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1.
J Vet Pharmacol Ther ; 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31490556

RESUMO

We examined the tissue distribution and elimination of quinocetone (QCT) and its major metabolites 1-desoxyquinocetone (1-DQCT), di-desoxyquinocetone (BDQCT), and 3-methyl-quinoxaline-2-carboxylic (MQCA) in ducks. The analytes were simultaneously quantitated using a UPLC-MS/MS method after oral administration of QCT at 100 mg·kg-1 day-1 for 7 days. We found that QCT and its major metabolites were widely distributed in duck tissues. The concentrations indicated that the primary compound in the liver, kidney, and heart was MQCA and the primary compound in the stomach, intestine, spleen, and lung was QCT. We also identified that MQCA was the most appropriate compound for QCT residue monitoring. The liver and kidney are the primary QCT target organs in ducks, and this study provides clear monitoring tools and important data to evaluate its safety.

2.
BMC Vet Res ; 15(1): 210, 2019 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-31234851

RESUMO

BACKGROUND: Oxyclozanide is an anthelmintic drug that is widely used to treat fasciolosis. However, the pharmacokinetics of oxyclozanide in cattle are not yet clearly understood. The present study was designed to develop a sensitive method to determine oxyclozanide levels in cattle plasma using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) and to study its pharmacokinetics for application in cattle. RESULTS: A simple and rapid HPLC-MS/MS analytical method was established and validated to quantify oxyclozanide levels in cattle plasma using niclosamide as the internal standard (IS) in negative ion mode. Chromatographic separation of the analytes was achieved using a C18 analytical column (75 × 4.6 mm, 2.7 µm) at 30 °C. The mobile phase comprised 0.01% v/v acetic acid (HOAc) diluted in water:acetonitrile (MeCN) (90:10% v/v) and 5 mM ammonium formate in methanol (MeOH):MeCN (75:25, v/v) at a 10:90 ratio (v/v) and was delivered at a flow rate of 0.4 mL min- 1. A good linear response across the concentration range of 0.02048-25.600 µg/mL was achieved (r2 = 0.994). The method was validated with respect to linearity, matrix effect, accuracy, precision, recovery and stability. The lower limit of quantification (LLOQ) was 0.020 µg/mL, and the extraction recovery was > 98% for oxyclozanide. The inter- and intra-day accuracy and precision of the method showed the relative standard deviation (RSD) less than 10%. The method was successfully applied to an assessment of the pharmacokinetics of oxyclozanide in cattle plasma. In healthy cattle, a single oral dose of an oxyclozanide suspension followed the one-compartment model, with a half-life (T1/2) of 64.40 ± 30.18 h, a plasma clearance rate (CL/F) of 11.426 ± 2.442 mL/h/kg, and an average area under the curve (AUC) of 965.608 ± 220.097 h*µg/mL. The peak concentration (Cmax) was 15.870 ± 2.855 µg/mL, which occurred at a peak time (Tmax) = 22.032 ± 3.343 h. CONCLUSIONS: A reliable, accurate HPLC-MS/MS analytical method was established in our study and successful applied to study the pharmacokinetics of oxyclozanide in cattle plasma. These results will be useful for further evaluations of the pharmacokinetic properties of oxyclozanide or for monitoring therapeutic drugs in animals.


Assuntos
Antiplatelmínticos/farmacocinética , Bovinos/metabolismo , Cromatografia Líquida de Alta Pressão/veterinária , Oxiclozanida/farmacocinética , Espectrometria de Massas em Tandem/veterinária , Animais , Cromatografia Líquida de Alta Pressão/métodos , Feminino , Masculino , Niclosamida/farmacocinética , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Espectrometria de Massas em Tandem/métodos
3.
J Agric Food Chem ; 67(22): 6125-6132, 2019 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-31083998

