Design and Synthesis of Indazole-Indole Hybrid via tert-Butyl Nitrite Mediated Cascade Diazotization/Isomerization/Cyclization.

In this report, a tert-butyl nitrite (TBN)-mediated straightforward metal-free approach has been presented for the synthesis of a diverse range of C-3-substituted indazole-indole hybrids using readily accessible 2-(indolin-3-ylidenemethyl)aniline derivatives. This strategy is proposed to occur via a diazonium salt intermediate that is capable of cascade isomerization and intramolecular C-N bond formation through a 5-endo-dig cyclization to achieve a wide variety of indazole-indole hybrids in good yields.

DDQ/Fe(NO3)3-Catalyzed Aerobic Synthesis of 3-Acyl Indoles and an In Silico Study for the Binding Affinity of N-Tosyl-3-acyl Indoles toward RdRp against SARS-CoV-2.

In the present study, we herein report a DDQ-catalyzed new protocol for the synthesis of substituted 3-acylindoles. Being a potential system for virtual hydrogen storage, introduction of catalytic DDQ in combination with Fe(NO3)3·9H2O and molecular oxygen as co-catalysts offers a regioselective oxo-functionalization of C-3 alkyl-/aryllidine indolines even with scale-up investigations. Intermediate isolation, their spectroscopic characterization, and the density functional theory calculations indicate that the method involves dehydrogenative allylic hydroxylation and 1,3-functional group isomerization/aromatization followed by terminal oxidation to afford 3-acylindoles quantitatively with very high regioselectivity. This method is very general for a large number of substrates with varieties of functional groups tolerance emerging high-yield outcome. Moreover, molecular docking studies were performed for some selected ligands with an RNA-dependent RNA polymerase complex (RdRp complex) of SARS-CoV-2 to illustrate the binding potential of those ligands. The docking results revealed that few of the ligands possess the potential to inhibit the RdRp of SARS-Cov-2 with binding energies (-6.7 to -8.19 kcal/mol), which are comparably higher with respect to the reported binding energies of the conventional re-purposed drugs such as Remdesivir, Ribavirin, and so forth (-4 to -7 kcal/mol).

Iron(III)-catalyzed synthesis of indole-xanthydrol hybrid through oxidative cycloisomerization/hydroxylation reaction.

An efficient one-pot synthesis of an indole-xanthydrol hybrid is described in the presence of catalytic combinations of Fe(NO3)3/FeCl3. This strategy involves a series of reactions such as allylic oxidation, isomerisation, cyclisation and hydroxylation reactions in a tandem manner. This protocol offers several advantages including mild reaction conditions, operational simplicity, high selectivity, good yields and easily accessible starting materials. The synthetic utility of this protocol was further demonstrated by the one-pot synthesis of the highly substituted xanthene containing bis-indolylmethane derivative. The preliminary mechanistic studies reveal that the reaction is initiated by the generation of radicals in the presence of catalytic iron(III)-salts.

The synthesis of indole-3-carbinols (I3C) and their application to access unsymmetrical bis(3-indolyl)methanes (BIMs) bearing a quaternary sp3-carbon.

In the present study, the novel synthesis of tert-indole-3-carbinols is reported through the DDQ-mediated oxidation of the allylic C-H bond/aromatization/hydroxylation at the indolyl carbon using water as the hydroxyl source. The reaction is highly efficient and high yielding and it works under mild reaction conditions. Furthermore, the synthetic value of such indole-based tert-carbinols is explored through their use as excellent electrophilic methylene surrogates to develop medicinally important unsymmetrical bis(3-indolyl)methanes containing an all carbon quaternary center.

Iron-catalyzed carboarylation of alkynes via activation of π-activated alcohols: rapid synthesis of substituted benzofused six-membered heterocycles.

