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1.
Beilstein J Org Chem ; 15: 2486-2492, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31728162

RESUMO

Pyridine[4]arenes have previously been considered as anion binding hosts due to the electron-poor nature of the pyridine ring. Herein, we demonstrate the encapsulation of Me4N+ cations inside a dimeric hydrogen-bonded pyridine[4]arene capsule, which contradicts with earlier assumptions. The complexation of a cationic guest inside the pyridine[4]arene dimer has been detected and studied by multiple gas-phase techniques, ESI-QTOF-MS, IRMPD, and DT-IMMS experiments, as well as DFT calculations. The comparison of classical resorcinarenes with pyridinearenes by MS and NMR experiments reveals clear differences in their host-guest chemistry and implies that cation encapsulation in pyridine[4]arene is an anion-driven process.

2.
ACS Cent Sci ; 5(7): 1187-1198, 2019 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-31404239

RESUMO

The development and integration of Single-Molecule Magnets (SMMs) into molecular electronic devices continue to be an exciting challenge. In such potential devices, heat generation due to the electric current is a critical issue that has to be considered upon device fabrication. To read out accurately the temperature at the submicrometer spatial range, new multifunctional SMMs need to be developed. Herein, we present the first self-calibrated molecular thermometer with SMM properties, which provides an elegant avenue to address these issues. The employment of 2,2'-bipyrimidine and 1,1,1-trifluoroacetylacetonate ligands results in a dinuclear compound, [Dy2(bpm)(tfaa)6], which exhibits slow relaxation of the magnetization along with remarkable photoluminescent properties. This combination allows the gaining of fundamental insight in the electronic properties of the compound and investigation of optomagnetic cross-effects (Zeeman effect). Importantly, spectral variations stemming from two distinct thermal-dependent mechanisms taking place at the molecular level are used to perform luminescence thermometry over the 5-398 K temperature range. Overall, these properties make the proposed system a unique molecular luminescent thermometer bearing SMM properties, which preserves its temperature self-monitoring capability even under applied magnetic fields.

3.
Chemistry ; 25(64): 14625-14637, 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31448479

RESUMO

Lanthanide-complex-based luminescence thermometry and single-molecule magnetism are two effervescent fields of research, owing to the great promise they hold from an application standpoint. The high thermal sensitivity achievable, their contactless nature, along with sub-micrometric spatial resolution make these luminescent thermometers appealing for accurate temperature probing in miniaturised electronics. To that end, single-molecule magnets (SMMs) are expected to revolutionise the field of spintronics, thanks to the improvements made in terms of their working temperature-now surpassing that of liquid nitrogen-and manipulation of their spin state. Hence, the combination of such opto-magnetic properties in a single molecule is desirable in the aim of overcoming, among others, addressability issues. Yet, improvements must be made through design strategies for the realisation of the aforementioned goal. Moving forward from these considerations, we present a thorough investigation of the effect that changes in the ligand scaffold of a family of terbium complexes have on their performance as luminescent thermometers and SMMs. In particular, an increased number of electron-withdrawing groups yields modifications of the metal coordination environment and a lowering of the triplet state of the ligands. These effects are tightly intertwined, thus, resulting in concomitant variations of the SMM and the luminescence thermometry behaviour of the complexes. Supported by ab initio calculations, we can rationally interpret the observed trends and provide solid foundations for the development of opto-magnetic lanthanide complexes.

4.
Org Biomol Chem ; 17(29): 6980-6984, 2019 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-31276147

RESUMO

Pyridinearene macrocycles have previously shown unique host-guest properties in their capsular dimers including endo complexation of neutral molecules and exo complexation of anions. Here, we demonstrate for the first time the formation of hydrogen bonded hexamer of tetraisobutyl-octahydroxypyridinearene in all three states of matter - gas phase, solution and solid-state. Cationic tris(bipyridine)ruthenium(ii) template was found to stabilize the hexamer in gas phase, whereas solvent molecules do this in condensed phases. In solution, the capsular hexamer was found to be the thermodynamically favoured self-assembly product and transition from dimer to hexamer occurred in course of time. The crystal structure of hexamer revealed 24 N-HO direct intermolecular hydrogen bonds between the six pyridinearene macrocycles without any bridging solvent molecules. Hydrogen bond patterns correlate well with DFT computed structures. Thus, all structural chemistry methods (IM-MS, DOSY NMR, DFT, X-ray crystallography) support the same structure of the hexameric capsule that has a diameter of ca. 3 nm and volume of 1160 Å3.

