Enols of 2‐nitro‐ and related 2‐substituted malonamides

The structures of 2‐substituted malonamides, YCH(CONR¹R²)CONR³R⁴ (Y = Br, SO₂Me, CONH₂, COMe, and NO₂) were investigated. When Y = Br, R¹R² = R³R⁴ = HEt; Y = SO₂Me, R¹–R⁴ = H and for Y = CONH₂ or CONHPh, R¹–R⁴ = Me, the structure in solution is that of the amide tautomer. X‐ray crystallography shows solid‐state amide structures for Y = SO₂Me or CONH₂, R¹–R⁴ = H. Nitromalonamide displays an enol structure in the solid state with a strong hydrogen bond (O^…O distance = 2.3730 Å at 100 K) and d(OH) ≠ d(O^…H). An apparently symmetric enol was observed in solution, even in appreciable percentages in highly polar solvents such as DMSO‐d₆, but K_enol values decrease on increasing the solvent polarity. The N,N′‐dimethyl derivative is less enolic. Acetylmalonamides display a mixture of enol on the acetyl group and amide in non‐polar solvents, and only the amide in DMSO‐d₆. DFT calculations gave the following order of pK_enol values for Y: H > CONH₂ > COMe ≥ COMe (on acetyl) ≥ MeSO₂ > CN > NO₂ in the gas phase, CHCl₃, and DMSO. The enol on the C?O group is preferred to the aci‐nitro compound, and the N? O? H^…O?C is less favored than the C?O? H^…O?C hydrogen bond. Copyright © 2009 John Wiley & Sons, Ltd.     

<Emphasis Type="Italic">N</Emphasis>-arachidonoyl glycine,an abundant endogenous lipid,potently drives directed cellular migration through GPR18, the putative abnormal cannabidiol receptor

Background  

Microglia provide continuous immune surveillance of the CNS and upon activation rapidly change phenotype to express receptors that respond to chemoattractants during CNS damage or infection. These activated microglia undergo directed migration towards affected tissue. Importantly, the molecular species of chemoattractant encountered determines if microglia respond with pro- or anti-inflammatory behaviour, yet the signaling molecules that trigger migration remain poorly understood. The endogenous cannabinoid system regulates microglial migration via CB₂ receptors and an as yet unidentified GPCR termed the 'abnormal cannabidiol' (Abn-CBD) receptor. Abn-CBD is a synthetic isomer of the phytocannabinoid cannabidiol (CBD) and is inactive at CB₁ or CB₂ receptors, but functions as a selective agonist at this G_i/o-coupled GPCR. N-arachidonoyl glycine (NAGly) is an endogenous metabolite of the endocannabinoid anandamide and acts as an efficacious agonist at GPR18. Here, we investigate the relationship between NAGly, Abn-CBD, the unidentified 'Abn-CBD' receptor, GPR18, and BV-2 microglial migration.     

Location of a distribution center for a perishable product

A model that combines an inventory and location decision is presented, analyzed and solved. In particular, we consider a single distribution center location that serves a finite number of sales outlets for a perishable product. The total cost to be minimized, consists of the transportation costs from the distribution center to the sales outlets as well as the inventory related costs at the sales outlets. The location of the distribution center affects the inventory policy. Very efficient solution approaches for the location problem in a planar environment are developed. Computational experiments demonstrate the efficiency of the proposed solution approaches.     

Skin Microbiome Compositional Changes in Atopic Dermatitis Accompany Dead Sea Climatotherapy

Dead Sea climatotherapy (DSC) is a well‐established therapeutic modality for the treatment of several diseases, including atopic dermatitis. Skin microbiome studies have shown that skin microbiome diversity is anticorrelated with both atopic dermatitis severity and concurrent Staphylococcus aureus overgrowth. This study aimed to determine whether DSC induces skin microbiome changes concurrent with clinical improvements in atopic dermatitis. We sampled 35 atopic dermatitis patients and ten healthy controls on both the antecubital and popliteal fossa. High‐resolution microbial community profiling was attained by sequencing multiple regions of the 16S rRNA gene. Dysbiosis was observed in both lesional and nonlesional sites, which was partially attenuated following treatment. Severe AD skin underwent the most significant community shifts, and Staphylococcus epidermidis, Streptococcus mitis and Micrococcus luteus relative abundance were significantly affected by Dead Sea climatotherapy. Our study highlights the temporal shifts of the AD skin microbiome induced by Dead Sea climatotherapy and offers potential explanations for the success of climatotherapy on a variety of skin diseases, including AD.     

Combinatorics,graph theory,and computing

Journal of Algebraic Combinatorics -     

A rich array of reactions of Cyanomonothiocarbonylmalonamides RNHCSCH(CN)CONHR' and their Thioenols RNHC(SH)=C(CN)CONHR'1

The thioenols derived from cyanomonothiocarbonylmalonamides and a cyanodithiocarbonylmalonamide were found to be very reactive species. They react under a variety of conditions such as crystallization, reaction with several carbonyl compounds, and reactions with another thioenol molecule to give a variety of products, mostly heterocycles, including substituted 2,3-dihydroisothiazole-3-ones and 3-thione, 2-substituted methylenethiazoles, 3,4-dihydro-1,3-thiazine-4-ones and 4-thiones, divinyl sulfides, a 1,2-dithiolane radical, and a 3,7-diaza[3.3.0]bicyclooctane derivative. Mechanisms suggested for these reactions include radical mechanisms, nucleophilic substitutions, and condensations.