylbutyrolactone lignans [M−H−44]− at m/z 313, which corresponds to the loss of CO2 from the lactone ring [30. Compound 30 produced a fragment ion at m/z 342 [M−H−15]− corresponding to the loss of methyl radical, and at m/z 151 (guaiacyl) and m/z 136, which were the products of α,β-cleavage in the side chain. This fragmentation pattern was characteristic for furofuran lignans −. They both formed a fragment ion at m/z 355 [M−H−18]− corresponding to the loss of water. For compound 22, a fragment ion at m/z 311 [M−H−62]− could be found, corresponding to the loss of water and CO2 from the lactone ring (again suggesting the compound belonged to the dibenzylbutyrolactone group). On the other hand, compound 29 did not produce a fragment ion at m/z 311; instead, an ion at m/z 327 [M−H−46]− which corresponds to the loss of water and CO was observed,. Both fragmentation patterns and differences among them have been previously observed − which fragmented into m/z 373 [M−H]− corresponding to the loss of formate adduct. Based on literature data, it was tentatively identified as α-conidendric acid [Compounds observed . Accordiric acid . It was 27 (tr = 16.1 min) had its pseudomolecular ion at m/z 405 which fragmented to m/z 359 [M−H]−, corresponding to the presence of formyl adduct. We also observed another compound, 20 (tr = 12.7 min), exhibiting its pseudomolecular ion at m/z 359 [M−H]−. Differences in further fragmentation could be observed for these compounds. For peak 27 we could observe a fragment ion at m/z 329 [M−H−30]− resulting from the loss of formaldehyde. Compound 20 exhibited fragment ions at m/z 344 [M−H−15]−, corresponding to the loss of methyl radical, at m/z 313 [M−H−46]−, formed by the loss of methoxyl and methyl radicals, and at m/z 189, which was a product of β-cleavage in the side chain. Both fragmentation patterns have been previously observed − and fragment ions at m/z 346 [M−H−15]−, corresponding to the loss of methyl radical, at m/z 313 [M−H−48]−, formed by the loss of formaldehyde and water in the diol structure and at m/z 299 [M−H−48−15]−, corresponding to both rearrangements. This structure was compared to fragmentation data described in the literature [Apart from cyclolariciresinol  exhibited a pseudomolecular ion at m/z 557 [M−H]− and fragment ions at m/z 539 [M−H−18]− corresponding to the loss of water, m/z 525 [M−H−32]−, m/z 521 [M−H−36]−, m/z 509 [M−H−48]−, formed by the loss of formaldehyde and water in the diol structure, m/z 415 and m/z 361 [M−H−196]−, corresponding to the cleavage of guaiacylglyceryl moiety. The fragmentation pattern was in accordance with the data for oligolignans isolated from Norway spruce and Scots pine knots − and fragment ions at m/z 525 [M−H−20]−, m/z 507 [M−H−48]− from the loss of formaldehyde and water, m/z 359 [M−H−196]−, corresponding to the cleavage of guaiacylglyceryl moiety, and at m/z 329 [M−H−196−30]−, resulting from the loss of formaldehyde. This compound was tentatively identified as lariciresinol 4-O-guaiacylglyceryl ether in accordance to previous MS/MS data [Compound /MS data . It was 10 (tr = 8.1 min) and 14 (tr = 10.8 min) exhibited two pseudomolecular ions at m/z 811 [2M−H]− and m/z 405 [M−H]− with similar fragmentation patterns. Primary ion at m/z 405 fragmented into m/z 243 [M−H−162]−, corresponding to the cleavage of hexose, and showed fragments at m/z 225 [M−H−18]−, corresponding to the loss of water, m/z 201 [M−H−42]−, corresponding to the losses of C2H2O, characteristic for stilbenoids, m/z 173 [M−H−42−28]−, and m/z 159 [M−H−42−42]−. Based on elution order and comparison with literature data − and gave one fragment ion at m/z 227 [M−H−162]−, corresponding to the cleavage of hexose, and showed fragments of aglycon at m/z 185 [M−H−42]− and 183 [M−H−42−H2]−, corresponding to the losses of C2H2O, characteristic for stilbenoids, m/z 157 [M−H−42−28]− and m/z 143 [M−H−42−42]− [O-glucoside) in comparison with literature data [19 exhibited a pseudomolecular ion at m/z 465 [M−H+HCOOH]− which showed fragment ions at m/z 419 [M−H]−, corresponding to the loss of formyl adduct, at m/z 257 [M−H−162]−, corresponding to the cleavage of hexose, at m/z 242 [M−H−162−15]− and at m/z 241 [M−H−162−16]− [O-glucoside).Compounds −42−42]− . It was ure data . Compoun7 M−H−42−− and m/z34 (tr = 26.3 min) and 37 (tr = 33.6 min) were characterized as stilbenes based on their primary pseudomolecular ion and UV maxima at around 300 nm. Comparing mass of [M−H]− ion at m/z 211 [M−H−]− and m/z at 225 [M−H]− with literature reports on stilbenes isolated previously from conifer wood and their elution order − corresponding to the losses of C2H2O, characteristic for stilbenoids [37) pseudomolecular ion gave a fragment ion at 210 m/z [M−H−15]−, corresponding to the loss of methyl radical. Their occurrence was limited to the genus Pinus, with only Scots pine and mountain pine containing all the above  exhibited a pseudomolecular ion at m/z 265 [M+H]+ and fragmented into m/z 251, m/z 233, m/z 205, m/z 187 m/z 176 and m/z 83. It was tentatively identified as dehydrojuvabione by comparison with MS/MS data found in literature [39 (tr = 52.0 min) and 40 (tr = 52.3 min) both exhibited a pseudomolecular ion at m/z 303 [M+H]+ with similar fragmentation patterns: m/z 285, m/z 257 and m/z 123. Based on UV maxima, 251 nm for compound 39, and 241 nm for compound 40, their elution order, comparing this data to the literature [39 as neoabietic acid and compound 40 as abietic acid. Dehydrojuvabione was only found in A. alba while both abietane-type resin acids were present in all studied conifer species wood  have been identified as a good source of many polyphenols. Willfor and his team characterized wood knots of spruces, pines and firs, isolating many lignans in the process ,39,66,67athogens . Anotherère bark . To the Pinaceae family are rich in otherwise scarce compounds, such as lignans and stilbenes, offering a large variety of these structures.Referring to previous research, our study confirms that conifers from the Pinus nigra Aiton and lariciresinol from Larix decidua Mill. [Pinaceae family offers a much easier-to-extract source of these polyphenols, with much fewer steps required to obtain pure compounds (directly in aglycone form with much larger structure variety). Wood from all studied species contained detectable amounts of lignans, with silver fir being the richest source of these polyphenols. Although A. alba offered large quantities of lignans, especially secoisolariciresinol and lariciresinol, P. sylvestris was far richer than all other species in nortrachelogenin, pinoresinol, and matairesinol. This is particularly interesting, as Scots pine is the most abundant and economically most important tree in Europe. Another important notion from our study is the detection of a lignan (namely matairesinol) in P. cembra, which was previously described as the only pine not containing lignans [Lignans are a group of natural polyphenols (and one of the most lipophilic), located in plant cell walls. According to the recent nomenclature: lignans dimers of two coniferyl, sinapyl, 4-hydroxycinnamyl alcohol or similar alcohol monomers. Some authors restrict the term lignan only to those molecules coupled by the central carbon of the sidechain  . They weua Mill. . Althoug lignans .A. alba wood knots [Through our analysis, we did not detect few lignans that have been previously found in some of the studied species. Willfor et al. reported presence of matairesinol, pinoresinol, and nortrachelogein in od knots , but we Pinaceae family are considered as one of the richest in stilbenes content. These rare polyphenols consist of two aromatic rings linked by a C2 ethylene sidechain, formed through cyclization of 3 malonyl-CoA with cinnamoyl-CoA, coumaroyl-CoA or caffeoyl-CoA, followed by hydroxylation of aromatic rings [P. abies and P. jezoensis bark, with their levels in wood being much lower [P. abies heartwood and knotwood; however, their analysis was limited to pinosylvins [trans-astringin was much stronger than that of most abundant lignan reported in these species, i.e., 7-hydroxymatairesinol, which could imply higher content of stilbenes than lignans in spruce wood.Species from the ic rings . It has ch lower ,32. Hoveosylvins . Our stu2 fragmentations for some of these compounds, yet we see the need for further exploration of ESI fragmentation. Additional focus should be directed at differentiation