Study of binding and denaturation dynamics of IgG and anti-IgG using dual color fluorescence correlation spectroscopy

In this article, we present a systematic study on IgG and Fab fragment of anti-IgG molecules using fluorescence auto- and cross-correlation spectroscopy to investigate their diffusion characteristics, binding kinetics, and the effect of small organic molecule, urea on their binding. Through our analysis, we found that the diffusion coefficient for IgG and Fab fragment of anti-IgG molecules were 37 ± 2 μm² s⁻¹ and 56 ± 2 μm² s⁻¹, respectively. From the binding kinetics study, the respective forward (k_a) and backward (k_d) reaction rates were (5.25 ± 0.25) × 10⁶ M⁻¹ s⁻¹ and 0.08 ± 0.005 s⁻¹, respectively and the corresponding dissociation binding constant (K_D) was 15 ± 2 nM. We also found that urea inhibits the binding of these molecules at 4 M concentration due to denaturation.     

A general and efficient synthesis of 3,6-diazabicyclo[3.2.1]octanes

A convenient and efficient synthesis of N⁶-substituted 3,6-diazabicyclo[3.2.1]octanes (6a-c) has been achieved starting from suitably substituted lactams, which were converted to nitroenamines followed by reductive cyclization to afford 3,6-diazabicyclo[3.2.1]octane-2-ones in good yields. These bicyclic lactams were then reduced to the corresponding 3,6-diazabicyclo[3.2.1]octanes and converted to the required N³,N⁶-disubstituted 3,6-diazabicyclo[3.2.1]octanes (7a-h), which were screened for α₁-adrenoceptors antagonistic activities.     

Effects of abiotic stressors on synthesis of the mycosporine-like amino acid shinorine in the Cyanobacterium Anabaena variabilis PCC 7937

In the present investigation we show that the cyanobacterium Anabaena variabilis PCC 7937 produces a single mycosporine-like amino acid (MAA), shinorine (retention time = 2.3 min and absorption maximum at 334 nm) when isolated and purified by HPLC. Although there was significant induction of MAA synthesis from its initial value under 395 or 320 nm cutoff filters, MAA induction was significantly more pronounced in samples covered with 295 nm cutoff filters after 72 h of exposure. Heat as a stress factor had no effect on MAA induction with or without UV radiation. In contrast, salt and ammonium treatment had synergistic effects with UV stress. MAA synthesis was also induced by salt and ammonium in a concentration-dependent manner without UV stress in samples covered with 395 nm cutoff filters. The results indicate that MAAs may have other functions in addition to photoprotection in this organism.     

Materials Science Challenges in Skin UV Protection: A Review

UV radiation is one of the critical environmental stress factors for human skin, which can trigger various problems such as pruritus, burning, erythema, premature skin aging and skin cancer. Hence, UV protection has become an indispensable daily routine and the use of topical sunscreen products is rapidly increasing. However, there are emerging concerns over the efficiency and safety of existing chemical and physical UV filters used in consumer products. Furthermore, there is no universally approved method for assessing sun protection efficiency regardless of the immediate end user need to develop safer sunscreen products that afford broad-spectrum photoprotection. It is evident that the current organic and inorganic UV filters have significant unfavorable impacts on human, environmental, and marine safety. Therefore, effective alternative UV filters should be established. This article comprehensively reviews the properties, safety, health and ecological concerns of various UV filters including TiO₂ and ZnO nanoparticles as well as the limitations of the testing protocols and guidelines provided by major regulatory bodies. The photoreactivity of UV filters used in sunscreen remains a major challenge, and it is crucial to develop new sunscreen ingredients, which not only protect the consumer, but also the environment.     

Structural and proton conductivity study of BaZr1-xRExO3-δ(RE = Dy,Sm) ceramics for intermediate temperature solid oxide fuel cell electrolyte

Journal of Solid State Electrochemistry - Proton-conducting BaZr1-xRExO3-δ (RE = Dy, Sm) (x = 0.05, 0.10, 0.15, 0.20) ceramics were synthesized via a conventional mixed...     

Diastereoselective one-pot Wittig olefination-Michael addition and olefin cross metathesis strategy for total synthesis of cytotoxic natural product (+)-varitriol and its higher analogues

A stereoselective route for the total synthesis of anticancer marine natural product (+)-varitriol (1) is detailed herein. The impressive biological activity and interesting structural features of natural (+)-varitriol fuelled us to undertake the synthesis of some higher analogues (1a-j) of this molecule. The key features of the synthetic strategy include one-pot Wittig olefination followed by a highly diastereoselective oxa-Michael addition to assemble stereochemically pure tetrasubstituted THF moiety of the natural varitriol and olefin cross metathesis to couple the aromatic part with tetrasubstituted THF moiety. The total synthesis of title natural product is efficient with 21.8% overall yield for 9 linear steps from D-ribose and thus facilitates the more scaled-up practical route for the synthesis of 1 and its analogues as well. The synthetic (+)-varitriol (1) and its analogues were screened for their cytotoxicity. The present synthetic approach paves the way for preparation of numerous analogues of the title natural product for drug development.     

