Novel radioiodinated desvenlafaxine-loaded lipid nanocapsule for brain delivery.

Lipid nanocapsules (LNCs) are lipid nanocarriers developed for drug delivery enhancement. The antidepressant drug desvenlafaxine (DSV) was entrapped in LNC to improve its brain delivery. Different DSV-loaded LNCs formulae using different oils and surfactants were studied to obtain the optimum formula for further studies. In vivo biodistribution studies were done using Swiss albino mice by intravenous injection of DSV-loaded LNCs by radioiodination technique. The optimum DSV-loaded LNC formula was obtained by using Labrafil® M1944CS as the oil and Solutol® HS15 as the surfactant in the ratio of 1:1, with a particle size of 34.28 ± 0.41 nm, a polydispersity index of 0.032 ± 0.05, a zeta potential of -25.77 ± 1.41, and good stability for up to 6 months. The in vivo biodistribution and pharmacokinetics data ensure the bioavailability improvement for DSV brain delivery as Cmax and AUC(1-t) increased more than double for intravenously DSV-loaded LNCs compared with the DSV solution. In conclusion, the results obtained from this study give an insight into the great potential of using DSV-loaded LNC for the enhancement of brain delivery.

Otoacoustic emissions value in patients with idiopathic sudden sensorineural hearing loss.

Objectives: This study aimed to determine the prognostic value of otoacoustic emissions (OAEs) in idiopathic sudden sensorineural hearing loss patients. Methods: The study included 30 subjects with unilateral idiopathic sudden sensorineural hearing loss (ISSNHL). Each patient was evaluated four times: at baseline and after one week, one month, and three months of treatment. During each visit, each patient was subjected to full audiological history, otoscopic examination, basic audiological evaluations, and transiently evoked and distortion product otoacoustic emission (TEOAEs & DEOAEs). Results: The hearing thresholds (frequency range 250-8000 Hz) and word recognition scores of patients with detectable TEOAEs and DPOAEs improved significantly, whereas no significant improvements were observed in those with no response. Conclusion: Hearing improvement is better in patients with detectable TEOAEs and DPOAEs. As a result, TEOAEs and DPOAEs are recommended as routine tests in all SSNHL patients to predict outcomes and monitor treatment as TEOAEs and DPOAEs reflect the cochlear OHCs activity.

Male sexual health predictors during the Covid-19 outbreak: a multicenter study.

Background: Pandemic-induced feelings of fear and worry are all psychological implications of the COVID-19 pandemic. The goal of this study was to see how the COVID-19 pandemic affected male Sexual Health and to look for plausible predictors. Methods: Married males were asked to fill out an Arabic Sexual Health questionnaire. Before and during the lockdown. Additionally, generalized Anxiety Disorder-7 and International Index of Erectile Function-5 questionnaires. Results: A multicenter study. The survey was completed by 281 men in total. Only 130 males (47.3%) were satisfied with their Sexual performance before lockdown, compared to 170 males (56.5%) who were not satisfied (P 0.000). Financial issues (P ≤ 0.000), smoking habit prior to lockdown (P ≤ 0.001), spots practice (P ≤ 0.001), smoking during lockdown (P ≤ 0.001), presence of depressive disorder on the PHQ-9 total score (P ≤ 0.001), diagnosis of anxiety on the GAD-7 score (P ≤ 0.001), and presence of ED on the IIEf-5 questionnaire (P ≤ 0.001) were all found to be significant on univariate analysis. On bivariate analysis, financial issues (odds ratio [OR]: 3.56, P ≤ 0.000), presence of anxiety on GAD-7 (OR: 6.40, P ≤ 0.001), PHQ score (OR: 2.50, P ≤ 0.001), and diagnosis of ED on the IIEF-5 scale (OR: 7.50, P ≤ 0.001) were significantly associated with Sexual relationship stress and Sexual Health. Conclusion: During and after COVID-19 lockdown, the presence of anxiety on the GAD-7 scale, PHQ score, and the diagnosis of ED on the IIEF-5 scale were all independent predictors of Sexual Health.

Copper nanoparticles on controlled pore glass (CPG) as highly efficient heterogeneous catalysts for "click reactions".

