Tandem InCl3-Promoted Hydroperoxide Rearrangements and Nucleophilic Additions: A Straightforward Entry to Benzoxacycles.

The acid-catalyzed rearrangement of organic peroxides is generally associated with C-C-bond cleavages (Hock and Criegee rearrangements), with the concomitant formation of an oxocarbenium intermediate. This article describes the tandem process between a Hock or Criegee oxidative cleavage and a nucleophilic addition onto the oxocarbenium species (in particular a Hosomi-Sakurai-type allylation), under InCl3 catalysis. It was applied to the synthesis of 2-substituted benzoxacycles (chromanes and benzoxepanes), including a synthesis of the 2-(aminomethyl)chromane part of sarizotan, and a total synthesis of erythrococcamide B.

Characterization of photoproducts and global ecotoxicity of chlorphenesin: A preservative used in skin care products.

Photolysis experiments of chlorphenesin, used as a preservative in cosmetic products, were performed in aqueous solution and on a cream used in cosmetics. Three by-products resulting from the direct UV-visible photodegradation of chlorphenesin were characterized by chromatography (gas and liquid) coupled with tandem mass spectrometry (GC-MS/MS and LC-HR MS/MS) and found in both solutions. In vitro tests on Vibrio fischeri bacteria showed that the overall ecotoxicity of chlorphenesin increased with increasing irradiation time in both samples. In silico QSAR (Quantitative Structure Activity Relationship) tests were performed using T.E.S.T. (Toxicity Estimation Software Tool). Among the degradation compounds identified, 4-chlorophenol must contribute to the increased ecotoxicity of the photolyzed solution since the in silico LC50 estimated for all tests performed are always lower than those obtained for chlorphenesin.

Les expériences de photolyse de la chlorphénésine, qui s'utilise comme conservateur dans les produits cosmétiques, ont été réalisées en solution aqueuse et sur une crème utilisée dans les cosmétiques. Trois sous-produits résultant de la photodégradation directe UV-visible de la chlorphénésine ont été caractérisés par chromatographie (gaz et liquide) couplée à une spectrométrie de masse en tandem (GC-MS/MS et LC-HR MS/MS) et trouvés dans les deux solutions. Les tests in vitro sur les bactéries Vibrio fischeri ont montré que l'écotoxicité globale de la chlorphénésine augmentait avec l'augmentation du temps d'irradiation dans les deux échantillons. Des tests QSAR (Quantitative Structure Activity Relationship, relation d'activité de structure quantitative) in silico ont été réalisés à l'aide du logiciel T.E.S.T. (Toxicity Estimation Software Tool, outil logiciel d'estimation de la toxicité). Parmi les composés de dégradation identifiés, le 4-chlorophénol doit contribuer à l'augmentation de l'écotoxicité de la solution photolysée puisque la LC50 in silico estimée pour l'ensemble des essais réalisés est toujours inférieure à celle obtenue pour la chlorphénésine.

Reaction of Phosphines with 1-Azido-(2-halogenomethyl)benzene Giving Aminophosphonium-Substituted Indazoles.

The reaction between a 1-azido-(2-halogenomethyl)benzene and a phosphine gives different products depending on the nature of the halogen, the phosphine itself, and the solvent employed. While PPh3 (2 equiv) reacts with the chloro reagent in toluene to give the expected iminophosphorane-phosphonium adduct, trialkylphosphines (PCy3 and PEt3) surprisingly furnish an aminophosphonium substituted by a zwitterionic indazole. The bicyclic product can also form from PPh3 using the bromo reagent in acetonitrile. A mechanism is proposed for this cyclization based on DFT calculations.

Use of ß3-methionine as an amino acid substrate of Escherichia coli methionyl-tRNA synthetase.

Polypeptides containing ß-amino acids are attractive tools for the design of novel proteins having unique properties of medical or industrial interest. Incorporation of ß-amino acids in vivo requires the development of efficient aminoacyl-tRNA synthetases specific of these non-canonical amino acids. Here, we have performed a detailed structural and biochemical study of the recognition and use of ß3-Met by Escherichia coli methionyl-tRNA synthetase (MetRS). We show that MetRS binds ß3-Met with a 24-fold lower affinity but catalyzes the esterification of the non-canonical amino acid onto tRNA with a rate lowered by three orders of magnitude. Accurate measurements of the catalytic parameters required careful consideration of the presence of contaminating α-Met in ß3-Met commercial samples. The 1.45 Å crystal structure of the MetRS: ß3-Met complex shows that ß3-Met binds the enzyme essentially like α-Met, but the carboxylate moiety is mobile and not adequately positioned to react with ATP for aminoacyl adenylate formation. This study provides structural and biochemical bases for engineering MetRS with improved ß3-Met aminoacylation capabilities.

