Synthesis and preliminary biological evaluation for the anticancer activity of organochalcogen (S/se) tethered chrysin-based organometallic RuII(η6-p-cymene) complexes

Organochalcogen (S/Se) functionalized chrysin derivatives were synthesized and coordinated with Ru^II(η⁶-p-cymene) to efficiently form ruthenium-based chemotherapeutic drug entities [C₃₁H₃₅O₄SRuCl]; [C₃₁H₃₅O₄SeRuCl]; [C₃₃H₃₁O₄SRuCl]; and [C₃₃H₃₁O₄SeRuCl]. The complexes were thoroughly characterized by analytical and various spectroscopic techniques which include elemental analysis, UV–vis, IR, NMR (¹H, ¹³C, and ⁷⁷Se NMR), and HR-MS. The interaction studies of these Ru(II) complexes were carried out with CT DNA/HSA by employing UV–vis, fluorescence and circular dichroic techniques in view to examine their chemotherapeutic potential. The complexes demonstrated predominant binding toward CTDNA via electrostatic interaction while, the extent of binding was quantified by calculating intrinsic binding constant (K_b) and binding constant (K) values which revealed higher binding affinity of selenium-based chrysin complexes as compared to their thio-analogs, following the order [C₃₁H₃₅O₄SeRuCl]?>?[C₃₃H₃₁O₄SeRuCl]?>?[C₃₁H₃₅O₄SRuCl]?>?[C₃₃H₃₁O₄SRuCl]. Moreover, interaction of these complexes with human serum albumin (HSA) was also investigated which suggested spontaneous interactions of complexes with the protein by hydrogen bonding and van der Waals forces. To visualize the preferential binding sites and affinity of complexes with DNA and HSA molecular docking studies were performed. Additionally, in vitro anticancer activity of the complexes were evaluated by SRB assay on selected cancer cell lines viz., HeLa (cervical), MIA-PA-CA-2 (pancreatic), MCF-7 (breast), Hep-G2 (Hepatoma), and SK-OV-3 (ovarian) which exhibited the superior cytotoxicity of complex [C₃₁H₃₅O₄SeRuCl] as compared to other analogs on selective cancer phenotypes.

Communicated by Ramaswamy H. Sarma     

Synergistic Crystal and Interface Engineering for Efficient and Stable Perovskite Photovoltaics

The presence of bulk and surface defects in perovskite light harvesting materials limits the overall efficiency of perovskite solar cells (PSCs). The formation of such defects is suppressed by adding methylammonium chloride (MACl) as a crystallization aid to the precursor solution to realize high‐quality, large‐grain triple A‐cation perovskite films and that are combined with judicious engineering of the perovskite interface with the electron and hole selective contact materials. A planar SnO₂/TiO₂ double layer oxide is introduced to ascertain fast electron extraction and the surface of the perovskite facing the hole conductor is treated with iodine dissolved in isopropanol to passivate surface trap states resulting in a retardation of radiationless carrier recombination. A maximum solar to electric power conversion efficiency (PCE) of 21.65% and open circuit photovoltage (V_oc) of ≈1.24 V with only ≈370 mV loss in potential with respect to the band gap are achieved, by applying these modifications. Additionally, the defect healing enhances the operational stability of the devices that retain 96%, 90%, and 85% of their initial PCE values after 500 h under continuously light illumination at 20, 50, and 65 °C, respectively, demonstrating one of the most stable planar PSCs reported so far.     

Two‐photon excitation and direct emission from S2 state of U.S. Food and Drug Administration approved near‐infrared dye: Application of anti‐Kasha's rule for two‐photon fluorescence imaging

In recent years, two‐photon fluorescence microscopy has gained significant interest in bioimaging. It allows the visualization of deeply buried inhomogeneities in tissues. The near‐infrared (NIR) dyes are also used for deep tissue imaging. Indocyanine green (ICG) is the only U.S. Food and Drug Administration (FDA) approved exogenous contrast agent in the NIR region for clinical applications. However, despite its potential candidature, it had never been used as a two‐photon contrast agent for biomedical imaging applications. This letter provides an insight into the scope and application of the two‐photon excitation property of ICG to the second excited singlet (S₂) state in aqueous solution. Furthermore, in this work, we demonstrate the two‐photon cellular imaging application of ICG using direct fluorescence emission from S₂ state for the first time. Our results show that two‐photon excitation to S₂ state of ICG could be achieved with approximately 790 nm wavelength of femtosecond laser, which lies in well‐known “tissue‐optical window.” This property would enable light to penetrate much deeper in the turbid medium such as biological tissues. Thus, ICG could be used as the first FDA approved NIR exogenous contrast agent for two‐photon imaging. These findings can make remarkable influence on preclinical and clinical cell imaging.      

