Leonardo Dos Santos | Instituto Nacional de Pesquisas Espaciais (original) (raw)
Papers by Leonardo Dos Santos
Pathology, 1996
Chromoblastomycosis, a localized chronic cutaneous and subcutaneous infection of the skin caused ... more Chromoblastomycosis, a localized chronic cutaneous and subcutaneous infection of the skin caused by pigmented fungi, is most common in the world's tropical and subtropical zones. The condition rarely occurs in Australia. We present 6 cases of chromoblastomycosis seen at the Royal Darwin Hospital, Northern Territory, from 1989 to 1994 and affecting predominantly male Caucasians ranging from 38 to 71 yrs of age. Clinically the lesions were verrucous or nodular. They mimicked basal or squamous cell carcinoma, nevi or solar keratoses. Histopathologic findings were nonspecific. The only pathognomonic finding was the presence of brown spores or sclerotic bodies within granulomata or within microabscesses in the skin.
International Journal of Mass Spectrometry, 2005
The general concepts, advantages, and applications of on-line and off-line screening to organic r... more The general concepts, advantages, and applications of on-line and off-line screening to organic reaction mechanistic studies applying API-MS are reviewed. An overview is presented of the development and the present stage of connected microreactors to API ion-sources. Examples of the successful application of API in revealing, elucidating, and helping to consolidate several proposed mechanisms of organic reactions are summarized. Finally, a variety of outstanding features and advantages that make API-MS the most suitable tool for the fast screening of intermediates directly from solution, and the exceptional gains in chemical information for organic chemists are also emphasized.
Angewandte Chemie-international Edition, 2006
Journal of Organic Chemistry, 2004
Described are the first enantioselective total syntheses of (+)-arborescidine A ((+)-1), (-)arbor... more Described are the first enantioselective total syntheses of (+)-arborescidine A ((+)-1), (-)arborescidine B ((-)-2), and (-)-arborescidine C ((-)-3), via routes that proceeded in five steps and 50% overall yield, eight steps and 61% overall yield, and nine steps and 51% overall yield, respectively, from 6-bromotryptamine . The syntheses feature the use of the Noyori catalytic asymmetric hydrogen-transfer reaction to introduce chirality in dihydro--carbolines 6 and 8. On the basis of an ample precedent from Noyori's work, the reduction produces dihydro--carbolines, and ultimately the natural products, possessing the R absolute configuration. The synthetic arborescidines displayed optical rotations that were opposite in sign those of the natural products, thereby supporting the S configuration for natural arborescidines A (1) and B (2) and the (3S,17S) configuration for natural arborescidine C (3). Our results are in agreement with the initial stereochemical assignment by Païs and co-workers, and are counter to their recently revised assignment.
Rapid Communications in Mass Spectrometry, 2006
Electrospray ionization (ESI) mass spectrometry (MS) and tandem mass spectrometry (MS/MS) were us... more Electrospray ionization (ESI) mass spectrometry (MS) and tandem mass spectrometry (MS/MS) were used to monitor the oxidation of phenol by a novel heterogeneous Fenton system based on a Fe0/Fe3O4 composite and H2O2. On-line ESI-MS(/MS) shows that this heterogeneous system promotes prompt oxidation of phenol to hydroquinone, which is subsequently oxidized to quinone, other cyclic poly-hydroxylated intermediates and an acyclic carboxylic acid. A peroxide-type intermediate, probably formed via an electrophilic attack of HOO. on the phenol ring, was also intercepted and characterized. ESI-MS(/MS) monitoring of the oxidation of two other model aromatic compounds, benzene and chlorobenzene, indicates the participation of analogous intermediates. These results suggest that oxidation by the heterogeneous system is promoted by highly reactive HO. and HOO. radicals generated from H2O2 on the surface of the Fe0/Fe3O4 composite via a classical Fenton-like mechanism. Copyright © 2006 John Wiley & Sons, Ltd.