FeIII and FeII Phosphasalen Complexes: Synthesis, Characterization, and Catalytic Application for 2-Naphthol Oxidative Coupling.

We report on the synthesis and characterization of three iron(III) phosphasalen complexes, [FeIII (Psalen)(X)] differing in the nature of the counter-anion/exogenous ligand (X- =Cl- , NO3 - , OTf- ), as well as the neutral iron(II) analogue, [FeII (Psalen)]. Phosphasalen (Psalen) differs from salen by the presence of iminophosphorane (P=N) functions in place of the imines. All the complexes were characterized by single-crystal X-ray diffraction, UV/Vis, EPR, and cyclic voltammetry. The [FeII (Psalen)] complex was shown to remain tetracoordinated even in coordinating solvent but surprisingly exhibits a magnetic moment in line with a FeII high-spin ground state. For the FeIII complexes, the higher lability of triflate anion compared to nitrate was demonstrated. As they exhibit lower reduction potentials compared to their salen analogues, these complexes were tested for the coupling of 2-naphthol using O2 from air as oxidant. In order to shed light on this reaction, the interaction between 2-naphthol and the FeIII (Psalen) complexes was studied by cyclic voltammetry as well as UV/Vis spectroscopy.

Ultraviolet-visible phototransformation of dehydroacetic acid - Structural characterization of photoproducts and global ecotoxicity.

RATIONALE: The present work is devoted to the structural elucidation of by-products issued from the direct ultraviolet-visible (UV-vis) irradiation of dehydroacetic acid (DHA) in solution and in cosmetic emulsion. METHODS: Analyses were carried out using gas chromatography coupled with ion trap mass spectrometry and by high-performance liquid chromatography coupled with ultrahigh-resolution Fourier transform ion cyclotron resonance mass spectrometry (LC/UHRMS). The potential toxicities of by-products were estimated by in silico calculations based on a QSAR (Quantitative Structure-Activity Relationship) approach and by in vitro bioassays conducted on Vibrio fischeri bacteria. RESULTS: Three photoproducts were detected by LC/MS while one photoproduct was detected by GC/MS. The first photoproduct (PP1) corresponds to an isomer of DHA while two isomeric compounds correspond to dimeric structures. The oral rat LD50 of PP1 was evaluated to be 4.5 times lower than that of the parent molecule which classes it in the category 'moderately toxic' on the Hodge and Sterne toxicity classification. In vitro assays on Vibrio fischeri bacteria showed that the global ecotoxicity of the DHA solution increases with irradiation time. CONCLUSIONS: With the exception of one photoproduct, the structures proposed for the photoproducts on the basis of mass spectral interpretation have not been reported in previous studies. All photoproducts, with the exception of dimers, were detected after irradiation in the cosmetic emulsion. This result shows that personal care products containing DHA must be protected from direct sunlight to prevent photodegradation.

Nanostructure Changes upon Polymerization of Aqueous and Organic Phases in Organized Mixtures.

The nanostructure of a microemulsion can be strongly affected by the liquid-to-solid transition during polymerization. Here, we examined the evolution of nanostructures of different ternary mixtures, including two microemulsions and a single lamellar phase that upon polymerization are quantitatively studied by SAXS/WAXS and DSC experiments systematically performed before and after the polymerization of both aqueous and organic phases. Samples are mixtures of the poly(2-acrylamido-2-methylpropanesulfonic acid) network as the aqueous phase and poly(hexyl methacrylate) as the organic phase stabilized by Brij35 surfactant. Upon polymerization, the surfactant is excluded from the water/oil interface and crystallizes, strongly changing the nanostructure of samples where it is the main component. In samples where the aqueous phase is the main component, only a few changes in structure are observed upon polymerization. This study demonstrates quantitatively the possibility to preserve nanostructures during polymerization, thus inducing a templating effect.

Photodegradation of cyprodinil under UV-visible irradiation - chemical and toxicological approaches.