of cis/trans isomers and the site of glucose substitution. In the case of our study, no differences were observed for such compounds and identification had to be based on elution order.As was the case with lignans, fragmentation patterns for stilbenes are rarely reported in the literature, thus making LC-DAD–ESI-MS/MS analysis of these compounds difficult. This study offers MSOur analysis also offered an insight into flavonoid, flavan-3-ol, and diterpene composition of conifer wood. These compounds were present in all studied samples, with differences concerning structures and their exact content. Larches and Douglas fir could be considered the richest in flavonoids and flavan-3-ols.Overall, results obtained from this study show that conifer wood is a significant source of different phytochemicals, with many rare structures present. Silver fir wood could be a rich source of lignans, pine wood offer both lignans and stilbenes aglycones, while spruce wood had stilbenes glycosides as dominant metabolites. Larch and Douglas fir wood can be considered abundant sources of flavonoids and flavan-3-ols.Furthermore, isolation of these metabolites from the plant matrix can be easily achieved. As these plant metabolites have already proven numerous pharmacological and dietary activities, they may find applications in pharmaceutical, cosmetic and food industries. Additionally, LC-ESI-MS has been established as quite a successful method for conifer wood metabolites detection and identification, allowing for simultaneous identification of phytoconstituents from different groups.


Lysophosphatidylcholine acyltransferase 1 (LPCAT1) is overexpressed in multiple human tumors. However, the role of LPCAT1 in hepatocellular carcinoma (HCC) has not been understood. We aim to explore the relationships between LPCAT1 expression and prognosis, clinicopathological features, tumor microenvironment (TME), immune cell infiltration, immune checkpoint gene expression, and related signaling pathways in HCC. Furthermore, we also explored the relationship between LPCAT1 expression and drug sensitivity to HCC treatment.The expression profiles were acquired from the Cancer Genome Atlas (TCGA) and the Human Protein Atlas (THPA). Immune status and infiltration in cancer tissues were explored using the single sample gene set enrichment analysis (ssGSEA) and CIBERSORT algorithm.LPCAT1 was overexpressed in HCC, and its expression was related to poor prognosis, LPCAT1 was an independent prognostic biomarker in HCC. Expression of LPCAT1 increased statistically with the increase of clinical stage and grade of HCC patients. GO and KEGG network analysis revealed that LPCAT1 positively associated molecules were mostly enriched in functions related to cell adhesion. The TME score of high-LPCAT1 group was significantly higher than that of low-LPCAT1 group. Immune infiltrating cells positively correlated with LPCAT1 expression were Macrophages M0, B cells memory, Dendritic cells activated, T cells regulatory and T cells gamma delta in HCC. We found a positive correlation between LPCAT1 and most immune checkpoint gene expression. The IC50 of 5-Fluorouracil, Gemcitabine, Mitomycin C, Sorafenib and Cabozantinib in patients with high-LPCAT1 expression was lower than that in patients with low-LPCAT1 expression. Our findings provide a wealth of information for further understanding of the biological functions and signaling pathways of LPCAT1 in HCC.LPCAT1 is an independent prognostic biomarker and associated with tumor microenvironment, immune cell infiltration, immune checkpoint expression and drug sensitivity in hepatocellular carcinoma. HCC is the most frequent type of malignant liver tumor worldwide, with a complex etiology, insidious onset and high malignancy . CurrentMetabolic pathways, including lipid metabolism, are frequently reprogrammed within cancer cells to adapt to environmental challenges and promote their expansion and metastasis –5. As a In our study, we analyzed the relationship between LPCAT1 expression and clinicopathological features and prognosis in HCC. The correlation of LPCAT1 expression with TME score, immune cell infiltration and immune checkpoint gene expression were further