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1.
J Phys Chem Lett ; 15(27): 6935-6942, 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38935930

ABSTRACT

Molecular structural elucidation can be accomplished by different techniques, such as nuclear magnetic resonance or X-ray diffraction. However, the former does not give information about the three-dimensional atomic arrangement, and the latter needs crystallizable solid samples. An alternative is direct, real-space visualization of the molecules by cryogenic scanning tunneling microscopy (STM). This technique is usually limited to thermally robust molecules because an annealing step is required for sample deposition. A landmark development has been the coupling of STM with electrospray deposition (ESD), which smooths the process and widens the scope of the visualization technique. In this work, we present the on-surface characterization of air-, light-, and temperature-sensitive rhamnopolyene with relevance in molecular biology. Supported by theoretical calculations, we characterize two isomers of this flexible molecule, confirming the potential of the technique to inspect labile, non-crystallizable compounds.

2.
Genes (Basel) ; 14(2)2023 02 09.
Article in English | MEDLINE | ID: mdl-36833369

ABSTRACT

The NSAID ibuprofen (2-(4-isobutylphenyl)propanoic acid) and the structurally related 3-phenylpropanoic acid (3PPA), are widely used pharmaceutical and personal care products (PPCPs) which enter municipal waste streams but whose relatively low rates of elimination by wastewater treatment plants (WWTPs) are leading to the contamination of aquatic resources. Here, we report the isolation of three bacterial strains from a municipal WWTP, which as a consortium are capable of mineralizing ibuprofen. These were identified as the Pseudomonas citronellolis species, termed RW422, RW423 and RW424, in which the first two of these isolates were shown to contain the catabolic ipf operon responsible for the first steps of ibuprofen mineralization. These ipf genes which are associated with plasmids could, experimentally, only be transferred between other Sphingomonadaceae species, such as from the ibuprofen degrading Sphingopyxis granuli RW412 to the dioxins degrading Rhizorhabdus wittichii RW1, generating RW421, whilst a transfer from the P. citronellolis isolates to R. wittichii RW1 was not observed. RW412 and its derivative, RW421, as well as the two-species consortium RW422/RW424, can also mineralize 3PPA. We show that IpfF can convert 3PPA to 3PPA-CoA; however, the growth of RW412 with 3PPA produces a major intermediate that was identified by NMR to be cinnamic acid. This and the identification of other minor products from 3PPA allows us to propose the major pathway used by RW412 to mineralize 3PPA. Altogether, the findings in this study highlight the importance of ipf genes, horizontal gene transfer, and alternative catabolic pathways in the bacterial populations of WWTPs to eliminate ibuprofen and 3PPA.


Subject(s)
Ibuprofen , Water Purification , Ibuprofen/chemistry , Ibuprofen/metabolism , Anti-Inflammatory Agents, Non-Steroidal , Bacteria/metabolism , Biodegradation, Environmental
3.
Environ Pollut ; 274: 116536, 2021 Apr 01.
Article in English | MEDLINE | ID: mdl-33529903

ABSTRACT

The high global consumption of ibuprofen and its limited elimination by wastewater treatment plants (WWTPs), has led to the contamination of aquatic systems by this common analgesic and its metabolites. The potentially negative environmental and public health effects of this emerging contaminant have raised concerns, driving the demand for treatment technologies. The implementation of bacteria which mineralize organic contaminants in biopurification systems used to decontaminate water or directly in processes in WWTPs, is a cheap and sustainable means for complete elimination before release into the environment. In this work, an ibuprofen-mineralizing bacterial strain isolated from sediments of the River Elbe was characterized and assayed to remediate different ibuprofen-polluted media. Strain RW412, which was identified as Sphingopyxis granuli, has a 4.48 Mb genome which includes plasmid sequences which harbor the ipf genes that encode the first steps of ibuprofen mineralization. Here, we confirm that these genes encode enzymes which initiate CoA ligation to ibuprofen, followed by aromatic ring activation by a dioxygenase and retroaldol cleavage to unequivocally produce 4-isobutylcatechol and propionyl-CoA which then undergo further degradation. In liquid mineral salts medium, the strain eliminated more than 2 mM ibuprofen within 74 h with a generation time of 16 h. Upon inoculation into biopurification systems, it eliminated repeated doses of ibuprofen within a few days. Furthermore, in these systems the presence of RW412 avoided the accumulation of ibuprofen metabolites. In ibuprofen-spiked effluent from a municipal WWTP, ibuprofen removal by this strain was 7 times faster than by the indigenous microbiota. These results suggest that this strain can persist and remain active under environmentally relevant conditions, and may be a useful innovation to eliminate this emerging contaminant from urban wastewater treatment systems.


