Measurements of radon exhalations and radiological doses using LR-115 (II) nuclear track detectors in Tiru region of the Naga Schuppen Belt, India.

In this present study, the nuclear track detector LR-115 (II) was employed to assess radon (222Rn) exhalation rate, effective radium (226Ra) content, and the annual effective dose from coal and soil samples collected in and around the coal mining area of Tiru region of Nagaland, India. The 222Rn mass and surface exhalation rates and 226Ra contents were found to be in the ranges of 7.3-17.3 mBq kg-1 h-1, 242.9-573.6 mBq m-2 h-1 and 1.0-2.3 Bq kg-1, respectively, for coal and 15.8-22.0 mBq kg-1 h-1, 523.8-730.4 mBq m-2 h-1 and 2.1-2.9 Bq kg-1, respectively, for soil. The 222Rn exhalation rates and 226Ra contents in soils were found to be higher than in coal. The estimated annual effective doses for coal and soils were found to be in the ranges of 17.6-41.6 and 38.0-53.0 µSv y-1, respectively. This study is an important contribution to the understanding of radiation exposure in the coal mining area of the thrust-bound sedimentary sequence of the Naga Schuppen Belt, and it would have potential impact on further human health studies. However, the measured values for all the samples were found to be within the globally recognised permissible range.

Synthesis and Photophysical Properties of 3-Substituted-1H-Indazoles: A Pd-Catalyzed Double C-N Bond Formation Strategy via 1,6-Conjugate Addition.

A Pd-catalyzed cascade process for the direct synthesis of 3-substituted-1H-indazole employing p-quinone methide (p-QM) and arylhydrazine through Pd-catalyzed double C-N bond formation via 1,6-conjugate addition is reported. This reaction strategy affords efficient and practical access to synthetically important diverse 3-substituted-1H-indazoles in good yields. The photophysical properties of the synthesized 3-substituted-1H-indazoles are investigated, and some of them showed very good fluorescence properties with quantum yields up to 85%. Also, the synthesized 3-substituted-1H-indazole exhibits an acid-sensitive fluorescence turn-off activity.

Mitochondria-targeted biotin-conjugated BODIPYs for cancer imaging and therapy.

Two BODIPY-biotin conjugates KDP1 and KDP2 are designed and synthesized for targeted PDT applications. Both have good absorption with a high molar absorption coefficient and decent singlet oxygen generation quantum yields. The photosensitizers KDP1 and KDP2 were found to be localized in the mitochondria with excellent photocytotoxicity of up to 18.7 nM in MDA-MB-231 breast cancer cells. The cell death predominantly proceeded through the apoptosis pathway via ROS production.

Biocompatible Aza-BODIPY-Biotin Conjugates for Photodynamic Therapy of Cancer.

With an objective to develop efficient photosensitizers to cancerous tissues, we synthesized two novel biocompatible sensitizers based on aza-BODIPYs incorporated with heavy atoms and biotin moieties. The bioconjugates DPR2a and DPR2b exhibited a favorable absorption range (600-750 nm) with excellent triplet-state quantum yields (up to 79%) and singlet oxygen generation yields (up to 75%). In vitro photobiological investigations employing MDA-MB-231 breast cancer cell lines exhibited rapid cellular uptake, negligible dark toxicity, and high photocytotoxicity. The mechanism of cell death of these systems was predominantly due to the mitochondrial damage, leading to apoptosis mediated via the generation of singlet oxygen-triggered reactive oxygen species. The in vivo studies with the representative conjugate DPR2a employing female NOD/SCID mice models showed inhibition in tumor growth and significantly decreased tumor volume post photodynamic therapy (PDT) treatment. Our results validate that both DPR2a and DPR2b with iodine incorporation exhibit favorable and superior photophysical and photobiological aspects and demonstrate thereby their potential applications in imaging and PDT of cancer.

Synthesis of π-Extended Benzofulvenes: A Pd-Catalyzed Cascade Annulation Process Comprising C-C Bond Formation Followed by 1,6-Conjugate Addition.

A Pd-catalyzed cascade annulation process comprising C-C bond formation followed by 1,6-conjugate addition for π-extended benzofulvenes is reported. This process is compatible with a wide range of functionalities for both the p-quinone methides and internal alkynes, leading to diverse π-extended benzofulvenes. Additionally, this strategy is also applicable for aryne annulation with p-quinone methides.

Substituted Isocoumarins: An Assemble of Synthetic Strategies Towards 3-Substituted and 3,4-Disubstituted Isocoumarins.