RATIONALE: Cyprodinil is a fungicide active on grapes, strawberries, tomatoes, and many other fruits. Under UV-visible irradiation, it undergoes photodegradation through various processes to form transformation products (TPs) whose structures and potential toxicities are unknown. The structures of the TPs were elucidated by comparing the photodegradation of cyprodinil and cyprodinil-D5 . The potential toxicities of these compounds were compared with that of cyprodinil. METHODS: Aqueous solutions of cyprodinil were irradiated in a reactor equipped with a mercury vapor lamp. Analyses were carried out using high-performance liquid chromatography coupled to a quadrupole time-of-flight (QTOF) mass spectrometer or to a SolarixXR 9.4 Tesla Fourier transform (FT) mass spectrometer. High-resolution mass measurements, MS/MS and isotopic labeling experiments allowed structural elucidation of the cyprodinil TPs. The toxicities were estimated by three tests in silico using the TEST software and in vitro bioassays using Vibrio fischeri bacteria. These bioassays were carried out on irradiated solution for several exposure times and non-irradiated solutions. RESULTS: The structures of 19 photoproducts were characterized by LC/HRMS/MS after 4 h of irradiation of a cyprodinil aqueous solution. The use of cyprodinil-D5 allowed the TPs to be characterized with more confidence. Knowing the structure of the TPs allows the estimation of their potential toxicities by in silico tests. Most of the photoproducts are potentially more toxic than the parent compound, based on the oral rat LD50 values, and most of them might induce more developmental and mutagenic toxicities. In vitro assays on Vibrio fischeri bacteria showed that the global ecotoxicity of the cyprodinil solution significantly increases with irradiation time. CONCLUSIONS: Structures of photoproducts were characterized after irradiation of a cyprodinil aqueous solution combining LC/HRMS, LC/HRMS/MS and the use of a labeled compound. Their formations imply several photodegradation reactions, namely direct bond cleavages, cyclization, isomerization and hydroxylation. Most of the TPs exhibit a toxicity significantly higher than that of the parent molecule. Copyright © 2016 John Wiley & Sons, Ltd.

Structural elucidation of metolachlor photoproducts by liquid chromatography/high-resolution tandem mass spectrometry.

RATIONALE: Metolachlor is one of the most intensively used chloroacetanilide herbicides in agriculture. It has been detected in water; consequently, under UV-visible irradiation, it can be transformed in degradation products (TPs). The structures of TPs were elucidated by liquid chromatography/high-resolution tandem mass spectrometry (LC/HR-MS/MS). The potential toxicities of these TPs were estimated by in silico tests. METHODS: Aqueous solutions of metolachlor were irradiated in a self-made reactor equipped with a mercury vapor lamp. Analyses were carried out using high-performance liquid chromatography coupled to quadrupole time-of-flight (QTOF) mass spectrometer. High-resolution m/z measurements, MS/MS and isotopic labeling experiments allowed structural elucidation of metolachlor TPs. Their toxicities were estimated in silico, using the T.E.S.T. RESULTS: Ten major metolachlor photoproducts were characterized by LC/MS/MS after irradiation of metolachlor in aqueous solution. Elucidation of their chemical structures was identified using high-resolution measurements and MS/MS experiments. They resulted from the combination of dehalogenation, hydroxylation and cyclisation processes. The potential oral rat lethal dose (LD50) was assessed with QSAR tests for metolachlor and each photoproduct. Results indicate that most of the TPs are much more toxic than metolachlor. CONCLUSIONS: UV-vis irradiation of metolachlor in aqueous solution leads to the formation of ten photoproducts. QSAR estimations show that the location of added hydroxyl group(s) is of key relevance as regards to biological activity and that routine water analysis should take into account the TPs are more toxic than the parent molecule.

Isomerization of fenbuconazole under UV-visible irradiation - chemical and toxicological approaches.

RATIONALE: Fenbuconazole is a fungicide commonly used for the protection of vineyards, vegetables and grain crops. Under UV-visible irradiation, it undergoes isomerization through various cyclization processes. Isomeric structures were elucidated by liquid chromatography/high-resolution multiple-stage mass spectrometry (LC/HR-MS(n) ) coupling. The potential toxicities of these isomers were estimated by in silico tests. METHODS: Aqueous solutions of fenbuconazole and grapes treated with this fungicide were irradiated in a self-made reactor equipped with a mercury vapor lamp. Analyses were carried out using high-performance liquid chromatography (HPLC) coupled with Fourier transform ion cyclotron resonance mass spectrometry (FT-ICRMS). High-resolution m/z measurements, multiple-stage mass spectrometry and isotopic labeling experiments allowed structural elucidation of the isomers of fenbuconazole. In silico toxicity estimations were carried out using the T.E.S.T. RESULTS: Seven isomers of fenbuconazole were detected after irradiation of the fungicide in aqueous solution; the major ones were also detected in the flesh of treated grapes irradiated under laboratory conditions. Elucidation of their chemical structures owing to high resolution measurements and multi-stage collision induced dissociation experiments allowed confirmation of photo-transformation pathways mainly dominated by cyclization processes. Photo-induced isomers exhibited higher potential toxicities than fenbuconazole for Daphnia magna and fathead minnow species. CONCLUSIONS: UV-visible irradiation of fenbuconazole in aqueous solution and on grapes leads to the formation of isomers, all of which being potentially much more toxic than the parent fungicide.

