Visible-Light-Induced Hydrogen Atom Transfer En Route to Exocylic Alkenylation of Cyclic Ethers Enabled by Electron Donor-Acceptor Complex.

An electron donor-acceptor (EDA)-triggered hydrogen atom transfer (HAT) process is developed for the efficient generation of an α-alkoxy radical from cyclic ethers to synthesize exocyclic alkenylated ethers with exclusive E-selectivity. A judiciously chosen donor-acceptor pair (DABCO and maleimide) serves as the desired HAT reagent under visible light irradiation without using any photocatalyst or peroxide. A wide variety of substrates were explored to demonstrate the diverse applicability and practical viability of this cross-dehydrogenative transformation. Detailed mechanistic studies revealed a radical reaction pathway under the oxidative environment.

Photoinduced Electron Donor-Acceptor Complex-Mediated Radical Cascade Involving N-(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 N-(acyloxy)phthalimides and N-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. Detailed mechanistic investigations including density functional theory studies provide insight into the reaction pathway.

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

An organophotoredox-catalyzed radical cascade of allenamides and alkyl N-(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.

Fluorometric trace methanol detection in ethanol and isopropanol in a water medium for application in alcoholic beverages and hand sanitizers.

Detection of methanol (MeOH) in an ethanol (EtOH)/isopropanol ( i PrOH) medium containing water is crucial to recognize MeOH poisoning in alcoholic beverages and hand sanitizers. Although chemical sensing methods are very sensitive and easy to perform, the chemical similarities between the alcohols make MeOH detection very challenging particularly in the presence of water. Herein, the fluorometric detection of a trace amount of MeOH in EtOH/ i PrOH in the presence of water using alcohol coordinated Al(iii)-complexes of an aldehydic phenol ligand containing a dangling pyrazole unit is described. The presence of MeOH in the EtOH/ i PrOH causes a change of the complex geometry from tetrahedral (Td) to octahedral (Oh) due to the replacement of the coordinated EtOH/ i PrOH by MeOH molecules. The Td-complex exhibited fluorescence but the Oh-species did not, because of the intramolecular photo-induced electron transfer (PET). By interacting the Oh species with water, its one MeOH coordination is replaced by a water molecule followed by the proton transfer from the water to pyrazole-N which generates strong fluorescence by inhibiting the PET. In contrast, the water interaction dissociates the Td-complex to exhibit fluorescence quenching. The water induced reversal of the fluorescence response from the decrease to increase between the absence and presence of MeOH is utilized to detect MeOH in an EtOH/ i PrOH medium containing water with a sensitivity of ∼0.03-0.06% (v/v). The presence of water effected the MeOH detection and allows the estimation of the MeOH contamination in alcoholic beverages and hand sanitizers containing large amounts of water.

Organophotoredox-Catalyzed Cascade Radical Annulation of 2-(Allyloxy)arylaldehydes with N-(acyloxy)phthalimides: Towards Alkylated Chroman-4-one Derivatives.

An organophotoredox catalyzed efficient and robust approach for the synthesis of highly important 3-alkyl substituted chroman-4-one scaffold is developed using visible light induced radical cascade cyclization strategy. The reaction is initiated through the generation of alkyl radicals from N-(acyloxy)phthalimides under photoredox conditions, which subsequently undergo intermolecular cascade radical cyclization on 2-(allyloxy)arylaldehydes to afford chroman-4-one scaffolds. The presented strategy is attractive with regard to mild reaction conditions, operational simplicity, high functional group tolerance and broad substrate scope.

An aluminium fluorosensor for the early detection of micro-level alcoholate corrosion.

The detection of the dry alcoholate corrosion of aluminium is vital to design a corrosion resistive aluminium alloy for the storage and transportation of biofuel (methanol or ethanol). By synthesizing an Al3+ fluorescent probe operable in an alcoholic medium, we quantified the alcoholate corrosion in terms of the fluorometrically estimated soluble alkoxide (Al(OR)3) generation under nitrogen atmosphere. With time, a linear increase in corrosion with specific aluminium dissolution rate constants ∼2.0 and 0.9 µg per day per cm2 were estimated for aluminium and Al-7075 alloy, respectively. During open atmosphere monitoring, the adsorbed moisture converted small extent of Al(OR)3 to the insoluble Al(OH)3 at the alloy surface which retarded the alcoholate corrosion appreciably.