studied. Moreover, biological functions and related signaling pathways of LPCAT1 was explored in HCC. Finally, we explored the relationship between LPCAT1 expression and drug sensitivity to HCC treatment.U test was performed using the “ggplot2” R package. The immunohistochemistry of LPCAT1 was obtained from THPA, a program which aims to map all the human proteins in cells, tissues and organs using integration of various omics technologies [All available data of 21 cancer types were downloaded from TCGA as Fragments per kilobase per million (FPKM), and then, the data were transformed into transcripts per million (TPM). Finally, Mann Whitney nologies . This stClinical data from TCGA were used to analyze the overall survival and progression-free survival of HCC patients between 2 groups. Clinical characteristics including Age, Gender, Grade, Stage, T, M, and N were included to analyze whether there were differences between 2 groups. “ggplot2” R package was used to analyze differential genes expression between 2 groups. General immune status of each patient was assessed by ESTIMATE score, stromal score, immune score and tumor purity score. In addition, in each HCC sample, we utilized CIBERSORT algorithm and depicted the profile of 22 immunocyte subtypes . The obtp.adj < 0.05 and q value < 0.2.GO is a database established for the definition and description of gene and protein functions applicable to various species. KEGG is a comprehensive database that integrates genomic, chemical, and systemic functional information. The enrichment analysis of LPCAT1-related genes was performed by the “clusterProfiler” R package  . R software was utilized to construct the heatmaps, forest plots, and circle plot. p < 0.05 was set as statistically significant. All statistical analyses were conducted by R software (v.4.1.3).In this study, Student’s To determine the expression of LPCAT1 in human tumors, we first performed its expression analysis in 21 human tumors. As shown in Fig. p < 0.001). Further multivariate analysis showed that LPCAT1 was an independent prognostic factor in HCC patients . These results demonstrated the prognostic values of LPCAT1 expression in HCC and can be used as an independent prognostic biomarker for HCC patients.Next, we performed the prognosis analysis of LPCAT1 expression in HCC. As shown in Fig. p = 7.6e−03; G1 vs G3, p = 1.6e−06; G1 vs G4, p = 4.8e−03; G2 vs G3, p = 7.7e−04; Stage: StageI vs Stage II, p = 2.7e−04; StageI vs Stage III, p = 3.7e−06; T: T1 vs T2, p = 9.2e−05; T1 vs T3, p = 4.9e−05). We didn’t find any relationship between LPCAT1 expression and Age, M and N . We elucidated the correlation of LPCAT1 expression with clinicopathological features of HCC in detail. Together, our results demonstrated that LPCAT1 expression is positively correlated with the risk of HCC, which can well reflect the clinical stage and grade of HCC patients.Here, we used TCGA to further explore the correlation between LPCAT1 expression and clinicopathological features. As shown in Fig. p < 0.01) in TCGA, and these significantly associated genes were classified as 7169 positively and 1533 negatively associated genes. Subsequently, we generated a circle plot of co-expression, as shown in Fig. To further explore the biological significance of LPCAT1 in HCC, we performed a genome-wide gene profiling analysis of LPCAT1-related genes. Our results showed that there were 8702 genes associated with LPCAT1 expression , B cells memory (p = 0.015), Dendritic cells activated (p = 0.017), T cells regulatory (p = 0.026) and T cells gamma delta (p = 0.047), while the immune infiltrating cells negatively correlated with LPCAT1 expression were B cells naive (p = 0.015) and Monocytes (p = 0.011) in HCC. Next, we analyzed the differences in the infiltration of various immune cells within high- and low-LPCAT1 groups. As shown in Fig. LPCAT1 is thought to play an important role in the immune system, so we explored the correlation between LPCAT1 expression and immune cell infiltration. As shown in Fig.  p = 0.02 and T ceIt is well-known that immunotherapy plays an important role in HCC, and the expression of immune checkpoint genes can not only predict prognosis, but also predict the response