5.
Psychiatry Res Neuroimaging ; 281: 43-52, 2018 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-30219591

RESUMO

The aim of this paper was to investigate differences in brain structure volumes between schizophrenia and affective psychoses, and whether cumulative lifetime antipsychotic or benzodiazepine doses relate to brain morphology in these groups. We conducted two systematic reviews on the topic and investigated 44 schizophrenia cases and 19 with affective psychoses from the Northern Finland Birth Cohort 1966. The association between lifetime antipsychotic and benzodiazepine dose and brain MRI scans at the age of 43 was investigated using linear regression. Intracranial volume, sex, illness severity, and antipsychotic/benzodiazepine doses were used as covariates. There were no differences between the groups in brain structure volumes. In schizophrenia, after adjusting for benzodiazepine dose and symptoms, a negative association between lifetime antipsychotic dose and the nucleus accumbens volume remained. In affective psychoses, higher lifetime benzodiazepine dose associated with larger volumes of total gray matter and hippocampal volume after controlling for antipsychotic use and symptoms. It seems that in addition to antipsychotics, the severity of symptoms and benzodiazepine dose are also associated with brain structure volumes. These results suggest, that benzodiazepine effects should also be investigated also independently and not only as a confounder.


Assuntos
Transtornos Psicóticos Afetivos/patologia , Antipsicóticos/uso terapêutico , Benzodiazepinas/uso terapêutico , Encéfalo/patologia , Esquizofrenia/patologia , Adulto , Transtornos Psicóticos Afetivos/diagnóstico por imagem , Transtornos Psicóticos Afetivos/tratamento farmacológico , Estudos de Coortes , Feminino , Finlândia , Humanos , Modelos Lineares , Imagem por Ressonância Magnética , Masculino , Tamanho do Órgão/efeitos dos fármacos , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/tratamento farmacológico
7.
Molecules ; 23(5)2018 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-29702628

RESUMO

Cancer is a widespread and life-threatening disease and its early-stage diagnosis is vital. One of the most effective, non-invasive tools in medical diagnostics is magnetic resonance imaging (MRI) with the aid of contrast agents. Contrast agents that are currently in clinical use contain metals, causing some restrictions in their use. Also, these contrast agents are mainly non-specific without any tissue targeting capabilities. Subsequently, the interest has notably increased in the research of organic, metal-free contrast agents. This study presents a new, stable organic radical, TEEPO-Met, where a radical moiety 2,2,6,6-tetraethylpiperidinoxide (TEEPO) is attached to an amino acid, methionine (Met), as a potentially tumour-targeting moiety. We describe the synthesis, stability assessment with electron paramagnetic resonance (EPR) spectroscopy and relaxation enhancement abilities by an in vitro nuclear magnetic resonance (NMR) and phantom MRI studies of TEEPO-Met. The new compound proved to be stable notably longer than the average imaging time in conditions mimicking a biological matrix. Also, it significantly reduced the relaxation times of water, making it a promising candidate as a novel tumour targeting contrast agent for MRI.


Assuntos
Meios de Contraste/síntese química , Óxidos N-Cíclicos/química , Compostos Heterocíclicos/síntese química , Metionina/química , Piperidinas/química , Animais , Meios de Contraste/química , Espectroscopia de Ressonância de Spin Eletrônica/métodos , Compostos Heterocíclicos/química , Humanos , Imagem por Ressonância Magnética/métodos , Estrutura Molecular , Neoplasias/diagnóstico por imagem , Imagens de Fantasmas
8.
Dalton Trans ; 46(39): 13582-13589, 2017 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-28952629

RESUMO

The synthesis and structural characterization of two benzoquinone-bridged dinuclear rare-earth complexes [BQ(MCl2·THF3)2] (BQ = 2,5-bisoxide-1,4-benzoquinone; M = Y (1), Dy (2)) are described. Of these reported metal complexes, the dysprosium analogue 2 is the first discrete bridged dinuclear lanthanide complex in which both metal centres reside in pentagonal bipyramidal environments. Interestingly, both complexes undergo significant thermal expansion upon heating from 120 K to 293 K as illustrated by single-crystal X-ray and powder diffraction experiments. AC magnetic susceptibility measurements reveal that 2 does not show the slow relation of magnetization in zero dc field. The absent of single-molecule behaviour in 2 arises from the rotation of the principal magnetic axis as compared to the pseudo-C5 axis of the pentagonal bipyramidal environment as suggested by ab initio calculations. The cyclic voltammetry and chemical reduction experiments demonstrated that complexes 1 and 2 can be reduced to radical species containing [BQ3˙-]. This study establishes efficient synthetic strategy to make bridged redox-active multinuclear lanthanide complexes with a pentagonal bipyramidal coordination environment that are potential precursors for single-molecule magnets.

