Phenalenyl-Based Photocatalyst for Bioinspired Oxidative Dehydrogenation of N-Heterocycles and Benzyl Alcohols.

The environmental benefits of molecular oxygen as the oxidizing agent in oxidation reactions that synthesize fine chemicals cannot be overstated. Increased interest in developing robust photocatalysts is stimulated by the fact that the current photocatalytic transformation boom has made previously inaccessible synthetic approaches possible. Motivated by enzymatic catalysis, employing a reusable phenalenyl-based photocatalyst, we have successfully developed oxidative dehydrogenation utilizing molecular oxygen as a greener oxidant. Under photoinduced oxidative dehydrogenation conditions, different types of saturated N-heterocycles and alcohols were successfully dehydrogenated. The versatility of this bioinspired protocol is demonstrated by the fact that a wide variety of N-heteroaromatics, such as quinoline, carbazole, quinoxaline, acridine, and indole derivatives, as well as aldehydes and ketones, were successfully synthesized. Detailed mechanistic studies validate the proposed mechanism. Fluorescence lifetime and CV experiments revealed the crucial role of water on the efficiency of the reaction. The present protocol also provides chemoselectivity and scalability, leading to superior results and allowing for the functionalization of bioactive molecules at a late stage in a sustainable manner.

Isolation of (Aryl)-(Imino) Phosphide and (Aryl)-(Phosphaalkene) Amide Complexes of Alkali Metals from Carbene-Phosphinidenes under Reductive-Thermal Rearrangements.

Invited for the cover of this issue are Sudipta Roy and co-workers at the Indian Institute of Science Education and Research (IISER) Tirupati. The image depicts the rearrangement of cyclic alkyl(amino) carbene (cAAC)-supported chloro-phosphinidenes affording two ligands, of which one was used for the solid-state isolation of three cyclic alkyl(amino-boryl) phosphaalkenes and two coinage metal clusters. Read the full text of the article at 10.1002/chem.202302120.

Isolation of (Aryl)-(Imino) Phosphide and (Aryl)-(Phosphaalkene) Amide Complexes of Alkali Metals from Carbene-Phosphinidenes under Reductive-Thermal Rearrangements.

Two-electron reduction of cyclic alkyl(amino) carbene (cAAC)-supported chloro-phosphinidene cAAC=P-Cl (1) followed by unprecedented thermal rearrangements afforded the alkali metal complexes of (aryl)-(cyclic alkyl(imino)) phosphides 3 a-3 c, 4 a-4 b through migration of the 2,6-diisopropylphenyl (dipp) group from N to the P centre, and the (aryl)-(cyclic alkyl(phosphaalkene)) amide 5 through cleavage of the CMe2 -N bond followed by energetically favoured 5-exo-tet ring-closure in the presence of the alkali metals Cs (3 a-3 c), K (4 a, 4 b), and Li (5). Compound 3 a was found to be photoluminescent (PL), emitting bright orange light under a laboratory UV lamp of wavelength 365 nm with PL quantum yield (ϕPL ) of 2.6 % (λem =600 nm), and an average lifetime (τ) of 4.8 µs. Reaction of 3 a with CuCl and AgOTf afforded (aryl)-(cyclic alkyl(imino)) phosphide-stabilized tetra-nuclear CuI (6), and octa-nuclear AgI (7) clusters, respectively. Moreover, complexes 3 a-3 c provided a direct route for the stabilization of cyclic alkyl(aminoboryl) phosphaalkenes 8 a-8 c when treated with 1-bromo-N,N,N',N'-tetraisopropylboranediamine.

Unified Approach to Diverse Heterocyclic Synthesis: Organo-Photocatalyzed Carboacylation of Alkenes and Alkynes from Feedstock Aldehydes and Alcohols.

We report an organo-photocatalyzed carboacylation reaction that offers a springboard to create chemical complexity in a diversity-driven approach. The modular one-pot method uses feedstock aldehydes and alcohols as acyl surrogates and commercially available Eosin Y as the photoredox catalyst, making it simple and affordable to introduce structural diversity. Several biologically relevant skeletons have been easily synthesized under mild conditions in the presence of visible light irradiation by fostering a radical acylation/cyclization cascade. The proposed reaction mechanism was further illuminated by a number of spectroscopic studies. Furthermore, we applied this protocol for the late-stage functionalization of pharmaceuticals and blockbuster drugs.