to immunotherapy. We, therefore, analyzed the correlation between LPCAT1 expression and immune checkpoint gene expression. As shown in Fig. To explore the relationship between LPCAT1 and drug sensitivity, we performed a drug sensitivity analysis within high- and low-LPCAT1 groups. As shown in Fig. Metabolic pathways, including lipid metabolism, are frequently reprogrammed within cancer cells to adapt to environmental challenges and promote their expansion and metastasis . As an iLPCAT1 expression correlates with clinicopathological features in HCC. Zhang found that LPCAT1 expression was related to tumor grade, ECOG score, AFP and TNM stage , 22. We There have been several studies on the mechanism of LPCAT1 in tumor cells. Wei demonstrated that LPCAT1 was up-regulated in NSCLC cells and tissues, and promoted NSCLC progression via PI3K/AKT/MYC pathway, can be used as a target for the NSCLC treatment . LPCAT1 Immunotherapy has increasingly become an important part of the treatment of tumor therapy , 27. TheIn conclusion, we clarified that LPCAT1 is an independent prognostic biomarker associated with TME score, immune cell infiltration, immune checkpoint gene expression, which can well reflect the clinical stage and grade of HCC patients. LPCAT1 is associated with drug sensitivity, which provides support for oncologists to formulate anti-HCC treatment strategies. At last, our findings provide a wealth of information for further understanding of the biological functions and signaling pathways of LPCAT1 in HCC.


As expected, CHA exhibits an above-room-temperature solid phase transition at 325 K (Tc), which was confirmed by the differential scanning calorimetry measurement and variable temperature single crystal X-ray diffraction analyses. Further analyses indicate the phase transition is mainly governed by the order–disorder transformation of organic cyclohexylaminium cations. Interestingly, during the process of phase transition, the dielectric constant (ε′) of CHA shows an obvious step-like anomaly, which displays a low dielectric constant state below Tc and a high dielectric constant state above Tc. Furthermore, variable temperature conductivity combined with theoretical calculations demonstrate the notable semiconducting feature of CHA. It is believed that our work will provide useful strategies for exploring lead-free organic–inorganic semiconducting hybrid materials with above room temperature dielectric phase transitions.Recently, organic–inorganic hybrid lead halide perovskites have attracted great attention for optoelectronic applications, such as light-emitting diodes, photovoltaics and optoelectronics. Meanwhile, the flexible organic components of these compounds give rise to a large variety of important functions, such as dielectric phase transitions. However, those containing Pb are harmful to the environment in vast quantities. Herein, a lead-free organic–inorganic hybrid, (C Recently, organic–inorganic hybrid lead halide perovskites have attracted great attention for optoelectronic applications, such as light-emitting diodes, photovoltaics and optoelectronics. Polar molecules in the solid state usually show smaller electric permittivities than in the liquid state because of the “freezing” and “melting” of the molecular reorientations, which respectively corresponds to a low temperature phase (LTP) and a high temperature phase (HTP), which makes phase transition materials promising candidates as new dielectric switches. In addition, in consideration of practical applications, the optimal phase transition temperature range of dielectric switching materials is between 290 K and 365 K, particularly at room temperature, which can benefit from changes in the environment.9 On the other hand, an economical and environmentally friendly solution is also required for a wide range of applications.9,10 Therefore, it is of great significance to explore above room-temperature lead free dielectric phase transition materials.Solid state switchable dielectric materials have attracted great attention due to their significant roles in signal processing, phase shifters, data communication, varactors and sensors, 11–15 Switchable dielectric materials have been found