Luminescence feature of new 3,6-di(thiazolidin-5-one-2-yl)-carbazole derivative: synthesis, photophysical properties, density functional theory studies, and crystal shape effect.

A new carbazole chromophore conjugated with substituted thiazolidine-4-one (CzPT) was synthesized by applying the Knoevenagel reaction between 3,6-diformyl-N-hexylcarbazole and ethyl 2-aceto-2-(5-oxo-3-phenylthiazolidin-2-ylidene)acetate. The chemical structure of the new derivative (CzPT) was elucidated by spectral studies. The CzPT absorption spectra in different solvents exhibited a red shift for λmax by increasing solvent polarity. Bands at 430-474 nm appeared and were attributed to intramolecular charge transfer with high π-π* characteristics. CzPT fluorescence spectra exhibited a red shift after increasing the solvent polarity. To understand the Stokes' shift ( ∆ ν ¯ ) behaviour of the CzPT derivative referring to the polarity of solvents, Lippert-Mataga and linear solvation-energy relationship (LSER) models were employed in which the LSER exhibited respectable results compared with Lippert-Mataga (r2 = 0.9707). Moreover, time-dependent density functional theory absorption spectra in hexane and dimethylformamide showed that λmax had a major contribution in the highest occupied molecular orbital to lowest unoccupied molecular orbital transition in both solvents. In addition, the reduced uniformity of crystal features may lead to dislocation or anomalous arrangement of crystals with irregular spacing, which automatically enhances the optical properties of such crystals.

Synthesis and Characterization of New Mixed-Ligand Complexes; Density Functional Theory, Hirshfeld, and In Silico Assays Strengthen the Bioactivity Performed In Vitro.

N'-Acetyl-2-cyanoacetohydrazide (H2L1) and 2-cyano-N-(6-ethoxybenzo thiazol-2-yl) acetamide (HL2) ligands were used to synthesize [Cr(OAc)(H2L1)(HL2)]·2(OAc) and [Mn(H2L1)(HL2)]·Cl2·2H2O as mixed ligand complexes. All new compounds were analyzed by analytical, spectral, and computational techniques to elucidate their chemical formulae. The bidentate nature was suggested for each coordinating ligand via ON donors. The electronic transitions recorded are attributing to 4A2g(F) → 4T2g(F)(υ2) and 4A2g(F) → 4T1g(F)(υ3) types in the octahedral Cr(III) complex, while 6A1 → 4T2(G) and 6A1 → 4T1(G) transitions are attributing to the tetrahedral Mn(II) complex. These complexes were optimized by the density functional theory method to verify the bonding mode which was suggested via N(3), O(8), N(9), and N(10) donors from the mixed-ligands. Hirshfeld crystal models were demonstrated for the two ligands to indicate the distance between the functional groups within the two ligands and supporting the exclusion of self-interaction in between. Finally, the biological activity of the two mixed ligand complexes was tested by in silico ways as well as in vitro ways for confirmation. Three advanced programs were applied to measure the magnitude of biological efficiency of the two complexes toward kinase enzyme (3nzs) and breast cancer proliferation (3hy3). All in silico data suggest the superiority of the Mn(II) complex. Moreover, the in vitro assays for the two complexes that measure their antioxidant and cytotoxic activity support the distinguished activity of the Mn(II) complex.

Experimental and Computational Exploration of Chitin, Pectin, and Amylopectin Polymers as Efficient Eco-Friendly Corrosion Inhibitors for Mild Steel in an Acidic Environment: Kinetic, Thermodynamic, and Mechanistic Aspects.

Herein, the inhibition impacts of chitin, pectin, and amylopectin as carbohydrate polymers on the corrosion of mild steel in 0.5 M HCl were researched utilizing various experimental and theoretical tools. The acquired outcomes showed that the inhibition efficiencies (% IEs) of the tested carbohydrate polymers were increased by raising their concentrations and these biopolymers acting as mixed-kind inhibitors with major anodic ones. The acquired % IEs values were reduced with rising temperature. The higher % IEs of the tested polymers were inferred via powerful adsorption of the polymeric molecules on the steel surface and such adsorption obeyed the Langmuir isotherm. The computed thermodynamic and kinetic quantities confirmed the mechanism of physical adsorption. The kinetics and mechanisms of corrosion and its protection by polymeric compounds were illuminated. The results obtained from all the techniques used confirmed that there was good agreement with each other, and that the % of IEs followed the sequence: chitin > amylopectin > pectin.

Microwave-assisted synthesis of gold nanoparticles supported on Mn3O4 catalyst for low temperature CO oxidation.