RESUMO

With environmental pollution, residual hazards accumulate and severe drug resistance and many other problems appear; some highly toxic drugs have been banned, and antifungal agents are far from satisfactory. Natural products play an important role in the discovery and development of new pesticides. The natural product griseofulvin (1) has been known as an antifungal agent in the treatment of dermatomycoses for decades. In this study, a series of new griseofulvin derivatives were synthesized with good yields. Their structures were characterized by 1H and 13C nuclear magnetic resonance and high-resolution mass spectrometry (electrospray ionization). The antifungal activities of griseofulvin analogues were first evaluated against five phytopathogenic fungi ( Cytospora sp., Colletotrichum gloeosporioides, Botrytis cinerea, Alternaria solani, and Fusarium solani) in vitro. Of significance is that most of them showed excellent antifungal activities against C. gloeosporioides. The antifungal activities of the four best compounds (6a, 6c, 6e, and 6f) against C. gloeosporioides were further investigated in vivo using infected apples. The results suggested that compounds 6c, 6e, and 6f [half-maximal inhibitory concentration (IC50) = 47.25 ± 1.46, 49.44 ± 1.50, and 53.63 ± 1.74 µg/mL, respectively] were better than thiophanate-methyl (IC50 = 69.66 ± 6.07 µg/mL). Furthermore, comparative molecular field analysis was performed on the basis of the antifungal activity results of all 22 of the compounds against C. gloeosporioides in vitro. The three-dimensional coefficient contour plots revealed that the suitable bulky and electronegative acyl-substituted groups seem to be more favorable for increasing activity at the 4' position of griseofulvin. The structure-activity relationships were also discussed. Griseofulvin derivatives can be used for the development of highly effective and safe agricultural fungicides.


Assuntos
Fungos/efeitos dos fármacos , Fungicidas Industriais/química , Fungicidas Industriais/farmacologia , Griseofulvina/análogos & derivados , Griseofulvina/farmacologia , Doenças das Plantas/microbiologia , Fungos/crescimento & desenvolvimento , Estrutura Molecular , Relação Quantitativa Estrutura-Atividade
4.
Regul Toxicol Pharmacol ; 103: 21-33, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30634022

RESUMO

The aim of this study was to determine the potential toxicity risk of an oxyclozanide suspension to the target animal, bovine. In this experiment, 32 Simmental beef cattle were fattened and fed a full-price diet without antimicrobial agents. The test cattle were divided into 4 groups, which were treated with 0, 1, 3, and 5 times the recommended dosage through continuous intermittent oral administration at intervals of 2 days. The body weight of the cattle was recorded before and after the experiment, and the weight changes were calculated. The safety of the drugs was evaluated by weight gain, observation of clinical toxicity, haematology, clinical chemistry and histopathology. The results showed that the cattle had different degrees of diarrhoea, loss of appetite and depression after administration. The results of clinicopathology had no significant effect. The results of pathological examination showed that there was a certain degree of damage in the 5 times recommended dose group. The recommended dose was safe to use. Thus, the recommended dose should be given by a single oral administration to ensure the safe use of this drug in the clinic.


Assuntos
Fasciolíase/tratamento farmacológico , Oxiclozanida/administração & dosagem , Oxiclozanida/efeitos adversos , Salicilanilidas/administração & dosagem , Administração Oral , Animais , Bovinos , Relação Dose-Resposta a Droga , Feminino , Masculino , Oxiclozanida/uso terapêutico , Salicilanilidas/efeitos adversos
5.
J Am Chem Soc ; 140(17): 5860-5865, 2018 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-29618202

RESUMO

The [2+2] cycloaddition is a versatile strategy for the synthesis of strained cyclobutenes of high synthetic value. In this study, two efficient intermolecular [2+2] cycloadditions between two different types of chloroalkynes and unactivated alkene are realized with gold catalysis. Of significance is that the reaction works with challenging monosubstituted unactivated alkenes, which is unprecedented in gold catalysis and scarcely documented in other metal-catalyzed/promoted reactions; moreover, the reaction exhibits excellent regioselectivities, which are much better than those reported in literature. With 1,2-disubstituted unactivated alkenes, the reaction is largely stereospecific. The cyclobutene products can be prepared in nearly gram scale and readily undergo further reactions including various cross-coupling reactions using the C(sp2)-Cl and/or C(sp2)-SPh bond, which in turn substantially broaden the scope of accessible cyclobutenes and enhance the synthetic utility of this bimolecular reaction.

