Luminescent Cyclometalated Platinum(II) Complex Forms Emissive Intercalating Adducts with Double‐Stranded DNA and RNA: Differential Emissions and Anticancer Activities

Luminescent metallo‐intercalators are potent biosensors of nucleic acid structure and anticancer agents targeting DNAs. There are few examples of luminescent metallo‐intercalators which can simultaneously act as emission probes of nucleic acid structure and display promising anticancer activities. Herein, we describe a luminescent platinum(II) complex, [Pt(C^N^N)(C≡NtBu)]ClO₄ ( 1 a , HC^N^N= 6‐phenyl‐2,2′‐bipyridyl), that intercalates between the nucleobases of nucleic acids, accompanied by an increase in emission intensity and/or a significant change in the maximum emission wavelength. The changes in emission properties measured with double‐stranded RNA (dsRNA) are different from those with dsDNA used in the binding reactions. Complex 1 a exhibited potent anticancer activity towards cancer cells in vitro and inhibited tumor growth in a mouse model. The stabilization of the topoisomerase I–DNA complex with resulting DNA damage by 1 a is suggested to contribute to its anticancer activity.     

Solid Phase Extraction of Molybdenum on Modified Octadecyl Silica Sorbents in the Presence of Cationic Surfactants and on Silica-Based Anionic Exchanger and its Determination by Inductively Coupled Plasma Emission Spectrometry

Molybdenum was separated and preconcentrated as molybdate on microcolumns of octadecyl silica sorbents and silica-based strongly basic anion exchanger prior to its determination by ICP-AES. With octadecyl silica Separon SGX C18 and Separon SGX RPS, the retention of 0.01–0.4µg·mL^–1 Mo from 50–1000mL sample solutions was quantitative in the presence of the cationic surfactants carbethoxypentadecyltrimethylammonium bromide (Septonex^®), dodecylbenzyldimethylammonium bromide (Ajatin^®) or tetradecylbenzyldimethylammonium chloride (Zephyramine^®) at pH 6–8. 96% ethanol was the most suitable eluent of the molybdate/surfactant associate. For the strongly basic anion exchanger Separon SGX AX, the optimal conditions for sorption of 5–20µg Mo from 50–250mL sample solutions were at pH 2 in the presence of 0.05M ascorbic acid and ammonium citrate. 3M HNO₃ was a satisfactory eluent in this case. Organic solvents and excess of acids were removed by evaporation prior to the determination of Mo by ICP-AES in eluates. Both procedures can be used for the determination of ion-level molybdenum in waters.     

Exchange reactions in selectively excited Br2(B3Π)

Laser-controlled bimolecular isotopic exchange reactions in bromine leading to alterations in natural isotopic abundance ratios have been directly observed using laser-modulated molecular beams and mass analysis. Several instances of selective excitation and subsequent rapid isotope exchange are observed within the 7 GHz gain curve of the exciting 514.5 nm line of an argon-ion laser. These exchange processes are attributed to the direct photochemical participation of excited molecular states in the B³Π_ou⁺ system of Br₂.     

Reappraisal of neutron scattering results on micellar solutions of dodecylhexaoxyethylene glycol monoether (C12E6)

SANS data on micellar solutions of C₁₂E₆ as a function of temperature have been reanalysed using a cylinder growth model. Reasonably good fits to the experimental curves were obtained using only the rod length as an adjustable parameter. The effect of polydispersity in the micelle size on the scattering profile was also investigated. Our main conclusion is that SANS is not a sufficiently sensitive technique to allow a clear identification of the micelle structure(s) at elevated temperatures.     

Stress corrosion cracking of alloy C-22 and Ti Gr-12 using double-cantilever-beam technique

Susceptibility to stress corrosion cracking (SCC) of two candidate alloys for the inner container of the multi-barrier nuclear waste package was evaluated by using wedge-loaded precracked double-cantilever-beam (DCB) specimens in deaerated acidic brine (pH≈2.70) at 90°C. Materials tested included Alloy C-22 and Ti Grade-12. Duplicate samples of each material were loaded at different initial stress intensity factor (K_I) values ranging between 22 and 43 MPa√m. Both metallography and the compliance methods were used to determine the final crack length. The final stress intensity for SCC (K_f) was computed from the measured final wedge load and the average crack length. The results indicate that, in general, the final crack lengths measured by metallography and compliance agreed well with one another, thus, providing very similar K_f values. The alloy C-22 showed higher susceptibility to SCC than Ti Grade-12 in terms of the average crack growth. Fractographic evaluation by scanning electron microscopy (SEM) of broken DCB specimens revealed three distinct regions showing the characteristics of fatigue precrack, SCC, and fast fracture.     

