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1.
Chembiochem ; 25(10): e202400079, 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38477872

RESUMEN

S-Adenosyl-l-methionine (SAM) is an important cosubstrate in various biochemical processes, including selective methyl transfer reactions. Simple methods for the (re)generation of SAM analogs could expand the chemistry accessible with SAM-dependent transferases and go beyond methylation reactions. Here we present an efficient enzyme engineering strategy to synthesize different SAM analogs from "off-the-shelf" iodoalkanes through enzymatic alkylation of S-adenosyl-l-homocysteine (SAH). This was achieved by mutating multiple hydrophobic and structurally dynamic amino acids simultaneously. Combinatorial mutagenesis was guided by the natural amino acid diversity and generated a highly functional mutant library. This approach increased the speed as well as the scale of enzyme engineering by providing a panel of optimized enzymes with orders of magnitude higher activities for multiple substrates in just one round of enzyme engineering. The optimized enzymes exhibit catalytic efficiencies up to 31 M-1 s-1, convert various iodoalkanes, including substrates bearing cyclopropyl or aromatic moieties, and catalyze S-alkylation of SAH with very high stereoselectivities (>99 % de). We further report a high throughput chromatographic screening system for reliable and rapid SAM analog analysis. We believe that the methods and enzymes described herein will further advance the field of selective biocatalytic alkylation chemistry by enabling SAM analog regeneration with "off-the-shelf" reagents.


Asunto(s)
Ingeniería de Proteínas , S-Adenosilmetionina , S-Adenosilmetionina/metabolismo , S-Adenosilmetionina/química , Alquilación , Hidrocarburos Yodados/química , Biocatálisis , Estructura Molecular
2.
J Labelled Comp Radiopharm ; 67(7): 254-262, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38703027

RESUMEN

Reductive N-11C-methylation using [11C]formaldehyde and amines has been used to prepare N-11C-methylated compounds. However, the yields of the N-11C-methylated compounds are often insufficient. In this study, we developed an efficient method for base-free reductive N-11C-methylation that is applicable to a wide variety of substrates, including arylamines bearing electron-withdrawing and electron-donating substituents. A 2-picoline borane complex, which is a stable and mild reductant, was used. Dimethyl sulfoxide was used as the primary reaction solvent, and glacial acetic acid or aqueous acetic acid was used as a cosolvent. While reductive N-11C-methylation efficiently proceeded under anhydrous conditions in most cases, the addition of water to the reductive N-11C-methylation generally increased the yield of the N-11C-methylated compounds. Substrates with hydroxy, carboxyl, nitrile, nitro, ester, amide, and phenone moieties and amine salts were applicable to the reaction. This proposed method for reductive N-11C-methylation should be applicable to a wide variety of substrates, including thermo-labile and base-sensitive compounds because the reaction was performed under relatively mild conditions (70°C) without the need for a base.


Asunto(s)
Aminas , Radioisótopos de Carbono , Formaldehído , Hidrocarburos Yodados , Metilación , Radioisótopos de Carbono/química , Aminas/química , Formaldehído/química , Hidrocarburos Yodados/química , Oxidación-Reducción
3.
J Am Chem Soc ; 144(7): 3285-3296, 2022 02 23.
Artículo en Inglés | MEDLINE | ID: mdl-35156815

RESUMEN

Micelles on the surfaces of individual metallic zinc particles are imaged by fluorescence microscopy with sensitivity up to single micelles. These micelles are made fluorescent to enable imaging, through the incorporation of boron dipyrromethene fluorophores as representative organic molecular "cargo". Highlighting an advantage of this in situ and sensitive fluorescence technique, the same micelles are not visible by ex situ scanning electron microscopy/energy dispersive X-ray spectroscopy analysis. Examination of micellar solutions with zinc reveals an aging process: micelles do not immediately adhere to the zinc surfaces upon mixing but rather build up over time. Furthermore, at longer times, smaller zinc particles become fully encased in micelle "shells". Once adhered, micelles remain in the local regions of the zinc surface for the duration of the imaging experiments (>2 h). Single micelles are imaged in solution, and their molecular contents are characterized. Two-color fluorescence crossover experiments show that micelles adhered to the surface of the zinc exchange molecular contents with micelles in solution, achieving molecular exchange equilibrium in ∼2.5 h. Unique (non-ensemble averaged) exchange kinetics are displayed by micelles at different locations on the zinc surface, consistent with exchange kinetics of single micelles or small local clusters of micelles. The aging of the micellar solutions and the rate of exchange while on the surface of the zinc suggest that micelle mass transport processes may contribute to overall reaction barriers in sustainable organozinc cross-coupling reactions in micellar water. The observed aging of the system suggests routes for improvement of preparative, bench-scale synthetic reactions involving micellar preparations of organozinc compounds.