An Fe(OTf)3-catalysed carboarylation of alkynes is reported for the straightforward synthesis of densely substituted 1,2-dihydroquinolines from N-propargyl anilides and π-activated alcohols. The reaction provides a new method for the synthesis of highly substituted benzofused six-membered heterocycles by the formation of two carbon-carbon bonds and one ring in a single step. The power of the methodology was further extended to the synthesis of substituted chromene and thiochromene derivatives in high yields. In addition, substituted quinoline derivatives were also achieved in a single step in the presence of FeCl3 through detosylation/aromatisation. A number of control experiments have been performed and a plausible mechanism has also been proposed to explain the formation of the products.

DDQ/FeCl3-mediated tandem oxidative carbon-carbon bond formation for the Synthesis of indole-fluorene hybrid molecules.

A series of diverse and complex hybrid structures of indole bearing fluorene were obtained in the presence of DDQ with high regioselectivity under mild conditions from biaryl tethered 3-(methylene)indoline in good to excellent yields. The strategy involves tandem allylic Csp3-H oxidation and subsequent intramolecular carbon-carbon bond formation. The yield of the product was dramatically improved in the presence of additives such as FeCl3 and molecular sieves (4 Å). A possible mechanism is proposed for this tandem process.

Application of the Povarov Reaction in Biaryls under Iron Catalysis for the General Synthesis of Dibenzo[a,c]Acridines.

A modified Povarov reaction involving 2'-alkynylbiaryl-2-carbaldehydes and aryl amines with tandem oxidation was performed using catalytic FeCl3. The outcome was an efficient general synthesis of dibenzo[a,c]acridines with moderate to high yields. This method offers simplicity in the preparation of substrates, diverse substrate scope, and high atom economy. The generality of the protocol was verified by synthesizing a tribenzo[a,c,h]acridine derivative. Photophysical properties of the synthesized compounds were also studied. The compounds absorb UV light typically in the range 230-330 nm and emit in the visible range of 400-420 nm.

Learning Category-Specific Deformable 3D Models for Object Reconstruction.

We address the problem of fully automatic object localization and reconstruction from a single image. This is both a very challenging and very important problem which has, until recently, received limited attention due to difficulties in segmenting objects and predicting their poses. Here we leverage recent advances in learning convolutional networks for object detection and segmentation and introduce a complementary network for the task of camera viewpoint prediction. These predictors are very powerful, but still not perfect given the stringent requirements of shape reconstruction. Our main contribution is a new class of deformable 3D models that can be robustly fitted to images based on noisy pose and silhouette estimates computed upstream and that can be learned directly from 2D annotations available in object detection datasets. Our models capture top-down information about the main global modes of shape variation within a class providing a "low-frequency" shape. In order to capture fine instance-specific shape details, we fuse it with a high-frequency component recovered from shading cues. A comprehensive quantitative analysis and ablation study on the PASCAL 3D+ dataset validates the approach as we show fully automatic reconstructions on PASCAL VOC as well as large improvements on the task of viewpoint prediction.

Origins of concentration gradients for diffusiophoresis.

Fluid transport that is driven by gradients of pressure, gravity, or electro-magnetic potential is well-known and studied in many fields. A subtler type of transport, called diffusiophoresis, occurs in a gradient of chemical concentration, either electrolyte or non-electrolyte. Diffusiophoresis works by driving a slip velocity at the fluid-solid interface. Although the mechanism is well-known, the diffusiophoresis mechanism is often considered to be an esoteric laboratory phenomenon. However, in this article we show that concentration gradients can develop in a surprisingly wide variety of physical phenomena - imposed gradients, asymmetric reactions, dissolution, crystallization, evaporation, mixing, sedimentation, and others - so that diffusiophoresis is in fact a very common transport mechanism, in both natural and artificial systems. We anticipate that in georeservoir extractions, physiological systems, drying operations, laboratory and industrial separations, crystallization operations, membrane processes, and many other situations, diffusiophoresis is already occurring - often without being recognized - and that opportunities exist for designing this transport to great advantage.

Self-Generated Electrokinetic Fluid Flows during Pseudomorphic Mineral Replacement Reactions.