6.
Mol Divers ; 20(4): 887-896, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27599494

RESUMO

5,6-Diarylpyrazolo[1,5-a]pyrimidines (3) and 6,7-diarylpyrazolo[1,5-a]pyrimidines (4) were chemoselectively synthesized by the condensation of isoflavone (1) and 3-aminopyrazole (2). 5,6-Diarylpyrazolo[1,5-a]pyrimidines (3) were obtained via microwave irradiation, and 6,7-diarylpyrazolo[1,5-a]pyrimidines (4) were obtained via conventional heating. In addition, the pyrimidine derivatives 3 and 4 were evaluated against five phytopathogenic fungi (Cytospora sp., Colletotrichum gloeosporioides, Botrytis cinerea, Alternaria solani, and Fusarium solani) using the mycelium growth rate method. Some of them were effective in inhibiting the growth of the five phytopathogenic fungi. For instance, 6,7-diarylpyrazolo[1,5-a]pyrimidines (4j) inhibited the growth of A. solani with an [Formula: see text] value of 17.11 [Formula: see text], and 6,7-diarylpyrazolo[1,5-a]pyrimidines (4h) inhibited the growth of both Cytospora sp. and F. solani with [Formula: see text] values of 27.32 and 21.04 [Formula: see text], respectively. A chemoselective synthesis of 5,6-pyrazolo[1,5-a]pyrimidines 3 derivatives in excellent yields was performed under microwave irradiation and 6,7-pyrazolo[1,5-a]pyrimidines 4 were also prepared using heating method. The antifungal properties of 3 and 4 were tested against Cytospora sp., Colletotrichum gloeosporioides, Botrytis cinerea, Alternaria solani, and Fusarium solani.


Assuntos
Antifúngicos/síntese química , Antifúngicos/farmacologia , Fungos/efeitos dos fármacos , Pirazóis/síntese química , Pirazóis/farmacologia , Pirimidinas/síntese química , Pirimidinas/farmacologia , Antifúngicos/química , Testes de Sensibilidade Microbiana , Estrutura Molecular , Pirazóis/química , Pirimidinas/química , Relação Estrutura-Atividade
7.
J Am Chem Soc ; 138(37): 12013-6, 2016 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-27584734

RESUMO

We present a diastereodivergent strategy for constructing bicyclic γ-lactones bearing quaternary carbon centers via ketone hydroacylation. By applying a Rh catalyst and JoSPOphos ligand, either the anti or syn bicyclic γ-lactones can be accessed with high enantio- and diastereoselectivities, depending on the choice of solvent, temperature, and counterion.


Assuntos
Cetonas/química , Lactonas/síntese química , Acilação , Catálise , Estrutura Molecular , Ródio , Estereoisomerismo
8.
Steroids ; 112: 103-8, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27137356

RESUMO

Using progesterone as the starting material, we synthesized a series of steroidal derivatives possessing a D-ring substituted benzamidothiazole. All of the final structures were reported and identified by NMR and HRMS spectrometry for the first time. The antiproliferative activity of the synthesized compounds against PC-3 (human prostate cancer cell line) and SKOV-3 (ovarian cancer cells) were investigated. The preliminary results showed that compounds 8b, 8d and 8g possessed moderate antiproliferative activities.


Assuntos
Esteroides/síntese química , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Esteroides/química , Esteroides/farmacologia , Relação Estrutura-Atividade
9.
Nat Prod Res ; 30(10): 1166-9, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-25978007

RESUMO

A series of 17 simple 1-(2,4-dihydroxyphenyl) ethanones were synthesised, and their structures characterised by (1)H, (13)C NMR and ESI-MS. Their in vitro antifungal activities were evaluated against five phytopathogenic fungi including Glomerella cingulate, Botrytis cirerea, Fusarium graminearum, Curvularia lunata and Fusarium oxysporum f. sp. vasinfectum by the mycelial growth inhibition assay. Compounds 2g and 2h exhibited broad-spectrum inhibitory activity against the mycelial growth of the tested pathogens with IC50 values in the range of 16-36 µg/mL, and in particular being more active to G. cingulate, with IC50 values of 16.50 and 19.25 µg/mL, respectively, than the other pathogens. Preliminary SAR indicated that an α,ß-unsaturated ketone unit of the alkyl chain of the compounds is the structure requirement for fungicidal action. The results suggested that 2g and 2h may be promising leads in the development of new antifungal agents.


