Electrochemical C-H Alkylation of Azauracils Using -(Acyloxy)phthalimides.

We present an electrochemical alkylation of azauracils using -(acyloxy)phthalimides (NHPI esters) as readily available alkyl radical progenitors under metal- and additive-free conditions. Several azauracils are shown to undergo alkylation with an array of NHPI esters (1°, 2°, 3°, and sterically congested), providing the desired products in good to excellent yields. This operationally simple method is robust, scalable, and suitable for both batch and flow setups.

Photodecarboxylative Radical Cascade Involving -(Acyloxy)phthalimides for the Synthesis of Pyrazolones.

We disclose '-arylidene--acryloyltosylhydrazides as novel skeletons for the synthesis of biologically relevant alkylated pyrazolones through a photoinduced radical cascade with -(acyloxy)pthalimides as readily available alkyl surrogates. The reaction proceeds through the formation of a photoactivated electron donor-acceptor (EDA) complex between alkyl -(acyloxy)phthalimide (NHPI) esters and LiI/PPh as a commercially available donor system. The reaction exhibits a broad scope and scalability, thereby enabling synthesis of a broad spectrum of functionally orchestrated alkylated pyrazolones under mild and transition-metal-free conditions.

A General Electron Donor-Acceptor Photoactivation Platform of Diaryliodonium Reagents: Arylation of Heterocycles.

We report a photoredox system comprising sodium iodide, triphenyl phosphine, and ,,','-tetramethylethylenediamine (TMEDA) that can form a self-assembled tetrameric electron donor-acceptor (EDA) complex with diaryliodonium reagents (DAIRs) and furnish aryl radicals upon visible light irradiation. This practical mode of activation of DAIRs enables arylation of an array of heterocycles under mild conditions to provide the respective heteroaryl-(hetero)aryl assembly in moderate to excellent yields. Detailed mechanistic investigations comprising photophysical and DFT studies provided insight into the reaction mechanism.

Photodecarboxylative C-H Alkylation of Azauracils with -(Acyloxy)phthalimides.

We disclose a transition-metal-free NaI/PPh-mediated direct C-H alkylation of azauracils using -(acyloxy)pthalimides (NHPIs) as readily available alkyl surrogates under visible light irradiation. Detailed mechanistic studies reveal formation of a photoactivated electron donor-acceptor (EDA) complex between NaI/PPh, TMEDA, and alkyl NHPI ester and establish the crucial role of TMEDA in increasing the activity of the photoredox system. The reaction demonstrates a broad scope, scalability, and appreciable functional group tolerance.

Photoinduced Electron Donor-Acceptor Complex-Mediated Radical Cascade Involving -(Acyloxy)phthalimides: Synthesis of Tetrahydroquinolines.

We conceptualized a novel disconnection approach for the synthesis of fused tetrahydroquinolines that exploits a visible light-mediated radical (4 + 2) annulation between alkyl -(acyloxy)phthalimides and -substituted maleimides in the presence of DIPEA as an additive. The reaction proceeds through the formation of a photoactivated electron donor-acceptor complex between alkyl NHPI esters and DIPEA, and the final tetrahydroquinolines were obtained in a complete regioselective fashion. The methodology features a broad scope and good functional group tolerance and operates under metal- and catalyst-free reaction conditions.

An organophotoredox-catalyzed redox-neutral cascade involving -(acyloxy)phthalimides and allenamides: synthesis of indoles.

An organophotoredox-catalyzed radical cascade of allenamides and alkyl -(acyloxy)phthalimides for the synthesis of indoles is documented. The method features mild and robust reaction conditions, and exhibits broad scope. The tandem process enriches the limited repertoire of alkyl NHPI ester addition on electron-rich π-bonds as well as radical chemistry involving allenamides.

Genetic variations in NADPH-CYP450 oxidoreductase in a Czech Slavic cohort.

Aim: Estimating polymorphic allele frequencies of the NADPH-CYP450 oxidoreductase (POR) gene in a Czech Slavic population.

Methods: The POR gene was analyzed in 322 individuals from a control cohort by sequencing and high resolution melting analysis.

Results: We identified seven unreported SNP genetic variations, including two SNPs in the 5' flanking region (g.

Intra- and inter-molecular effects of a conserved arginine residue of neuronal and inducible nitric oxide synthases on FMN and calmodulin binding.

Nitric oxide synthases (NOSs) synthesize nitric oxide (NO), a signaling molecule, from l-arginine, utilizing electrons from NADPH. NOSs are flavo-hemo proteins, with two flavin molecules (FAD and FMN) and one heme per monomer, which require the binding of calcium/calmodulin (Ca(2+)/CaM) to produce NO. It is therefore important to understand the molecular factors influencing CaM binding from a structure/function perspective.

Oxygen metabolism by endothelial nitric-oxide synthase.

Nitric-oxide synthase (NOS) catalyzes both coupled and uncoupled reactions that generate nitric oxide and reactive oxygen species. Oxygen is often the overlooked substrate, and the oxygen metabolism catalyzed by NOS has been poorly defined. In this paper we focus on the oxygen stoichiometry and effects of substrate/cofactor binding on the endothelial NOS isoform (eNOS).

Oxygen metabolism by neuronal nitric-oxide synthase.

Nitric-oxide synthases (NOS) catalyze nitric oxide (NO) formation from the amino acid L-arginine. NOS is known to catalyze more than one reaction: the NO-producing reaction is considered to be the coupled reaction, and the uncoupled reactions are those that produce reactive (reduced) oxygen species (ROS), such as superoxide anion (O-2.) and/or hydrogen peroxide (H2O2).

The role of a conserved serine residue within hydrogen bonding distance of FAD in redox properties and the modulation of catalysis by Ca2+/calmodulin of constitutive nitric-oxide synthases.

The crystal structure of the neuronal nitric-oxide synthase (nNOS) NADPH/FAD binding domain indicated that Ser-1176 is within hydrogen bonding distance of Asp-1393 and the O4 atom of FAD and is also near the N5 atom of FAD (3.7 A). This serine residue is conserved in most of the ferredoxin-NADP+ reductase family of proteins and is important in electron transfer.