Subject(s)
Sphingomonadaceae , Water Pollutants, Chemical , Water Purification , Decontamination , Ibuprofen , Waste Disposal, Fluid , Wastewater , Water Pollutants, Chemical/analysis
4.
Nat Commun ; 11(1): 1502, 2020 03 20.
Article in English | MEDLINE | ID: mdl-32198389

ABSTRACT

Although certain microbial lipids are toxins, the structural features important for cytotoxicity remain unknown. Increased functional understanding is essential for developing therapeutics against toxic microbial lipids. Group B Streptococci (GBS) are bacteria associated with preterm births, stillbirths, and severe infections in neonates and adults. GBS produce a pigmented, cytotoxic lipid, known as granadaene. Despite its importance to all manifestations of GBS disease, studies towards understanding granadaene's toxic activity are hindered by its instability and insolubility in purified form. Here, we report the synthesis and screening of lipid derivatives inspired by granadaene, which reveal features central to toxin function, namely the polyene chain length. Furthermore, we show that vaccination with a non-toxic synthetic analog confers the production of antibodies that inhibit granadaene-mediated hemolysis ex vivo and diminish GBS infection in vivo. This work provides unique structural and functional insight into granadaene and a strategy to mitigate GBS infection, which will be relevant to other toxic lipids encoded by human pathogens.


Subject(s)
Hemolysis , Lipids/chemistry , Polyenes/chemistry , Premature Birth/microbiology , Streptococcal Infections/metabolism , Adult , Animals , B-Lymphocytes , Bacterial Toxins/chemistry , Bacterial Vaccines , CD4-Positive T-Lymphocytes , Disease Models, Animal , Female , Humans , Infant, Newborn , Lipids/immunology , Lipids/toxicity , Male , Mice , Mice, Inbred C57BL , Polyenes/immunology , Pregnancy , Streptococcal Infections/immunology , Streptococcal Infections/microbiology , Streptococcal Infections/prevention & control , Streptococcus agalactiae , Vaccination
6.
Sci Rep ; 9(1): 15545, 2019 10 29.
Article in English | MEDLINE | ID: mdl-31664134

ABSTRACT

In recent years, a large number of biological properties and an important role in the organoleptic characteristics of olive oil have been attributed to phenolic secoiridoids, such as oleacein, oleocanthal, oleuropein aglycone and ligstroside aglycone. Consequently, quantifying them is of great interest for the olive oil sector. Currently, there is no consensus in which analytical method must be use to accurately determine these compounds in olive oil, mainly owing to the lack of reference standards for calibration. In this work, analytical standards of phenolic secoiridoids have been used to develop a quantitative and rapid analytical method by UHPLC-MS/MS, in which sample extraction is not carried out. Simple dilutions of the sample with dry tetrahydrofuran and dry acetonitrile were performed before analysing them. It is worth noting that under these conditions the generation of artefacts such as acetals and hemiacetals of the aldehydic forms is highly reduced. The detection and quantification was performed with a Xevo TQS tandem quadrupole mass spectrometer. The method was validated at four concentration levels and finally applied to six samples of extra virgin olive oil.


Subject(s)
Food Analysis , Iridoids/analysis , Olive Oil/analysis , Tandem Mass Spectrometry , Chromatography, High Pressure Liquid
7.
Front Microbiol ; 10: 3123, 2019.
Article in English | MEDLINE | ID: mdl-32038561

ABSTRACT

Group B Streptococcus (GBS) is a ß-hemolytic, Gram-positive bacterium that commonly colonizes the female lower genital tract and is associated with fetal injury, preterm birth, spontaneous abortion, and neonatal infections. A major factor promoting GBS virulence is the ß-hemolysin/cytolysin, which is cytotoxic to several host cells. We recently showed that the ornithine rhamnolipid pigment, Granadaene, produced by the gene products of the cyl operon, is hemolytic. Here, we demonstrate that heterologous expression of the GBS cyl operon conferred hemolysis, pigmentation, and cytoxicity to Lactococcus lactis, a model non-hemolytic Gram-positive bacterium. Similarly, pigment purified from L. lactis is hemolytic, cytolytic, and identical in structure to Granadaene extracted from GBS, indicating the cyl operon is sufficient for Granadaene production in a heterologous host. Using a systematic survey of phyletic patterns and contextual associations of the cyl genes, we identify homologs of the cyl operon in physiologically diverse Gram-positive bacteria and propose undescribed functions of cyl gene products. Together, these findings bring greater understanding to the biosynthesis and evolutionary foundations of a key GBS virulence factor and suggest that such potentially toxic lipids may be encoded by other bacteria.