![Research paper thumbnail of Synthesis and crystal structure of 2,4-dihydro-4-[(5-hydroxy-3-methyl-1-phenyl-1H-pyrazol-4-yl)imino]-5-methyl-2-phenyl-3H-pyrazol-3-one and its copper(II) complex](https://attachments.academia-assets.com/49985797/thumbnails/1.jpg)
](Polyhedron, 2006
2-Diazo-3-methyl-1-phenyl-5-pyrazolone (2) and 2,4-dihydro-4-[(5-hydroxy-3-methyl-1-phenyl-1H-pyr... more 2-Diazo-3-methyl-1-phenyl-5-pyrazolone (2) and 2,4-dihydro-4-[(5-hydroxy-3-methyl-1-phenyl-1H-pyrazol-4-yl)imino]-5-methyl-2phenyl-3H-pyrazol-3-one (3) were obtained in a one-pot reaction from 3-methyl-1-phenylpyrazol-5-one (1), mesyl azide, and K 2 CO 3 in MeOH or CH 2 Cl 2 solution. NMR, IR and ESI mass spectra as well as the crystal structure are reported for red colored 3. The crystal structure determined at 150 K reveals that the corresponding bonds in the two phenylpyrazol-5-one moieties in each of the two independent ''U'' shaped molecules have essentially the same lengths, with an extensive delocalization in the central O-C-C-N-C-C-O fragment of the molecule. In particular, the hydrogen atom, formally a part of a hydroxyl group, is found near-midway [O1-HY and O11-HY = 1.24(4) and 1.19(4) Å , in molecule 1, and O21-HX and O31-HY = 1.203(4) and 1.19(4) Å , in molecule 2] between the two oxygen atoms (formally in a carbonyl and a hydroxy group), with near linear O-H-O bond angles of 173.8(4)°and 172.7(4)°in the two independent molecules. All C-O bond lengths are in the narrow range of 1.271(3)-1.288(3) Å . Further, since this compound shows different coordinating groups, its binding ability towards copper(II) ions was investigated. A dark red complex 4, obtained by reaction of 3 with copper(II) ions at stoichiometric ratio, was characterized as a neutral 1:1 species, [3:CuCl 2 ], involving tautomeric forms, by ESI-MS, ESI-MS/MS, IR, UV/Vis and EPR spectra. Interestingly, copper coordination to ligand 3 occurs solely by oxygen atoms, in spite of the presence of nitrogen donor centers. The deprotonation of 4 was monitored by UV/Vis, and a corresponding pKa value was determined as (5.6 ± 0.2).
Journal of Organic Chemistry, 2004
Nonionic hydrazine reacts with anionic bis(2,4-dinitrophenyl) phosphate (BDNPP), giving 2,4dinitr... more Nonionic hydrazine reacts with anionic bis(2,4-dinitrophenyl) phosphate (BDNPP), giving 2,4dinitrophenyl hydrazine and dianionic 2,4-dinitrophenyl phosphate by an S N 2(Ar) reaction, and at the phosphoryl center, giving 2,4-dinitrophenoxide ion and a transient phosphorylated hydrazine that rearranges intramolecularly to N-(2,4-dinitrophenyl)-N-phosphonohydrazine. Approximately 58% of the reaction at pD ) 10 occurs by N-phosphorylation, as shown by 31 P NMR spectroscopy. Reaction of HO 2is wholly at phosphorus, and the intermediate peroxophosphate reacts intramolecularly, displacing a second 2,4-dinitrophenoxide ion, or with H 2 O 2 , giving 2,4-dinitrophenyl phosphate and O 2 . Rate constants of O-and N-phosphorylation in reactions at phosphorus of NH 2 -NH 2 , HO 2 -, and NH 2 OH and its methyl derivatives follow Brönsted relationships with similar slopes, but plots differ for oxygen and nitrogen nucleophiles. The reaction with NH 2 NH 2 has been probed by using both NMR spectroscopy and electrospray ionization mass and tandem mass spectrometry, with the novel interception of key reaction intermediates in the course of reaction.
