RESUMEN
The process of selective oxy-functionalization of hydrocarbons using peroxide, O3, H2O2, O2, and transition metals can be carried out by the reactive oxygen species such as hydroxyl/hydroperoxyl radical and/or metal oxygenated species generated in the catalytic reaction. Thus, a variety of mechanisms have been proposed for the selective catalytic oxidation of various hydrocarbons including light alkanes, olefins, and simple aromatics by the biological metalloproteins and their biomimetics either in their homogeneous or heterogeneous platforms. Most studies involving these metalloproteins are Fe or Cu monooxygenases. The pathways carried out by these metalloenzymes in the oxidation of C-H bonds invoke either radical reaction mechanisms including Fenton's chemistry and hydrogen atom transfer followed by radical rebound reaction mechanism or electrophilic oxygenation/O-atom transfer by metal-oxygen species. In this review, we discuss the metal oxide nano-catalysts obtained from metal salts/molecular precursors (M = Cu, Fe, and V) that can easily form in situ through the oxidation of substrates using H2O2(aq) in CH3CN, and be facilely separated from the reaction mixtures as well as recycled for several times with comparable catalytic efficiency for the highly selective conversion from hydrocarbons including aromatics to oxygenates. The mechanistic insights revealed from the oxy-functionalization of simple aromatics mediated by the novel biomimetic metal oxide materials can pave the way toward developing facile, cost-effective, and highly efficient nano-catalysts for the selective partial oxidation of simple aromatics.
RESUMEN
A study of the oxygen reduction reaction (ORR) on a screen printed carbon electrode surface mediated by the tricopper cluster complex Cu3 (7-N-Etppz(CH2 OH)) dispersed on electrochemically reduced carbon black, where 7-N-Etppz(CH2 OH) is the ligand 3,3'-(6-(hydroxymethyl)-1,4-diazepane-1,4-diyl)bis(1-(4-ethyl piperazin-1-yl)propan-2-ol), is described. Onset oxygen reduction potentials of about 0.92â V and about 0.77â V are observed at pHâ 13 and pHâ 7 vs. the reversible hydrogen electrode, which are comparable to the best values reported for any synthetic copper complex. Based on half-wave potentials (E1/2 ), the corresponding overpotentials are about 0.42â V and about 0.68â V, respectively. Kinetic studies indicate that the trinuclear copper catalyst can accomplish the 4 e- reduction of O2 efficiently and the ORR is accompanied by the production of only small amounts of H2 O2 . The involvement of the copper triad in the O2 activation process is also verified.
RESUMEN
An unprecedented method for the efficient conversion of C3-C12 linear alkanes to their corresponding primary alcohols mediated by the membrane-bound alkane hydroxylase (AlkB) from Pseudomonas putida GPo1 is demonstrated. The X-ray absorption spectroscopy (XAS) studies support that electrons can be transferred from the reduced AlkG (rubredoxin-2, the redox partner of AlkB) to AlkB in a two-phase manner. Based on this observation, an approach for the electrocatalytic conversion from alkanes to alcohols mediated by AlkB using an AlkG immobilized screen-printed carbon electrode (SPCE) is developed. The framework distortion of AlkB-AlkG adduct on SPCE surface might create promiscuity toward gaseous substrates. Hence, small alkanes including propane and n-butane can be accommodated in the hydrophobic pocket of AlkB for C-H bond activation. The proof of concept herein advances the development of artificial C-H bond activation catalysts.