9.
Angew Chem Int Ed Engl ; 56(36): 10942-10946, 2017 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-28665506

RESUMO

The formation of complexes between hexafluorophosphate (PF6- ) and tetraisobutyloctahydroxypyridine[4]arene has been thoroughly studied in the gas phase (ESI-QTOF-MS, IM-MS, DFT calculations), in the solid state (X-ray crystallography), and in chloroform solution (1 H, 19 F, and DOSY NMR spectroscopy). In all states of matter, simultaneous endo complexation of solvent molecules and exo complexation of a PF6- anion within a pyridine[4]arene dimer was observed. While similar ternary complexes are often observed in the solid state, this is a unique example of such behavior in the gas phase.

10.
Psychiatry Res Neuroimaging ; 266: 73-82, 2017 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-28618327

RESUMO

High doses of antipsychotics have been associated with loss in cortical and total gray matter in schizophrenia. However, previous imaging studies have not taken benzodiazepine use into account, in spite of evidence suggesting adverse effects such as cognitive impairment and increased mortality. In this Northern Finland Birth Cohort 1966 study, 69 controls and 38 individuals with schizophrenia underwent brain MRI at the ages of 34 and 43 years. At baseline, the average illness duration was over 10 years. Brain structures were delineated using an automated volumetry system, volBrain, and medication data on cumulative antipsychotic and benzodiazepine doses were collected using medical records and interviews. We used linear regression with intracranial volume and sex as covariates; illness severity was also taken into account. Though both medication doses associated to volumetric changes in subcortical structures, after adjusting for each other and the average PANSS total score, higher scan-interval antipsychotic dose associated only to volume increase in lateral ventricles and higher benzodiazepine dose associated with volume decrease in the caudate nucleus. To our knowledge, there are no previous studies reporting associations between benzodiazepine dose and brain structural changes. Further studies should focus on how these observations correspond to cognition and functioning.


Assuntos
Antipsicóticos/efeitos adversos , Benzodiazepinas/efeitos adversos , Encéfalo , Núcleo Caudado , Esquizofrenia , Adulto , Encéfalo/diagnóstico por imagem , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Núcleo Caudado/diagnóstico por imagem , Núcleo Caudado/efeitos dos fármacos , Núcleo Caudado/patologia , Estudos de Coortes , Feminino , Finlândia , Humanos , Imagem por Ressonância Magnética , Masculino , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/tratamento farmacológico , Esquizofrenia/patologia
11.
Psychiatry Res ; 247: 130-138, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27888683

RESUMO

This naturalistic study analysed the association between cumulative lifetime antipsychotic dose and cognition in schizophrenia after an average of 16.5 years of illness. Sixty participants with schizophrenia and 191 controls from the Northern Finland Birth Cohort 1966 were assessed at age 43 years with a neurocognitive test battery. Cumulative lifetime antipsychotic dose-years were collected from medical records and interviews. The association between antipsychotic dose-years and a cognitive composite score based on principal component analysis was analysed using linear regression. Higher lifetime antipsychotic dose-years were significantly associated with poorer cognitive composite score, when adjusted for gender, onset age and lifetime hospital treatment days. The effects of typical and atypical antipsychotics did not differ. This is the first report of an association between cumulative lifetime antipsychotic dose and global cognition in midlife schizophrenia. Based on these data, higher lifetime antipsychotic dose-years may be associated with poorer cognitive performance at age 43 years. Potential biases related to the naturalistic design may partly explain the results; nonetheless, it is possible that large antipsychotic doses harm cognition in schizophrenia in the long-term.