Plant diversity of the Kangchenjunga Landscape,Eastern Himalayas

The Kangchenjunga Landscape (KL) in the Eastern Himalayas is a transboundary complex shared by Bhutan, India, and Nepal. It forms a part of the ‘Himalayan Biodiversity Hotspot’ and is one of the biologically richest landscapes in the Eastern Himalayas. In this paper, we use secondary information to review and consolidate the knowledge on the flora of the KL. We reviewed 215 journal articles, analysed the history of publications on the flora of the KL, their publication pattern in terms of temporal and spatial distribution and key research areas. Our review shows that the landscape has a long history of botanical research that dates back to the 1840s and progressed remarkably after the 1980s. Most of the studies have been carried out in India, followed by Nepal and Bhutan. The majority of these have been vegetation surveys, followed by research on ethnobotanical aspects and Non-Timber Forest Products (NTFPs). This paper describes the forest types and characteristic species of the KL and details the species richness, diversity and dominant families of seed plants. A total of 5198 species of seed plants belonging to 1548 genera and 216 families have been recorded from the landscape, including 3860 dicots, 1315 monocots and 23 gymnosperms. Among families, Orchidaceae is the most diversely represented family in terms of species richness. This paper also draws attention to the threatened and endemic flora of the KL, including 44 species that are threatened at national and global level and 182 species that are endemic. Finally, the paper reviews the major challenges facing the KL, the conservation efforts and practices that are currently in place and recommends systematic and comprehensive floral surveys, particularly long-term data collection and monitoring and transboundary collaboration, to address the existing knowledge gaps on floral diversity of the KL.     

Small Peptide Binding Stiffens the Ubiquitin-like Protein SUMO1

Posttranslational modification by small ubiquitin-like modifiers (SUMOs), known as SUMOylation, is a key regulatory event in many eukaryotic cellular processes in which SUMOs interact with a large number of target proteins. SUMO binding motifs (SBMs) are small peptides derived from these target proteins that interact noncovalently with SUMOs and induce conformational changes. To determine the effect of SBMs on the mechanical properties of SUMO1 (the first member of the human SUMO family), we performed single-molecule force spectroscopy experiments on SUMO1/SBM complexes. The unfolding force of SUMO1 (at a pulling speed of 400 nm/s) increased from ∼130 pN to ∼170 pN upon binding to SBMs, indicating mechanical stabilization upon complexation. Pulling-speed-dependent experiments and Monte Carlo simulations measured a large decrease in distance to the unfolding transition state for SUMO1 upon SBM binding, which is by far the largest change measured for any ligand binding protein. The stiffness of SUMO1 (measured as a spring constant for the deformation response along the line joining the N- and C-termini) increased upon SBM binding from ∼1 N/m to ∼3.5 N/m. The relatively higher flexibility of ligand-free SUMO1 might play a role in accessing various conformations before binding to a target.     

Sulfide Oxidation by a Noncanonical Pathway in Red Blood Cells Generates Thiosulfate and Polysulfides

A cardioprotectant at low concentrations, H₂S is a toxin at high concentrations and inhibits cytochrome c oxidase. A conundrum in H₂S homeostasis is its fate in red blood cells (RBCs), which produce H₂S but lack the canonical mitochondrial sulfide oxidation pathway for its clearance. The sheer abundance of RBCs in circulation enhances the metabolic significance of their clearance strategy for H₂S, necessary to avoid systemic toxicity. In this study, we demonstrate that H₂S generation by RBCs is catalyzed by mercaptopyruvate sulfurtransferase. Furthermore, we have discovered the locus of sulfide oxidation in RBCs and describe a new role for an old protein, hemoglobin, which in the ferric or methemoglobin state binds H₂S and oxidizes it to a mixture of thiosulfate and hydropolysulfides. Our study reveals a previously undescribed route for the biogenesis of hydropolysulfides, which are increasingly considered important for H₂S-based signaling, but their origin in mammalian cells is unknown. An NADPH/flavoprotein oxidoreductase system restores polysulfide-carrying hemoglobin derivatives to ferrous hemoglobin, thus completing the methemoglobin-dependent sulfide oxidation cycle. Methemoglobin-dependent sulfide oxidation in mammals is complex and has similarities to chemistry reported for the dissolution of iron oxides in sulfidic waters and during bioleaching of metal sulfides. The catalytic oxidation of H₂S by hemoglobin explains how RBCs maintain low steady-state H₂S levels in circulation, and suggests that additional hemeproteins might be involved in sulfide homeostasis in other tissues.