in some organic–inorganic phase transition hybrid. Meanwhile, it has been proved that cyclic organic amines is promising candidates to design dielectric phase transition materials due to their flexible structures. As a result, some dielectric phase transition hybrid have been developed using 3-, 5-, 6- and 7-heterocyclic organic amines.15–22 For example, bis(cyclohexylaminium) tetrabromo lead, a layered hybrid compound, which has excellent dielectric switching performance, that is, the dielectric constant values vary from 25 to 400 at different temperature, which features an excellent property of dielectric switching.23 Recently reported (hexamethyleneimine)PbBr3, a one-dimensional ABX3-type perovskite-like hybrid, also exhibits a phase transition with high dielectric switching property.24 However, these Pb containing materials are harmful to the environment in their vast quantities of use.25–28 One of the most effective approaches is to move away environmentally harmful element lead.29,30 As same as Pb2+ ions electron configurations (6s26p0), Bi3+ ions are low toxicity to the environment, which also can form a variety of organic–inorganic compound.31 Therefore, it is expected as an environmentally friendly alternative for lead containing materials.Organic–inorganic hybrid materials have attracted significant attention owing to their diverse properties, such as phase transitions and semiconducting properties.6H14N)2BiCl5 , in which the corner-sharing BiCl6 octahedral clusters construct a zero-dimensional perovskite-like anionic framework. CHA shows remarkable dielectric responses that can be switched by phase transition at ∼325 K (Tc). The mechanism is the order–disorder transformation of organic cyclohexylaminium cation. The order–disorder of organic cations accounts for its switchable dielectric activities. Therefore, CHA is considered as a dielectric switch owing to its phase transition. Moreover, CHA displays notable semiconducting properties with an optical bandgap of ∼3.20 eV. Thus, it is expected that our work will provide useful strategies for exploring organic–inorganic semiconducting hybrid materials with the above room temperature dielectric phase transitions.Herein, we present an above-room-temperature lead-free organic–inorganic hybrid material,  (1 g) with excessive hydrochloric acid in a bath. Secondly, an appropriate amount of cyclohexylamine (0.43 g) was added into the above solution (the stoichiometric molar ratio of cyclohexylamine and bismuth(iii) with a 2 : 1 molar ratio) after stirring for 20 minutes. Then, the mixture was heated for 20 minutes until the precipitate dissolved completely at 373 K. At room temperature, white crystals grow slowly over several days from an aqueous solution  analysis, with a temperature range of 285–1000 K and a heating rate of 10 K min−1.DSC analyse was carried out on a NETZSCH DSC 200 F3 with the temperature range of 290–350 K. CHA crystal was put on aluminum crucibles under a nitrogen atmosphere. The cooling or heating rates was 10 K minε = ε′ − iε′′, where ε′′ is the imaginary part) of the real part on the conditions of temperature dependence.The CHA a powder-pressed pellet was covered by silver conductive paste were subjected to dielectric experiments. For CHA, the temperature dependence of the dielectric constants was performed on the TH2828A impedance analyzer with a temperature range of 315–335 K. The frequencies of 100 KHz, 200 KHz, 500 KHz and 1 MHz were recorded by the complex dielectric constant (λ = 0.77 A) at 333 K and 200 K.Single crystal X-ray diffraction analyses were measured from the Bruker D8 Quest/Venture diffractometer by using Mo Ka radiation  analysis was performed to determine the purity of CHA with the 232 From DSC curve of CHA  and 200 K (LTP) by means of variable temperature X-ray diffraction  Å, b = 12.4092(4) Å, c = 15.8390(6) Å, α = 76.4740(10)°, β = 69.2450(10)°, γ = 89.3230(10)°, Z = 2, V = 2132.77 Å3. It contains the basic unit of a discrete inorganic dual-core [Bi2Cl10]4− clusters and four equivalent of cationic organic cyclohexylamine. Interestingly, the negative ion framework is composed of surface-shared octahedra in which the central Bi atoms are coordinated by six iodine