Gas-phase lithium cation affinity of glycine.

The gas-phase lithium cation binding thermochemistry of glycine has been determined theoretically by quantum chemical calculations at the G4 level and experimentally by the extended kinetic method using electrospray ionization quadrupole time-of-flight tandem mass spectrometry. The lithium cation affinity of glycine, ∆(Li)H°(298)(GLY), i.e. the∆(Li)H°(298) of the reaction GlyLi(+)→ Gly + Li(+)) given by the G4 method is equal to 241.4 kJ.mol(-1) if only the most stable conformer of glycine is considered or to 242.3 kJ.mol(-1) if the 298K equilibrium mixture of neutral conformers is included in the calculation. The ∆(Li)H°(298)(GLY) deduced from the extended kinetic method is obviously dependent on the choice of the Li(+) affinity scale, thus∆(Li)H°(298)(GLY) is equal to 228.7±0.9(2.0) kJ.mol(- 1) if anchored to the recently re-evaluated lithium cation affinity scale but shifted to 235.4±1.0 kJ.mol(-1) if G4 computed lithium cation affinities of the reference molecules is used. This difference of 6.3 kJ.mol(-1) may originate from a compression of the experimental lithium affinity scale in the high ∆(Li)H°(298) region. The entropy change associated with the reaction GlyLi(+)→Gly + Li(+) reveals a gain of approximately 15 J.mol(-) 1.K(-1) with respect to monodentate Li(+) acceptors. The origin of this excess entropy is attributed to the bidentate interaction between the Li(+) cation and both the carbonyl oxygen and the nitrogen atoms of glycine. The computed G4 Gibbs free energy,∆(Li)G°(298)(GLY) is equal to 205.3 kJ.mol(-1), a similar result, 201.0±3.4 kJ.mol(-1), is obtained from the experiment if the∆(Li)G°(298) of the reference molecules is anchored on the G4 results.

UV-visible degradation of boscalid--structural characterization of photoproducts and potential toxicity using in silico tests.

RATIONALE: Boscalid is a carboximide fungicide mainly used for vineyard protection as well as for tomato, apple, blueberry and various ornamental cultivations. The structural elucidation of by-products arising from the UV-visible photodegradation of boscalid has been investigated by gas chromatography/multi-stage mass spectrometry (GC/MS(n) ) and liquid chromatography/tandem mass spectrometry (LC/MS/MS) couplings. The potential toxicities of transformation products were estimated by in silico calculations. METHODS: Aqueous solutions of boscalid were irradiated up to 150 min in a self-made reactor equipped with a mercury lamp. Analyses were carried out using a gas chromatograph coupled with an ion trap mass spectrometer operated in both electron ionization (EI) and chemical ionization (CI) modes and a liquid chromatograph coupled with a quadrupole time-of-flight (Q-TOF) mass spectrometer operated in electrospray ionization (ESI) mode. Multiple-stage collision-induced dissociation (CID) experiments were performed to establish dissociation pathways of ions. The QSAR (Quantitative Structure-Activity Relationship) T.E.S.T. program allowed the estimation of the toxicities of the by-products. RESULTS: Eight photoproducts were investigated. Chemical structures were proposed not only on the interpretation of multi-stage CID experiments, but also on kinetics data. These structures led us to suggest photodegradation pathways. Three photoproducts were finally detected in Lebanon in a real sample of grape leaves for which routine analysis had led to the detection of boscalid at 4 mg kg(-1). CONCLUSIONS: With one exception, the structures proposed for the photoproducts on the basis of mass spectra interpretation have not been reported in previous studies. In silico toxicity predictions showed that two photoproducts are potentially more toxic than the parent compound considering oral rat LD50 while five photoproducts may induce mutagenic toxicity. With the exception of one compound, all photoproducts may potentially induce developmental toxicity.