European Journal of Organic Chemistry, 2008
During the last two decades there has been considerable growth in the development of electrospray... more During the last two decades there has been considerable growth in the development of electrospray ionization mass spectrometry (ESI-MS) as a practical method for studying reaction mechanisms. This tool allows interception and characterization of several key intermediates, either as transient species or as protonated/deprotonated forms of neutral species. Reaction pathways shown by ESI-MS(/MS) have been probed by gas-phase ion/molecule reactions, and expanded mechanisms have been elaborated based on mass spectrometric data. The successful application of ESI-MS in reveal-
Journal of Organic Chemistry, 2007
Tetrahedron Letters, 2001
Homopumiliotoxin 321B, R= Homopumiliotoxin 223G R=(CH 3 ) 2 CH Homopumiliotoxin 319B, R= Homopumi... more Homopumiliotoxin 321B, R= Homopumiliotoxin 223G R=(CH 3 ) 2 CH Homopumiliotoxin 319B, R= Homopumiliotoxin 319A, R= N OH R O O OH TETRAHEDRON LETTERS Tetrahedron Letters 42 (
Analytical Chemistry, 2004
Fast screening of low-MW compounds is performed by thin-layer chromatography (TLC) followed by di... more Fast screening of low-MW compounds is performed by thin-layer chromatography (TLC) followed by direct onspot matrix-assisted laser desorption/ionization time-offlight mass spectrometry identification with nearly "matrixfree" mass spectra using an UV-absorbing ionic liquid matrix. Owing to minimal background ions from the proton donor triethylamine/r-cyano-4-hydroxycinnamic acid ionic liquid matrix, three arborescidine alkaloids, the anesthesics levobupivacaine and mepivacaine, and the antibiotic tetracycline were readily characterized most frequently by the MS detection of their protonated molecules. The technique is fast and sensitive, requires little sample preparation and manipulation, and is therefore suitable for fast screening with TLC separation and MS identification of low-MW compounds, with potential applications in areas such as phytochemistry, synthetic chemistry, and product manufacturing quality monitoring.
Rapid Communications in Mass Spectrometry, 2006
Recently, it has been proposed (M. Claeys et al., Science 2004; 303: 1173) that the atmospheric O... more Recently, it has been proposed (M. Claeys et al., Science 2004; 303: 1173) that the atmospheric OHradical-mediated photooxidation of isoprene is a source of two major secondary organic aerosol (SOA) components, that is, 2-methylthreitol and 2-methylerythritol. These diastereoisomeric tetrols, which were characterized for the first time in the fine size fraction (<2.5 mm aerodynamic diameter) of aerosols collected in the Amazon rain forest during the wet season, were proposed to enhance the capability of the aerosols to act as cloud-condensation nuclei. In the present study, we performed the oxidation of isoprene in aqueous solution under conditions that attempted to mimic atmospheric OH-radical-induced photooxidization, and monitored and characterized on-line the reaction products via electrospray ionization mass (and tandem mass) spectrometry in the negative ion mode. The results show that the reaction of isoprene with photo-or chemically generated hydroxyl radicals indeed yields 2-methyltetrols. Other polyols were also detected, and they may therefore be considered as plausible SOA components eventually formed in normal or more extreme OH-radicalmediated photooxidation of biogenic isoprene.
Angewandte Chemie-international Edition, 2004
Scheme 3. The single Baylis-Hillman intermediate so far isolated and characterized by X-ray cryst... more Scheme 3. The single Baylis-Hillman intermediate so far isolated and characterized by X-ray crystallography. Scheme 4. Baylis-Hillman reactions monitored by ESI(+)-MS/MS. Reagents and conditions: a) DABCO (1 a), methyl acrylate (2 a), MeOH, RT. Scheme 5. Baylis-Hillman reaction of methyl acrylate and aldehydes catalyzed by DABCO. The protonated species expected to be intercepted and structurally characterized by ESI(+)-MS/MS, with their respective m/z ratios.
Journal of Organic Chemistry, 2005
From previous results with lower homologues, dehydroiodination of the three alkenyl--enamino este... more From previous results with lower homologues, dehydroiodination of the three alkenyl--enamino esters 3a-c was expected to provide six-membered N-heterocyclic products. The reactions of 3a-c with triethylamine are found to lead, however, to the unexpected stereoselective synthesis of the trisubstituted cyclopentane derivatives 4a-c, as confirmed by IR and NMR spectroscopy. Cyclopentanes 4a-c bear two chiral centers and a γ-amino ester moiety, and are therefore conformationally restricted analogues of γ-amino butyric acid (GABA), which is the major inhibitory neurotransmitter in the central nervous system. Use of electrospray ionization mass (ESI-MS) and tandem mass spectrometry (ESI-MS/MS) allowed the key iminium ion intermediates 5a-c + , as well as the protonated molecules of both the reactant and final products, [3a-c + H] + and [4a-c + H] + , to be intercepted and structurally characterized. From these findings a mechanism for this unexpected but synthetically attractive and efficient stereoselective reaction is proposed.
