Chemical and Redox Speciation of Uranyl with Three Environmentally Relevant Bifunctional Chelates: Multi-Technique Approach Combined with Theoretical Estimations.

Carbon and phosphorous are two primary elements common to the bio-geosphere and are omnipresent in both biotic and abiotic arenas. Phosphonate and carboxylate are considered as building blocks of glyphosate and humic substances and constituents of the cellular wall of bacteria and are the driving functionalities for most of the chemical interactions involving these two elements. Phosphonocarboxylates, a combination of both the functionalities in one moiety, are ideal models to dig deep into for understanding the chemical interactions of the two functional groups with metal ions. Phosphorous and carbon majorly exist as inorganic/organic phosphate and carboxylate, respectively, in the bio-geosphere. Aquatic contamination is a major concern for uranium, and the presence of complexing agents would alter the uranium concentrations in aquifers. Determination of solution thermodynamic parameters, speciation plots, redox patterns, Eh-pH diagrams, coordination structures, and molecular-level understanding by density functional theory calculations was carried out to interpret the uranyl (UO22+) interaction with three environmentally relevant phosphonocarboxylates, namely, phosphono-formic acid (PFA), phosphono-acetic acid (PAA), and phosphono-propanoic acid (PPA). UO22+ forms 1:1 complexes with the three phosphonocarboxylates in the monoprotonated form, having nearly the same stability, and the complexes [UO2(PFAH)], [UO2(PAAH)], and [UO2(PPAH)] involve chelate formation of five, six, and seven membered rings, respectively, through the participation of an oxygen each from the carboxylate and phosphonate, strengthened by an intra-molecular hydrogen bonding through the proton of the phosphonate moiety with uranyl oxygen. The complex formations are favored both enthalpically and entropically, with the latter being more contributive to the overall free energy of formation. The redox speciation showed an aqueous soluble complex formation over a wide pH range of 1-8. Electrospray ionization mass spectrometry and extended X-ray absorption fine structure established the coordination modes, which are further corroborated by density functional calculations. The knowledge gained from the present studies provide potential inputs in framing the cleanup, sequestering, microbial, and bio-remediation strategies for uranyl from aquatic environments.

Virtual screening of phytochemicals from Indian medicinal plants against the endonuclease domain of SFTS virus L polymerase.

Severe fever with thrombocytopenia syndrome virus (SFTSV) causes a highly infectious disease with reported mortality in the range 2.8% to 47%. The replication and transcription of the SFTSV genome is performed by L polymerase, which has both an RNA dependent RNA polymerase domain and an N-terminal endonuclease (endoN) domain. Due to its crucial role in the cap-snatching mechanism required for initiation of viral RNA transcription, the endoN domain is an ideal antiviral drug target. In this virtual screening study for the identification of potential inhibitors of the endoN domain of SFTSV L polymerase, we have used molecular docking and molecular dynamics (MD) simulation to explore the natural product space of 14 011 phytochemicals from Indian medicinal plants. After generating a heterogeneous ensemble of endoN domain structures reflecting conformational diversity of the corresponding active site using MD simulations, ensemble docking of the phytochemicals was performed against the endoN domain structures. Apart from the ligand binding energy from docking, our virtual screening workflow imposes additional filters such as drug-likeness, non-covalent interactions with key active site residues, toxicity and chemical similarity with other hits, to identify top 5 potential phytochemical inhibitors of endoN domain of SFTSV L polymerase. Further, the stability of the protein-ligand docked complexes for the top 5 potential inhibitors was analyzed using MD simulations. The potential phytochemical inhibitors, predicted in this study using contemporary computational methods, are expected to serve as lead molecules in future experimental studies towards development of antiviral drugs against SFTSV.

Effect of silicon application with mycorrhizal inoculation on Brassica juncea cultivated under water stress.

Brassica juncea L. is a significant member of the Brassicaceae family, also known as Indian mustard. Water is a limiting factor in the successful production of this crop. Here, we tested the effect of water shortage in B. juncea plants supplemented with or without the application of silicon and arbuscular mycorrhizal fungi in total 8 different treatments compared under open filed conditions using a randomised complete block design (RCBD). The treatments under control conditions were control (C, T1); C+Silicon (Si, T2); C+My (Mycorrhiza; T3); and C+Si+My (T4). In contrast, treatments under stress conditions were S (Stress; T5); S+Si (T6); S+My (T7) and S+Si+My (T8), respectively. In total, we evaluated 16 traits, including plant response to stress by evaluating peroxidase (POD), superoxide dismutase (SOD), and catalase (CAT) activity. The fresh weight (g) increased only 7.47 percent with mycorrhiza (C+My) and 22.39 percent with silicon (C+Si) but increased 291.08 percent with both mycorrhiza and silicon (C+Si+My). Using mycorrhiza (S+My) or silicon (S+Si) alone produced a significant increase of 53.16 percent and 55.84 percent in fresh weight, respectively, while using both mycorrhiza and silicon (S+Si+My) together produced a dramatic increase of 380.71 percent under stress conditions. Superoxidase dismutase concentration (Ug-1 FW) was found to be increased by 29.48 percent, 6.71 percent, and 22.63 percent after applying C+My, C+Si and C+Si+My, but treatment under stress revealed some contrasting trends, with an increase of 11.21 percent and 19.77 percent for S+My, S+Si+My, but a decrease of 13.15 percent for S+Si. Finally, in the presence of stress, carotenoid content (mg/g FW) increased by 58.06 percent, 54.83 percent, 183.87 percent with C+My, and 23.81 percent with S+My and S+Si+My, but decreased by 22.22 percent with S+Si. Silicon application proved to be more effective than AMF treatment with Rhizophagus irregularis, and the best results were obtained with the combination of Si and AMF. This work will help to suggest the measures to overcome the water stress in B. juncea.