atoms that act as bridging agents  Å, b = 12.7479(2) Å, c = 31.1058(6) Å, β = 108.8270(10)°, Z = 4 and V = 4488.5 Å3. From LTP to HTP, the volume of the crystal cell was significantly doubled. The change of the crystal cell parameter confirmed that the crystal cell had a phase change in CHA, which matches well with the DSC measurement. The CHA phase change was confirmed from another perspective. The difference in the high-temperature phase is that organic cation disordered in high temperature phase due to thermal effect. While the protonated cyclohexylamine cation becomes highly disordered, and the pentachlorobium negative ion skeleton remains in an ordered fashion. As shown in Fig. S5b,P1̄ to P21/c. As shown in Fig. S6,m point group.The HTP structure is in a monoclinic system with the space group ε′ shows a relatively large step-like transition at about 325 K, consistent with the results of variable temperature PXRD and thermal analysis discussed above , followed by a significant step-like at Tc, where the value of epsilon is moved rapidly from 9.5 in the vicinity of the Tc to 12.5. The change of dielectric behavior with temperature is obviously consistent with the properties of switchable molecules. The intense dielectric anomaly in the Tc region triggered by this temperature brings to mind the typical characteristics of the switchable dielectric material. This switch medium is considered to be due to order–disorder behavior of the cyclohexylaminium cation. These results indicate that CHA is a promising above-room-temperature switchable dielectric material.Dielectric response, usually apparently unusual at the phase transformation point, is one of the important indices for characterization of structure transformation. The dielectric constant were measured at four fixed frequencies  in the temperature range of 315 to 335 K. With increasing temperature, the dielectric constant ed above . HTP hasg). As shown in 34 (inset of hνF(R)]n1/versus the energy (eV), where linear region was extrapolated to the x-axis intercept. Variable-temperature conductivity was performed to further understand the semiconducting feature of CHA, and We performed Ultraviolet-visible (UV-vis) spectroscopy to explore the optical bandgap  illustrate that the valence band maximum is mainly derived from CI 3p states, while the conduction band minimum mostly attributed to Bi 6p and Cl 3p states.To obtain further discernment of the electronic properties, the electron energy band structure and partial state density (PDOS) are calculated by means of density functional theory. In conclusion, we have presented a lead-free organic inorganic hybrid, CHA, which features a dielectric phase transition at 325 K. The phase transition was confirmed by dielectric measurements, DSC and variable temperature single-crystal structural analyses. Structural analysis shows that the order–disorder dynamics of organic moieties accounts for its phase transition. Moreover, the obvious step-like dielectric pattern indicates that CHA can be considered as switchable dielectric material. Interestingly, CHA also exhibits a semiconducting feature. This successful example may provide a new approach to design new lead-free dielectric phase transition materials.There are no conflicts to declare.RA-010-C9RA09289G-s001RA-010-C9RA09289G-s002


Copper (Cu) is an essential micronutrient, and its deficiency can cause plants to undergo metabolic changes at several levels of organization. It has been shown that leaf age can play a role in nutrient partitioning along the shoot axis of poplar. In this study, we investigated the effect of Cu deficiency on the altered partitioning of essential macro and micronutrients in leaves and stems of different age. Cu deficiency was associated with higher concentrations of calcium, magnesium, sulfur, iron, zinc, manganese, and molybdenum in leaves and relatively higher concentrations of calcium, phosphorus, iron, and zinc in stems. Leaf and stem age had significant effects on nutrient partitioning. Principal component analyses revealed patterns that point to inverse influences in leaves and stems on nutrient partitioning. Specifically, these analyses revealed that nutrient partitioning in