Assuntos
Antipsicóticos/uso terapêutico , Cognição/efeitos dos fármacos , Esquizofrenia/tratamento farmacológico , Psicologia do Esquizofrênico , Adulto , Fatores Etários , Estudos de Coortes , Esquema de Medicação , Feminino , Finlândia , Humanos , Masculino , Testes Neuropsicológicos , Fatores de Tempo
12.
Angew Chem Int Ed Engl ; 55(18): 5521-5, 2016 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-26997130

RESUMO

Reducing hexaazatrinaphthylene (HAN) with potassium in the presence of 18-c-6 produces [{K(18-c-6)}HAN], which contains the S=1/2 radical [HAN](.-) . The [HAN](.-) radical can be transferred to the cobalt(II) amide [Co{N(SiMe3 )2 }2 ], forming [K(18-c-6)][(HAN){Co(N'')2 }3 ]; magnetic measurements on this compound reveal an S=4 spin system with strong cobalt-ligand antiferromagnetic exchange and J≈-290 cm(-1) (-2 J formalism). In contrast, the Co(II) centres in the unreduced analogue [(HAN){Co(N'')2 }3 ] are weakly coupled (J≈-4.4 cm(-1) ). The finding that [HAN](.-) can be synthesized as a stable salt and transferred to cobalt introduces potential new routes to magnetic materials based on strongly coupled, triangular HAN building blocks.

13.
Psychiatry Res ; 235: 160-8, 2016 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-26652841

RESUMO

The information on the use of psychiatric medications in general population-based samples is limited. Our aim was to analyse the use of psychiatric medications and factors associated with antipsychotic use in psychoses in a general population sample. Fifty-five persons with schizophrenia, 21 with bipolar psychosis or psychotic depression and 20 with other psychoses from the Northern Finland Birth Cohort 1966 were examined at about 43 years of age. The frequency of use and dosage of psychiatric medication and the factors associated with the use of antipsychotics were analysed. Antipsychotics were used by 85% of schizophrenia, 65% of bipolar psychosis or psychotic depression and 62% of other psychoses cases; antidepressants were used by 22%, 60% and 33%; and benzodiazepines by 42%, 35% and 10%, respectively. In all the diagnostic groups, higher symptom scores and a higher number of hospital days were associated with the use of antipsychotics. In schizophrenia and other psychoses, poorer social and occupational functioning, and in other psychoses, female gender and lower education were also associated with the use of antipsychotics. Our results may partly indicate that, especially in schizophrenia, the effectiveness of antipsychotics is not as good as expected.


Assuntos
Antipsicóticos/uso terapêutico , Transtornos Psicóticos/tratamento farmacológico , Esquizofrenia/tratamento farmacológico , Adulto , Antidepressivos/uso terapêutico , Benzodiazepinas/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Estudos de Coortes , Transtorno Depressivo Maior/tratamento farmacológico , Escolaridade , Feminino , Finlândia/epidemiologia , Humanos , Masculino , Fatores Sexuais
14.
Dalton Trans ; 44(41): 18247-59, 2015 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-26426745

RESUMO

The reactions of dipyridylmethane (dpma) with group 13 trichlorides were investigated in 1 : 1 and 1 : 2 molar ratios using NMR spectroscopy and X-ray crystallography. With 1 : 1 stoichiometry and Et2O as solvent, reactions employing AlCl3 or GaCl3 gave mixtures of products with the salt [(dpma)2MCl2](+)[MCl4](-) (M = Al, Ga) as the main species. The corresponding reactions in 1 : 2 molar ratio gave similar mixtures but with [(dpma)MCl2](+)[MCl4](-) as the primary product. Pure salts [(dpma)AlCl2](+)[Cl](-) and [(dpma)AlCl2](+)[AlCl4](-) could be obtained by performing the reactions in CH3CN. In the case of InCl3, a neutral monoadduct (dpma)InCl3 formed regardless of the stoichiometry employed. A neutral adduct (dpma)(BCl3)2 was obtained from the reaction between dpma and BCl3 in Et2O using 1 : 2 stoichiometry. With 1 : 1 molar ratio of reagents, a mixture of products and deprotonation of the methylene bridge in [(dpma)BCl2](+) was observed. The experimental data showed that the structural flexibility of the dpma ligand results in more diverse coordination chemistry with group 13 elements than that observed for bipyridine (bpy), while computational investigations indicated that the investigated metal-ligand interactions are, to a first approximation, independent of the ligand type. Electrochemical and chemical attempts to reduce the cations [(dpma)MCl2](+) showed that, in stark contrast to the chemistry of the related [(bpy)BCl2](+) cation, the neutral radicals [(dpma)MCl2]˙ are extremely unstable. Differences in the redox behaviour of dpma and bpy could be rationalized with the electronic structure of the ligand and that of the methylene bridge in particular. As a whole, the facile reactivity of the methylene bridge in the dpma ligand renders it amenable to further reactivity and functionalization that is not possible in the case of bpy.