Discovery of a series of portimine-A fatty acid esters in mussels.

Vulcanodinium rugosum is a benthic dinoflagellate known for producing pinnatoxins, pteriatoxins, portimines and kabirimine. In this study, we aimed to identify unknown analogs of these emerging toxins in mussels collected in the Ingril lagoon, France. First, untargeted data acquisitions were conducted by means of liquid chromatography coupled to hybrid quadrupole-orbitrap mass spectrometry. Data processing involved a molecular networking approach, and a workflow dedicated to the identification of biotransformed metabolites. Additionally, targeted analyses by liquid chromatography coupled to triple quadrupole mass spectrometry were also implemented to further investigate and confirm the identification of new compounds. For the first time, a series of 13-O-acyl esters of portimine-A (n = 13) were identified, with fatty acid chains ranging between C12:0 and C22:6. The profile was dominated by the palmitic acid conjugation. This discovery was supported by fractionation experiments combined with the implementation of a hydrolysis reaction, providing further evidence of the metabolite identities. Furthermore, several analogs were semi-synthesized, definitively confirming the discovery of these metabolization products. A new analog of pinnatoxin, with a molecular formula of C42H65NO9, was also identified across the year 2018, with the highest concentration observed in August (4.5 µg/kg). The MS/MS data collected for this compound exhibited strong structural similarities with PnTX-A and PnTX-G, likely indicating a substituent C2H5O2 in the side chain at C33. The discovery of these new analogs will contribute to deeper knowledge of the chemodiversity of toxins produced by V. rugosum or resulting from shellfish metabolism, thereby improving our ability to characterize the risks associated with these emerging toxins.

Ultraviolet degradation of procymidone--structural characterization by gas chromatography coupled with mass spectrometry and potential toxicity of photoproducts using in silico tests.

RATIONALE: Procymidone is a dicarboximide fungicide mainly used for vineyard protection but also for different crops. The structural elucidation of by-products arising from the UV-visible photodegradation of procymidone has been investigated by gas chromatography coupled with mass spectrometry. The potential toxicities of photoproducts were estimated by in silico tests. METHODS: Aqueous solutions of procymidone were irradiated for up to 90 min in a self-made reactor equipped with a mercury lamp. Analyses were carried out on a gas chromatograph coupled with an ion trap mass spectrometer operated in electron ionization and methanol positive chemical ionization. Multistage collision-induced dissociation (CID) experiments were performed to establish dissociation pathways of ions. Toxicities of byproducts were estimated using the QSAR T.E.S.T. program. RESULTS: Sixteen photoproducts were investigated. Chemical structures were proposed mainly based on the interpretation of multistage CID experiments, but also on their relative retention times and kinetics data. These structures enabled photodegradation pathways to be suggested. Only three photoproducts remain present after 90 min of irradiation. Among them, 3,5-dichloroaniline presents a predicted rat LD50 toxicity about ten times greater than that of procymidone. CONCLUSIONS: 3,5-Dichloroaniline is the only photoproduct reported in previous articles. Eight by-products among the sixteen characterized might be as toxic, if not more, than procymidone itself considering the QSAR-predicted rat LD50.

Phosphinoquinoline supported CoII, NiII, and FeII complexes: divergent behaviour upon reduction.

The reduction of [CoLBr2], a CoII complex supported by a diisopropylphosphinoquinoline (L) ligand, induced a ligand coupling giving access to a (PNNP) supported CoII complex which was isolated in 70% yield. This complex was formed using a minimum of 2 equivalents of a reductant (either Mn or KC8). The fate of [CoLBr2] in the presence of 1 equivalent of a reductant was more difficult to study; nevertheless, a CoI complex was characterised in the solid state. In order to determine whether this ligand coupling could occur with other 3d metals, L supported FeII and NiII complexes were synthesised. While no compound could be identified upon reduction of [FeLBr2], both [NiLBr2] and [NiL2Br](Br) led to the reduction at the metal center allowing the isolation of an original Ni0 trimer in a satisfactory yield. This study shows the different behaviours of these 3d metal complexes in the presence of a reductant.

Investigation of the unusual behavior of metolachlor under chemical ionization in a hybrid 3D ion trap mass spectrometer.