Genetic characterization of dengue virus from patients presenting multi-serotypic infections in the Northern West Bengal, India.

Northern West Bengal, popularly known as North Bengal, is a dengue-endemic area, which has been severely affected by Dengue in the past few years resulting in massive hospitalizations and deaths. Genetic characterization of the circulating endemic dengue virus (DENV) serotypes is of paramount importance for the epidemiological understanding of the infection and subsequent vaccine development. The present study was conceived to characterize circulating dengue serotypes and to undertake phylogenetic study. EDTA blood samples of all (N = 83) NS1-positive cases of patients with acute febrile illness referred to different health care facilities were collected and processed for RNA isolation followed by the complementary DNA (cDNA) preparation. Serotype determination of dengue infection was done using conventional PCR by targeting the viral C-prM region. Phylogenetic tree was constructed by implementing the Maximum likelihood method. Out of 83 blood samples 17 were detected to be positive for the presence of dengue viral RNA. DENV3 was found to be the predominant serotype in the single-infection cases; however, we have detected multi-serotypic co-infections throughout the study. Joint pain was found to be the most valuable symptom for the prognosis of dengue. Sequence analyses suggested that both DENV1- and DENV3-circulating genotypes are in the genotype III group and remain closely related to the Indian clade. To the best of our knowledge, this is the first report on the genetic characterization of circulating DENVs in North Bengal, which may contribute to the study of dengue epidemic and pathogenesis.

Co-clinical FDG-PET radiomic signature in predicting response to neoadjuvant chemotherapy in triple-negative breast cancer.

PURPOSE: We sought to exploit the heterogeneity afforded by patient-derived tumor xenografts (PDX) to first, optimize and identify robust radiomic features to predict response to therapy in subtype-matched triple negative breast cancer (TNBC) PDX, and second, to implement PDX-optimized image features in a TNBC co-clinical study to predict response to therapy using machine learning (ML) algorithms. METHODS: TNBC patients and subtype-matched PDX were recruited into a co-clinical FDG-PET imaging trial to predict response to therapy. One hundred thirty-one imaging features were extracted from PDX and human-segmented tumors. Robust image features were identified based on reproducibility, cross-correlation, and volume independence. A rank importance of predictors using ReliefF was used to identify predictive radiomic features in the preclinical PDX trial in conjunction with ML algorithms: classification and regression tree (CART), Naïve Bayes (NB), and support vector machines (SVM). The top four PDX-optimized image features, defined as radiomic signatures (RadSig), from each task were then used to predict or assess response to therapy. Performance of RadSig in predicting/assessing response was compared to SUVmean, SUVmax, and lean body mass-normalized SULpeak measures. RESULTS: Sixty-four out of 131 preclinical imaging features were identified as robust. NB-RadSig performed highest in predicting and assessing response to therapy in the preclinical PDX trial. In the clinical study, the performance of SVM-RadSig and NB-RadSig to predict and assess response was practically identical and superior to SUVmean, SUVmax, and SULpeak measures. CONCLUSIONS: We optimized robust FDG-PET radiomic signatures (RadSig) to predict and assess response to therapy in the context of a co-clinical imaging trial.

Isolation of Elusive Phosphinidene-Chlorotetrylenes: The Heavier Cyanogen Chloride Analogues.