leaves was influenced by Cu feeding status more than developmental stage, whereas nutrient partitioning in stems was influenced by developmental stage more than Cu feeding status. These results suggest that Cu deficiency and developmental stage can significantly influence the partitioning and homeostasis of macro and micronutrients in poplar organs. Macro- g g–1 DW , and theg g–1 DW . Developficiency .Soil or media that lack essential micronutrients can cause nutrient-specific deficiency symptoms in plant tissues and trigger metabolic remodeling at several levels of organization . For insGiven the different demand for elements of various plant organs, we were interested to investigate how Cu deficiency affects nutrient partitioning in different plant parts. Because of the possibility of crosstalk between homeostasis of micronutrients , we hypoPopulus tremula × P. alba, INRA 717-1B4) were grown hydroponically as described by in vitro on ½ strength Murashige and Skoog  hormone free media with sucrose (20 g L–1) and agar (7 g L–1). Explants that were rooted and approximately 8 cm tall with an average age of 3 months were randomly distributed to 20-L black plastic buckets (3 plants per bucket) with an aerated one-tenth strength modified Hoagland’s solution (4. The hydroponic solution for the Cu-deficient treatment (–Cu) was the same as that for +Cu except CuSO4 was omitted. Plants were then grown for 6 weeks in a climate-controlled room under a 16 h photoperiod of 150 μmol photons m–2 s–1 (and 8 h dark period) with air temperature maintained at 22 ± 1°C.Hybrid white poplar (solution . The hydFo) and maximal (Fm) chlorophyll fluorescence with an FMS system  or a MAXI version IMAGING-PAM . Steady-state (F), maximal (Fm′), and minimal (Fo′) chlorophyll fluorescence were then measured under a series of increasing light intensities as described previously (Fm – Fo)/Fm = Fv/Fm  or (Fm′ – F)/Fm′ /(Fm′ – Fo′) = 1 – qP . The digest was heated for 2 h at 60°C and 6 h at 130°C and subsequently diluted up to 10 mL with double distilled water. Samples were analyzed using an ELAN-DRC Inductively Coupled Plasma-Optical Emission Spectroscopy instrument  as well as the five antecedent leaves  software. One-way ANOVAs were performed using the “lm” function and Tukey mean separation was done using the “emmeans” package  after 6 weeks of growth. The plants grew similarly until week 4  was similarly high in leaves from +Cu and –Cu conditions , Potassium (K) concentration were almost identical between the treatments . K conceP was variable across leaf age in +Cu plants with Leaf 3 having the highest concentration . Cu defiP = 0.009; Ca was distributed to Leaf 5–7 at a higher concentration versus Leaf 0–2, 3, and 4 in Cu sufficient plants . The samP = 0.005) on S partitioning in leaves, but Cu treatment did not (S concentration were 79% lower in –Cu Leaf 0–2 than +Cu Leaf 0–2 . Leaf 3  did not . S conce did not . There w did not . There w did not .–1 DW greater in young stems versus mature stems (–1 DW) and 84% lower than +Cu Mg concentration in mature stem  and then increased with age (Leaf 6–7) in the –Cu treatment , whereasMn concentration was similar in Leaf 4–7 of +Cu plants and present at higher concentration in Leaf 0–2 and Leaf 3 . In –Cu Mo had a similar trend in leaf age as Zn with older leaves having less Mo in both +Cu and –Cu treatments , 4G. LeaLeaves and PC2Leaves, explained approximately two-thirds  of the variation in the macro- and micronutrient concentrations. Leaves from +Cu and –Cu conditions  of the variation in the macro- and micronutrient concentrations. Stems of different ages  and positive PC2Stems scores for –Cu conditions  by S, Mo, Mg, Mn, and Ca, whereas PC2Stems was loaded predominantly (86.6%) by Fe, P, Zn, and K  occurred under Cu deficiency  for all measured nutrients compared to English oak  as well .The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.CH and MP conceived and designed the study. CH carried out the experiments. CH, MP, JS, and SG analyzed the data. CH wrote the manuscript with input and contributions from MP, JS, and SG. All authors have read and agreed to the final version of the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.