Redox-switchable superhydrophobic silver composite

Unique packaging of Ag(2)O on the surface of polycrystalline AgCl allows fabrication of a new useful, superhydrophobic composite material. This pure inorganic material with surface porosity of submicrometer aperture size fabricates air pockets, which make the composite material superhydrophobic. The new material behaves like lotus leaves, butterfly wings, or water strider's leg in relation to superhydrophobicity. Visible light induces photoreduction of solid Ag(2)O surface layer and generates Ag(0), making the composite surface superhydrophilic. Reoxidation of Ag(0) on the composite surface gives back the hydrophobicity that represents the redox-switchable wetting property of the material.     

Ultrafast UPLC‐ESI‐MS and HPLC with monolithic column for determination of principal flavor compounds in vanilla pods

In this study, two novel chromatographic methods based on monolithic column high‐performance liquid chromatography (HPLC) and ultra‐performance liquid chromatography (UPLC) were developed for the ultrafast determination of principal flavor compounds namely vanillin, vanillic acid, p‐hydroxybenzoic acid, and p‐hydroxybenzaldehyde in ethanolic extracts of Vanilla planifolia pods. Good separation was achieved within 2.5 min using Chromolith RP18e column (100 mm×4.6 mm) for HPLC and Acquity BEH C‐18 (100 mm×2.1 mm, 1.7 μm) column for UPLC. Both methods were compared in terms of total analysis time, mobile phase consumption, sensitivity, and validation parameters like precision, accuracy, LOD, and LOQ. Further, system suitability test data including resolution, capacity factor, theoretical plates, and tailing factor was determined for both the methods by ten replicate injections. Monolithic column based HPLC gave better results for most of the selected parameters while UPLC was found to be more eco‐friendly with low mobile phase consumption and better sensitivity. Both methods may be used conveniently for the high throughput analysis of large number of samples in comparison to traditional particulate column.     

Rhenium(VII) oxide catalyzed heteroacylative ring-opening dimerization of tetrahydrofuran

Re(2)O(7), which is known primarily as a strong oxidant, was found to be a highly selective Lewis acid catalyst that affects the heteroacylative dimerization of THF at room temperature. This multicomponent reaction, which involves THF, trifluoroacetic anhydride (TFAA), and a carboxylic acid, produces a nonsymmetrical diester, RCO(2)(CH(2))(4)O(CH(2))(4)OCOCF(3), in high yields. The reaction is quite general with respect to the carboxylic acid but is highly selective for unsubstituted THF in preference to other cyclic ethers. It is also highly selective for TFAA in preference to other anhydrides. Isotope labeling experiments indicate that two of the five oxygen atoms in the product originate from THF; one comes from rhenium oxide, and the two carbonyl oxygens originate from the carboxylic acid and from TFAA. The catalytic cycle, which is proposed on the basis of these experiments, involves a multistep sequence of nucleophilic attacks, starting with an attack of a rhenium oxo ligand on a coordinated THF, then attack of the resultant alkoxide ligand on a second coordinated THF, nucleophilic addition of the resultant alkoxide ligand to the coordinated carboxylic acid (an intramolecular metal-oxygen bond metathesis), and, finally, electrophilic cleavage of the other coordinated alkoxide by TFAA to produce the nonsymmetrical diester. This synthetically useful reaction highlights the unique, frequently avoided Lewis acidity of transition-metal oxides.     

Virtual screening studies to design potent CDK2-cyclin A inhibitors

The cell division cycle is controlled by cyclin-dependent kinases (CDK), which consist of a catalytic subunit (CDK1-CDK8) and a regulatory subunit (cyclin A-H). Pharmacophore analysis indicates that the best inhibitor model consists of (1) two hydrogen bond acceptors, (2) one hydrogen bond donor, and (3) one hydrophobic feature. The HypoRefine pharmacophore model gave an enrichment factor of 1.31 and goodness of fit score of 0.76. Docking studies were carried out to explore the structural requirements for the CDK2-cyclin A inhibitors and to construct highly predictive models for the design of new inhibitors. Docking studies demonstrate the important role of hydrogen bond and hydrophobic interactions in determining the inhibitor-receptor binding affinity. The validated pharmacophore model is further used for retrieving the most active hits/lead from a virtual library of molecules. Subsequently, docking studies were performed on the hits, and novel series of potent leads were suggested based on the interaction energy between CDK2-cyclin A and the putative inhibitors.