Assuntos
Acetofenonas/farmacologia , Fungicidas Industriais/farmacologia , Acetofenonas/síntese química , Ascomicetos/efeitos dos fármacos , Produtos Biológicos , Botrytis/efeitos dos fármacos , Fungicidas Industriais/isolamento & purificação , Fusarium/efeitos dos fármacos , Concentração Inibidora 50 , Relação Estrutura-Atividade
10.
J Agric Food Chem ; 63(11): 3059-66, 2015 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-25757044

RESUMO

Identification and evaluation of safety of forchlorfenuron ((1-(2-chloro-4-pyridyl)-3-phenylurea)), 1, metabolites after biotransformation in kiwifruit is the objective of this study. To elucidate properties of these metabolites, liquid chromatography hybrid ion trap time-of-flight mass spectrometry (LC-IT-TOF-MS) was applied, with MetID Solution and Formula Predictor Software in positive mode. Cytotoxicity of forchlorfenuron and its metabolites were tested through sulforhodamine B assays against normal Chinese hamster ovary cells (CHO). As deduced from characteristic fragment ions of forchlorfenuron, then confirmed by comparison with synthetic standards, as well as characterized by NMR and mass spectrometry techniques, results indicate the presence of 4-hydroxyphenyl-forchlorfenuron, 2, 3-hydroxyphenyl-forchlorfenuron, 3, and forchlorfenuron-4-O-ß-D-glucoside, 5. Forchlorfenuron (IC50 = 12.12 ± 2.14 µM) and 4-hydroxyphenyl-forchlorfenuron (IC50 = 36.15 ± 1.59 µM), exhibits significant cytotoxicity against CHO, while 3-hydroxyphenyl-forchlorfenuron and forchlorfenuron-4-O-ß-D-glucoside show no cytotoxicity.


Assuntos
Actinidia/metabolismo , Compostos de Fenilureia/química , Reguladores de Crescimento de Planta/química , Piridinas/química , Actinidia/química , Animais , Células CHO , Sobrevivência Celular/efeitos dos fármacos , Cricetinae , Cricetulus , Frutas/química , Frutas/metabolismo , Espectrometria de Massas , Compostos de Fenilureia/síntese química , Compostos de Fenilureia/metabolismo , Compostos de Fenilureia/farmacologia , Reguladores de Crescimento de Planta/síntese química , Reguladores de Crescimento de Planta/metabolismo , Reguladores de Crescimento de Planta/farmacologia , Piridinas/síntese química , Piridinas/metabolismo , Piridinas/farmacologia
11.
Bioconjug Chem ; 26(1): 101-9, 2015 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-25438187

RESUMO

Folate-conjugated cryptophane was developed for targeting cryptophane to membrane-bound folate receptors that are overexpressed in many human cancers. The cryptophane biosensor was synthesized in 20 nonlinear steps, which included functionalization with folate recognition moiety, solubilizing peptide, and Cy3 fluorophore. Hyperpolarized (129)Xe NMR studies confirmed xenon binding to the folate-conjugated cryptophane. Cellular internalization of biosensor was monitored by confocal laser scanning microscopy and quantified by flow cytometry. Competitive blocking studies confirmed cryptophane endocytosis through a folate receptor-mediated pathway. Flow cytometry revealed 10-fold higher cellular internalization in KB cancer cells overexpressing folate receptors compared to HT-1080 cells with normal folate receptor expression. The biosensor was determined to be nontoxic in HT-1080 and KB cells by MTT assay at low micromolar concentrations typically used for hyperpolarized (129)Xe NMR experiments.