Pseudomorphic mineral replacement reactions involve one mineral phase replacing another, while preserving the original mineral's size and texture. Macroscopically, these transformations are driven by system-wide equilibration through dissolution and precipitation reactions. It is unclear, however, how replacement occurs on the molecular scale and what role dissolved ion transport plays. Here, we develop a new quantitative framework to explain the pseudomorphic replacement of KBr crystal in a saturated KCl solution through a combination of microscopic, spectroscopic, and modeling techniques. Our observations reveal that pseudomorphic mineral replacement (pMRR) is transport-controlled for this system and that convective fluid flows, caused by diffusioosmosis, play a key role in the ion transport process across the reaction-induced pores in the product phase. Our findings have important implications for understanding mineral transformations in natural environments and suggest that replacement could be exploited in commercial and laboratory applications.

Reductions in indoor black carbon concentrations from improved biomass stoves in rural India.

Deployment of improved biomass burning cookstoves is recognized as a black carbon (BC) mitigation measure that has the potential to achieve health benefits and climate cobenefits. Yet, few field based studies document BC concentration reductions (and resulting human exposure) resulting from improved stove usage. In this paper, data are presented from 277 real-world cooking sessions collected during two field studies to document the impacts on indoor BC concentrations inside village kitchens as a result of switching from traditional stoves to improved forced draft (FD) stoves. Data collection utilized new low-cost cellphone methods to monitor BC, cooking duration, and fuel consumption. A cross sectional study recorded a reduction of 36% in BC during cooking sessions. An independent paired sample study demonstrated a statistically significant reduction of 40% in 24 h BC concentrations when traditional stoves were replaced with FD stoves. Reductions observed in these field studies differ from emission factor reductions (up to 99%) observed under controlled conditions in laboratory studies. Other nonstove sources (e.g., kerosene lamps, ambient concentrations) likely offset the reductions. Health exposure studies should utilize reductions determined by field measurements inside village kitchens, in conjunction with laboratory data, to assess the health impacts of new cooking technologies.

Enhanced transport into and out of dead-end pores.

Dead-end micro- and nanoscale channels are ubiquitous in nature and are found in geological and biological systems subject to frequent disruptions. Achieving fluid flows in them is not possible through conventional pressure-driven mechanisms. Here we show that chemically driven convective flows leading to transport in and out of dead-end pores can occur by the phenomenon of "transient diffusioosmosis". The advective velocity depends on the presence of an in situ-generated transient ion gradient and the intrinsic charge on the pore wall. The flows can reach speeds of 50 µm/s and cause extraction of otherwise-trapped materials. Our results illustrate that chemical energy, in the form of a transient salt gradient, can be transduced into mechanical motion with the pore wall acting as the pump. As discussed, the phenomena may underlie observed transport in many geological and biological systems involving tight or dead-end micro- and nanochannels.

Particle deposition on microporous membranes can be enhanced or reduced by salt gradients.

Colloidal particle deposition on membranes is a continuing scientific and technological challenge. In this paper we examine the role of a previously unexplored phenomenon-diffusiophoretic particle transport toward a membrane-in relation to fouling. Diffusiophoresis is an electrokinetic transport mechanism that arises in salt gradients, especially when the ions have different diffusion coefficients. Through experiments conducted with salt diffusing across microdialysis membranes, with no advection, we show experimentally that diffusiophoresis induces colloidal deposition on the surface of microporous surfaces. We used transient salt (NaCl, KCl, LiCl) gradients and fundamental electrokinetic modeling to assess the role of diffusiophoresis in colloidal fouling. Based on (i) difference in diffusion coefficients of ions, (ii) zeta potential on the particles, and (iii) ionic gradient applied across the walls of the membrane, colloidal fouling could be both quantitatively and qualitatively predicted. Our understanding enabled us to stop particle deposition by adding calcium carbonate outside the membrane, which generates a stronger electric field in a direction opposite to that created by salt diffusing from the membrane. We propose that accounting for this diffusiophoretic mode of particle deposition is important in understanding membrane fouling.