Asunto(s)
Micelas , Compuestos Organometálicos/química , Zinc/química , Adhesividad , Compuestos de Boro/química , Colorantes Fluorescentes/química , Hidrocarburos Yodados/química , Microscopía Fluorescente , Tensoactivos/química , Tocoferoles/química , Agua/química
4.
Angew Chem Int Ed Engl ; 61(1): e202110391, 2022 01 03.
Artículo en Inglés | MEDLINE | ID: mdl-34664354

RESUMEN

Canonical nucleosides are vulnerable to enzymatic and chemical degradation, yet their stable mimics-C-aryl nucleosides-have demonstrated potential utility in medicinal chemistry, chemical biology, and synthetic biology, although current synthetic methods remain limited in terms of scope and selectivity. Herein, we report a cross-electrophile coupling to prepare C-aryl nucleoside analogues from readily available furanosyl acetates and aryl iodides. This nickel-catalyzed modular approach is characterized by mild reaction conditions, broad substrate scope, excellent ß-selectivity, and high functional-group compatibility. The exclusive chemoselectivity with respect to the aryl iodide enables efficient preparation of a variety of C-aryl halide furanosides suitable for various downstream transformations. The practicality of this transformation is demonstrated through the synthesis of a potent analogue of a naturally occurring NF-κB activator.


Asunto(s)
Acetatos/química , Furanos/química , Hidrocarburos Yodados/química , Níquel/química , Nucleósidos/síntesis química , Catálisis , Estructura Molecular , Nucleósidos/química , Estereoisomerismo
5.
Bioorg Chem ; 108: 104615, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33484942

RESUMEN

One current approach in the treatment of cancer is the inhibition of cyclin dependent kinase (CDK) enzymes with small molecules. CDK are a class of enzymes, which catalyze the transfer of the terminal phosphate of a molecule of ATP to a protein that acts as a substrate. Among CDK enzymes, CDK2 has been implicated in a variety of cancers, supporting its potential as a novel target for cancer therapy across many tumor types. Here the discovery and development of arylidene-hydrazinyl-thiazole as a potentially CDK2 inhibitors is described, including details of the design and successful synthesis of the series analogs (27a-r) using one-pot approach under eco-friendly ultrasound and microwave conditions. Most of the newly synthesized compounds showed good growth inhibition when assayed for their in-vitro anti-proliferative activity against three cancer cell lines (HepG2, MCF-7 and HCT-116) compared to the reference drug roscovitine, with little toxicity on the normal fibroblast cell lines (WI-38). Furthermore, the compounds exhibiting the highest anti-proliferative activities were tested against a panel of kinase enzymes. These derivatives displayed an outstanding CDK2 inhibitory potential with varying degree of inhibition in the range of IC50 0.35-1.49 µM when compared with the standard inhibitor roscovitine having an IC50 value 0.71 µM. The most promising CDK2 inhibitor (27f) was selected for further studies to determine its effect on the cell cycle progression and apoptosis in HepG2 cell line. The results indicated that this compound implied inhibition in the G2/M phase of the cell cycle, and it is a good apoptotic agent. Finally, Molecular docking study was performed to identify the structural elements which involved in the inhibitory activity with the prospective target, CDK2, and to rationalize the structure-activity relationship (SAR).


Asunto(s)
Antineoplásicos/farmacología , Quinasa 2 Dependiente de la Ciclina/antagonistas & inhibidores , Hidrazinas/farmacología , Hidrocarburos Yodados/farmacología , Simulación del Acoplamiento Molecular , Inhibidores de Proteínas Quinasas/farmacología , Tiazoles/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Proliferación Celular/efectos de los fármacos , Quinasa 2 Dependiente de la Ciclina/metabolismo , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Hidrazinas/química , Hidrocarburos Yodados/química , Estructura Molecular , Inhibidores de Proteínas Quinasas/síntesis química , Inhibidores de Proteínas Quinasas/química , Relación Estructura-Actividad , Tiazoles/química , Células Tumorales Cultivadas
6.
J Am Chem Soc ; 142(35): 14831-14837, 2020 09 02.
Artículo en Inglés | MEDLINE | ID: mdl-32799536