Reversible modulation of circadian time with chronophotopharmacology.

The circadian clock controls daily rhythms of physiological processes. The presence of the clock mechanism throughout the body is hampering its local regulation by small molecules. A photoresponsive clock modulator would enable precise and reversible regulation of circadian rhythms using light as a bio-orthogonal external stimulus. Here we show, through judicious molecular design and state-of-the-art photopharmacological tools, the development of a visible light-responsive inhibitor of casein kinase I (CKI) that controls the period and phase of cellular and tissue circadian rhythms in a reversible manner. The dark isomer of photoswitchable inhibitor 9 exhibits almost identical affinity towards the CKIα and CKIδ isoforms, while upon irradiation it becomes more selective towards CKIδ, revealing the higher importance of CKIδ in the period regulation. Our studies enable long-term regulation of CKI activity in cells for multiple days and show the reversible modulation of circadian rhythms with a several hour period and phase change through chronophotopharmacology.

Aquatic interaction of uranium with two naturally ubiquitous pyrazine compounds: Speciation studies by experiment and theory.

The present studies interpret the speciation of uranyl (UO22+) with the most ubiquitous class of natural species named pyrazines in terms of stability, speciation and its identification, thermodynamics, spectral properties determined by a range of experimental techniques and further evidenced by theoretical insights. UO22+ forms ML and ML2 kind of species with a qualitative detection of ML3 species, while the ESI-MS identified the formation of all the complexes including ML3. Both the ligands act as bidentate chelators with a difference in ring size and coordinating atoms in the complex formed. The ML3 complexes involve the third ligand participation as monodentate via carboxylate only due to the restricted coordination number and space around the UO22+ ion to accommodate three ligand molecules in its primary coordination sphere. All the complexes are found to be endothermic and purely entropy driven formations. The complex formations showed redshift in the absorption spectra and the shift was further enhanced from ML to ML2 formation. The UO22+ ion redox properties are used to explore the redox potential and heterogeneous electron-transfer kinetic parameters as a function of pH and concentration of UO22+ in presence of pyrazine carboxylates. Interestingly, the cyclic voltammograms identified the ligands also as redox sensitive. The theoretical calculation gave inputs to understand the complex formation at the molecular level with major emphasis on geometry optimization, energetics, bonding parameters, molecular orbital diagrams and bond critical point analyses. The experimental observations in combination with theoretical addendum provided detailed knowledge on the interaction of UO22+ with pyrazine-2-carboxylate and pyrazine-2,3-dicarboxylates.

Determination of pesticide and phthalate residues in tea by QuEChERS method and their fate in processing.

In this study, the quick, easy, cheap, effective, rugged, and safe (QuEChERS) method was applied for the analysis of the multiclass pesticide residues of 12 organochlorines (OCs), 9 organophosphates (OPs), 11 synthetic pyrethroids (SPs), 4 herbicides, 6 phthalates in raw tea (loose tea, branded tea and herbal tea), and tea infusion in 4 different containers (glass cup, earthen cup, plastic bag and disposal cup). In loose tea and branded tea residues, malathion (0.257 and 0.118 mg kg-1), cypermethrin (0.065 and 0.030 mg kg-1), and fenvalerate (0.032 and 0.030 mg kg-1) were detected, respectively. In herbal tea, residues of only cypermethrin (0.053 mg kg-1) and fenvalerate (0.045 mg kg-1) were detected. Tea infusion samples contained in a plastic bag were found to be contaminated with only dibutyl phthalate (DBP) (0.038 mg kg-1). Disposable cup was found to be contaminated with DBP (0.026 mg kg-1) and diethyl phthalate (DEP) (0.004 mg kg-1). Further, to know the processing behavior of pesticides, the spiked raw tea was subjected to tea infusion at different brewing times (2, 5, 10 min). The analysis demonstrated that dimethoate, dichlorvos, and malathion had shown more than 10 % of translocation at 5 min of brewing time. Further brewing for 10 min revealed the reduction in concentration of pesticides. Leaching of phthalate residues from different plastic containers was also studied at 10, 30, and 60 min. DBP, benzyl butyl phthalate (BzBP), and di-2-(ethylhexyl) phthalate (DEHP) were leached in the tea infusion samples packed in plastic bags. On the other hand, in disposable cups, leaching of DBP, DEP, and dimethyl phthalate were found. The concentration of phthalate residues increased with retention time. Pesticide and phthalate contaminants were recorded at low quantities in few samples only.

Antifungal activity of bioactive triterpenoid saponin from the seeds of Cassia angustifolia.

A novel oleanen type triterpenoid glycoside has been isolated from butanolic seed extracts of Cassia angustifolia. Its structure was elucidated as 3-O-{beta-D-glucuronopyranosyl-(1 --> 4)-[beta-D-galactopyranosyl-(1 --> 2)]-beta-D-xylopyranosyl-(1 --> 3)-beta-D-glucopyranosyl}-2, 16alpha-dihydroxy-4, 20-hydroxy methyl olean-12-ene-28-oic acid on the basis of spectral evidence (i.e. FTIR, (1)H NMR, (13)C NMR and FAB-MS data). The isolated saponin was tested for its antifungal activity, where the maximum inhibition was found in Colletotrichium dematium.