RESUMO
The cytochrome P450 (CYP) superfamily of monooxygenase enzymes play important roles in the metabolism of molecules which contain heterocyclic, aromatic functional groups. Here we study how oxygen- and sulfur-containing heterocyclic groups interact with and are oxidized using the bacterial enzyme CYP199A4. This enzyme oxidized both 4-(thiophen-2-yl)benzoic acid and 4-(thiophen-3-yl)benzoic acid almost exclusively via sulfoxidation. The thiophene oxides produced were activated towards Diels-Alder dimerization after sulfoxidation, forming dimeric metabolites. Despite X-ray crystal structures demonstrating that the aromatic carbon atoms of the thiophene ring were located closer to the heme than the sulfur, sulfoxidation was still favoured with 4-(thiophen-3-yl)benzoic acid. These results highlight a preference of this cytochrome P450 enzyme for sulfoxidation over aromatic hydroxylation. Calculations predict a strong preference for homodimerization of the enantiomers of the thiophene oxides and the formation of a single major product, in broad agreement with the experimental data. 4-(Furan-2-yl)benzoic acid was oxidized to 4-(4'-hydroxybutanoyl)benzoic acid using a whole-cell system. This reaction proceeded via a γ-keto-α,ß-unsaturated aldehyde species which could be trapped inâ vitro using semicarbazide to generate a pyridazine species. The combination of the enzyme structures, the biochemical data and theoretical calculations provides detailed insight into the formation of the metabolites formed from these heterocyclic compounds.
Assuntos
Ácido Benzoico , Sistema Enzimático do Citocromo P-450 , Sistema Enzimático do Citocromo P-450/metabolismo , Oxirredução , Óxidos , TiofenosRESUMO
Epoxy and aziridinyl enolsilanes react as oxyallylic cation equivalents in highly chemo- and diastereoselective intramolecular (3+2) cycloadditions with a range of dienes and olefins. With acyclic dienes, the (3+2) cycloaddition outcompetes the (4+3) pathway traditionally observed in this kind of system almost exclusively. With both conjugated dienes and isolated olefins, excellent diastereoselectivities are observed, and cycloadducts can be obtained in optically-enriched forms. Computational studies indicate that the stepwise (3+2) cycloaddition involves an activated epoxy/aziridinyl intermediate and the conformational flexibility of the intermediate determines the preference for (3+2) cycloadduct formation. Further transformations of the (3+2) cycloadducts produce densely functionalized trans-hydrindane scaffolds.
Assuntos
Alcenos , Polienos , Reação de Cicloadição , Conformação Molecular , EstereoisomerismoRESUMO
Hyperfluorescent organic light-emitting diodes (HF-OLEDs) enable a cascading Förster resonance energy transfer (FRET) from a suitable thermally activated delayed fluorescent (TADF) assistant host to a fluorescent end-emitter to give efficient OLEDs with relatively narrowed electroluminescence compared to TADF-OLEDs. Efficient HF-OLEDs require optimal FRET with minimum triplet diffusion via Dexter-type energy transfer (DET) from the TADF assistant host to the fluorescent end-emitter. To hinder DET, steric protection of the end-emitters has been proposed to disrupt triplet energy transfer. In this work, the first HF-OLEDs based on structurally well-defined macromolecules, dendrimers is reported. The dendrimers contain new highly twisted dendrons attached to a Cibalackrot core, resulting in high solubility in organic solvents. HF-OLEDs based on dendrimer blend films are fabricated to show external quantum efficiencies of >10% at 100 cd m-2 . Importantly, dendronization with the bulky dendrons is found to have no negative impact to the FRET efficiency, indicating the excellent potential of the dendritic macromolecular motifs for HF-OLEDs. To fully prevent the undesired triplet diffusion, Cibalackrot dendrimers HF-OLEDs are expected to be further improved by adding additional dendrons to the Cibalackrot core and/or increasing dendrimer generations.
Assuntos
Dendrímeros , Corantes , Transferência Ressonante de Energia de FluorescênciaRESUMO
The (4 + 3) cycloaddition of 2-trialkylsilyl-4-alkylbutadienes with an N-methyloxidopyridinium ion affords cycloadducts with high regioselectivity and excellent endo selectivity.