RESUMEN

We report an iodoarene-catalyzed enantioselective synthesis of ß,ß-difluoroalkyl bromide building blocks. The transformation involves an oxidative rearrangement of α-bromostyrenes, utilizing HF-pyridine as the fluoride source and m-CPBA as the stoichiometric oxidant. A catalyst decomposition pathway was identified, which, in tandem with catalyst structure-activity relationship studies, facilitated the development of an improved catalyst providing higher enantioselectivity with lower catalyst loadings. The versatility of the difluoroalkyl bromide products was demonstrated via highly enantiospecific substitution reactions with suitably reactive nucleophiles. The origins of enantioselectivity were investigated using computed interaction energies of simplified catalyst and substrate structures, providing evidence for both CH-π and π-π transition state interactions as critical features.


Asunto(s)
Hidrocarburos Bromados/síntesis química , Hidrocarburos Yodados/química , Catálisis , Halogenación , Hidrocarburos Bromados/química , Estructura Molecular , Estereoisomerismo
7.
J Am Chem Soc ; 142(37): 16090-16096, 2020 09 16.
Artículo en Inglés | MEDLINE | ID: mdl-32845619

RESUMEN

We report a strategy for effecting catalytic, enantioselective carbocationic rearrangements through the intermediacy of alkyl iodanes as stereodefined carbocation equivalents. Asymmetric Wagner-Meerwein rearrangements of ß-substituted styrenes are catalyzed by the C2-symmetric aryl iodide 1 to provide access to enantioenriched 1,3-difluorinated molecules possessing interesting and well-defined conformational properties. Hammett and kinetic isotope effect studies, in combination with computational investigations, reveal that two different mechanisms are operative in these rearrangement reactions, with the pathway depending on the identity of the migrating group. In reactions involving alkyl-group migration, intermolecular fluoride attack is product- and enantio-determining. In contrast, reactions in which aryl rearrangement occurs proceed through an enantiodetermining intramolecular 1,2-migration prior to fluorination. The fact that both pathways are promoted by the same chiral aryl iodide catalyst with high enantioselectivity provides a compelling illustration of generality across reaction mechanisms in asymmetric catalysis.


Asunto(s)
Hidrocarburos Yodados/química , Estirenos/síntesis química , Catálisis , Estructura Molecular , Estereoisomerismo , Estirenos/química
8.
J Am Chem Soc ; 142(37): 15673-15677, 2020 09 16.
Artículo en Inglés | MEDLINE | ID: mdl-32857506

RESUMEN

Flavin-dependent "ene"-reductases can generate stabilized alkyl radicals when irradiated with visible light; however, they are not known to form unstabilized radicals. Here, we report an enantioselective radical cyclization using alkyl iodides as precursors to unstabilized nucleophilic radicals. Evidence suggests this species is accessed by photoexcitation of a charge-transfer complex that forms between flavin and substrate within the protein active site. Stereoselective delivery of a hydrogen atom from the flavin semiquinone to the prochiral radical formed after cyclization provides high levels of enantioselectivity across a variety of substrates. Overall, this transformation demonstrates that photoenzymatic catalysis can address long-standing selectivity challenges in the radical literature.


Asunto(s)
Hidrocarburos Yodados/metabolismo , Oxidorreductasas/metabolismo , Ciclización , Radicales Libres/química , Radicales Libres/metabolismo , Hidrocarburos Yodados/química , Estructura Molecular , Oxidación-Reducción , Oxidorreductasas/química , Procesos Fotoquímicos , Estereoisomerismo
9.
Macromol Rapid Commun ; 41(9): e2000075, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32267036

RESUMEN

Organocatalyzed living radical polymerizations of itaconates are studied, yielding low-dispersity linear and star polymers (D = Mw /Mn = 1.28-1.46) up to Mn = 20 000 and monomer conversion = 62%, where Mn and Mw are the number- and weight-average molar masses, respectively. The block polymerization with functional methacrylates, an acrylate, and styrene yields various rod-coil block copolymers. Linear A-B diblock, linear B-A-B triblock, and 3-arm star A-B diblock copolymers generate spherical micelles (nanoparticles) and vesicles (nanocapsules), depending on the polymer structures. Itaconates can be derived from bioresources, and thus the obtained polymers may serve as green polymers. Because of the biocompatibility of polyitaconates, the assemblies may serve as biocompatible nanocarriers.


