[3+2] Cascade Ring-Closing/Ring-Opening Strategy: Access to N-Indene-Tethered Amino Alcohols.

An unprecedented atom-economic redox neutral regioselective Rh(III)-catalyzed cascade [3+2] annulation of 2-aryl oxazoline with α,ß-unsaturated nitro olefins has been accomplished, furnishing a novel set of nitro-functionalized indene-tethered amino alcohols through a synergistic ring-closing/ring-opening strategy via the formation of two new C-C bonds and the regioselective cleavage of the C2-O bond of oxazoline under silver free mild reaction conditions with a broad substrate scope.

A condition-tuned unorthodox approach to indole-3-carboxylic acids and anthranilic acids via carbon atom translocation.

We describe a robust one-pot cascade method for the synthesis of indole-3-carboxylic acids using isatins and DMSO via a one-carbon translocation involving in situ generation of α,ß-unsaturated methylvinylsulfoxide followed by amide bond cleavage and ring closure. The methodology has been extended to afford anthranilic acid derivatives by tuning the reaction conditions in the presence of molecular oxygen. Importantly, easy access to commercially available drugs, including tropisetron, is demonstrated.

Exploring the Structural Importance of the C3=C4 Double Bond in Plant Alkaloids Harmine and Harmaline on Their Binding Interactions with Hemoglobin.

Harmine and harmaline are two structurally similar heterocyclic ß-carboline plant alkaloids with various therapeutic properties, having a slight structural difference in the C3=C4 double bond. In the present study, we have reported the nature of the interaction between hemoglobin (Hb) with harmine and harmaline by employing several multispectroscopic, calorimetric, and molecular docking approaches. Fluorescence spectroscopic studies have shown stronger interaction of harmine with Hb compared to that of almost structurally similar harmaline. Steady-state anisotropy experiments further show that the motional restriction of harmine in the presence of Hb is substantially higher than that of the harmaline-Hb complex. Circular dichroism (CD) study demonstrates no conformational change of Hb in the presence of both alkaloids, but CD study in 1-cm cuvette path length also demonstrates stronger affinity of harmine toward Hb compared to harmaline. From the thermal melting study, it has been found that both harmine and harmaline slightly affect the stability of Hb. From isothermal titration calorimetry (ITC), we have found that the binding process is exothermic and enthalpy driven. Molecular docking studies indicated that both harmine and harmaline prefer identical binding sites in Hb. This study helps us to understand that slight structural differences in harmine and harmaline can alter the interaction properties significantly, and this key information may help in the drug discovery processes.

Uncovering the Contrasting Binding Behavior of Plant Flavonoids Fisetin and Morin Having Subsidiary Hydroxyl Groups (-OH) with HRAS1 and HRAS2 i-Motif DNA Structures: Decoding the Structural Alterations and Positional Influences.

Research on the interactions of naturally existing flavonoids with various noncanonical DNA such as i-motif (IM) DNA structures is helpful in comprehending the molecular basis of binding mode as well as providing future direction for the application and invention of novel effective therapeutic drugs. IM DNA structures have been identified as prospective anticancer therapeutic targets, and flavonoids are smaller molecules with a variety of health-promoting attributes, including anticancer activities. The extensive investigation comprising a series of techniques reveals the contrasting mode of the binding behavior of fisetin and morin with various IM DNA structures. We have discovered that structural alterations of hydroxyl groups located at different places of aromatic rings influence flavonoid's reactivity. This minor structural alteration appears to be critical for fisetin and morin's capacity to interact differentially with HRAS1 and HRAS2 IM DNA. Hence, fisetin appears to be an efficient ligand for HRAS1 and morin is considered to be an efficient ligand for HRAS2 IM DNA. This novel exploration opens up the possibility of employing the strategy for regulation of gene expression in cancerous cells. Our finding also reveals the flavonoid-mediated specific interaction with IM DNA while pointing toward tangible strategies for drug discovery and other essential cellular functions.

Electrochemical C(sp3)-C(sp3) cross-dehydrogenative coupling: enabling access to 9-substituted fluorescent acridanes.

A straightforward strategy for direct access of C9-functionalized N-alkyl-acridanes in good to excellent yields has been established via a metal- and external oxidant-free sustainable electrochemical C(sp3)-C(sp3) cross-dehydrogenative coupling reaction between acridanes and benzo fused lactones at ambient temperature. A broad substrate scope with superior functional-group tolerance via anodic oxidation of acridanes permitted the synthesis of a vast spectrum of fluorescence-active acridanes with high quantum yields.

Synthesis of indene-fused spiro-dibenz(ox)azepines via Rh(III)-catalyzed cascade regioselective C-H activation/annulation.

We report an unprecedented atom-economic one-pot Cp*Rh(III)-catalyzed regioselective [3+2]-spiroannulation reaction between dibenz(ox)azepines and ynones, allowing the synthesis of biologically relevant novel spirocyclic dibenz(ox)azepines under operationally simple and mild reaction conditions. The reaction proceeds without any silver additive or external oxidant implementing a redox-neutral pathway. A broad substrate scope with diverse functional group tolerance permitted the regioselective synthesis of a wide spectrum of indene-containing spirocyclic dibenz(ox)azepines in good to excellent yields. Also, we showcased detailed mechanistic studies to justify the formation of spirocycles. In addition, the synthetic utility of this process was also demonstrated by the modular synthesis of various steroid conjugates.

A Simplified Approach for the Aqueous Synthesis of Luminescent CdSe/ZnS Core/Shell Quantum Dots and Their Applications in Ultrasensitive Determination of the Biomarker 3-Nitro-l-tyrosine.