Genistein: A Potential Natural Lead Molecule for New Drug Design and Development for Treating Memory Impairment

Genistein is a naturally occurring polyphenolic molecule in the isoflavones group which is well known for its neuroprotection. In this review, we summarize the efficacy of genistein in attenuating the effects of memory impairment (MI) in animals. Scopus, PubMed, and Web of Science databases were used to find the relevant articles and discuss the effects of genistein in the brain, including its pharmacokinetics, bioavailability, behavioral effects, and some of the potential mechanisms of action on memory in several animal models. The results of the preclinical studies highly suggested that genistein is highly effective in enhancing the cognitive performance of the MI animal models, specifically in the memory domain, including spatial, recognition, retention, and reference memories, through its ability to reduce oxidative stress and attenuate neuroinflammation. This review also highlighted challenges and opportunities to improve the drug delivery of genistein for treating MI. Along with that, the possible structural modifications and derivatives of genistein to improve its physicochemical and drug-likeness properties are also discussed. The outcomes of the review proved that genistein can enhance the cognitive performance and ameliorate MI in different preclinical studies, thus indicating its potential as a natural lead for the design and development of a novel neuroprotective drug.     

Chemistry,Biosynthesis and Pharmacology of Sarsasapogenin: A Potential Natural Steroid Molecule for New Drug Design,Development and Therapy

Sarsasapogenin is a natural steroidal sapogenin molecule obtained mainly from Anemarrhena asphodeloides Bunge. Among the various phytosteroids present, sarsasapogenin has emerged as a promising molecule due to the fact of its diverse pharmacological activities. In this review, the chemistry, biosynthesis and pharmacological potentials of sarsasapogenin are summarised. Between 1996 and the present, the relevant literature regarding sarsasapogenin was obtained from scientific databases including PubMed, ScienceDirect, Scopus, and Google Scholar. Overall, sarsasapogenin is a potent molecule with anti-inflammatory, anticancer, antidiabetic, anti-osteoclastogenic and neuroprotective activities. It is also a potential molecule in the treatment for precocious puberty. This review also discusses the metabolism, pharmacokinetics and possible structural modifications as well as obstacles and opportunities for sarsasapogenin to become a drug molecule in the near future. More comprehensive preclinical studies, clinical trials, drug delivery, formulations of effective doses in pharmacokinetics studies, evaluation of adverse effects and potential synergistic effects with other drugs need to be thoroughly investigated to make sarsasapogenin a potential molecule for future drug development.     

Antibacterial Potential of Bacopa monnieri (L.) Wettst. and Its Bioactive Molecules against Uropathogens—An In Silico Study to Identify Potential Lead Molecule(s) for the Development of New Drugs to Treat Urinary Tract Infections

Urinary tract infections (UTIs) are becoming more common, requiring extensive protection from antimicrobials. The global expansion of multi-drug resistance uropathogens in the past decade emphasizes the necessity of newer antibiotic treatments and prevention strategies for UTIs. Medicinal plants have wide therapeutic applications in both the prevention and management of many ailments. Bacopa monnieri is a medicinal plant that is found in the warmer and wetlands regions of the world. It has been used in Ayurvedic systems for centuries. The present study aimed to investigate the antibacterial potential of the extract of B. monnieri leaves and its bioactive molecules against UTIs that are caused by Klebsiella pneumoniae and Proteus mirabilis. This in vitro experimental study was conducted by an agar well diffusion method to evaluate the antimicrobial effect of 80% methanol, 96% ethanol, and aqueous extracts of B. monnieri leaves on uropathogens. Then, further screening of their phytochemicals was carried out using standard methods. To validate the bioactive molecules and the microbe interactions, AutoDock Vina software was used for molecular docking with the Klebsiella pneumoniae fosfomycin resistance protein (5WEW) and the Zn-dependent receptor-binding domain of Proteus mirabilis MR/P fimbrial adhesin MrpH (6Y4F). Toxicity prediction and drug likeness were predicted using ProTox-II and Molinspiration, respectively. A molecular dynamics (MD) simulation was carried out to study the protein ligand complexes. The methanolic leaves extract of B. monnieri revealed a 22.3 mm ± 0.6 mm to 25.0 mm ± 0.5 mm inhibition zone, while ethanolic extract seemed to produce 19.3 mm ± 0.8 mm to 23.0 mm ± 0.4 mm inhibition zones against K. pneumoniae with the use of increasing concentrations. In the case of P. mirabilis activity, the methanolic extracts showed a 21.0 mm ± 0.8 mm to 24.0 mm ± 0.6 mm zone of inhibition and the ethanol extract produced a 17.0 mm ± 0.9 mm to 23.0 mm ± 0.7 mm inhibition zone with increasing concentrations. Carbohydrates, flavonoids, saponin, phenolic, and terpenoid were common phytoconstituents identified in B. monnieri extracts. Oroxindin showed the best interactions with the binding energies with 5WEW and 6Y4F, −7.5 kcal/mol and −7.4 kcal/mol, respectively. Oroxindin, a bioactive molecule, followed Lipinski’s rule of five and exhibited stability in the MD simulation. The overall results suggest that Oroxindin from B. monnieri can be a potent inhibitor for the effective killing of K. pneumoniae and P. mirabilis. Additionally, its safety has been established, indicating its potential for future drug discovery and development in the treatment for UTIs.