Asunto(s)
Hidrocarburos Yodados/química , Polímeros/síntesis química , Succinatos/síntesis química , Catálisis , Radicales Libres/síntesis química , Radicales Libres/química , Micelas , Estructura Molecular , Polimerizacion , Polímeros/química , Succinatos/química
10.
Chem Pharm Bull (Tokyo) ; 68(3): 288-291, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32115536

RESUMEN

We report a Pd-catalyzed ß-arylation of cyclic α,ß-unsaturated O-methyl oximes with aryl iodides. This reaction shows complete regioselectivity and excellent functional group tolerance. ß-Arylation of 2-cyclohexen-1-one O-methyl oxime (existing as 2 : 1 E/Z mixture) with certain aryl iodides such as 4-iodoanisole affords only ß-arylated (E)-O-methyl oximes.


Asunto(s)
Hidrocarburos Yodados/química , Oximas/química , Paladio/química , Catálisis , Estructura Molecular
11.
Molecules ; 25(18)2020 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-32947763

RESUMEN

Consecutive alkylation of 4-hydroxy-2-thioxo-1,2-dihydroquinoline-3-carboxylate by CH3I has been investigated to establish regioselectivity of the reaction for reliable design and synthesis of combinatorial libraries. In the first stage, the product of S-methylation-methyl 4-hydroxy-2-(methylthio)quinoline-3-carboxylate was obtained. The subsequent alkylation with CH3I led to the formation of both O- and N-methylation products mixture-methyl 4-methoxy-2-(methylthio)quinoline-3-carboxylate and methyl 1-methyl-2-(methylthio)-4-oxo-1,4-dihydroquinoline-3-carboxylate with a predominance of O-methylated product. The structure of synthesized compounds was confirmed by means of elemental analysis, 1H-NMR, 13C-NMR, LC/MS, and single-crystal X-ray diffraction. The quantum chemical calculations of geometry and electron structure of methyl 4-hydroxy-2-(methylthio)quinoline-3-carboxylate's anion were carried out. According to molecular docking simulations, the studied compounds can be considered as potent inhibitors of Hepatitis B Virus replication. Experimental in vitro biological studies confirmed that studied compounds demonstrated high inhibition of HBV replication in 10 µM concentration.


Asunto(s)
Simulación del Acoplamiento Molecular , Quinolinas/química , Sitios de Unión , Proteínas de la Cápside/antagonistas & inhibidores , Proteínas de la Cápside/metabolismo , Virus de la Hepatitis B/metabolismo , Hidrocarburos Yodados/química , Enlace de Hidrógeno , Metilación , Conformación Molecular , Teoría Cuántica , Quinolinas/metabolismo
12.
Molecules ; 25(9)2020 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-32397334

RESUMEN

The 3,3',5,5'-tetrachloro-2-iodo-4,4'-bipyridine structure is proposed as a novel chemical scaffold for the design of new transthyretin (TTR) fibrillogenesis inhibitors. In the frame of a proof-of-principle exploration, four chiral 3,3',5,5'-tetrachloro-2-iodo-2'-substituted-4,4'- bipyridines were rationally designed and prepared from a simple trihalopyridine in three steps, including a Cu-catalysed Finkelstein reaction to introduce iodine atoms on the heteroaromatic scaffold, and a Pd-catalysed coupling reaction to install the 2'-substituent. The corresponding racemates, along with other five chiral 4,4'-bipyridines containing halogens as substituents, were enantioseparated by high-performance liquid chromatography in order to obtain pure enantiomer pairs. All stereoisomers were tested against the amyloid fibril formation (FF) of wild type (WT)-TTR and two mutant variants, V30M and Y78F, in acid mediated aggregation experiments. Among the 4,4'-bipyridine derivatives, interesting inhibition activity was obtained for both enantiomers of the 3,3',5,5'-tetrachloro-2'-(4-hydroxyphenyl)-2-iodo-4,4'-bipyridine. In silico docking studies were carried out in order to explore possible binding modes of the 4,4'-bipyridine derivatives into the TTR. The gained results point out the importance of the right combination of H-bond sites and the presence of iodine as halogen-bond donor. Both experimental and theoretical evidences pave the way for the utilization of the iodinated 4,4'-bipyridine core as template to design new promising inhibitors of TTR amyloidogenesis.