8.
Phytochem Anal ; 30(1): 89-94, 2019 Jan.
Article in English | MEDLINE | ID: mdl-30216583

ABSTRACT

INTRODUCTION: L-Dopa, a key neurotransmitter used to treat neural disorders such as Parkinson's disease, is found in the seeds of the genus Mucuna at a sufficient concentration for possible commercial use. OBJECTIVE: To develop a simple and reliable method to extract L-Dopa from M. pruriens seeds in an aqueous medium and then quantitate this compound using a 1 H qNMR method (internal standard); and also to evaluate the accuracy and reproducibility of this method with an NMR calibration curve. METHODOLOGY: The extraction method of L-Dopa from M. pruriens was optimized. The quantitation with single point quantitative NMR (qNMR) and NMR calibration curve was based on the resonance properties of the main functional groups of the L-Dopa molecule, in particular the signals of the three aromatic protons, which were compared with the signal of an internal standard such as syringic acid. The accuracy (precision and trueness) and reproducibility of both NMR techniques were evaluated. RESULTS: The methods of single point qNMR and NMR calibration curve, applied to the seeds of two M. pruriens varieties, gave very similar L-Dopa contents: 3.0-3.2% and 3.0-3.1%, respectively. CONCLUSION: The statistical analysis confirmed the accuracy and reproducibility of this single point qNMR method (internal standard) for determining L-Dopa, as well as other commercial preparations of this species, without performing an NMR calibration curve.


Subject(s)
Levodopa/analysis , Mucuna/embryology , Proton Magnetic Resonance Spectroscopy/methods , Seeds/chemistry , Gallic Acid/analogs & derivatives , Gallic Acid/chemistry , Gallic Acid/standards , Levodopa/isolation & purification , Mucuna/classification , Reference Standards , Species Specificity , Water
9.
J Sep Sci ; 41(23): 4272-4280, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30298978

ABSTRACT

An analytical method for the analysis of relevant secoiridoid-based components in olive oil, oleacein and oleuropein aglycone, is described using for the first time deuterated surrogates. 0.2 g of sample was necessary to perform the analysis using liquid-liquid extraction and ultrasound-assisted extraction with a mixture of methanol/water (4:1, v/v). To avoid the formation of by-products, normal-phase ultra high performance liquid chromatography was chosen for the chromatographic separation. The selected mobile phase was a gradient mixture of tetrahydrofurane and hexane, and an ACE Excel 3 CN-ES column as stationary phase. The detection and quantification was performed with a SYNAPT G2-Si mass spectrometer. The calibration curves for oleacein and oleuropein aglycone were linear and quadratic, respectively. The validation was done at three levels of concentration. Relative errors from 0.1 to 10.5% and relative standard deviations lower than 9% were obtained. The method was applied to study different samples of olive oil.


Subject(s)
Acetates/analysis , Aldehydes/analysis , Olive Oil/chemistry , Phenols/analysis , Pyrans/analysis , Chromatography, High Pressure Liquid , Cyclopentane Monoterpenes , Mass Spectrometry , Molecular Structure
10.
Org Lett ; 20(22): 7007-7010, 2018 11 16.
Article in English | MEDLINE | ID: mdl-30371091

ABSTRACT

An expeditious route to obtaining cassane-type furan diterpenes starting from (+)-sclareolide, an inexpensive commercially available natural lactone, has been achieved by using a solvent-free Diels-Alder cycloaddition and an unprecedented decarboxylative dienone-phenol rearrangement as key steps. Its applicability is showcased by the first synthesis of (5α)-vouacapane-8(14),9(11)-diene. The synthesis, which requires no protecting group, is efficient and atom- and step-economical (10 steps, 20% global).

11.
Org Lett ; 18(22): 5964-5967, 2016 11 18.
Article in English | MEDLINE | ID: mdl-27934483

ABSTRACT

A short route toward aromatic cassane diterpenes from labdane terpenoids has been developed. In the key step, the aromatic ring with the oxygenated function at C-12 and the characteristic carbon group at C-14 of the target compounds is elaborated via a Diels-Alder/aromatization sequence of a furanosesquiterpene and methyl propiolate. On this basis, the synthesis of the proposed structure of benthaminin 1 from trans-communic acid has been achieved. The physical properties of the synthetic compound are somewhat different from those reported for the natural product.