Environmental Science & Technology, 2005
High performance liquid chromatography (HPLC), ultraviolet spectroscopy (UV), and total organic c... more High performance liquid chromatography (HPLC), ultraviolet spectroscopy (UV), and total organic carbon (TOC) analyses show that caffeine is quickly and completely degraded under the oxidative conditions of the UV/H 2 O 2 , TiO 2 / UV, and Fenton systems but that the organic carbon content of the solution decreases much more slowly. Continuous on-line and real-time monitoring by electrospray ionization mass (ESI-MS) and tandem mass spectrometric experiments (ESI-MS/MS) as well as high accuracy MS measurements and gas chromatography-mass spectrometry analysis show that caffeine is first oxidized to N-dimethylparabanic acid likely via initial OH insertion to the C4dC8 caffeine double bond. A second degradation intermediate, di(N-hidroxymethyl)parabanic acid, has been identified by ESI-MS and characterized by ESI-MS/MS and high accuracy mass measurements. This polar and likely relatively unstable compound, which is not detected by offline GC-MS analysis, is likely formed via further oxidation of N-dimethylparabanic acid at both of its N-methyl groups and constitutes an unprecedented intermediate in the degradation of caffeine.
Analytica Chimica Acta, 2007
This work describes the optimization of a cloud point extraction (CPE) method for casein proteins... more This work describes the optimization of a cloud point extraction (CPE) method for casein proteins from cow milk samples. To promote phase separation, polyoxyethylene(8) isooctylphenyl ether (Triton ® X-114) and sodium chloride (NaCl) were used as nonionic surfactant and electrolyte, respectively. Using multivariate studies, four major CPE variables were evaluated: Triton ® X-114 concentration, sample volume, NaCl concentration, and pH. The results show that surfactant concentration and sample volume were the main variable affecting the CPE process, with the following optimized parameters: 1% (w/v) Triton ® X-114 concentration, 50 L of sample volume, 6% (w/v) NaCl concentration and extractions carried out at pH 7.0. At these conditions, 923 ± 66 and 67 ± 2 g mL −1 of total protein were found in the surfactant-rich and surfactant-poor phases, respectively. Finally, matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) was then used to evaluate those target proteins (␣ s1 -casein, ␣ s2 -casein and -casein) separation as well as to check the efficiency of the extraction procedure, making a fingerprint of those target proteins possible.
Journal of Organic Chemistry, 2004
Mono-and dimethylation of hydroxylamine on nitrogen does not significantly affect rates of initia... more Mono-and dimethylation of hydroxylamine on nitrogen does not significantly affect rates of initial attack of NHMeOH and NMe 2 OH on bis(2,4-dinitrophenyl)phosphate (BDNPP), which is largely by oxygen phosphorylation. O-Methylation, however, blocks this reaction and NH 2 OMe then slowly reacts with BDNPP via N-attack at phosphorus and at the aryl group. With NHMeOH, the initial product of O-attack at phosphorus reacts further, either by reaction with a second NHMeOH or by a spontaneous shift of NHMe to the aryl group via a transient cyclic intermediate. There is a minor N-attack of NHMeOH on BDNPP in an S N 2(Ar) reaction. Reactions occurring via N-attack are blocked by N-dimethylation, and reaction of NMe 2 OH with BDNPP occurs via O-attack, generating a long-lived product. Reaction mechanisms have been probed, and intermediates identified, by using both NMR and MS spectroscopy, with the novel interception of key reaction intermediates in the course of reaction by electrospray ionization mass and tandem mass spectrometry.
Chemistry-a European Journal, 2004
Analytical Chemistry, 2005
Efficient detection of aflatoxins B 1 , B 2 , G 1 , and G 2 has been performed by matrix-assisted... more Efficient detection of aflatoxins B 1 , B 2 , G 1 , and G 2 has been performed by matrix-assisted laser desorption/ ionization time-of-flight mass spectrometry using a UVabsorbing ionic liquid matrix to obtain "matrix-free" mass spectra and addition of NaCl to enhance sensitivity via Na + cationization. Using ionic r-cyano-4-hydroxycinnamic acid (Et 3 N-r-CHCA) as the matrix, matrix-free mass spectra in the m/z range of interest are acquired, and the B 1 , B 2 , G 1 , and G 2 aflatoxins are readily detected with an LOD as low as 50 fmol. The technique is fast, requires little sample preparation and no derivatization or chromatographic separation, and seems therefore to be suitable for high-throughput aflatoxin screening. It should be easily extended to other micotoxins and provide an attractive technique to control the quality of major crops subjected to huge world commercial trades such as peanuts, corn, and rice as well as to monitor bioterrorism threats by micotoxin poisoning.