Assuntos
Ácido Fólico/química , Sondas Moleculares/química , Sondas Moleculares/metabolismo , Compostos Policíclicos/química , Compostos Policíclicos/metabolismo , Transporte Biológico , Linhagem Celular Tumoral , Corantes Fluorescentes/química , Transportadores de Ácido Fólico/metabolismo , Humanos , Espectroscopia de Ressonância Magnética , Sondas Moleculares/síntese química , Sondas Moleculares/toxicidade , Compostos Policíclicos/síntese química , Compostos Policíclicos/toxicidade
12.
Supramol Chem ; 27(1-2): 65-71, 2015 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-25506191

RESUMO

The (+) and (-) enantiomers for a cryptophane-7-bond-linker-benzenesulfonamide biosensor (C7B) were synthesized and their chirality confirmed by electronic circular dichroism (ECD) spectroscopy. Biosensor binding to carbonic anhydrase II (CAII) was characterized for both enantiomers by hyperpolarized (hp) 129Xe NMR spectroscopy. Our previous study of the racemic (+/-) C7B biosensor-CAII complex [Chambers, et al., J. Am. Chem. Soc. 2009, 131, 563-569], identified two "bound" 129Xe@C7B peaks by hp 129Xe NMR (at 71 and 67 ppm, relative to "free" biosensor at 64 ppm), which led to the initial hypothesis that (+) and (-) enantiomers produce diastereomeric peaks when coordinated to Zn2+ at the chiral CAII active site. Unexpectedly, the single enantiomers complexed with CAII also identified two "bound" 129Xe@C7B peaks: (+) 72, 68 ppm and (-) 68, 67 ppm. These results are consistent with X-ray crystallographic evidence for benzenesulfonamide inhibitors occupying a second site near the CAII surface. As illustrated by our studies of this model protein-ligand interaction, hp 129Xe NMR spectroscopy can be useful for identifying supramolecular assemblies in solution.

13.
Chem Sci ; 5(8): 3197-3203, 2014 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-25089181

RESUMO

Previously, we reported hyperpolarized 129Xe chemical exchange saturation transfer (Hyper-CEST) NMR techniques for the ultrasensitive (i.e., 1 picomolar) detection of xenon host molecules known as cryptophane. Here, we demonstrate a more general role for Hyper-CEST NMR as a spectroscopic method for probing nanoporous structures, without the requirement for cryptophane or engineered xenon-binding sites. Hyper-CEST 129Xe NMR spectroscopy was employed to detect Bacillus anthracis and Bacillus subtilis spores in solution, and interrogate the layers that comprise their structures. 129Xe-spore samples were selectively irradiated with radiofrequency pulses; the depolarized 129Xe returned to aqueous solution and depleted the 129Xe-water signal, providing measurable contrast. Removal of the outermost spore layers in B. anthracis and B. subtilis (the exosporium and coat, respectively) enhanced 129Xe exchange with the spore interior. Notably, the spores were invisible to hyperpolarized 129Xe NMR direct detection methods, highlighting the lack of high-affinity xenon-binding sites, and the potential for extending Hyper-CEST NMR structural analysis to other biological and synthetic nanoporous structures.

14.
Steroids ; 78(9): 874-9, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23665407

RESUMO

A series of novel derivatives of 21E-benzylidene-pregn-1,4-diene-3,20-dione 7a-g and 21E-benzylidene-4-chloro-pregn-1,4-diene-3,20-dione 8a-g was synthesized from the commercially available progesterone. These title compounds were evaluated for their cytotoxic activity against brine shrimp (Artemia salina) and murine Lewis lung carcinoma cells (LLC). It was found that compounds 7a-g exhibited stronger activities than 8a-g against the brine shrimps, and some of the tested compounds possessed weak inhibition of LLC cells.