We herein report that supported copper nanoparticles (CuNPs) on commercially available controlled pore glass (CPG), which exhibit high mechanical, thermal and chemical stability as compared to other silica-based materials, serve as a useful heterogeneous catalyst system for 1,3-dipolar cycloadditions ("click" reactions) between terminal alkynes and organic azides under green chemistry conditions. The supported CuNPs-CPG catalyst exhibited a broad substrate scope and gave the corresponding triazole products in high yields. The CuNPs-CPG catalyst exhibit recyclability and could be reuced multiple times without contaminating the products with Cu.

A palladium/chiral amine co-catalyzed enantioselective dynamic cascade reaction: synthesis of polysubstituted carbocycles with a quaternary carbon stereocenter.

Polysubstituted 5- and 6-membered carbocycles were synthesized by the title reaction. The one-pot dynamic relay process generates four new stereocenters, including a quaternary carbon center, in a highly enantioselective fashion (99.5:0.5→99:0.5 e.r.) by using a simple combination of palladium and chiral amine co-catalysts.

Direct regiospecific and highly enantioselective intermolecular α-allylic alkylation of aldehydes by a combination of transition-metal and chiral amine catalysts.

The first direct intermolecular regiospecific and highly enantioselective α-allylic alkylation of linear aldehydes by a combination of achiral bench-stable Pd(0) complexes and simple chiral amines as co-catalysts is disclosed. The co-catalytic asymmetric chemoselective and regiospecific α-allylic alkylation reaction is linked in tandem with in situ reduction to give the corresponding 2-alkyl alcohols with high enantiomeric ratios (up to 98:2 e.r.; e.r.=enantiomeric ratio). It is also an expeditious entry to valuable 2-alkyl substituted hemiacetals, 2-alkyl-butane-1,4-diols, and amines. The concise co-catalytic asymmetric total syntheses of biologically active natural products (e.g., Arundic acid) are disclosed.

Enol ethers as substrates for efficient Z- and enantioselective ring-opening/cross-metathesis reactions promoted by stereogenic-at-Mo complexes: utility in chemical synthesis and mechanistic attributes.

The first examples of catalytic enantioselective ring-opening/cross-metathesis (EROCM) reactions that involve enol ethers are reported. Specifically, we demonstrate that catalytic EROCM of several oxa- and azabicycles, cyclobutenes and a cyclopropene with an alkyl- or aryl-substituted enol ether proceed readily in the presence of a stereogenic-at-Mo monopyrrolide-monoaryloxide. In some instances, as little as 0.15 mol % of the catalytically active alkylidene is sufficient to promote complete conversion within 10 min. The desired products are formed in up to 90% yield and >99:1 enantiomeric ratio (er) with the disubstituted enol ether generated in >90% Z selectivity. The enol ether of the enantiomerically enriched products can be easily differentiated from the terminal alkene through a number of functionalization procedures that lead to the formation of useful intermediates for chemical synthesis (e.g., efficient acid hydrolysis to afford the enantiomerically enriched carboxaldehyde). In certain cases, enantioselectivity is strongly dependent on enol ether concentration: larger equivalents of the cross partner leads to the formation of products of high enantiomeric purity (versus near racemic products with one equivalent). The length of reaction time can be critical to product enantiomeric purity; high enantioselectivity in reactions that proceed to >98% conversion in as brief a reaction time as 30 s can be nearly entirely eroded within 30 min. Mechanistic rationale that accounts for the above characteristics of the catalytic process is provided.

Catalytic enantioselective ß-alkylation of α,ß-unsaturated aldehydes by combination of transition-metal- and aminocatalysis: total synthesis of bisabolane sesquiterpenes.

Branching out! The first co-catalytic enantioselective (up to 98:2 e.r.) ß-alkylation of α,ß-unsaturated aldehydes by combination of simple chiral amine and copper catalysts provides ß-branched aldehydes in a one-pot protocol. The methodology was applied to the short total syntheses of bisabolane sesquiterpenes (S)-(+)-curcumene, (E)-(S)-(+)-3-dehydrocurcumene and (S)-(+)-tumerone.

Catalytic asymmetric aziridination of α,ß-unsaturated aldehydes.