The versatility of isocoumarin frameworks offers the privilege to access many pharmacological targets. This unique heterocycle core present in many natural products and complex organic molecules contribute to medicinal chemistry as anti-cancer, anti-inflammatory and immunomodulatory agents. The attractive properties exhibited by its analogues urged the scientists to explore their synthetic analogues. In regard to the myriads of synthetic methodologies, we have compiled a review update covering all the articles that have been published towards the synthesis of 3-substituted and 3,4-disubstituted isocoumarins. Additionally, we have also highlighted a systematic survey of catalytic methods for their synthesis along with their scope towards diverse functionalizations and plausible mechanistic aspects.

Pd-Catalyzed Alkyne and Aryne Annulations: Synthesis and Photophysical Properties of π-Extended Coumarins.

A Pd-catalyzed alkyne and aryne annulation strategy via C-H activation has been implemented for the synthesis of π-extended coumarins. This synthetic strategy provides a wide range of π-extended coumarins in moderate to good yields with good functional group compatibility. Photophysical properties of the synthesized π-extended coumarins have been evaluated, and some of them show interesting fluorescent properties. Three of the synthesized coumarins have been unambiguously established by a single-crystal XRD study.

Radiological risk estimation from indoor radon, thoron, and their progeny concentrations using nuclear track detectors.

In this paper, we report the results of seasonal variations of indoor radon and thoron concentrations, equilibrium factors for gas progeny, and radiological risks to dwellers in the hilly area of Guwahati City, Assam, India. Twin-cup dosemeters with LR-115 (II) nuclear track detectors were used in this study. The findings show that values vary significantly, with winter having the highest values and summer having the lowest, with spring and autumn having moderate values. In winter, radon concentrations range from 61.6 ± 11.2 Bq m-3 (Mud) to 115.3 ± 34.3 Bq m-3 (AT), with geometric mean values of 69.2 ± 13.8 Bq m-3 and 109.4 ± 27.9 Bq m-3, and in summer, they range from 21.1 ± 5.9 Bq m-3 (Mud) to 28.4 ± 8.3 Bq m-3 (AT), with geometric mean values of 22.7 ± 6.3 Bq m-3 and 26.1 ± 7.1 Bq m-3, whereas thoron concentrations range from 13.1 ± 5.1 Bq m-3 (Mud) to 58.8 ± 12.6 Bq m-3 (AT), with geometric mean values of 27.6 ± 7.0 Bq m-3 and 52.9 ± 10.1 Bq m-3 in winter, respectively, and in summer, from 8.8 ± 2.3 Bq m-3 (Mud) to 13.0 ± 5.5 Bq m-3 (Mud), with a geometric mean value of 1.87 ± 1.29 Bq m-3. Radon and thoron progeny levels are reported to vary from 4.1 ± 0.3 mWL (Mud) to 15.1 ± 4.3 mWL (AT) and 2.6 ± 0.9 mWL (Mud) to 14.3 ± 4.2 mWL (AT) in winter and from 1.5 ± 0.7 mWL (AT) to 3.0 ± 2.5 mWL (Mud) and 0.9 ± 0.3 mWL (AT) to 2.7 ± 0.5 mWL (Mud) in summer, respectively. The equilibrium factors for radon and its progeny have been reported to range from 0.23 ± 0.1 (Mud) to 0.51 ± 0.3 (AT) in winter, whereas from 0.23 ± 0.1 (AT) to 0.48 ± 0.4 (Mud) in summer, respectively. The equilibrium factors for thoron and its progeny have been estimated in the range of 0.02 ± 0.01 (Mud) to 0.09 ± 0.06 (AT) in winter, whereas 0.02 ± 0.02 (AT) to 0.07 ± 0.05 (Mud) in summer, respectively. The inhalation dose rates differed from house to house, having values in the range of 1.2 ± 0.2 mSv year-1 (Mud) to 4.6 ± 1.3 mSv year-1 (AT) in winter, whereas 0.5 ± 0.3 mSv year-1 (AT) to 0.9 ± 0.5 mSv year-1 (Mud) in summer, respectively. The effective doses (EDs) due to the exposure of radon and thoron in the study area have been found to range from 2.5 ± 0.3 mSv (Mud) to 9.1 ± 2.7 mSv (AT) in winter and 0.9 ± 0.4 mSv (AT) to 1.8 ± 1.3 mSv (Mud) in summer, respectively. The levels of radon and thoron in similar types of construction were found to be significantly different from one house to another. The estimated radon and thoron concentrations in the houses of that region during winter are found to be substantially higher than the global averages as reported by UNSCEAR.

Design, Synthesis, Biological Activity, and Structural Analysis of Novel Des-C-Ring and Aromatic-D-Ring Analogues of 1α,25-Dihydroxyvitamin D3.