Protonation-induced pH increase at the triblock copolymer micelle interface for transient membrane permeability at neutral pH.

Achieving controlled membrane permeability using pH-responsive block copolymers is crucial for selective intercellular uptake. We have shown that the pH at the triblock-copolymer micelle interface as compared to its bulk pH can help regulate membrane permeability. The pH-dependent acid/base equilibriums of two different interface-interacting pH probes were determined in order to measure the interfacial pH for a pH-responsive triblock copolymer (TBP) micelle under a wide range of bulk pH (4.5-9.0). According to 1H NMR studies, both pH probes provided interfacial pH at a similar interfacial depth. We revealed that the protonation of the amine moiety at the micelle interface and the subsequent formation of a positive charge caused the interface to become relatively less acidic than that of the bulk as well as an increase in the bulk-to-interfacial pH deviation (ΔpH) from ∼0.9 to 1.9 with bulk pH reducing from 8.0 to 4.5. From the ΔpH vs. interface and bulk pH plots, the apparent and intrinsic protonations or positive charge formation pKa values for the micelle were estimated to be ∼7.3 and 6.0, respectively. When the TBP micelle interacted with an anionic large unilamellar vesicle (LUV) of a binary lipid (neutral and anionic) system at the bulk pH of 7.0, fluorescence leakage studies revealed that the pH increase at the micelle interface from that of the LUV interface (pH ∼ 5.5) made the micelle interface partially protonated/cationic, thereby exhibiting transient membrane permeability. Although the increasing interface protonation causes the interface to become relatively less acidic than the bulk at any bulk pH below 6.5, the pH increase at the micelle interface may not be sufficiently large to maintain the threshold for the amine-protonated condition for effecting transient leakage and therefore, a continuous leakage was observed due to the slow disruption of the lipid bilayer.

Determination of proton concentration at cardiolipin-containing membrane interfaces and its relation with the peroxidase activity of cytochrome c.

The activities of biomolecules are affected by the proton concentrations at biological membranes. Here, we succeeded in evaluating the interface proton concentration (-log[H+] defined as pH') of cardiolipin (CL)-enriched membrane models of the inner mitochondrial membrane (IMM) using a spiro-rhodamine-glucose molecule (RHG). According to fluorescence microscopy and 1H-NMR studies, RHG interacted with the Stern layer of the membrane. The acid/base equilibrium of RHG between its protonated open form (o-RHG) and deprotonated closed spiro-form (c-RHG) at the membrane interface was monitored with UV-vis absorption and fluorescence spectra. The interface pH' of 25% cardiolipin (CL)-containing large unilamellar vesicles (LUVs), which possess similar lipid properties to those of the IMM, was estimated to be ∼3.9, when the bulk pH was similar to the mitochondrial intermembrane space pH (6.8). However, for the membranes containing mono-anionic lipids, the interface pH' was estimated to be ∼5.3 at bulk pH 6.8, indicating that the local negative charges of the lipid headgroups in the lipid membranes are responsible for the deviation of the interface pH' from the bulk pH. The peroxidase activity of cyt c increased 5-7 fold upon lowering the pH to 3.9-4.3 or adding CL-containing (10-25% of total lipids) LUVs compared to that at bulk pH 6.8, indicating that the pH' decrease at the IMM interface from the bulk pH enhances the peroxidase activity of cyt c. The peroxidase activity of cyt c at the membrane interface of tetraoleoyl CL (TOCL)-enriched (50% of total lipids) LUVs was higher than that estimated from the interface pH', while the peroxidase activity was similar to that estimated from the interface pH' for tetramyristoyl CL (TMCL)-enriched LUVs, supporting the hypothesis that when interacting with TOCL (not TMCL), cyt c opens the heme crevice to substrates. The present simple methodology allows us to estimate the interface proton concentrations of complex biological membranes.