Asunto(s)
Amiloide/química , Hidrocarburos Yodados , Simulación del Acoplamiento Molecular , Prealbúmina/química , Agregado de Proteínas , Piridinas , Sustitución de Aminoácidos , Amiloide/genética , Humanos , Hidrocarburos Yodados/síntesis química , Hidrocarburos Yodados/química , Mutación Missense , Prealbúmina/genética , Piridinas/síntesis química , Piridinas/química
13.
J Am Chem Soc ; 141(32): 12464-12469, 2019 08 14.
Artículo en Inglés | MEDLINE | ID: mdl-31373807

RESUMEN

We have developed a method for stereospecific synthesis of E-alkenes from terminal alkynes and alkyl iodides. The hydroalkylation reaction is enabled by a cooperative action of copper and nickel catalysts and proceeds with excellent anti-Markovnikov selectivity. We demonstrate the broad scope of the reaction, which can be accomplished in the presence of esters, nitriles, aryl bromides, ethers, alkyl chlorides, anilines, and a wide range of nitrogen-containing heteroaromatic compounds. Mechanistic studies provide evidence that the copper catalyst activates the alkyne by hydrocupration, which controls both the regio- and diastereoselectivity of the overall reaction. The nickel catalyst activates the alkyl iodide and promotes cross coupling with the alkenyl copper intermediate.


Asunto(s)
Alquenos/síntesis química , Alquinos/química , Catálisis , Complejos de Coordinación/química , Cobre/química , Hidrocarburos Yodados/química , Hidroxilación , Modelos Químicos , Estereoisomerismo
14.
J Am Chem Soc ; 141(45): 18127-18135, 2019 11 13.
Artículo en Inglés | MEDLINE | ID: mdl-31634428

RESUMEN

A simple protocol for performing chromium-catalyzed highly diastereoselective alkylations of arylmagnesium halides with cyclohexyl iodides at ambient temperature has been developed. Furthermore, this ligand-free CrCl2 enables efficient electrophilic alkenylations of primary, secondary, and tetiary alkylmagnesium halides with readily available alkenyl acetates. Moreover, this chemoselective C-C coupling reaction with stereodefined alkenyl acetates proceeds in a stereoretentive fashion. A wide range of functional groups on alkyl iodides and alkenyl acetates are well tolerated, thus furnishing functionalized Csp2-Csp3 coupling products in good yields and high diastereoselectivity. Detailed mechanistic studies suggest that the in situ generated low-valent chromium(I) species might be the active catalyst for these Csp2-Csp3 cross-couplings.


Asunto(s)
Cromo/química , Ciclohexanos/química , Hidrocarburos Yodados/química , Indicadores y Reactivos/química , Compuestos Organometálicos/química , Alquilación , Catálisis , Ciclohexanos/síntesis química , Magnesio/química , Modelos Químicos , Estereoisomerismo
15.
J Am Chem Soc ; 141(49): 19458-19465, 2019 12 11.
Artículo en Inglés | MEDLINE | ID: mdl-31722521

RESUMEN

Several perfluoroalkylcopper compounds have been reported previously that serve as reagents or catalysts for the perfluoroalkylation of aryl halides. However, the relationships between the reactivity of such complexes and the electronic properties of the ancillary ligands are unknown, and such relationships are not well-known in general for copper complexes that mediate or catalyze cross coupling. We report the synthesis and characterization of a series of pentafluoroethylcopper(I) complexes ligated by bipyridine ligands possessing varied electronic properties. In contrast to the limited existing data on the reactivity of L2Cu(I)-X complexes bearing amine and pyridine-type ligands in Ullmann-type aminations with aryl halides, the reactions of aryl halides with pentafluoroethylcopper(I) complexes bearing systematically varied bipyridine ligands were faster for complexes bearing less electron-donating bipyridines than for complexes bearing more electron-donating bipyridines. Analysis of the rates of reaction and the relative populations of the neutral complexes [(R2bpy)CuC2F5] and ionic complexes [(R2bpy)2Cu][Cu(C2F5)2] formed by these reagents in solution suggests that this effect of electronics on the reaction rate results from an unusual trend of faster oxidative addition of aryl halides to [(R2bpy)CuC2F5] complexes containing less electron-donating R2bpy ligands than to those containing more electron-donating R2bpy ligands.