The elusive phosphinidene-chlorotetrylenes, [PGeCl] and [PSiCl] have been stabilized by the hetero-bileptic cyclic alkyl(amino) carbene (cAAC), N-heterocyclic carbene (NHC) ligands, and isolated in the solid state at room temperature as the first neutral monomeric species of this class with the general formulae (L)P-ECl(L') (E=Ge, 3 a-3 c; E=Si, 6; L=cAAC; L'=NHC). Compounds 3 a-3 c have been synthesized by the reaction of cAAC-supported potassium phosphinidenides [cAAC=PK(THF)x ]n (1 a-1 c) with the adduct NHC:→GeCl2 (2). Similarly, compound 6 has been synthesized via reaction of 1 a with NHC:→SiCl2 adduct (4). Compounds 3 a-3 c, and 6 have been structurally characterized by single-crystal X-ray diffraction, NMR spectroscopy and mass spectrometric analysis. DFT calculations revealed that the heteroatom P in 3 bears two lone pairs; the non-bonding pair with 67.8 % of s- and 32 % of p character, whereas the other lone pair is involved in π backdonation to the CcAAC -N π* of cAAC. The Ge atom in 3 contains a lone pair with 80 % of s character, and slightly involved in the π backdonation to CNHC . EDA-NOCV analyses showed that two charged doublet fragments {(cAAC)(NHC)}+ , and {PGeCl}- prefer to form one covalent electron-sharing σ bond, one dative σ bond, one dative π bond, and a charge polarized weak π bond. The covalent electron-sharing σ bond contributes to the major stabilization energy to the total orbital interaction energy of 3, enabling the first successful isolations of this class of compounds (3, 6) in the laboratory.

Isolation of Homo-/Mixed-Valence Ag12 , Ag29 , and Ag8 Clusters Stabilized by Cyclic Alkyl(amino) Carbene-Anchored Monoanionic Phosphorus Ligand.

Silver clusters are attractive candidates for their promising optical properties, and biomedical activities. Herein, we report on the first syntheses and isolation of three homo-/mixed-valence silver nanoclusters (NCs) with Ag12 Cl3 , Ag29 , and Ag8 cores [((cAAC)P)6 Ag12 Cl3 ](OTf)3 (1), [((cAAC)P)6 Ag29 ] (2), and [((cAAC)P)4 Ag8 ] (3) having three-/twofold symmetry, employing cyclic alkyl(amino) carbene (cAAC)-supported phosphinidenide (cAACP- ) as the π-accepting stabilizing ligand. The average diameters of Ag NCs 1, and 2 are approximately 1.6 to 2 nm. The redox non-innocent mono-atomic phosphorus anions (P- ) anchored with cAAC ligands are generated in situ by the reaction of AgOTf with a boryl-phosphaalkene (cAAC)P-B(Ni Pr2 )2 through cleavage of the P-B bond with the help of a triflate anion (OTf- ) as a weak nucleophile. Equivalent number of the (cAAC)P- anions generated in situ are oxidized to produce the corresponding bis-phosphinidene (cAAC)2 P2 leading to the generation of Ag0 ions in solution for the formation of the unprecedented mixed-valence Ag NC 2. Complex 3 is achieved by treating potassium phosphinidenide cAACPK with AgNTf2 . The ligand field and the steric hindrance of the (cAAC)P units play crucial roles in stabilizing complexes 1-3, further providing a three- (1, 2)/two- (3) fold stand. The Ag12 Cl3 NC (1) with a tricationic core [AgI 12 Cl3 ] was found to be diamagnetic, and fluorescent, emitting green light at 563 nm when excited at 400 nm. In contrast, the neutral Ag29 (2) and Ag8 (3) clusters were found to be paramagnetic, and NMR silent showing characteristic EPR signals for Ag0 at room temperature.

Synergistic Effect of Cerium in Dual Photoinduced Ligand-to-Metal Charge Transfer and Lewis Acid Catalysis: Diastereoselective Alkylation of Coumarins.

We report the dual role of cerium to promote the photoinduced ligand-to-metal charge transfer (LMCT) process for the generation of the alkyl radical and subsequent Lewis acid catalysis to construct stereodefined C-C bonds. This paradigm utilized ubiquitous carboxylic acids as alkyl radical surrogates and offers excellent diastereoselectivity for the formation of C-4 alkylated coumarins in good to excellent yield. UV-vis spectroscopy studies in combination with in situ Fourier transform infrared spectroscopy are consistent with the proposed mechanism, supporting the participation of the CeIV-carboxylate complex in photoinduced LMCT and its subsequent homolysis to generate the alkyl radial through the exclusion of CO2. Finally, the oxophilicity of cerium enables a two-point complexation with the in situ generated enolate intermediate and facilitates the diastereoselective protonation to form the desired product. Furthermore, this mild and atom-economical catalytic manifolds allow the late-stage modification of pharmaceuticals.

Transforming Non-innocent Phenalenyl to a Potent Photoreductant: Captivating Reductive Functionalization of Aryl Halides through Visible-Light-Induced Electron Transfer Processes.