Cobalt-Catalyzed Sustainable Synthesis of Benzimidazoles by Redox-Economical Coupling of o-Nitroanilines and Alcohols.

This study reveals cobalt-catalyzed sustainable synthesis of benzimidazoles by redox-economical coupling of o-nitroanilines and alcohols. The major advantage of this report is the use of a commercially available cheap cobalt catalyst to produce a wide variety of 2-substituted benzimidazoles by hydrogen autotransfer without using any additional external redox reagent and costly ligand system. A thorough mechanistic insight of the reaction is proposed by performing a series of control experiments.

Synthesis of Polysubstituted Quinolines from α-2-Aminoaryl Alcohols Via Nickel-Catalyzed Dehydrogenative Coupling.

This study reports a nickel-catalyzed sustainable synthesis of polysubstituted quinolines from α-2-aminoaryl alcohols by a sequential dehydrogenation and condensation process that offers the advantages of a low catalyst loading and wide substrate scope. In contrast to earlier reported methods, this strategy allows the use of both primary as well as secondary α-2-aminoaryl alcohols in combination with either ketones or secondary alcohols for desired product formation. Using this methodology, 30 substituted quinoline derivatives were synthesized with up to 93% isolated yields.

Detection of Curvature-Radius-Dependent Interfacial pH/Polarity for Amphiphilic Self-Assemblies: Positive versus Negative Curvature.

It is possible that a defined curvature at the membrane interface controls its pH/polarity to exhibit specific bioactivity. By utilizing an interface-interacting spiro-rhodamine pH probe and the Schiff base polarity probe, we have shown that the pH deviation from the bulk phase to the interface (ΔpH)/interfacial dielectric constant (κ(i)) for amphiphilic self-assemblies can be regulated by the curvature geometry (positive/negative) and its radius. According to 1H NMR and fluorescence anisotropy investigations, the probes selectively interact with an anionic interfacial Stern layer. The ΔpH/κ(i) values for the Stern layer are estimated by UV-vis absorption and fluorescence studies. For the anionic sodium bis-2-ethylhexyl-sulfosuccinate (AOT) inverted micellar (IM) negative interface, the highly restricted water and proton penetration into the Stern layer owing to tight surfactant packing or a reduced water-exposed headgroup area may be responsible for the much lower ΔpH ≈ -0.45 and κ(i) ≈ 28 in comparison to ∼-2.35 and ∼44, respectively, for the anionic sodium dodecyl sulfate (SDS) micellar positive interface with a close similar Stern layer. With increasing AOT IM water-pool radius (1.7-9.5 nm) or [water]/[AOT] ratio ( w0) (8.0-43.0), the ΔpH and κ(i) increase maximally up to ∼-1.22 and ∼45, respectively, due to a greater water-exposed headgroup area. However, the unchanged ΔpH ≈ -0.65 and κ(i) ≈ 53.0 within radii ∼3.5-8.0 nm for the positive interface of a mixed Triton X-100 (TX-100)/SDS (4:1) micelle justify its packing flexibility. Interestingly, the continuously increasing ΔpH trend for IM up to its largest possible water-pool radius of ∼9.5 nm may rationalize the increase in ΔpH (∼-1.4 to -1.6) with the change in the curvature radii (∼15 to 50 nm) for sodium 1,2-dimyristoyl- sn-glycero-3-phosphorylglycerol (DMPG)/1,2-dimyristoyl- sn-glycero-3-phosphocholine (DMPC) (2:1) large unilamellar vesicles (LUV) owing to its negative interface. Whereas, similar to the micellar positive interface, the unchanged ΔpH at the positive LUV interface was confirmed by fluorescence microscopic studies with giant unilamellar vesicles of identical lipids composition. The present study offers a unique and simple method of monitoring the curvature-radius-dependent interfacial pH/polarity for biologically related membranes.

A ratiometric solvent polarity sensing Schiff base molecule for estimating the interfacial polarity of versatile amphiphilic self-assemblies.

