RESUMEN
An environmentally friendly oxidation system has proposed for the practical and scalable production of value-added 2,5-furandicarboxylic acid from 1â kg of 5-hydroxymethylfurfural. The system is composed of a simple base, oxygen, and a green solvent, thereby providing a sustainable and economical approach to organic synthesis. To gain insight into the mechanism of this oxidation process, NMR spectroscopic analysis and kinetic study are used for the mechanistic investigation of this environmentally friendly oxidation process.
RESUMEN
By performing RNA-targeted structure-activity relationship studies, we discovered a novel peptidomimetic containing squaryldiamide as a potential bioisostere replacement for guanidine that binds transactivation responsive RNA with high affinity.
Asunto(s)
Fármacos Anti-VIH/síntesis química , Diamida/síntesis química , Productos del Gen tat/química , Duplicado del Terminal Largo de VIH/efectos de los fármacos , VIH-1/química , Oligopéptidos/síntesis química , Fármacos Anti-VIH/farmacología , Ciclobutanos , Diamida/farmacología , Diseño de Fármacos , Guanidina , Imitación Molecular , Oligopéptidos/metabolismo , Oligopéptidos/farmacología , Proteínas de Unión al ARN/química , Relación Estructura-Actividad , Productos del Gen tat del Virus de la Inmunodeficiencia HumanaRESUMEN
Excessive amounts of protein deposits, beta-amyloid (Abeta) plaques, are commonly detected in the postmortem brains of Alzheimer's disease (AD) patients. These Abeta plaques are believed to play an important role in the pathogenesis of the disease. Development of Abeta plaque-specific imaging agents for detecting and monitoring the changes of Abeta plaque deposition in living brains are reported. These agents, if successfully developed, may serve as potential biomarkers for the disease. Several iodinated derivatives based on variety of core structures are labeled with radioiodine as single photon emission computed tomography (SPECT) imaging agents. Thioflavin (or benzothiazole) derivatives displayed excellent in vitro characteristics with high binding affinities for Abeta aggregates (in subnanomolar to nanomolar range) and excellent plaque labeling of AD brain sections. However, the in vivo kinetic properties appeared unfavorable for further development. A novel series of imidazo-pyridine derivative, such as 2-(4'-dimethylaminophenyl)-6-iodo-imidazo[1,2-a]pyridine (IMPY), exhibited highly desirable in vivo properties. Additional structural modification resulting in stilbene derivatives displayed good binding affinities for Abeta aggregates. In addition, fluorene compounds with a rigid tricyclic structure showed in vitro and in vivo characteristics as potential SPECT imaging agents. Criteria for selection of radioiodinated tracers with suitable in vivo properties to detect amyloid plaques are discussed.
Asunto(s)
Enfermedad de Alzheimer/diagnóstico por imagen , Radioisótopos de Yodo , Placa Amiloide/diagnóstico por imagen , Radiofármacos , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/metabolismo , Animales , Autorradiografía , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Humanos , Técnicas In Vitro , Radioisótopos de Yodo/química , Radioisótopos de Yodo/farmacocinética , Masculino , Ratones , Ratones Endogámicos ICR , Placa Amiloide/metabolismo , Radiofármacos/química , Radiofármacos/farmacocinética , Tomografía Computarizada de Emisión de Fotón Único/métodosRESUMEN
Formation of beta-amyloid (Abeta) plaques in the brain is a major contributing factor in the pathogenesis of Alzheimer's disease (AD). Detection of Abeta plaques in the brain will be potentially useful in early diagnosis and monitoring the progression of the disease. A series of novel Abeta aggregate-specific ligands based on fluorenes, which are simple and rigid tricyclic molecules, are synthesized and characterized. Starting with 2- or 3-aminofluorenes, 1a-1f, the amino group was converted to the N,N-dimethylamino group (2a-2f) in excellent yield. It was found that 7-iodo-2-N,N-dimethylaminofluorene (2f) showed an extremely high binding affinity to preformed Abeta40 aggregates (K(i) = 0.9 nM). In vitro autoradiography study using brain sections obtained from transgenic mice (Tg2576) with [(125)I]2f showed exquisitely high specific binding to Abeta plaques. The same section also displayed an equivalent labeling when stained by Thioflavin-S, a commonly used fluorescent dye for Abeta plaques. When [(125)I]2f was injected intravenously into normal mice, it exhibited an excellent brain uptake. Taken together the data suggest that [(125)I]2f may be useful as an in vivo imaging agent to detect Abeta plaques in the brain.
Asunto(s)
Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/metabolismo , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Fluorenos/farmacocinética , Tomografía Computarizada de Emisión/métodos , Animales , Autorradiografía , Radioisótopos de Yodo/farmacocinética , Marcaje Isotópico/métodos , Masculino , Ratones , Ratones Endogámicos ICR , Ratones Transgénicos , Especificidad de Órganos , Radiofármacos/síntesis química , Radiofármacos/farmacocinética , Distribución TisularRESUMEN
A benzene-based tripodal imidazolium receptor utilizing the strong (C-H)(+)...X(-) hydrogen bonding interaction between imidazolium moieties and halide anions is extensively investigated both theoretically and experimentally. Ab initio calculations predict that this receptor has a very high affinity for fluoride ion (F(-)). The association constant and free energy gain of the N-butyl receptor 2 for F(-) in acetonitrile were measured to be 2.1 x 10(5) M(-1) and -7.25 kcal/mol, respectively, showing that the receptor has a high affinity for F(-) in highly polar organic solvents.