This article describes the strange behavior of the widely used herbicide metolachlor under chemical ionization conditions in a hybrid source ion trap mass spectrometer in gas chromatography/mass spectrometry (GC/MS) coupling. With the use of ammonia as the reagent gas, metolachlor provides a chlorinated ion at m/z 295/297, almost as abundant as the protonated molecule at m/z 284/286, which cannot be isolated to perform tandem mass spectrometry (MS(n)) experiments. Curiously, this ion at m/z = M + 12 is not observed for the herbicides acetochlor and alachlor, which present very similar chemical structures. The chemical structure of the m/z 295/297 ions and the explanation of the observed phenomenon based on the metastable behavior of these ions were elucidated on the basis of experiments including isotopic labeling and modifications of the operating conditions of the ion trap mass spectrometer. This work allows one to give new recommendations for an optimized use of hybrid source ion trap mass spectrometers.

Investigation of the dissociation pathways of metolachlor, acetochlor and alachlor under electron ionization - application to the identification of ozonation products.

With the future aim of using gas chromatography coupled with mass spectrometry to characterize the transformation products of ozonated herbicides: metolachlor, acetochlor and alachlor, an interpretation of their electron ionization mass spectra is presented. Fragmentation mechanisms are proposed on the basis of isotopic labelling and multiple-stage mass spectrometry experiments carried out on an ion trap mass spectrometer. We also give examples in order to demonstrate how the elucidation of such fragmentation mechanisms for herbicides may simplify the characterization of their ozonation products.

Development of a liquid chromatography-tandem mass spectrometry method to determine colistin, bacitracin and virginiamycin M1 at cross-contamination levels in animal feed.

Cross-contamination of animal feed with antibiotics may occur during manufacturing in feed mills, because shared production lines can be used for medicated and non-medicated feed, but may also occur during transport, storage and at the farm level. This is a major issue in the current context where antimicrobial usage must be controlled in order to maintain their effectiveness. A LC-MS/MS method was developed for the determination of colistin, bacitracin A and virginiamycin M1 in feed for pigs, poultry and rabbits at concentrations similar to those encountered in cross-contamination. After investigating various issues related to colistin behaviour and matrix effects, we successfully validated this method according to the requirements of European regulations in terms of linearity, trueness, precision, limit of quantification and limit of decision. Trueness ranged 88.6-107.8% and precision ranged 12.6-21.2%. We then applied this method to the analysis of medicated pig feed to check the performance of the method on "real" samples of medicated feed. We subsequently analysed non-medicated pig, and rabbit feed samples, collected directly on farms, to check the rate of cross-contamination. No samples were contaminated by colistin, bacitracin, or virginiamycin.

Elucidation of the dissociation pathways of electro-ionized estrone.

With the future aim of using gas chromatography coupled with mass spectrometry to characterize the transformation products of estrone submitted to UV-photolysis or to waste water treatment plants, an interpretation of the electron impact mass spectrum of estrone is presented. Fragmentation mechanisms are proposed on the basis of high-resolution measurements performed with a magnetic sector analyzer. Multiple-stage mass spectrometry experiments were carried out using an ion trap mass spectrometer. The structures proposed for product ions were confirmed by the m/z shifts observed in the estrone-d(4) and estrone methyl ether electron ionization mass spectra. If the formation of some of the most abundant ions may easily be explained by alpha-cleavages and retro-Diels-Alder type rearrangements, complex mechanisms need to be considered to rationalize the formation of others. Isotope labelling allows discrimination of isobaric ions.

Elucidation of the decomposition pathways of protonated and deprotonated estrone ions: application to the identification of photolysis products.

With the future aim of elucidating the unknown structures of estrogen degradation products, we characterized the dissociation pathways of protonated estrone (E1) under collisional activation in liquid chromatography/tandem mass spectrometry (LC/MS/MS) experiments employing a quadrupole time-of-flight mass spectrometer. Positive ion and negative ion modes give information on the protonated and deprotonated molecules and their product ions. The mass spectra of estrone methyl ether (CH(3)-E1) and estrone-d(4) (E1-d(4)) were compared with that of E1 in order (i) to elucidate the dissociation mechanisms of protonated and deprotonated molecules and (ii) to propose likely structures for each product ions. The positive ion acquisition mode yielded more fragmentation. The mass spectra of E1 were compared with those of estradiol (E2), estriol (E3) and 17-ethynylestradiol (EE2). This comparison allowed the identification of marker ions for each ring of the estrogenic structure. Accurate mass measurements have been carried out for all the identified ions. The resulting ions revealed to be useful for the characterization of structural modifications induced by photolysis on each ring of the estrone molecule. These results are very promising for the determination of new metabolites in the environment.