A newly synthesised Schiff base molecule (PMP) existing in equilibrium between non-ionic and zwitterionic forms displays solvent polarity induced ratiometric interconversion from one form to another, such novelty being useful to detect the medium polarity. The specific interface localisation of PMP in versatile amphiphilic self-assembled systems has been exploited to monitor their interfacial polarity by evaluating such interconversion equilibrium with simple UV-Vis spectroscopy. In spite of the large differences in pH and/or viscosity between the bulk and interface, the unchanged equilibrium between the two molecular forms on varying the medium pH or viscosity provides a huge advantage for the exclusive detection of interfacial polarity.

A simple interfacial pH detection method for cationic amphiphilic self-assemblies utilizing a Schiff-base molecule.

A simple pH-sensing method for cationic micelle and vesicle interfaces is introduced, utilizing a Schiff-base molecule, 2-((4H-1,2,4-triazol-4-ylimino)methyl)-6-(hydroxymethyl)-4-methylphenol (AH). AH containing a phenolic moiety was obtained by the reaction between 4-amino-4H-1,2,4-triazole containing polar O- and N-centres with opposite polarity to the cationic interface and 2-hydroxy-3-(hydroxymethyl)-5-methylbenzaldehyde. The acid/base equilibrium of AH was investigated at the interfaces of cetrimonium bromide (CTAB) micelles, tri-block-copolymeric micelles (TBPs) and large unilamellar vesicles (LUVs) of different lipid compositions using steady state UV-Vis absorption spectroscopy. AH interacted strongly with the micelle and vesicle interfaces, according to the binding studies with LUV. A larger amount of AH proton dissociation was observed when localized at the interface of micelles and vesicles compared to that in the bulk phase, indicating that the pH values at the cationic interfaces are higher than in the bulk phase. The pH values were about 2.2 and 1.6 units higher at the CTAB and TBP micelle interfaces, respectively, than the bulk pH. The pH variation decreased from 2.4 to 1.5 units by increasing the neutral 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) lipid content from 0 to 50% in the cationic dimethyldioctadecylammonium (DDAB) LUV, indicating that the interfacial positive charges are responsible for the higher interfacial pH. Detailed structural and absorption characteristics of neutral AH and its anionic A(-) forms were investigated by fluorescence spectroscopic measurements and DFT based theoretical calculations. The present simple pH detection method may be applied to various biological micelle and vesicle interfaces.

Why medical students do not like to join rural health service? An exploratory study in India.

INTRODUCTION: Inadequate, inequitable distribution of the medical workforce remains a challenge across the globe, and India is no exception. Odisha, a state in India faces a major shortage of doctors particularly in rural and remote areas. In order to address this challenge, it is essential to understand medical students' career plans, specialization preferences, choices of job location and sector, and views on working in rural and remote areas. This study explored the immediate and long-term career plans of final year medical students, their intended practice locations and underlying reasons for the choices. METHODOLOGY: A cross-sectional survey was conducted in all the medical colleges (three government and three private) in the state of Odisha. Through the systematic sampling method, data were gathered from 390 final year students. A semi-structured questionnaire was administered to the students and data were analyzed using SPSS version 20. RESULTS: Of the 390 students, 290 (74.35%) were from a government college. The most preferred immediate career goal was postgraduation studies (45.9% of students in government medical schools and 54% in private). About 17% of government students and 9% of private students showed willingness to work in rural areas, in the long run. Nearly 44.5% mentioned opportunities for career growth, followed by the possibilities for higher education (26.8%) as major the factors for preferring an urban posting. Similarly, higher pay scales, better working conditions were major factors for preferring the private sector. Most of the students maintained that good housing, better salaries, and adequate facilities at the workplace would attract more students toward rural service. CONCLUSION: Since public funded medical students are not motivated to serve in rural settings, increasing the number of places or establishing new medical institutions may not be an effective solution to the issue. Approaches such as extended clinical apprenticeship in rural health facilities, long-term community engagement during medical studentship could be considered.