Herein, we have established a phenalenyl-based molecular scaffold which serves as a potent photoreductant utilizing the empty NBMO in the presence of a base to form a radical anion which, upon photoexcitation, behaves as a stronger reductant and accomplishes the cleavage of strong C-X (X = Cl, Br, I) bonds under milder reaction conditions. The base was found to be involved in a dual role of electron and hydrogen atom donor. Further, the aryl radical formed by the homolysis of C-X bonds in this technique was captured for the Csp2-Csp2 coupling with unactivated arenes. The photoreductant potency of the phenalenyl-based catalytic system was further extended to C-P as well as C-B bond formation reactions. EPR and lifetime studies reveal the formation of a persistent radical having a sufficient lifetime to take part in the reaction by the PET mechanism. Different spectroscopic techniques combined with DFT calculations were utilized for the characterization of active catalytic species and for the elucidation of plausible mechanistic pathways. This not only is the initial report of the application of phenalenyl as a photoreductant but also provides a completely metal-free (alkali and transition metal) approach for the challenging reductive functionalization of aryl halides at room temperature.

Electrochemical Activation of the C-X Bond on Demand: Access to the Atom Economic Group Transfer Reaction Triggered by Noncovalent Interaction.

An atom economic method demonstrates the involvement of noncovalent interaction via hydrogen or halogen bonding interaction in triggering paired electrolysis for the group transfer reactions. Specifically, this method demonstrated the bromination of several aromatic and heteroaromatic compounds through the activation of the C(sp3)-Br bond of organic-bromo derivatives on demand. This electrochemical protocol is mild, and mostly no additional electrolyte is needed, which makes the workup process straightforward. Unlike the existing regioselective monobromination methods, this work utilizes a relatively small amount (1.2 equiv) of bromine surrogates that releases bromine on demand under the electrochemical condition and after completion of the reaction generates acetophenone as a useful byproduct. Green metrics indicate this protocol has a very good atom efficiency with an E-factor of 26.86 kg of waste/1 kg of product. In addition to the scale-up process, this strategy could be extended to the transfer of chlorine and thioaryl units. An extensive mechanistic study is accomplished to validate the hypothesis of noncovalent interaction using computational, spectroscopic, and cyclic voltammetry studies. Finally, the applicability of this newly developed nonbonding interaction to trigger paired electrolysis was extended to the chemoselective debromination of several dihalo organic compounds.

Carbene-Anchored Boryl- and Stibanyl-Phosphaalkenes as Precursors for Bis-Phosphaalkenyl Dichlorogermane and Mixed-Valence AgI/AgII Phosphinidenide.

Cyclic alkyl(amino) carbene (cAAC)-anchored boryl- and stibanyl-phosphaalkenes with general formula cAAC = P-ER2 [E = B, R = (NiPr2)2 (3a-c); E = Sb, R = 2,4,6-triisopropylphenyl (5a-b)] have been synthesized and utilized as precursors for the bis-phosphaalkenyl dichlorogermane [(cAAC = P)2GeCl2] (6) and the first molecular example of a neutral polymeric mixed-valence AgI/AgII phosphinidenide complex [(cAACP)2Ag4IAgIICl4]n (7). All compounds have been characterized by single-crystal X-ray diffraction and further investigated by nuclear magnetic resonance (NMR), mass spectrometric analysis, and UV-vis/fluorescence measurements. The paramagnetic complex 7 has been characterized by ESR spectroscopy. Cyclic voltammetry studies of compounds 3/5 have suggested possible one-electron quasi-reversible reductions, indicating their redox noninnocent behavior in solution. Quantum chemical studies revealed the electron-sharing nature of the P-B and P-Sb σ bonds in compounds 3 and 5, and the polar CcAAC = P bonds in compounds 3, 5, and 6 prevailing their phosphaalkene structures over phosphinidenes.

Mode selective chemistry for the dissociation of methane on efficient Ni/Pt-bimetallic alloy catalysts.