Assuntos
Antineoplásicos/síntese química , Progesterona/análogos & derivados , Progesterona/síntese química , Animais , Antineoplásicos/farmacologia , Artemia , Carcinoma Pulmonar de Lewis , Linhagem Celular Tumoral , Camundongos , Progesterona/farmacologia
15.
Acta Crystallogr Sect E Struct Rep Online ; 69(Pt 2): o229, 2013 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-23424509

RESUMO

The title compound, C(10)H(13)ClN(2)O, was obtained as a by-product in the reaction of 2-chloro-methyl-1H-benzimidazole, dimethyl sulfate and toluene to synthesise 2-chloro-methyl-1-methyl-benzimidazole. The dihedral angle between the benzene ring and the acetamide group is 89.72  (6)° while that between the aromatic ring and the chloracetyl group is 84.40 (4)°. In the crystal, adjacent mol-ecules are linked by pairs of N-H⋯O hydrogen bonds into inversion dimers.

16.
J Agric Food Chem ; 61(11): 2789-95, 2013 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-23419161

RESUMO

A series of 35 benzimidazole derivatives were synthesized from 2-chloromethyl-1H-benzimidazole in good yields. Their structures were characterized by (1)H and (13)C NMR and HRESIMS. Antifungal activities of all of the synthesized compounds were evaluated against five phytopathogens fungi (Cytospora sp., Colletotrichum gloeosporioides, Botrytis cinerea, Alternaria solani, and Fusarium solani) using the mycelium growth rate method. Compound 4m displayed strong growth inhibition of C. gloeosporioides, A. solani, and F. solani with IC50 of 20.76, 27.58, and 18.60 µg/mL, respectively. Selective inhibition of B. cinerea instead of the other fungal pathogenes was observed with 7f (IC50 of 13.36 µg/mL), comparable to that of positive control, a commercial agricultural fungicide hymexazol (IC50 of 8.92 µg/mL). Compound 5b exhibited remarkable antifungal properties against Cytospora sp., C. gloeosporioides, B. cinerea, and F. solani with IC50 values of 30.97, 11.38, 57.71, and 40.15 µg/mL, respectively; among the target fungi, 5b was the most active compound and superior to the reference against C. gloeosporioides alone. Structure-activity relationship (SAR) data of these compounds are as follows: (1) introduction of the chlorine atom on para-position in the benzene ring help to increase activity (4f vs 4c; 7f vs 7n), (2) the sulfonyl group is critical for the inhibition of C. gloeosporioides (5b and 5c vs 5a), and (3) the unsubstituted benzene ring improve activity (4m vs 4n, 4e and 4a). Thus, compounds 5b, 4m, and 7f emerged as a new leading structure for the development of new fungicides.


Assuntos
Benzimidazóis/farmacologia , Fungos/efeitos dos fármacos , Fungicidas Industriais/síntese química , Fungicidas Industriais/farmacologia , Doenças das Plantas/microbiologia , Benzimidazóis/química , Fungos/crescimento & desenvolvimento , Fungos/fisiologia , Fungicidas Industriais/química , Estrutura Molecular , Relação Estrutura-Atividade
17.
Anal Chem ; 84(22): 9935-41, 2012 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-23106513

RESUMO

Hyperpolarized (129)Xe chemical exchange saturation transfer ((129)Xe Hyper-CEST) NMR is a powerful technique for the ultrasensitive, indirect detection of Xe host molecules (e.g., cryptophane-A). Irradiation at the appropriate Xe-cryptophane resonant radio frequency results in relaxation of the bound hyperpolarized (129)Xe and rapid accumulation of depolarized (129)Xe in bulk solution. The cryptophane effectively "catalyzes" this process by providing a unique molecular environment for spin depolarization to occur, while allowing xenon exchange with the bulk solution during the hyperpolarized lifetime (T(1) ≈ 1 min). Following this scheme, a triacetic acid cryptophane-A derivative (TAAC) was indirectly detected at 1.4 picomolar concentration at 320 K in aqueous solution, which is the record for a single-unit xenon host. To investigate this sensitivity enhancement, the xenon binding kinetics of TAAC in water was studied by NMR exchange lifetime measurement. At 297 K, k(on) ≈ 1.5 × 10(6) M(-1) s(-1) and k(off) = 45 s(-1), which represent the fastest Xe association and dissociation rates measured for a high-affinity, water-soluble xenon host molecule near rt. NMR line width measurements provided similar exchange rates at rt, which we assign to solvent-Xe exchange in TAAC. At 320 K, k(off) was estimated to be 1.1 × 10(3) s(-1). In Hyper-CEST NMR experiments, the rate of (129)Xe depolarization achieved by 14 pM TAAC in the presence of radio frequency (RF) pulses was calculated to be 0.17 µM·s(-1). On a per cryptophane basis, this equates to 1.2 × 10(4)(129)Xe atoms s(-1) (or 4.6 × 10(4) Xe atoms s(-1), all Xe isotopes), which is more than an order of magnitude faster than k(off), the directly measurable Xe-TAAC exchange rate. This compels us to consider multiple Xe exchange processes for cryptophane-mediated bulk (129)Xe depolarization, which provide at least 10(7)-fold sensitivity enhancements over directly detected hyperpolarized (129)Xe NMR signals.