Angewandte Chemie-international Edition, 2006
Among the various outstanding properties exhibited by ionic liquids (ILs), two of the most peculi... more Among the various outstanding properties exhibited by ionic liquids (ILs), two of the most peculiar are their very low vapor pressure [1] and pronounced supramolecular self-organization both in the condensed and gas phases. This unique set of properties make ionic liquids very attractive alternatives to classical organic solvents and water, opening also a wealth of [*] Dr.
Pathology, 1996
Chromoblastomycosis, a localized chronic cutaneous and subcutaneous infection of the skin caused ... more Chromoblastomycosis, a localized chronic cutaneous and subcutaneous infection of the skin caused by pigmented fungi, is most common in the world's tropical and subtropical zones. The condition rarely occurs in Australia. We present 6 cases of chromoblastomycosis seen at the Royal Darwin Hospital, Northern Territory, from 1989 to 1994 and affecting predominantly male Caucasians ranging from 38 to 71 yrs of age. Clinically the lesions were verrucous or nodular. They mimicked basal or squamous cell carcinoma, nevi or solar keratoses. Histopathologic findings were nonspecific. The only pathognomonic finding was the presence of brown spores or sclerotic bodies within granulomata or within microabscesses in the skin.
International Journal of Mass Spectrometry, 2005
The general concepts, advantages, and applications of on-line and off-line screening to organic r... more The general concepts, advantages, and applications of on-line and off-line screening to organic reaction mechanistic studies applying API-MS are reviewed. An overview is presented of the development and the present stage of connected microreactors to API ion-sources. Examples of the successful application of API in revealing, elucidating, and helping to consolidate several proposed mechanisms of organic reactions are summarized. Finally, a variety of outstanding features and advantages that make API-MS the most suitable tool for the fast screening of intermediates directly from solution, and the exceptional gains in chemical information for organic chemists are also emphasized.
Angewandte Chemie-international Edition, 2006
Journal of Organic Chemistry, 2004
Described are the first enantioselective total syntheses of (+)-arborescidine A ((+)-1), (-)arbor... more Described are the first enantioselective total syntheses of (+)-arborescidine A ((+)-1), (-)arborescidine B ((-)-2), and (-)-arborescidine C ((-)-3), via routes that proceeded in five steps and 50% overall yield, eight steps and 61% overall yield, and nine steps and 51% overall yield, respectively, from 6-bromotryptamine . The syntheses feature the use of the Noyori catalytic asymmetric hydrogen-transfer reaction to introduce chirality in dihydro--carbolines 6 and 8. On the basis of an ample precedent from Noyori's work, the reduction produces dihydro--carbolines, and ultimately the natural products, possessing the R absolute configuration. The synthetic arborescidines displayed optical rotations that were opposite in sign those of the natural products, thereby supporting the S configuration for natural arborescidines A (1) and B (2) and the (3S,17S) configuration for natural arborescidine C (3). Our results are in agreement with the initial stereochemical assignment by Païs and co-workers, and are counter to their recently revised assignment.
Rapid Communications in Mass Spectrometry, 2006
Electrospray ionization (ESI) mass spectrometry (MS) and tandem mass spectrometry (MS/MS) were us... more Electrospray ionization (ESI) mass spectrometry (MS) and tandem mass spectrometry (MS/MS) were used to monitor the oxidation of phenol by a novel heterogeneous Fenton system based on a Fe0/Fe3O4 composite and H2O2. On-line ESI-MS(/MS) shows that this heterogeneous system promotes prompt oxidation of phenol to hydroquinone, which is subsequently oxidized to quinone, other cyclic poly-hydroxylated intermediates and an acyclic carboxylic acid. A peroxide-type intermediate, probably formed via an electrophilic attack of HOO. on the phenol ring, was also intercepted and characterized. ESI-MS(/MS) monitoring of the oxidation of two other model aromatic compounds, benzene and chlorobenzene, indicates the participation of analogous intermediates. These results suggest that oxidation by the heterogeneous system is promoted by highly reactive HO. and HOO. radicals generated from H2O2 on the surface of the Fe0/Fe3O4 composite via a classical Fenton-like mechanism. Copyright © 2006 John Wiley & Sons, Ltd.