15.
Schizophr Res ; 168(1-2): 297-304, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26189075

RESUMO

BACKGROUND: Progressive brain volume loss in schizophrenia has been reported in previous studies but its cause and regional distribution remains unclear. We investigated progressive regional brain reductions in schizophrenia and correlations with potential mediators. METHOD: Participants were drawn from the Northern Finland Birth Cohort 1966. A total of 33 schizophrenia individuals and 71 controls were MRI scanned at baseline (mean age=34.7, SD=0.77) and at follow-up (mean age=43.4, SD=0.44). Regional brain change differences and associations with clinical mediators were examined using FSL voxelwise SIENA. RESULTS: Schizophrenia cases exhibited greater progressive brain reductions than controls, mainly in the frontal and temporal lobes. The degree of periventricular brain volume reductions were predicted by antipsychotic medication exposure at the fourth ventricular edge and by the number of days in hospital between the scans (a proxy measure of relapse duration) at the thalamic ventricular border. Decline in social and occupational functioning was associated with right supramarginal gyrus reduction. CONCLUSION: Our findings are consistent with the possibility that antipsychotic medication exposure and time spent in relapse partially explain progressive brain reductions in schizophrenia. However, residual confounding could also account for the findings and caution must be applied before drawing causal inferences from associations demonstrated in observational studies of modest size. Less progressive brain volume loss in schizophrenia may indicate better preserved social and occupational functions.


Assuntos
Antipsicóticos/uso terapêutico , Esquizofrenia/tratamento farmacológico , Esquizofrenia/patologia , Psicologia do Esquizofrênico , Adulto , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Estudos de Coortes , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Estatísticas não Paramétricas
16.
Chem Commun (Camb) ; 51(57): 11478-81, 2015 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-26088395

RESUMO

Three-electron reduction of hexaazatrinaphthylene (HAN) with a magnesium(I) reagent leads to [(HAN){Mg(nacnac)}3] (1), containing a [HAN](3-) ligand with a spin of S = 1/2. Ab initio calculations reveal that the [HAN](3-) ligand in 1 has a ground-state wave function with multiconfigurational properties, and can be described as a triradicaloid species with a small amount of open-shell doublet character.

17.
PLoS One ; 9(7): e101689, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25036617

RESUMO

Studies show evidence of longitudinal brain volume decreases in schizophrenia. We studied brain volume changes and their relation to symptom severity, level of function, cognition, and antipsychotic medication in participants with schizophrenia and control participants from a general population based birth cohort sample in a relatively long follow-up period of almost a decade. All members of the Northern Finland Birth Cohort 1966 with any psychotic disorder and a random sample not having psychosis were invited for a MRI brain scan, and clinical and cognitive assessment during 1999-2001 at the age of 33-35 years. A follow-up was conducted 9 years later during 2008-2010. Brain scans at both time points were obtained from 33 participants with schizophrenia and 71 control participants. Regression models were used to examine whether brain volume changes predicted clinical and cognitive changes over time, and whether antipsychotic medication predicted brain volume changes. The mean annual whole brain volume reduction was 0.69% in schizophrenia, and 0.49% in controls (p = 0.003, adjusted for gender, educational level, alcohol use and weight gain). The brain volume reduction in schizophrenia patients was found especially in the temporal lobe and periventricular area. Symptom severity, functioning level, and decline in cognition were not associated with brain volume reduction in schizophrenia. The amount of antipsychotic medication (dose years of equivalent to 100 mg daily chlorpromazine) over the follow-up period predicted brain volume loss (p = 0.003 adjusted for symptom level, alcohol use and weight gain). In this population based sample, brain volume reduction continues in schizophrenia patients after the onset of illness, and antipsychotic medications may contribute to these reductions.