The toxic calcemic effects of the natural hormone 1α,25-dihydroxyvitamin D3 (1,25D3, 1,25-dihydroxycholecalciferol) in the treatment of hyperproliferative diseases demand the development of highly active and noncalcemic vitamin D analogues. We report the development of two highly active and noncalcemic analogues of 1,25D3 that lack the C-ring and possess an m-phenylene ring that replaces the natural D-ring. The new analogues (3a, 3b) are characterized by an additional six-carbon hydroxylated side chain attached either to the aromatic nucleus or to the triene system. Both compounds were synthesized by the Pd-catalyzed tandem cyclization/cross coupling approach starting from alkyne 6 and diphenol 8. Key steps include a stereoselective Cu-assisted addition of a Grignard reagent to an aromatic alkyne and a Takai olefination of an aromatic aldehyde. The new compounds are noncalcemic and show transcriptional and antiproliferative activities similar to 1,25D3. Structural analysis revealed that they induce a large conformational rearrangement of the vitamin D receptor around helix 6.

Regioselective Friedel-Crafts Acylation Reaction Using Single Crystalline and Ultrathin Nanosheet Assembly of Scrutinyite-SnO2.

Peculiar physicochemical properties of two-dimensional (2D) nanomaterials have attracted research interest in developing new synthetic technology and exploring their potential applications in the field of catalysis. Moreover, ultrathin metal oxide nanosheets with atomic thickness exhibit abnormal surficial properties because of the unique 2D confinement effect. In this work, we present a facile and general approach for the synthesis of single crystalline and ultrathin 2D nanosheets assembly of scrutinyite-SnO2 through a simple solvothermal method. The structural and compositional characterization using X-ray diffraction (Rietveld refinement analysis), high-resolution transmission electron microscopy, atomic force microscopy, X-ray photoelectron spectroscopy, and so on reveal that the as-synthesized 2D nanosheets are ultrathin and single crystallized in the scrutinyite-SnO2 phase with high purity. The ultrathin SnO2 nanosheets show predominant growth in the [011] direction on the main surface having a thickness of ca. 1.3 nm. The SnO2 nanosheets are further employed for the regioselective Friedel-Crafts acylation to synthesize aromatic ketones that have potential significance in chemical industry as synthetic intermediates of pharmaceuticals and fine chemicals. A series of aromatic substrates acylated over the SnO2 nanosheets have afforded the corresponding aromatic ketones with up to 92% yield under solvent-free conditions. Comprehensive catalytic investigations display the SnO2 nanosheet assembly as a better catalytic material compared to the heterogeneous metal oxide catalysts used so far in the view of its activity and reusability in solvent-free reaction conditions.

Copper-Catalyzed Direct Syntheses of Phenoxypyrimidines from Chloropyrimidines and Arylboronic Acids: A Cascade Avenue and Unconventional Substrate Pairs.

This letter describes the first synthetic methodology for phenoxypyrimidines that avoids the direct use of phenols or their salts. In contrast to the general trend of delivering Suzuki-Miyaura cross-coupling products in reactions between aryl or alky halides and arylboronic acids, the substrate pairs used herein (chloropyrimidines and arylboronic acids) led to C-O bond formation under the reaction conditions. In total, 25 phenoxypyrimidines were successfully synthesized using the described protocol, 6 of which had a structural resemblance to etravirine.

A Versatile Pd-Catalyzed Alkyne Annulation Process for Benzo[a]carbazoles and their Anticancer Analogues.

A Pd-catalyzed, simple, and divergent approach for the direct synthesis of benzo[a]carbazoles from internal alkynes and N-tosyl-iodoindoles has been demonstrated. This methodology highlights the influences of reaction media and temperature for the synthesis of either N-protected or N-deprotected benzo[a]carbazoles. This cascade strategy provides a series of electronically different benzo[a]carbazoles with good yields. The synthesized benzo[a]carbazoles were evaluated for in vitro anticancer activity against human lung cancer A549 cells and human breast cancer MDA-MB-231 cells. Notably, two of the representative analogues displayed potent anticancer activity against both cancer cell lines.

Overview of coumarin-fused-coumarins: synthesis, photophysical properties and their applications.

Coumarin-fused-coumarins have attracted significant attention in the scientific world owing to their boundless applications in interdisciplinary areas. Various synthetic pathways have been developed to construct novel coumarin-fused-coumarin analogues by the fusion of modern methodologies with a classical Pechmann reaction or Knoevenagel condensation. Owing to their extended molecular framework, they possess interesting photophysical properties depending on the fused coumarin ring systems. This review highlights previously published reports on the synthetic strategies for structurally diverse coumarin-fused-coumarins. Furthermore, the scope of the synthesized biscoumarin-fused entities is described by highlighting their photophysical properties and applications.

Access to diverse organosulfur compounds via arynes: a comprehensive review on Kobayashi's aryne precursor.