12.
Org Biomol Chem ; 11(36): 6176-85, 2013 Sep 28.
Article in English | MEDLINE | ID: mdl-23928887

ABSTRACT

The first synthesis of dasyscyphin B, an antitumoral metabolite obtained from the ascomycete Dasyscyphus niveus, has been achieved starting from commercial abietic acid. The key steps of the synthetic sequence are the diastereoselective α-methylation of a ketoaldehyde, followed by an intramolecular aldol condensation and the further Diels-Alder cycloaddition of a dienol ester. The procedure reported will allow the synthesis of related metabolites functionalized in the A ring.


Subject(s)
Antineoplastic Agents/chemical synthesis , Diterpenes/chemical synthesis , Antineoplastic Agents/chemistry , Ascomycota/chemistry , Diterpenes/chemistry , Molecular Conformation , Stereoisomerism
13.
Bioorg Med Chem ; 20(22): 6655-61, 2012 Nov 15.
Article in English | MEDLINE | ID: mdl-23043725

ABSTRACT

Streptococcus agalactiae is an important agent in the infection of neonates in the first world. One of the most extended methods for its identification is based on the detection of a characteristic red pigment in the patient samples, named [12]-granadaene (1). In this article, we present a modular and flexible approach to simple analogues of this ornithine rhamno-polyene 1 and the elucidation of the most important features of its structure: the absolute configuration at C-27, the stereochemistry of the anomeric center and the link of the amino acid ornithine to the rest of the structure.


Subject(s)
Ornithine/analogs & derivatives , Polyenes/chemistry , Streptococcus agalactiae/chemistry , Magnetic Resonance Spectroscopy , Molecular Conformation , Ornithine/chemical synthesis , Ornithine/chemistry , Polyenes/chemical synthesis , Stereoisomerism
14.
J Org Chem ; 77(1): 573-84, 2012 Jan 06.
Article in English | MEDLINE | ID: mdl-22118292

ABSTRACT

A new strategy for synthesizing taiwaniaquinoids, a group of terpenoids with an unusual rearranged 5(6→7) or 6-nor-5(6→7)abeo-abietane skeleton, which exhibit promising biological activities, is reported. The procedure, based on the cleavage of the C7-C8 double bond of abietane diterpenes, is the only one yet reported for synthesizing C(20) taiwaniaquinoids bearing a carbon function on the cyclopentane B ring; it is also applicable to the synthesis of the wide variety of existing taiwaniaquinoids. Utilizing this, (-)-taiwaniaquinone A, F, G, and H, (-)-taiwaniaquinol B, and (-)-dichroanone have been synthesized from (+)-abietic acid. The versatility of this strategy allows us to propose the abietane C7-C8 cleavage as a possible biosynthetic pathway to this type of rearranged diterpenes; this proposal seems to be supported by phytochemical evidence.


Subject(s)
Abietanes/chemistry , Diterpenes/chemistry , Diterpenes/chemical synthesis , Terpenes/chemistry , Terpenes/chemical synthesis , Molecular Structure , Stereoisomerism
15.
Chem Commun (Camb) ; 48(4): 606-8, 2012 Jan 14.
Article in English | MEDLINE | ID: mdl-22073392

ABSTRACT

The first enantiospecific synthesis of akaol A, a marine sesquiterpene quinol, has been achieved. Key steps of the synthetic sequence are the oxidative degradation of (-)-sclareol to a dinorlabdane ketoester, mediated by the ozone-lead(IV) acetate system, the diastereoselective α-methylation of a ketoaldehyde, followed by an intramolecular aldol condensation and the further Diels-Alder cycloaddition of a dienol ether.


Subject(s)
Biological Products/chemical synthesis , Quinones/chemical synthesis , Sesquiterpenes/chemical synthesis , Biological Products/chemistry , Chemistry Techniques, Synthetic , Oxidation-Reduction , Quinones/chemistry , Sesquiterpenes/chemistry , Stereoisomerism
16.
Dalton Trans ; 39(37): 8796-800, 2010 Oct 07.
Article in English | MEDLINE | ID: mdl-20714477

ABSTRACT

The H-atom transfer (HAT) from water to ketyl radicals, mediated by titanocene(iii) aqua-complexes, can explain the Ti(III)-promoted reduction of ketones in aqueous medium better than the conventional House mechanism. Moreover, we also report novel evidences supporting the existence of these titanocene(iii) aqua-complexes.