Assuntos
Antipsicóticos/farmacologia , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Cognição/efeitos dos fármacos , Esquizofrenia/patologia , Esquizofrenia/fisiopatologia , Adulto , Antipsicóticos/uso terapêutico , Encéfalo/fisiopatologia , Feminino , Humanos , Estudos Longitudinais , Imagem por Ressonância Magnética , Masculino , Tamanho do Órgão/efeitos dos fármacos , Prognóstico , Esquizofrenia/diagnóstico , Esquizofrenia/tratamento farmacológico
18.
Schizophr Res ; 158(1-3): 134-41, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25034761

RESUMO

BACKGROUND: The association between the course of cognition and long-term antipsychotic medication in schizophrenia remains unclear. We analysed the association between cumulative lifetime antipsychotic medication dose and change of verbal learning and memory during a 9-year follow-up. METHOD: Forty schizophrenia subjects and 73 controls from the Northern Finland Birth Cohort 1966 were assessed by California Verbal Learning Test (CVLT) at the ages of 34 and 43 years. Data on the lifetime antipsychotic doses in chlorpromazine equivalents were collected. The association between antipsychotic dose-years and baseline performance and change in CVLT was analysed, controlling for baseline performance, gender, age of onset and severity of illness. RESULTS: Higher antipsychotic dose-years by baseline were significantly associated with poorer baseline performance in several dimensions of verbal learning and memory, and with a larger decrease in short-delay free recall during the follow-up (p=0.031). Higher antipsychotic dose-years during the follow-up were associated with a larger decrease of immediate free recall of trials 1-5 during the follow-up (p=0.039). Compared to controls, decline was greater in some CVLT variables among those using high-doses, but not among those using low-doses. CONCLUSION: This is the first report of an association between cumulative lifetime antipsychotic use and change in cognition in a long-term naturalistic follow-up. The use of high doses of antipsychotics may be associated with a decrease in verbal learning and memory in schizophrenia years after illness onset. The results do not support the view that antipsychotics in general prevent cognitive decline or promote cognitive recovery in schizophrenia.


Assuntos
Antipsicóticos/efeitos adversos , Memória/efeitos dos fármacos , Esquizofrenia/tratamento farmacológico , Psicologia do Esquizofrênico , Percepção da Fala/efeitos dos fármacos , Aprendizagem Verbal/efeitos dos fármacos , Adulto , Antipsicóticos/administração & dosagem , Clorpromazina/administração & dosagem , Clorpromazina/efeitos adversos , Estudos de Coortes , Relação Dose-Resposta a Droga , Feminino , Finlândia , Seguimentos , Humanos , Masculino , Testes Neuropsicológicos
19.
Science ; 344(6179): 75-8, 2014 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-24700853

RESUMO

Why does cyanide not react destructively with the proximal iron center at the active site of 1-aminocyclopropane-1-carboxylic acid (ACC) oxidase, an enzyme central to the biosynthesis of ethylene in plants? It has long been postulated that the cyanoformate anion, [NCCO2](-), forms and then decomposes to carbon dioxide and cyanide during this process. We have now isolated and crystallographically characterized this elusive anion as its tetraphenylphosphonium salt. Theoretical calculations show that cyanoformate has a very weak C-C bond and that it is thermodynamically stable only in low dielectric media. Solution stability studies have substantiated the latter result. We propose that cyanoformate shuttles the potentially toxic cyanide away from the low dielectric active site of ACC oxidase before breaking down in the higher dielectric medium of the cell.


Assuntos
Aminoácido Oxirredutases/metabolismo , Formiatos/isolamento & purificação , Nitrilos/isolamento & purificação , Aminoácido Oxirredutases/química , Dióxido de Carbono/química , Domínio Catalítico , Cristalização , Cianetos/química , Etilenos/metabolismo , Formiatos/química , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Nitrilos/química , Termodinâmica , Difração de Raios X
20.
J Org Chem ; 79(5): 2006-14, 2014 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-24517514

RESUMO

Density functional theory (PBE0/def2-TZVPP) calculations in conjunction with a polarizable continuum model were used to assess the mechanism of the intramolecular oxime transfer reaction that leads to the formation of isoxazolines. Different diastereomers of the intermediates as well as different oximes (formaldehyde and acetone oxime) were considered. The computed reaction profile predicts the water-addition and -expulsion steps as the highest barriers along the pathway, a conclusion that is in line with the experimental evidence obtained previously for these reactions.

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