Asunto(s)
Alcoholes/metabolismo , Alcanos/metabolismo , Citocromo P-450 CYP4A/metabolismo , Técnicas Electroquímicas/métodos , Pseudomonas putida/enzimología , Rubredoxinas/metabolismo , Hidroxilación , Espectroscopía de Absorción de Rayos XRESUMEN
Engineered bacterial cytochromeâ P450s are noted for their ability in the oxidation of inert small alkanes. Cytochromeâ P450 BM3 L188P A328F (BM3â PF) and A74E L188P A328F (BM3â EPF) variants are able to efficiently oxidize n-butane to 2-butanol. Esterification of the 2-butanol derived from this reaction mediated by the aforementioned two mutants gives diastereomeric excesses (de) of -56±1 and -52±1 %, respectively, with the preference for the oxidation occurring at the C-HS bond. When tailored (2R,3R)- and (2S,3S)-[2-2 H1 ,3-2 H1 ]butane probes are employed as substrates for both variants, the obtained de values from (2R,3R)-[2-2 H1 ,3-2 H1 ]butane are -93 and -92 % for BM3â PF and EPF, respectively; whereas the obtained de values from (2S,3S)-[2-2 H1 ,3-2 H1 ]butane are 52 and 56 % in the BM3â PF and EPF systems, respectively. The kinetic isotope effects (KIEs) for the oxidation of (2R,3R)-[2-2 H1 ,3-2 H1 ]butane are 7.3 and 7.8 in BM3â PF and EPF, respectively; whereas KIEs for (2S,3S)-[2-2 H1 ,3-2 H1 ]butanes are 18 and 25 in BM3â PF and EPF, respectively. The discrepancy in KIEs obtained from the two substrates supports the two-state reactivity (TSR) that is proposed for alkane oxidation in cytochromeâ P450 systems. Moreover, for the first time, experimental evidence for tunneling in the oxidation mediated by P450 is given through the oxidation of the C-HR bond in (2S,3S)-[2-2 H1 ,3-2 H1 ]butane.
Asunto(s)
Proteínas Bacterianas/metabolismo , Butanos/metabolismo , Sistema Enzimático del Citocromo P-450/metabolismo , Bacterias/enzimología , Proteínas Bacterianas/química , Proteínas Bacterianas/genética , Biocatálisis , Butanos/química , Butanoles/análisis , Butanoles/química , Butanoles/metabolismo , Dominio Catalítico , Sistema Enzimático del Citocromo P-450/química , Sistema Enzimático del Citocromo P-450/genética , Escherichia coli/metabolismo , Cromatografía de Gases y Espectrometría de Masas , Hidroxilación , Cinética , Mutagénesis Sitio-Dirigida , Oxidación-Reducción , Estereoisomerismo , Especificidad por Sustrato , TermodinámicaRESUMEN
We demonstrate herein that wild-type cytochromeâ P450 BM3 can recognize non-natural substrates, such as fluorinated C12 -C15 chain-length fatty acids, and show better catalysis for their efficient conversion. Although the binding affinities for fluorinated substrates in the P450 BM3 pocket are marginally lower than those for non-fluorinated substrates, spin-shift measurements suggest that fluoro substituents at the ω-position can facilitate rearrangement of the dynamic structure of the bulk-water network within the hydrophobic pocket through a micro desolvation process to expel the water ligand of the heme iron that is present in the resting state. A lowering of the Michaelis-Menten constant (Km ), however, indicates that fluorinated fatty acids are indeed better substrates compared with their non-fluorinated counterparts. An enhancement of the turnover frequencies (kcat ) for electron transfer from NADPH to the heme iron and for CH bond oxidation by compoundâ I (Cpdâ I) to yield the product suggests that the activation energies associated with going from the enzyme-substrate (ES state) to the corresponding transition state (ES(≠) state) are significantly lowered for both steps in the case of the fluorinated substrates. Delicate control of the regioselectivity by the fluorinated terminal methyl groups of the C12 -C15 fatty acids has been noted. Despite the fact that residues Arg47/Tyr51/Ser72 exert significant control over the hydroxylation of the subterminal carbon atoms toward the hydrocarbon tail, the fluorine substituent(s) at the ω-position affects the regioselective hydroxylation. For substrate hydroxylation, we have found that fluorinated lauric acids probably give a better structural fit for the heme pocket than fluorinated pentadecanoic acid, even though pentadecanoic acid is by far the best substrate among the reported fatty acids. Interestingly, 12-fluorododecanoic acid, with only one fluorine atom at the terminal methyl group, exhibits a comparable turnover frequency to that of pentadecanoic acid. Thus, fluorination of the terminal methyl group introduces additional interactions of the substrate within the hydrophobic pocket, which influence the electron transfers for both dioxygen activation and the controlled oxidation of aliphatics mediated by high-valent oxoferryl species.