The mode selectivity of methane dissociation is studied on three different Ni/Pt-bimetallic alloy surfaces using a fully quantum approach based on reaction path Hamiltonian. Dissociative sticking probability depends on the composition of alloying metals, excited vibrational mode, and symmetry of the reaction path about the plane perpendicular to the catalyst surface containing the carbon atom and two hydrogen atoms. Our calculations show that symmetry of the minimum energy reaction path depends on the surface alloy composition. In the transition state, the dissociating C-H bond elongates significantly for the dissociation of methane on these alloy systems. A significant decrease in the frequency of the symmetric stretching mode and the two bending modes near the transition state is observed on all the alloy surfaces. Under the vibrational adiabatic limit, excitation of these softened modes enhanced the dissociation probability compared to the ground vibrational state. The reaction probability values decrease abruptly at the incident energies less than the zero-point energy corrected barrier height. With the inclusion of non-adiabatic vibrational coupling terms, reaction probability in the low incident energy region increases to a greater extent, and mode selective behavior also becomes different from that observed within the vibrational adiabatic limit. Symmetric stretching mode displayed the highest reactivity on all the alloy surfaces. Overall, Ni8/Pt(111) is found to be the most reactive toward the methane dissociation.

Solid-State Isolation of Cyclic Alkyl(Amino) Carbene (cAAC)-Supported Structurally Diverse Alkali Metal-Phosphinidenides.

Cyclic alkyl(amino) carbene (cAAC)-supported, structurally diverse alkali metal-phosphinidenides 2-5 of general formula ((cAAC)P-M)n (THF)x [2: M=K, n=2, x=4; 3: M=K, n=6, x=2; 4: M=K, n=4, x=4; 5: M=Na, n=3, x=1] have been synthesized by the reduction of cAAC-stabilized chloro-phosphinidene cAAC=P-Cl (1) utilizing metallic K or KC8 and Na-naphthalenide as reducing agents. Complexes 2-5 have been structurally characterized in solid state by NMR studies and single crystal X-ray diffraction. The proposed mechanism for the electron transfer process has been well-supported by cyclic voltammetry (CV) studies and Density Functional Theory (DFT) calculations. The solid state oligomerization process has been observed to be largely dependent on the ionic radii of alkali metal ions, steric bulk of cAAC ligands and solvation/de-solvation/recombination of the dimeric unit [(cAAC)P-M(THF)x ]2 .

Visible-Light-Mediated Cross Dehydrogenative Coupling of Thiols with Aldehydes: Metal-Free Synthesis of Thioesters at Room Temperature.

Thioesters play a crucial role in biological systems and serve as important building blocks for organic synthesis. Herein, Eosin Y and TBHP mediated photochemical cross dehydrogenative coupling (PCDC) between feedstock aldehydes and thiols has been described at room temperature to synthesize thioesters. This thioesterification protocol proceeds smoothly to give the desired products in good to excellent yields by the suitable PCDC of both alkyl/aryl- aldehydes with a variety of alkyl/aryl-thiols and generates water and tBuOH as green byproducts. This method is also found to be scalable with good efficiency. Mechanistic investigations reveal that under this photochemical condition, the formation of acyl radical can be achieved from aldehyde. This acyl radical was further intercepted with an intermediate disulfide, generated in situ via the dehydrogenation of thiol to give the desired thioester. Moreover, disulfides, which are relatively easier to handle, also provided good to excellent yields in the optimized reaction condition. This protocol was further extended toward the more challenging direct transformation of alcohols to thioesters.

Direct functionalization of quinoxalin-2(1H)-one with alkanes: C(sp2)-H/C(sp3)-H cross coupling in transition metal-free mode.

Considering the significance of pharmaceutically important heterocycles, efficient and highly versatile protocols for the functionalization of diverse heterocycles with easily accessible feedstock are crucial. Here, we have reported selective alkylation of quinoxalin-2(1H)-one with a broad class of hydrocarbons having different C(sp3)-H bonds with varying bond strengths using di-tert-butyl peroxide (DTBP) as an alkoxyl radical mediator for hydrogen atom transfer (HAT). This dehydrogenative coupling approach utilizes feedstock chemicals such as cycloalkanes, cyclic ethers and alkyl arenes as coupling partners. This protocol exhibits good functional group compatibility and selectivity regarding both heterocycles and unactivated alkanes. Moreover, this methodology allows functionalization of relatively strong C-H bonds of adamantane and exclusive selectivity towards 3° C(sp3)-H bonds is observed. We also illustrate the applicability of this C(sp2)-H/C(sp3)-H cross-coupling for practical access to bioactive pharmaceuticals.