Asunto(s)
Complejos de Coordinación/química , Cobre/química , Fluorocarburos/química , Hidrocarburos Aromáticos/química , Hidrocarburos Bromados/química , Hidrocarburos Yodados/química , 2,2'-Dipiridil/química , Alquilación , Transporte de Electrón , Enlace de Hidrógeno , Ligandos
16.
Anal Chem ; 91(18): 11794-11802, 2019 09 17.
Artículo en Inglés | MEDLINE | ID: mdl-31356052

RESUMEN

Glycosylation is an important post-translational modification of proteins. Many diseases, such as cancer, have proved to be related to aberrant glycosylation. High throughput quantitative methods have gained attention recently in the study of glycomics. With the development of high-resolution mass spectrometry, the sensitivity of detection in glycomics has largely improved; however, most of the commonly used MS-based techniques are focused on relative quantitative analysis, which can hardly provide direct comparative glycomic quantitation results. In this study, we developed a novel multiplex glycomic analysis method on an LC-ESI-MS platform. Reduced glycans were stable isotopic labeled during the permethylation procedure, with the use of iodomethane reagents CH2DI, CHD2I, CD3I, 13CH3I, 13CH2DI, 13CHD2I, 13CD3I, and CH3I. Up to 8-plex glycomic profiling was possible in a single analysis by LC-MS, and a 100 k mass resolution was sufficient to allow a baseline resolution of the mass differences among the 8-plex labeled glycans. The major advantages of this method are that it overcomes quantitative fluctuations caused by nanoESI, it facilitates a level of comparative quantitative glycomic analysis that accurately reflects the quantitative information in samples, and it dramatically shortens analysis time. Quantitation validation was tested on glycans released from bovine fetuin and model glycoprotein mixtures (RNase B, bovine fetuin, and IgG) with good linearity (R2 = 0.9884) and a dynamic range from 0.1 to 10. The 8-plex strategy was successfully applied to a comparative glycomic study of cancer cell lines. The results demonstrate that different distributions of sialylated glycans are related to the metastatic properties of cell lines and provide important clues for a better understanding of breast cancer brain metastasis.


Asunto(s)
Cromatografía Liquida/métodos , Glicómica/métodos , Hidrocarburos Yodados/química , Polisacáridos/análisis , Espectrometría de Masas en Tándem/métodos , Neoplasias Encefálicas/química , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/secundario , Neoplasias de la Mama/química , Neoplasias de la Mama/patología , Isótopos de Carbono , Línea Celular Tumoral , Femenino , Glicoproteínas/química , Humanos , Metilación , Polisacáridos/química , Reproducibilidad de los Resultados , Espectrometría de Masa por Ionización de Electrospray/instrumentación
17.
Biomacromolecules ; 20(2): 904-915, 2019 02 11.
Artículo en Inglés | MEDLINE | ID: mdl-30566330

RESUMEN

The present study demonstrates the controlled synthesis and biological potential of poly( N-acryloyl-l-methionine methyl sulfonium salt)s (poly(A-Met(S+)-OH)s), which mimic dimethylsulfoniopropionate (DMSP), a compound produced by marine algae to protect their proteins. The novel sulfonium-containing zwitterionic polymers were synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization of the amino acid-based monomer N-acryloyl-l-methionine (A-Met-OH) followed by a postmodification process in which the sulfide groups were reacted with iodomethane. The DMSP-mimic zwitterionic macromolecules were shown for the first time to exhibit low cytotoxicity and the ability to stabilize proteins. By adding the resulting poly(A-Met(S+)-OH)s to horse radish peroxidase (HRP) solution, the activity of HRP was maintained even after storage at 4 °C for several days. In addition, the protein activities were tested using peroxidase-labeled antibody to mouse immunoglobulin G (IgG-HRP) and alkaline phosphatase (ALP) after storage and for HRP after freeze-thaw cycles. Amphiphilic random copolymers, poly(A-Met(S+)-OH- co-BA)s, also exhibited excellent properties for protein stabilization.


Asunto(s)
Polímeros/síntesis química , Proteínas/química , Compuestos de Sulfonio/química , Fosfatasa Alcalina/química , Aminoácidos/química , Animales , Línea Celular , Peroxidasa de Rábano Silvestre/química , Hidrocarburos Yodados/química , Inmunoglobulina G/química , Metionina/química , Ratones , Polimerizacion
18.
Chem Pharm Bull (Tokyo) ; 67(10): 1042-1045, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31582624

RESUMEN

Biaryls are important compounds with widespread applications in many fields. Tetramethylammonium fluoride tetrahydrate was found to promote the biaryl coupling of aryl iodides bearing electron-withdrawing substituents with unactivated arenes. The reaction takes place at temperatures between 100 and 150°C and can be applied to a wide range of aromatic and heteroaromatic rings, affording the products in moderate to high yields. The reaction does not require strong bases or expensive additives that are employed in the existing methods and can be conducted in air and moisture without any precautions.