Polyhedron, 2006
2-Diazo-3-methyl-1-phenyl-5-pyrazolone (2) and 2,4-dihydro-4-[(5-hydroxy-3-methyl-1-phenyl-1H-pyr... more 2-Diazo-3-methyl-1-phenyl-5-pyrazolone (2) and 2,4-dihydro-4-[(5-hydroxy-3-methyl-1-phenyl-1H-pyrazol-4-yl)imino]-5-methyl-2phenyl-3H-pyrazol-3-one (3) were obtained in a one-pot reaction from 3-methyl-1-phenylpyrazol-5-one (1), mesyl azide, and K 2 CO 3 in MeOH or CH 2 Cl 2 solution. NMR, IR and ESI mass spectra as well as the crystal structure are reported for red colored 3. The crystal structure determined at 150 K reveals that the corresponding bonds in the two phenylpyrazol-5-one moieties in each of the two independent ''U'' shaped molecules have essentially the same lengths, with an extensive delocalization in the central O-C-C-N-C-C-O fragment of the molecule. In particular, the hydrogen atom, formally a part of a hydroxyl group, is found near-midway [O1-HY and O11-HY = 1.24(4) and 1.19(4) Å , in molecule 1, and O21-HX and O31-HY = 1.203(4) and 1.19(4) Å , in molecule 2] between the two oxygen atoms (formally in a carbonyl and a hydroxy group), with near linear O-H-O bond angles of 173.8(4)°and 172.7(4)°in the two independent molecules. All C-O bond lengths are in the narrow range of 1.271(3)-1.288(3) Å . Further, since this compound shows different coordinating groups, its binding ability towards copper(II) ions was investigated. A dark red complex 4, obtained by reaction of 3 with copper(II) ions at stoichiometric ratio, was characterized as a neutral 1:1 species, [3:CuCl 2 ], involving tautomeric forms, by ESI-MS, ESI-MS/MS, IR, UV/Vis and EPR spectra. Interestingly, copper coordination to ligand 3 occurs solely by oxygen atoms, in spite of the presence of nitrogen donor centers. The deprotonation of 4 was monitored by UV/Vis, and a corresponding pKa value was determined as (5.6 ± 0.2).
Journal of Organic Chemistry, 2004
Nonionic hydrazine reacts with anionic bis(2,4-dinitrophenyl) phosphate (BDNPP), giving 2,4dinitr... more Nonionic hydrazine reacts with anionic bis(2,4-dinitrophenyl) phosphate (BDNPP), giving 2,4dinitrophenyl hydrazine and dianionic 2,4-dinitrophenyl phosphate by an S N 2(Ar) reaction, and at the phosphoryl center, giving 2,4-dinitrophenoxide ion and a transient phosphorylated hydrazine that rearranges intramolecularly to N-(2,4-dinitrophenyl)-N-phosphonohydrazine. Approximately 58% of the reaction at pD ) 10 occurs by N-phosphorylation, as shown by 31 P NMR spectroscopy. Reaction of HO 2is wholly at phosphorus, and the intermediate peroxophosphate reacts intramolecularly, displacing a second 2,4-dinitrophenoxide ion, or with H 2 O 2 , giving 2,4-dinitrophenyl phosphate and O 2 . Rate constants of O-and N-phosphorylation in reactions at phosphorus of NH 2 -NH 2 , HO 2 -, and NH 2 OH and its methyl derivatives follow Brönsted relationships with similar slopes, but plots differ for oxygen and nitrogen nucleophiles. The reaction with NH 2 NH 2 has been probed by using both NMR spectroscopy and electrospray ionization mass and tandem mass spectrometry, with the novel interception of key reaction intermediates in the course of reaction.
European Journal of Organic Chemistry, 2008
During the last two decades there has been considerable growth in the development of electrospray... more During the last two decades there has been considerable growth in the development of electrospray ionization mass spectrometry (ESI-MS) as a practical method for studying reaction mechanisms. This tool allows interception and characterization of several key intermediates, either as transient species or as protonated/deprotonated forms of neutral species. Reaction pathways shown by ESI-MS(/MS) have been probed by gas-phase ion/molecule reactions, and expanded mechanisms have been elaborated based on mass spectrometric data. The successful application of ESI-MS in reveal-
Journal of Organic Chemistry, 2007
Tetrahedron Letters, 2001
Homopumiliotoxin 321B, R= Homopumiliotoxin 223G R=(CH 3 ) 2 CH Homopumiliotoxin 319B, R= Homopumi... more Homopumiliotoxin 321B, R= Homopumiliotoxin 223G R=(CH 3 ) 2 CH Homopumiliotoxin 319B, R= Homopumiliotoxin 319A, R= N OH R O O OH TETRAHEDRON LETTERS Tetrahedron Letters 42 (
Analytical Chemistry, 2004
Fast screening of low-MW compounds is performed by thin-layer chromatography (TLC) followed by di... more Fast screening of low-MW compounds is performed by thin-layer chromatography (TLC) followed by direct onspot matrix-assisted laser desorption/ionization time-offlight mass spectrometry identification with nearly "matrixfree" mass spectra using an UV-absorbing ionic liquid matrix. Owing to minimal background ions from the proton donor triethylamine/r-cyano-4-hydroxycinnamic acid ionic liquid matrix, three arborescidine alkaloids, the anesthesics levobupivacaine and mepivacaine, and the antibiotic tetracycline were readily characterized most frequently by the MS detection of their protonated molecules. The technique is fast and sensitive, requires little sample preparation and manipulation, and is therefore suitable for fast screening with TLC separation and MS identification of low-MW compounds, with potential applications in areas such as phytochemistry, synthetic chemistry, and product manufacturing quality monitoring.