RESUMEN
[structure: see text] In consideration of competition between cation-pi and hydrogen bond interaction forces, we designed a novel receptor, 1,3,5-tris(pyrrolyl)benzene, which shows high selectivity for acetylcholine (ACh). The selectivity of the receptor for ACh over other ammonium cations is demonstrated by the ion-selective electrode (ISE) method in buffer solution. The binding free energy of the receptor with ACh in chloroform solution is measured to be 3.65 kcal/mol in the presence of chloride anion by nuclear magnetic resonance spectroscopy, and that in water is estimated to be much greater ( approximately 6 kcal/mol).
Asunto(s)
Acetilcolina/química , Compuestos Heterocíclicos de 4 o más Anillos/química , Modelos Moleculares , Compuestos de Amonio Cuaternario/química , Acetilcolina/análisis , Acetilcolina/aislamiento & purificación , Benceno/química , Electrodos de Iones Selectos , Sustancias Macromoleculares , Estructura Molecular , Pirroles/química , Compuestos de Amonio Cuaternario/análisis , Compuestos de Amonio Cuaternario/aislamiento & purificación , SolucionesRESUMEN
A series of novel beta-amyloid (A beta) aggregate-specific ligands, 2-(4'-dimethylaminophenyl)-6-iodoimidazo[1,2-a]pyridine, 16(IMPY), and its related derivatives were prepared. An in vitro binding study with preformed A beta aggregates showed that 16(IMPY) and its bromo derivative competed with binding of 2-(4'-dimethylaminophenyl)-6-iodobenzothiazole, [125I]7(TZDM), a known ligand for A beta aggregates, with high binding affinities (K(i) = 15 and 10 nM, respectively). In vitro autoradiography of brain sections of a transgenic mouse (Tg2576) with [125I]16(IMPY) displayed high selective binding to amyloid-like structures, comparable to that observed by staining with thioflavin-S visualized under fluorescence. In vivo biodistribution after an intravenous injection of [125I]16(IMPY) in normal mice showed a high initial brain uptake and fast washout, indicating a low background activity associated with this iodinated ligand. Taken together, the data suggests that [123I]16(IMPY) may be useful for imaging A beta aggregates in patients with Alzheimer's disease.
Asunto(s)
Péptidos beta-Amiloides/metabolismo , Encéfalo/metabolismo , Imidazoles/síntesis química , Piridinas/síntesis química , Radiofármacos/síntesis química , Enfermedad de Alzheimer/diagnóstico , Animales , Encéfalo/patología , Imidazoles/química , Imidazoles/farmacocinética , Técnicas In Vitro , Radioisótopos de Yodo , Ligandos , Masculino , Ratones , Ratones Endogámicos ICR , Piridinas/química , Piridinas/farmacocinética , Radiofármacos/química , Radiofármacos/farmacocinética , Relación Estructura-ActividadRESUMEN
Using the computer-aided molecular design approach, we recently reported the synthesis of calix[4]hydroquinone (CHQ) nanotube arrays self-assembled with infinitely long one-dimensional (1-D) short hydrogen bonds (H-bonds) and aromatic-aromatic interactions. Here, we assess various calculation methods employed for both the design of the CHQ nanotubes and the study of their assembly process. Our calculations include ab initio and density functional theories and first principles calculations using ultrasoft pseudopotential plane wave methods. The assembly phenomena predicted prior to the synthesis of the nanotubes and details of the refined structure and electronic properties obtained after the experimental characterization of the nanotube crystal are reported. For better characterization of intriguing 1-D short H-bonds and exemplary displaced pi-pi stacks, the X-ray structures have been further refined with samples grown in different solvent conditions. Since X-ray structures do not contain the positions of H atoms, it is necessary to analyze the system using quantum theoretical calculations. The competition between H-bonding and displaced pi-pi stacking in the assembling process has been clarified. The IR spectroscopic features and NMR chemical shifts of 1-D short H-bonds have been investigated both experimentally and theoretically. The dissection of the two most important interaction components leading to self-assembly processes would help design new functional materials and nanomaterials.
Asunto(s)
Calixarenos , Hidroquinonas/síntesis química , Nanotecnología/métodos , Diseño Asistido por Computadora , Cristalografía por Rayos X , Enlace de Hidrógeno , Hidroquinonas/química , Modelos Moleculares , Quinonas/síntesis química , Quinonas/químicaRESUMEN
[formula: see text] A new molecular system, 2,11-dithio[4,4]metametaquinocyclophane containing a quinone moiety, was designed and synthesized. As the quinone moiety can readily be converted into an aromatic pi-system (hydroquinone) upon reduction, the nanomechanical molecular cyclophane system exhibits a large flapping motion like a molecular flipper from the electrochemical redox process. The conformational changes upon reduction and oxidation are caused by changes of nonbonding interaction forces (devoid of bond formation/breaking) from the edge-to-face to face-to-face aromatic interactions and vice versa, respectively.