In contrast to the hot-injection organometallic routes, synthesizing stable and highly luminescent core/shell nanocrystals with encapsulation of biocompatible groups through an aqueous route is a long-standing challenge. In recent years, relatively high quantum efficiency and unique properties of core/shell nanostructured materials (quantum dots) have contributed toward enhancement in sensing capability. The present work reports a facile aqueous synthesis process of core/shell CdSe/ZnS quantum dots (QDs) with encapsulation of glutathione (GSH). The optimal conditions for the synthesis of the most stable particles were ascertained, and the different experimental analyses suggest that the stable core/shell QDs in question have good crystallinity with a size around 4.7 nm with a shell thickness of 0.7 nm and a photoluminescence quantum yield of about 35%. Further, it is demonstrated that the as-synthesized material has great potential in detecting as low as 0.28 nM 3-nitro-l-tyrosine (3-NT), an important marker for oxidative stress, the level of which in our body signals several chronically diseased conditions. The enthalpy-driven interactions of CdSe/ZnS-GSH QDs with 3-NT were characterized through steady-state and time-resolved luminescence spectroscopy and isothermal microcalorimetry. The devised method of probing 3-NT was further validated with human serum samples. Thus, the proposed strategy may provide a protocol for selective determination of 3-NT under different pathological conditions.

Regio- and Diastereoselective [3 + 2]-Spiroannulation of Benzoxazines with Chalcones: A Rh(III)-Catalyzed Redox-Neutral Approach to α-Aroyl Spiro-Indanamines.

We report an atom-economic Rh(III)-catalyzed [3 + 2]-spiroannulation reaction between cyclic ketimines and α,ß-unsaturated carbonyl compounds, allowing the synthesis of novel spirocycles with concomitant generation of three stereogenic centers in one pot. The reaction does not require any silver additives or external oxidants and is believed to proceed in a redox-neutral manner. A broad substrate scope with good functional group tolerance permitted the synthesis of a vast spectrum of spirocyclic 1,4-benzoxazine derivatives containing polysubstituted α-aroyl-indanamines in good to excellent yields with high diastereoselectivity.

A radical-radical cross-coupling reaction of xanthene with sulfonyl hydrazides: facile access to xanthen-9-sulfone derivatives.

A straightforward strategy for direct incorporation of sulfonyl units into a xanthene moiety for accessing xanthen-9-sulfone derivatives in good to excellent yields has been established via metal-free radical-radical cross-coupling reaction of xanthenes and sulfonyl hydrazides. Using easily accessible starting materials, this methodology proceeds efficiently with a high degree of functional group compatibility and with a wide scope of both xanthenes and sulfonyl hydrazides under operationally simple reaction conditions. Mechanistic investigations revealed that sulfonyl radicals could be generated from sulfonyl hydrazides in the presence of TBHP under an oxygen atmosphere.

Physicochemical Understanding of Protein-Bound Quantum Dot-Based Sensitive Probing of Bilirubin: Validation with Real Samples and Implications of Protein Conformation in Sensing.

Precise and rapid determination of free bilirubin (BR), a key biomarker of pathological conditions of the liver, is important clinical issue. The present study demonstrates that the combination of the strong specific affinic properties of protein, bovine serum albumin (BSA), toward bilirubin and luminescence of well-characterized semiconductor quantum dots (QDs) can offer a simple, fast, and sensitive technique for the determination of free bilirubin through quenching analysis. Here, BSA molecule not only stabilizes the quantum dots in an aqueous environment but also helps bring BR closer to QDs during the interactions of CdSe-BSA QDs with BR. Further, it is revealed through photophysical investigation that the conformation of protein molecule may play an important role in biomolecular sensing considering bilirubin as a model target molecule. The luminescence of CdSe-BSA QDs was highly responsive toward bilirubin, where nearly 90% of emission intensity was quenched on adding only 40 µM bilirubin, suggesting strong interactions involved between synthesized QDs and bilirubin. Solvent polarity dependence on luminescence changes confirms strong electrostatic interaction between the QDs and BR. The applicability of the synthesized quantum dots in sensing bilirubin has been checked in the presence of different possible interfering agents and also with plasma isolated from real blood samples of both normal and hepatitis patients. It was observed that bilirubin as control sample as well as in human serum sample can be optimally measured at pH 7.5, 25 °C. Thus, the proposed strategy being able to measure free BR even at least two orders of magnitude lower than bilirubin level in normal blood may provide a reasonable protocol to determine BR in the pathophysiology of many critical human diseases, like hepatitis and Gilbert's syndrome in the near future.

Room temperature synthesis of NIR emitting Ag2S nanoparticles through aqueous route and its influence on structural modulation of DNA.

Near infra-red (NIR) light emitting nanomaterials had shown great promise in clinical imaging in view of negligible absorption by skin or tissue of mammalian. Thus, it demands for synthesizing stable NIR emitting nanomaterials in water environment. The present work presents synthesis of biologically acceptable luminescent near-IR emitting silver sulfide nanoparticles through an aqueous route using 2-mercaptoethanol. The prepared as-synthesized Ag2S nanoparticles exhibited bright photoluminescence with quantum yield of ca. 4%. X-ray diffraction (XRD) analysis indicated that the products were monoclinic α-Ag2S. Fourier transform infrared spectral analysis revealed that the stretching vibration at 2560 cm-1 responsible for S-H bond of thiol group disappeared suggesting the conjugation of 2-mercaptoethanol with Ag2S nanoparticles. In view of investigating any possible effect on genetic materials, interactions of the synthesized particles with calf thymus DNA was investigated employing Ethidium bromide (EB) as structural probe. To understand the binding mechanism, the UV-vis absorption, fluorescence and circular dichroism (CD) spectroscopic, as well as DNA melting studies measurements were carried out. The observed results confirm that nanoparticles interact with DNA through groove binding.