Asunto(s)
Hidrocarburos Aromáticos/química , Hidrocarburos Yodados/química , Compuestos de Amonio Cuaternario/química , Aire , Estructura Molecular , Temperatura , Agua/química
19.
J Labelled Comp Radiopharm ; 62(2): 86-94, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30556149

RESUMEN

To enable positron emission tomography (PET) imaging of the in vivo kinetics of ubiquinone and ubiquinol, which is referred to as coenzyme Q10 , their 11 C-radiolabeled counterparts were synthesized herein. 11 C-Labeled ubiquinone [11 C]-1 was realized by Pd-mediated rapid C-[11 C]methylation of [11 C]CH3 I with 39-demethyl-39-(pinacolboryl)ubiquinone, prepared by Ru-catalyzed olefin metathesis of unradiolabeled ubiquinone with 2-(pinacolboryl)propene. Subsequent reduction of [11 C]-1 using Na2 S2 O4 yielded 11 C-labeled ubiquinol [11 C]-2. The synthesis time and [11 C]CH3 I-based radiochemical yield of [11 C]-1 were within 36 minutes and up to 53%, while those of [11 C]-2 were within 38 minutes and up to 39%, respectively. After radiopharmaceutical formulation, the qualities of [11 C]-1 and [11 C]-2 were confirmed to be applicable for animal PET studies. The analytical values of [11 C]-1 and [11 C]-2 are as follows: radioactivity of up to 3.5 and 1.4 GBq, molar activity of 21 to 78 and 48 to 76 GBq/µmol, radiochemical purity of greater than 99% and greater than 95%, and chemical purity of greater than 99% and 77%, respectively. The concept behind this radiolabeling procedure is that unradiolabeled natural ubiquinone can be converted to 11 C-radiolabeled ubiquinone and ubiquinol via a pinacolborane-substituted ubiquinone derivative. Each PET probe was used for molecular imaging using rats to investigate the in vivo kinetics and biodistribution of the coenzyme Q10 .


Asunto(s)
Radioisótopos de Carbono/química , Radiofármacos/síntesis química , Ubiquinona/análogos & derivados , Hidrocarburos Yodados/química , Paladio/química , Tomografía de Emisión de Positrones/métodos
20.
Molecules ; 24(9)2019 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-31083344

RESUMEN

The intermolecular interaction in difluoromethane, dichloromethane, dibromomethane, and diiodomethane dimers has been investigated using high level quantum chemical methods. The potential energy curve of intermolecular interaction along the C⋯C bond distance obtained using the coupled-cluster theory with singles, doubles, and perturbative triples excitations CCSD(T) were compared with values given by the same method, but applying the local (LCCSD(T)) and the explicitly correlated (CCSD(T)-F12) approximations. The accuracy of other theoretical methods-Hartree-Fock (HF), second order Møller-Plesset perturbation (MP2), and dispersion corrected DFT theory-were also presented. In the case of MP2 level, the canonical and the local-correlation cases combined with the density-fitting technique (DF-LMP2)theories were considered, while for the dispersion-corrected DFT, the empirically-corrected BLYP-D and the M06-2Xexchange-correlation functionals were applied. In all cases, the aug-cc-pVTZ basis set was used, and the results were corrected for the basis set superposition error (BSSE) using the counterpoise method. For each molecular system, several dimer geometries were found, and their mutual orientations were compared with the nearest neighbor orientations obtained in recent neutron scattering studies. The nature of the intermolecular interaction energy was discussed.


Asunto(s)
Compuestos Inorgánicos/análisis , Compuestos Inorgánicos/química , Dimerización , Hidrocarburos Bromados/análisis , Hidrocarburos Bromados/química , Hidrocarburos Clorados/análisis , Hidrocarburos Clorados/química , Hidrocarburos Fluorados/análisis , Hidrocarburos Fluorados/química , Hidrocarburos Yodados/análisis , Hidrocarburos Yodados/química , Modelos Químicos , Modelos Moleculares , Teoría Cuántica
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