Asunto(s)
Ácidos Grasos/química , Ácidos Láuricos/química , Sistema Enzimático del Citocromo P-450 , Fluorocarburos , Halogenación , Enlace de Hidrógeno , Hidroxilación , Oxidación-ReducciónRESUMEN
Fibrates and WY-14643 are widely used as lipid-lowering drugs via modulation of peroxisome proliferator-activated receptor alpha (PPAR α) for the treatment of a wide range of metabolic disorders. Here, to address the question whether PPAR α agonists can affect the enzymatic activity of 11beta-hydroxysteroid dehydrogenase1 (11ß-HSD1), we tested fibrates and WY-14643 for the inhibition of cellular 11ß-HSD1 activity in C2C12 myotubes. Only fenofibrate but not fenofibric acid, an active agonist of PPAR α, exerted a potent inhibitory activity in the cell based assay, showing an IC(50) of 1.6 µM. Furthermore, we also demonstrated that the masking of carboxyl group in fenofibric acid via esterification or amidation was required for the inhibitory potencies of fenofibric acid derivatives against 11ß-HSD1. In this presentation, we propose that fenofibrate can display a pharmacodynamic role distinct from fenofibric acid through masking of carboxyl group in fenofibric acid.
Asunto(s)
11-beta-Hidroxiesteroide Deshidrogenasas/antagonistas & inhibidores , Fenofibrato/farmacología , Músculos/efectos de los fármacos , Animales , Línea Celular , Concentración 50 Inhibidora , Ratones , Músculos/citología , Músculos/enzimología , PPAR alfa/agonistas , Pirimidinas/farmacologíaRESUMEN
A new series of cyclic sulfonamide derivatives was synthesized and evaluated for their ability to inhibit 11beta-HSD1. Cyclic sulfonamides with phenylacetyl substituents at the 2-position showed nanomolar inhibitory activities. Among them, compound 4e exhibited a good in vitro inhibitory activity and selectivity toward human 11beta-HSD2.
Asunto(s)
11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 1/antagonistas & inhibidores , Descubrimiento de Drogas/métodos , Sulfonamidas/síntesis química , 11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 1/metabolismo , Animales , Línea Celular , Humanos , Ratones , Microsomas/efectos de los fármacos , Microsomas/enzimología , Sulfonamidas/metabolismo , Sulfonamidas/farmacologíaRESUMEN
Two new ent-clerodane-type diterpenoids, compounds 1 and 2, were isolated from the aerial parts of Pulicaria wightiana, together with three known constituents. Their structures were established based on spectroscopic data, and their antibacterial activities were evaluated (Table 2).
Asunto(s)
Diterpenos de Tipo Clerodano/aislamiento & purificación , Diterpenos/aislamiento & purificación , Componentes Aéreos de las Plantas , Pulicaria , Antibacterianos/química , Antibacterianos/aislamiento & purificación , Diterpenos/química , Diterpenos de Tipo Clerodano/química , Pruebas de Sensibilidad Microbiana , Componentes Aéreos de las Plantas/microbiología , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Pulicaria/microbiologíaRESUMEN
An efficient one-pot synthesis of polyhydroquinolines by four-component coupling reactions of aldehydes, ethyl acetoacetate, dimedone and ammonium acetate in the presence of HY-zeolite at ambient temperature has been achieved. The conversions took shorter times to form the products in excellent yields. HY-zeolite can be recovered and reused.
Asunto(s)
Quinolinas/química , Quinolinas/síntesis química , Zeolitas/química , Catálisis , Estructura Molecular , Polímeros/química , TemperaturaRESUMEN
Chemical investigation on Jatropha curcas resulted in the isolation of twenty constituents among which four diterpenoids were unknown and six compounds, tetradecyl-(E)-ferulate, 3-O-(Z)-coumaroyl oleanolic acid, heudelotinone, epi-isojatrogrossidione, 2alpha-hydroxy-epi-isojatrogrossidione, and 2-methyanthraquinone had not been reported earlier from this species. The structures of the new compounds were established by extensive studies of their 1D- and 2D-NMR spectra.