How do people in rural India perceive improved stoves and clean fuel? Evidence from Uttar Pradesh and Uttarakhand.

Improved cook stoves (ICS) have been widely touted for their potential to deliver the triple benefits of improved household health and time savings, reduced deforestation and local environmental degradation, and reduced emissions of black carbon, a significant short-term contributor to global climate change. Yet diffusion of ICS technologies among potential users in many low-income settings, including India, remains slow, despite decades of promotion. This paper explores the variation in perceptions of and preferences for ICS in Uttar Pradesh and Uttarakhand, as revealed through a series of semi-structured focus groups and interviews from 11 rural villages or hamlets. We find cautious interest in new ICS technologies, and observe that preferences for ICS are positively related to perceptions of health and time savings. Other respondent and community characteristics, e.g., gender, education, prior experience with clean stoves and institutions promoting similar technologies, and social norms as perceived through the actions of neighbours, also appear important. Though they cannot be considered representative, our results suggest that efforts to increase adoption and use of ICS in rural India will likely require a combination of supply-chain improvements and carefully designed social marketing and promotion campaigns, and possibly incentives, to reduce the up-front cost of stoves.

Self-generated diffusioosmotic flows from calcium carbonate micropumps.

Calcium carbonate particles, ubiquitous in nature and found extensively in geological formations, behave as micropumps in an unsaturated aqueous solution. The mechanism causing this pumping is diffusioosmosis, which drives flows along charged surfaces. Our calcium carbonate microparticles, roughly ∼10 µm in size, self-generate ionic gradients as they dissolve in water to produce Ca(2+), HCO(3)(-), and OH(-) ions that migrate into the bulk. Because of the different diffusion coefficients of these ions, spontaneous electric fields of roughly 1-10 V/cm arise in order to maintain electroneutrality in the solution. This electric field drives the diffusiophoresis of charged tracers (both positive and negative) as well as diffusioosmotic flows along charged substrates. Here we show experimentally how the directionality and speed of the tracers can be engineered by manipulating the tracer zeta potential, the salt gradients, and the substrate zeta potential. Furthermore, because the salt gradients are self-generated, here by the dissolution of solid calcium carbonate microparticles another manipulated variable is the placement of these particles. Importantly, we find that the zeta potentials on surfaces vary with both time and location because of the adsorption or desorption of Ca(2+) ions; this change affects the flows significantly.

Real-time assessment of black carbon pollution in Indian households due to traditional and improved biomass cookstoves.

Use of improved (biomass) cookstoves (ICs) has been widely proposed as a Black Carbon (BC) mitigation measure with significant climate and health benefits. ICs encompass a range of technologies, including natural draft (ND) stoves, which feature structural modifications to enhance air flow, and forced draft (FD) stoves, which additionally employ an external fan to force air into the combustion chamber. We present here, under Project Surya, the first real-time in situ Black Carbon (BC) concentration measurements from five commercial ICs and a traditional (mud) cookstove for comparison. These experiments reveal four significant findings about the tested stoves. First, FD stoves emerge as the superior IC technology, reducing plume zone BC concentration by a factor of 4 (compared to 1.5 for ND). Indoor cooking-time BC concentrations, which varied from 50 to 1000 µg m(-3) for the traditional mud cookstove, were reduced to 5-100 µg m(-3) by the top-performing FD stove. Second, BC reductions from IC models in the same technology category vary significantly: for example, some ND models occasionally emit more BC than a traditional cookstove. Within the ND class, only microgasification stoves were effective in reducing BC. Third, BC concentration varies significantly for repeated cooking cycles with same stove (standard deviation up to 50% of mean concentration) even in a standardized setup, highlighting inherent uncertainties in cookstove performance. Fourth, use of mixed fuel (reflective of local practices) increases plume zone BC concentration (compared to hardwood) by a factor of 2 to 3 across ICs.