The development, scope, and application of the highly enantioselective organocatalytic aziridination of α,ß-unsaturated aldehydes is presented. The aminocatalytic azirdination of α,ß-unsaturated aldehydes enables the asymmetric formation of ß-formyl aziridines with up to >19:1 d.r. and 99% ee. The aminocatalytic aziridination of α-monosubstituted enals gives access to terminal α-substituted-α-formyl aziridines in high yields and up to 99% ee. In the case of the organocatalytic aziridination of disubstituted α,ß-unsaturated aldehydes, the transformations were highly diastereo- and enantioselective and give nearly enantiomerically pure ß-formyl-functionalized aziridine products (99% ee). A highly enantioselective one-pot cascade sequence based on the combination of asymmetric amine and N-heterocyclic carbene catalysis (AHCC) is also disclosed. This one-pot three-component co-catalytic transformation between α,ß-unsaturated aldehydes, hydroxylamine derivatives, and alcohols gives the corresponding N-tert-butoxycarbonyl and N-carbobenzyloxy-protected ß-amino acid esters with ee values ranging from 92-99%. The mechanisms and stereochemistry of all these catalytic transformations are also discussed.

Dynamic kinetic asymmetric transformation (DYKAT) by combined amine- and transition-metal-catalyzed enantioselective cycloisomerization.

The first examples of one-pot highly chemo- and enantioselective dynamic kinetic asymmetric transformations (DYKATs) involving alpha,beta-unsaturated aldehydes and propargylated carbon acids are presented. These DYKATs, which proceed by a combination of catalytic iminium activation, enamine activation, and Pd(0)-catalyzed enyne cycloisomerization, give access to functionalized cyclopentenes with up to 99 % ee and can be used for the generation of all-carbon quaternary stereocenters.

Highly Z- and enantioselective ring-opening/cross-metathesis reactions catalyzed by stereogenic-at-Mo adamantylimido complexes.

The first highly Z- and enantioselective class of ring-opening/cross-metathesis reactions is presented. Transformations are promoted in the presence of <2 mol % of chiral stereogenic-at-Mo monoaryloxide complexes bearing an adamantylimido ligand that are prepared and used in situ. Reactions involve meso oxabicyclic substrates and afford the desired pyrans in 50-85% yield and up to >98:<2 enantiomer ratio. Importantly, the desired chiral pyrans thus obtained bear a Z olefin either exclusively (>98:<2 Z/E) or predominantly (>or=87:13 Z/E).

One-pot catalytic enantioselective domino nitro-michael/michael synthesis of cyclopentanes with four stereocenters.

A highly enantioselective organocatalytic one-pot synthesis of nitro-, formyl-, and ester-functionalized cyclopentanes with four stereocenters is presented. The cyclopentanes were formed as a predominant diasteroisomer and isolated in high yields with 97-99 % ee.

One-pot organocatalytic domino Michael/alpha-alkylation reactions: direct catalytic enantioselective cyclopropanation and cyclopentanation reactions.

The development of one-pot organocatalytic domino Michael/alpha-alkylation reactions between bromomalonates or bromoacetoacetate esters and alpha,beta-unsaturated aldehydes is presented. The chiral-amine-catalyzed reactions with bromomalonates as substrates give access to the corresponding 2-formylcyclopropane derivatives in high yields with excellent diastereoselectivity and up to 99 % ee. The catalytic domino Michael/alpha-alkylation reactions between 4-bromo-acetoacetate and enals provide a route for the synthesis of functionalized cyclopentanones in good to high yields with 93-99 % ee. The products from the organocatalytic reactions were also reduced with high diastereoselectivity to the corresponding cyclopropanols and cyclopentanols, respectively. Moreover, one-pot combinations of amine and heterocyclic carbene catalysis (AHCC) enabled the highly enantioselective synthesis of beta-malonate esters (91-97 % ee) from the reaction between bromomalonates and enals. The tandem catalysis included the catalytic domino reaction followed by catalytic in situ chemoselective ring-opening of the 2-formylcyclopropane intermediates.

One-pot catalytic asymmetric cascade synthesis of cycloheptane derivatives.

A regiospecific, highly chemo-, diastereo-, and enantioselective one-pot catalytic cascade synthesis of cycloheptane derivatives is presented. In this chiral-amine-catalyzed asymmetric process, six new bonds and five new stereocenters were formed with excellent stereocontrol (>25:1 d.r. and 98- >99 ee).

Organocatalytic asymmetric 5-hydroxyisoxazolidine synthesis: a highly enantioselective route to beta-amino acids.

The highly chemo- and enantioselective organocatalytic tandem reaction between N-protected hydroxyl amines and alpha,beta-unsaturated aldehydes is presented; the reaction provides access to 5-hydroxyisoxazolidines and beta-amino acids in high yields and with 90-99% ee.