Assuntos
Espectroscopia de Ressonância Magnética/métodos , Compostos Policíclicos/química , Água/química , Xenônio/química , Acetatos/química , Compostos Policíclicos/análise , Solubilidade
18.
Org Lett ; 14(14): 3580-3, 2012 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-22783828

RESUMO

The efficient synthesis of enantiopure, trisubstituted cryptophane-A derivatives, organic host molecules with unusually high xenon affinity, is reported. Synthesis and chromatographic separation of (±) tri-Mosher's acid substituted cryptophane diastereomers gave ready access to the enantiopure cryptophanes, which are critical components in the design of enantiomerically pure (129)Xe biosensors. Hyperpolarized (129)Xe NMR spectroscopy identified single resonances for both trisubstituted cryptophane diastereomers that were separated by 9.5 ppm. This highlights opportunities for using enantiopure xenon biosensors in the simultaneous detection of (129)Xe in different biochemical environments.


Assuntos
Compostos Policíclicos/síntese química , Técnicas Biossensoriais , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Compostos Policíclicos/química , Estereoisomerismo , Xenônio/química
19.
Proc Natl Acad Sci U S A ; 108(27): 10969-73, 2011 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-21690357

RESUMO

Xenon and radon have many similar properties, a difference being that all 35 isotopes of radon ((195)Rn-(229)Rn) are radioactive. Radon is a pervasive indoor air pollutant believed to cause significant incidence of lung cancer in many geographic regions, yet radon affinity for a discrete molecular species has never been determined. By comparison, the chemistry of xenon has been widely studied and applied in science and technology. Here, both noble gases were found to bind with exceptional affinity to tris-(triazole ethylamine) cryptophane, a previously unsynthesized water-soluble organic host molecule. The cryptophane-xenon association constant, K(a)=42,000 ± 2,000 M(-1) at 293 K, was determined by isothermal titration calorimetry. This value represents the highest measured xenon affinity for a host molecule. The partitioning of radon between air and aqueous cryptophane solutions of varying concentration was determined radiometrically to give the cryptophane-radon association constant K(a)=49,000 ± 12,000 M(-1) at 293 K.


Assuntos
Poluentes Radioativos do Ar/análise , Compostos Policíclicos/química , Radônio/análise , Xenônio/análise , Ar , Poluição do Ar em Ambientes Fechados , Sítios de Ligação , Cristalografia por Raios X , Modelos Químicos , Radiometria , Soluções , Água
20.
Org Lett ; 13(6): 1414-7, 2011 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-21332141

RESUMO

Efficient syntheses of trisubstituted cryptophane-A derivatives that are versatile host molecules for many applications are reported. Trihydroxy cryptophane was synthesized in six or seven steps with yields as high as 9.5%. By a different route, trihydroxy cryptophane modified with three propargyl, allyl, or benzyl protecting groups was synthesized with yields of 4.1-5.8% in just six steps. Hyperpolarized (129)Xe NMR chemical shifts of 57-65 ppm were measured for these trisubstituted cryptophanes.


Assuntos
Compostos Policíclicos/química , Compostos Policíclicos/síntese química , Xenônio/química , Espectroscopia de Ressonância Magnética , Estrutura Molecular
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