Rapid Communications in Mass Spectrometry, 2006
Recently, it has been proposed (M. Claeys et al., Science 2004; 303: 1173) that the atmospheric O... more Recently, it has been proposed (M. Claeys et al., Science 2004; 303: 1173) that the atmospheric OHradical-mediated photooxidation of isoprene is a source of two major secondary organic aerosol (SOA) components, that is, 2-methylthreitol and 2-methylerythritol. These diastereoisomeric tetrols, which were characterized for the first time in the fine size fraction (<2.5 mm aerodynamic diameter) of aerosols collected in the Amazon rain forest during the wet season, were proposed to enhance the capability of the aerosols to act as cloud-condensation nuclei. In the present study, we performed the oxidation of isoprene in aqueous solution under conditions that attempted to mimic atmospheric OH-radical-induced photooxidization, and monitored and characterized on-line the reaction products via electrospray ionization mass (and tandem mass) spectrometry in the negative ion mode. The results show that the reaction of isoprene with photo-or chemically generated hydroxyl radicals indeed yields 2-methyltetrols. Other polyols were also detected, and they may therefore be considered as plausible SOA components eventually formed in normal or more extreme OH-radicalmediated photooxidation of biogenic isoprene.
Angewandte Chemie-international Edition, 2004
Scheme 3. The single Baylis-Hillman intermediate so far isolated and characterized by X-ray cryst... more Scheme 3. The single Baylis-Hillman intermediate so far isolated and characterized by X-ray crystallography. Scheme 4. Baylis-Hillman reactions monitored by ESI(+)-MS/MS. Reagents and conditions: a) DABCO (1 a), methyl acrylate (2 a), MeOH, RT. Scheme 5. Baylis-Hillman reaction of methyl acrylate and aldehydes catalyzed by DABCO. The protonated species expected to be intercepted and structurally characterized by ESI(+)-MS/MS, with their respective m/z ratios.
Journal of Organic Chemistry, 2005
From previous results with lower homologues, dehydroiodination of the three alkenyl--enamino este... more From previous results with lower homologues, dehydroiodination of the three alkenyl--enamino esters 3a-c was expected to provide six-membered N-heterocyclic products. The reactions of 3a-c with triethylamine are found to lead, however, to the unexpected stereoselective synthesis of the trisubstituted cyclopentane derivatives 4a-c, as confirmed by IR and NMR spectroscopy. Cyclopentanes 4a-c bear two chiral centers and a γ-amino ester moiety, and are therefore conformationally restricted analogues of γ-amino butyric acid (GABA), which is the major inhibitory neurotransmitter in the central nervous system. Use of electrospray ionization mass (ESI-MS) and tandem mass spectrometry (ESI-MS/MS) allowed the key iminium ion intermediates 5a-c + , as well as the protonated molecules of both the reactant and final products, [3a-c + H] + and [4a-c + H] + , to be intercepted and structurally characterized. From these findings a mechanism for this unexpected but synthetically attractive and efficient stereoselective reaction is proposed.
Environmental Science & Technology, 2005
High performance liquid chromatography (HPLC), ultraviolet spectroscopy (UV), and total organic c... more High performance liquid chromatography (HPLC), ultraviolet spectroscopy (UV), and total organic carbon (TOC) analyses show that caffeine is quickly and completely degraded under the oxidative conditions of the UV/H 2 O 2 , TiO 2 / UV, and Fenton systems but that the organic carbon content of the solution decreases much more slowly. Continuous on-line and real-time monitoring by electrospray ionization mass (ESI-MS) and tandem mass spectrometric experiments (ESI-MS/MS) as well as high accuracy MS measurements and gas chromatography-mass spectrometry analysis show that caffeine is first oxidized to N-dimethylparabanic acid likely via initial OH insertion to the C4dC8 caffeine double bond. A second degradation intermediate, di(N-hidroxymethyl)parabanic acid, has been identified by ESI-MS and characterized by ESI-MS/MS and high accuracy mass measurements. This polar and likely relatively unstable compound, which is not detected by offline GC-MS analysis, is likely formed via further oxidation of N-dimethylparabanic acid at both of its N-methyl groups and constitutes an unprecedented intermediate in the degradation of caffeine.