Arynes are highly reactive transient intermediates having enormous applications in organic synthesis. In the last three decades aryne chemistry has shown incredible developments in carbon-carbon and carbon-heteroatom bond formation reactions. After the discovery of Kobayashi's protocol for the generation of aryne intermediates in a mild way, this field of chemistry witnessed rapid growth in synthetic organic chemistry. One aspect of development in this field involves C-S bond formation under mild conditions which has a tremendous scope for the synthesis of various important organosulfur building blocks.

Active and Recyclable Gold Metal Nanoparticles Catalyst Supported on Nitrogen-Doped Mesoporous Carbon for Chemoselective Hydrogenation of Cinnamaldehyde to Cinnamyl Alcohol.

Several supported gold metal catalysts with different Au nanoparticles sizes were prepared and evaluated for the chemoselective hydrogenation of cinnamaldehyde (CA) to cinnamyl alcohol (CAL). To investigate the structure-activity relationship, stability of catalyst, heterogeneity and recyclability, the structural characteristics of materials and Au catalysts (fresh and spent catalysts) were studied by employing variety of physico-chemical techniques. The interrelationship among Au nanoparticles size (nm) with turnover frequency (h-1 ) of Au catalysts has also been explored. Among the various Au catalysts tested, nitrogen-doped mesoporous carbon (NMC) supported Au catalyst having homogeneously dispersed (78.8%) Au nanoparticles (1.6 nm) synthesized by sol-immobilization method (Au-NMC-SI) demonstrated improved catalytic activity affording 78% CAL selectivity and 94.2% CA conversion without using any promoter. Moreover, Au-NMC-SI catalyst exhibited good recyclability and stability. The catalyst synthesis approach described in this investigation opens up a novel strategy for the design of highly efficient metal nano-catalysts supported on NMC materials.

Pd(II)-Catalyzed oxidative alkenylation of 4-hydroxycoumarin with maleimide via a C-H bond activation strategy.

A Pd(ii)-catalyzed oxidative alkenylation of 4-hydroxycoumarins with maleimides for the synthesis of 4-hydroxy-3-maleimidecoumarins has been described. This methodology proceeds via C-H activation and C(sp2)-C(sp2) bond formation providing a series of alkenylated Heck-type products.

A palladium-catalyzed cascade process for spirooxindole: an alternative way for the synthesis of spiro(indoline-3,2'-quinazolin)-2-ones.

A palladium-catalyzed cascade strategy has been developed for one-pot synthesis of functionalized spiro(indoline-3,2'-quinazolin)-2-one derivatives from readily available starting materials. The reaction proceeds via C-C and two C-N bond formations in a single reaction operation. This method offers an attractive pathway for the synthesis of a broad range of spiro(indoline-3,2'-quinazolin)-2-ones in good yields.

Oncology-Based Palliative Care Development: The Approach, Challenges, and Solutions From North-East Region of India, a Model for Low- and Middle-Income Countries.

BACKGROUND: Access to palliative care within healthcare systems of low- and middle-income countries (LMICs) has never been more pronounced than in current times. The Lancet Commission Report (2018) estimates that 80% of global serious health-related suffering (SHS), which demands access to palliative care for its relief, are in LMICs. Cancer is a major contributor to SHS and a rapidly growing burden in LMICs. Similar to many LMICs, cancer is a leading cause of death in India. The North-East Region (NER) of India has a high prevalence of cancer and paucity of services for cancer and palliative care. OBJECTIVES: To describe the strategies used to initiate and strengthen palliative care services integrated with the comprehensive cancer care initiatives in the state of Assam in NER. METHODS: After an initial assessment of the status of palliative care in the NER, a multipronged strategy was adopted that aligned with the WHO framework recommended for initiating palliative care services. A core team working with a government and private collaborative strategized and activated supportive policies, education, and training and improved access and availability to essential drugs, while implementing the components synchronously within the state. SIGNIFICANCE: This project demonstrates an informed regional adaptation of the WHO model. It highlights the strengths of integrating palliative care within cancer care program right from its inception. It emphasizes the sustainability of services activated across public healthcare systems, as compared with the donor- or champion-driven initiatives. The outcome of this project underlines the relevance of this model for LMIC regions with similar health systems and sociocultural and economic contexts.

o-Quinone Methides and o-Quinone Sulfides via Arynes: Synthesis of Ortho-Disubstituted Arenes and Heterocycles.

In recent decades, o-quinone methides and o-quinone sulfides have been extensively highlighted as reactive intermediates for the synthesis of diversely functionalized ortho-disubstituted arenes and heterocycles. Additionally, ortho-disubstituted arenes offer a constructive path for the synthesis of fused carbocycles, heterocycles, natural products, and drug candidates. In the lieu of that, this Synopsis highlights a comprehensive overview on the potential applications of in situ generated o-quinone methides and o-quinone sulfides for one-pot synthesis of ortho-disubstituted arenes and heterocycles via arynes.