Dengue virus: epidemiology, biology, and disease aetiology.

Dengue is a vector-borne viral disease caused by the flavivirus dengue virus (DENV). Approximately 400 million cases and 22 000 deaths occur due to dengue worldwide each year. It has been reported in more than 100 countries in tropical and subtropical regions. A positive-stranded enveloped RNA virus (DENV) is principally transmitted by Aedes mosquitoes. It has four antigenically distinct serotypes, DENV-1 to DENV-4, with different genotypes and three structural proteins and seven non-structural proteins. Clinical symptoms of dengue range from mild fever to severe dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS), with thrombocytopenia, leucopenia, and increased vascular permeability. Although primary infection causes activation of immune responses against DENV serotypes, the severity of the disease is enhanced via heterotypic infection by various serotypes as well as antibody-dependent enhancement (ADE). The first licensed DENV vaccine was tetravalent CYD Denvaxia, but it has not been approved in all countries. The lack of a suitable animal model, a proper mechanistic study in pathogenesis, and ADE are the main hindrances in vaccine development. This review summarizes the current knowledge on DENV epidemiology, biology, and disease aetiology in the context of prevention and protection from dengue virus disease.

Identification and characterization of differentially expressed genes in the rice root following exogenous application of spermidine during salt stress.

Salinity is a major limiting factor in crop production. Exogenous spermidine (spd) effectively ameliorates salt injury, though the underlying molecular mechanism is poorly understood. We have used a suppression subtractive hybridization method to construct a cDNA library that has identified up-regulated genes from rice root under the treatment of spd and salt. Total 175 high-quality ESTs of about 100-500 bp in length with an average size of 200 bp are isolated, clustered and assembled into a collection of 62 unigenes. Gene ontology analysis using the KEGG pathway annotation database has classified the unigenes into 5 main functional categories and 13 subcategories. The transcripts abundance has been validated using Real-Time PCR. We have observed seven different types of post-translational modifications in the DEPs. 44 transmembrane helixes are predicted in 6 DEPs. This above information can be used as first-hand data for dissecting the administrative role of spd during salinity.

Probing the versatility of metallo-electro hybrid catalysis: enabling access towards facile C-N bond formation.

The development of versatile and mild methodologies for C-N bond construction has always been a hot topic of interest in synthetic organic chemistry. In recent years, electrochemistry has emerged as a promising green and sustainable environmentally benign approach to carry out these transformations under mild conditions utilizing electrons as oxidizing/reducing agents. The current state-of-the-art in combining electrocatalysis with transition metal catalysis has gained significant attention. This hybrid synthetic methodology has increasingly become a common tool and offers many potential advantages compared to direct electrolysis. This review comprehensively highlights recent developments in the merging of transition metal catalysis in electro-organic synthesis for the facile construction of C-N bonds. In this review major emphasis is given to mechanistic investigations and their synthetic applications of this hybrid catalysis.

Detecting Pneumonia using Convolutions and Dynamic Capsule Routing for Chest X-ray Images.

An entity's existence in an image can be depicted by the activity instantiation vector from a group of neurons (called capsule). Recently, multi-layered capsules, called CapsNet, have proven to be state-of-the-art for image classification tasks. This research utilizes the prowess of this algorithm to detect pneumonia from chest X-ray (CXR) images. Here, an entity in the CXR image can help determine if the patient (whose CXR is used) is suffering from pneumonia or not. A simple model of capsules (also known as Simple CapsNet) has provided results comparable to best Deep Learning models that had been used earlier. Subsequently, a combination of convolutions and capsules is used to obtain two models that outperform all models previously proposed. These models-Integration of convolutions with capsules (ICC) and Ensemble of convolutions with capsules (ECC)-detect pneumonia with a test accuracy of 95.33% and 95.90%, respectively. The latter model is studied in detail to obtain a variant called EnCC, where n = 3, 4, 8, 16. Here, the E4CC model works optimally and gives test accuracy of 96.36%. All these models had been trained, validated, and tested on 5857 images from Mendeley.