Analytica Chimica Acta, 2007
This work describes the optimization of a cloud point extraction (CPE) method for casein proteins... more This work describes the optimization of a cloud point extraction (CPE) method for casein proteins from cow milk samples. To promote phase separation, polyoxyethylene(8) isooctylphenyl ether (Triton ® X-114) and sodium chloride (NaCl) were used as nonionic surfactant and electrolyte, respectively. Using multivariate studies, four major CPE variables were evaluated: Triton ® X-114 concentration, sample volume, NaCl concentration, and pH. The results show that surfactant concentration and sample volume were the main variable affecting the CPE process, with the following optimized parameters: 1% (w/v) Triton ® X-114 concentration, 50 L of sample volume, 6% (w/v) NaCl concentration and extractions carried out at pH 7.0. At these conditions, 923 ± 66 and 67 ± 2 g mL −1 of total protein were found in the surfactant-rich and surfactant-poor phases, respectively. Finally, matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) was then used to evaluate those target proteins (␣ s1 -casein, ␣ s2 -casein and -casein) separation as well as to check the efficiency of the extraction procedure, making a fingerprint of those target proteins possible.
Journal of Organic Chemistry, 2004
Mono-and dimethylation of hydroxylamine on nitrogen does not significantly affect rates of initia... more Mono-and dimethylation of hydroxylamine on nitrogen does not significantly affect rates of initial attack of NHMeOH and NMe 2 OH on bis(2,4-dinitrophenyl)phosphate (BDNPP), which is largely by oxygen phosphorylation. O-Methylation, however, blocks this reaction and NH 2 OMe then slowly reacts with BDNPP via N-attack at phosphorus and at the aryl group. With NHMeOH, the initial product of O-attack at phosphorus reacts further, either by reaction with a second NHMeOH or by a spontaneous shift of NHMe to the aryl group via a transient cyclic intermediate. There is a minor N-attack of NHMeOH on BDNPP in an S N 2(Ar) reaction. Reactions occurring via N-attack are blocked by N-dimethylation, and reaction of NMe 2 OH with BDNPP occurs via O-attack, generating a long-lived product. Reaction mechanisms have been probed, and intermediates identified, by using both NMR and MS spectroscopy, with the novel interception of key reaction intermediates in the course of reaction by electrospray ionization mass and tandem mass spectrometry.
Chemistry-a European Journal, 2004
Analytical Chemistry, 2005
Efficient detection of aflatoxins B 1 , B 2 , G 1 , and G 2 has been performed by matrix-assisted... more Efficient detection of aflatoxins B 1 , B 2 , G 1 , and G 2 has been performed by matrix-assisted laser desorption/ ionization time-of-flight mass spectrometry using a UVabsorbing ionic liquid matrix to obtain "matrix-free" mass spectra and addition of NaCl to enhance sensitivity via Na + cationization. Using ionic r-cyano-4-hydroxycinnamic acid (Et 3 N-r-CHCA) as the matrix, matrix-free mass spectra in the m/z range of interest are acquired, and the B 1 , B 2 , G 1 , and G 2 aflatoxins are readily detected with an LOD as low as 50 fmol. The technique is fast, requires little sample preparation and no derivatization or chromatographic separation, and seems therefore to be suitable for high-throughput aflatoxin screening. It should be easily extended to other micotoxins and provide an attractive technique to control the quality of major crops subjected to huge world commercial trades such as peanuts, corn, and rice as well as to monitor bioterrorism threats by micotoxin poisoning.
Angewandte Chemie-international Edition, 2006
Among the various outstanding properties exhibited by ionic liquids (ILs), two of the most peculi... more Among the various outstanding properties exhibited by ionic liquids (ILs), two of the most peculiar are their very low vapor pressure [1] and pronounced supramolecular self-organization both in the condensed and gas phases. This unique set of properties make ionic liquids very attractive alternatives to classical organic solvents and water, opening also a wealth of [*] Dr.