17.
Org Lett ; 12(20): 4450-3, 2010 Oct 15.
Article in English | MEDLINE | ID: mdl-20518529

ABSTRACT

The enantioselective total synthesis of liphagal, a selective inhibitor of PI3K α isolated from the marine sponge Aka coralliphaga, has been achieved. The novel tetracyclic "liphagane" skeleton is formed in one step, after the hydrogenation of a dihydroxydrimane phenol benzyl ether in the presence of cationic resin.


Subject(s)
Phosphoinositide-3 Kinase Inhibitors , Terpenes/chemical synthesis , Molecular Structure , Stereoisomerism
18.
Org Biomol Chem ; 7(24): 5146-55, 2009 Dec 21.
Article in English | MEDLINE | ID: mdl-20024110

ABSTRACT

A new methodology for the enantiospecific synthesis of taiwaniaquinoids, based on a thermal 6pi electrocyclization, is reported. Under this procedure, 4a-methylhexahydrofluorene terpenoids bearing an A/B trans-configuration has been prepared for the first time. This methodology also makes it feasible to synthesize taiwaniaquinoids with an A/B cis-configuration and 4a-methyltetrahydrofluorene terpenoids. Accordingly, the first synthesis of (-)-taiwaniaquinone G, (-)-taiwaniaquinone H and (-)-dichroanone has been achieved.


Subject(s)
Diterpenes/chemical synthesis , Cyclization , Methods , Stereoisomerism , Terpenes/chemical synthesis
19.
Clin Nutr ; 28(5): 565-74, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19477051

ABSTRACT

BACKGROUND AND AIMS: To evaluate if the antidiabetic properties of Salacia oblonga extract are mediated not only by inhibiting intestinal alpha-glycosidases but also by enhancing glucose transport in muscle and adipose cells. METHODS: S. oblonga extract effects on 2-deoxy-D-glucose uptake were assayed in muscle L6-myotubes and 3T3-adipocytes. In L6-myotubes, the amount and translocation of glucose transporters were assayed. A fractionation of the extract was carried out to identify the active compounds. Furthermore, we analyzed the phosphorylation status of key components of signaling pathways that are involved in the molecular mechanisms regulating glucose uptake. RESULTS: S. oblonga extract increased 2-deoxy-D-glucose uptake by 50% in L6-myotubes and 3T3-adipocytes. In L6-myotubes, the extract increased up to a 100% the GLUT4 content, activating GLUT4 promoter transcription and its translocation to the plasma membrane. Mangiferin was identified as the bioactive compound. Furthermore, mangiferin effects were concomitant with the phosphorylation of 5'-AMP-activated protein kinase without the activation of PKB/Akt. The effect of mangiferin on 2-deoxy-D-glucose uptake was blocked by GW9662, an irreversible PPAR-gamma antagonist. CONCLUSIONS: S. oblonga extract and mangiferin may exert their antidiabetic effect by increasing GLUT4 expression and translocation in muscle cells. These effects are probably mediated through two independent pathways that are related to 5'-AMP-activated protein kinase and PPAR-gamma.


Subject(s)
Glucose Transporter Type 4/metabolism , Hypoglycemic Agents/pharmacology , Muscle Fibers, Skeletal/drug effects , Plant Extracts/pharmacology , Salacia/chemistry , Xanthones/pharmacology , 3T3 Cells , AMP-Activated Protein Kinases/metabolism , Animals , Cell Line , Cell Membrane/drug effects , Cell Membrane/enzymology , Cell Membrane/metabolism , Deoxyglucose/metabolism , Dose-Response Relationship, Drug , Glucose Transporter Type 1/metabolism , Glucose Transporter Type 4/genetics , Insulin/pharmacology , Mice , Muscle Fibers, Skeletal/metabolism , PPAR gamma/antagonists & inhibitors , PPAR gamma/metabolism , Plant Extracts/chemistry , Plant Roots/chemistry , Rats , Rosiglitazone , Thiazolidinediones/pharmacology , Xanthones/analysis
20.
Chem Commun (Camb) ; (5): 592-4, 2009 Feb 07.
Article in English | MEDLINE | ID: mdl-19283301

ABSTRACT

The first route towards taiwaniaquinoid terpenes bearing an A/B trans-configuration has been developed through a sequence which includes a thermal 6pi electrocyclization.


Subject(s)
Diterpenes/chemical synthesis , Cyclization , Diterpenes/chemistry , Electrons , Stereoisomerism , Temperature
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