In the present work, Mn3O4 was prepared by various methods and successfully loaded with metallic Au nanoparticles reduced by hydrazine hydrate using microwave irradiation (MWI) method. The surface morphology and composition of the prepared samples were characterized with X-ray diffraction (XRD), N2 adsorption-desorption, temperature programmed reduction (H2-TPR), transmission electron microscope (TEM) and X-ray photoelectron spectroscopy (XPS). The experimental results showed that no significant changes in some textural and structural properties of the samples due to preparation method or Au nanoparticles deposition. While the surface composition and reducibility of the samples were greatly affected by preparation method and Au deposition. The CO oxidation reaction over the samples was selected as a model reaction to study the relation between surface properties of the samples and their catalytic performance. The results showed that a direct proportionality exists between the reducibility and the CO oxidation activity of catalysts. The kinetic study of the reaction showed that the reaction is first order. Moreover, the samples exhibited good stability in CO oxidation at 100% conversion for around 30 h under the reaction conditions.

An overview of viruses discovered over the last decades and drug development for the current pandemic.

Since the discovery of the yellow fever virus in 1901, thus far, two hundred nineteen viral species are recognized as human pathogens. Each year, the number of viruses causing infections in humans increases, triggering epidemics and pandemics, such as the current COVID-19 pandemic. Pointing to bats as the natural host, in 2019, a genome highly identical to a bat coronavirus (COVID-19) spread all over the world, and the World Health Organization (WHO) officially confirmed it as a pandemic. The virus mainly spreads through the respiratory tract, uses angiotensin-converting enzyme 2 (ACE2) as a receptor, and is characterized by symptoms of fever, cough, and fatigue. Antivirals and vaccines have provided improvements in some cases, but the discovery of a new and diverse variety of viruses with outbreaks has posed a challenge in timely treatments for medical scientists. Currently, few specific antiviral strategies are being used, and many of the effective antiviral drugs and reported active molecules are under vital exploration. In this review, with the details of viral diseases, we summarize the current attempts in drug development, epidemiology, and the latest treatments and scientific advancements to combat the COVID-19 epidemic. Moreover, we discuss ways to reduce epidemics and pandemics in the near future.

Novel Pyran-Linked Phthalazinone-Pyrazole Hybrids: Synthesis, Cytotoxicity Evaluation, Molecular Modeling, and Descriptor Studies.

A series of novel pyran-linked phthalazinone-pyrazole hybrids were designed and synthesized by a facile one-pot three-component reaction employing substituted phthalazinone, 1H-pyrazole-5-carbaldehyde, and active methylene compounds. Optimization studies led to the identification of L-proline and ethanol as efficient catalyst and solvent, respectively. This was followed by evaluation of anticancer activity against solid tumor cell lines of lung and cervical carcinoma that displayed IC50 values in the range of 9.8-41.6 µM. Molecular modeling studies were performed, and crucial interactions with the target protein were identified. The drug likeliness nature of the compounds and molecular descriptors such as molecular flexibility, complexity, and shape index were also calculated to understand the potential of the synthesized molecules to act as lead-like molecule upon further detailed biological investigations as well as 3D-QSAR studies.

Journey of anthraquinones as anticancer agents - a systematic review of recent literature.

Anthraquinones are privileged chemical scaffolds that have been used for centuries in various therapeutic applications. The anthraquinone moiety forms the core of various anticancer agents. However, the emergence of drug-resistant cancers warrants the development of new anticancer agents. The research endeavours towards new anthraquinone-based compounds are increasing rapidly in recent years. They are used as a core chemical template to achieve structural modifications, resulting in the development of new anthraquinone-based compounds as promising anticancer agents. Mechanistically, most of the anthraquinone-based compounds inhibit cancer progression by targeting essential cellular proteins. Herein, we review new anthraquinone analogues that have been developed in recent years as anticancer agents. This includes a systematic review of the recent literature (2005-2021) on anthraquinone-based compounds in cell-based models and key target proteins such as kinases, topoisomerases, telomerases, matrix metalloproteinases and G-quadruplexes involved in the viability of cancer cells. In addition to this, the developments in PEG-based delivery of anthraquinones and the toxicity aspects of anthraquinone derivatives are also discussed. The review dispenses a compact background knowledge to understanding anthraquinones for future research on the expansion of anticancer therapeutics.

Rational Design and Synthesis of Naphthalene Diimide Linked Bis-Naphthalimides as DNA Interactive Agents.

A molecular modeling assisted rational design and synthesis of naphthalene diimide linked bis-naphthalimides as potential DNA interactive agents is described. Chemical templates incorporating naphthalene diimide as a linker in bis-naphthalimide motif were subjected to molecular docking analysis at specific intercalation and telomeric DNA G-quadruplex sites. Excellent results were obtained, which were better than the standards. A short and convenient synthetic route was employed to access these hybrids experimentally, followed by evaluation of their ability to cause thermal denaturation of DNA and cytotoxic properties along with ADME predictions. The obtained results provided useful insights and two potential molecules were identified for further development.

New Imidazole-Based N-Phenylbenzamide Derivatives as Potential Anticancer Agents: Key Computational Insights.

An efficient atom-economical synthetic protocol to access new imidazole-based N-phenylbenzamide derivatives is described. A one-pot three-component reaction was utilized to provide a series of N-phenylbenzamide derivatives in a short reaction time (2-4 h) with an 80-85% yield. The cytotoxic evaluation revealed that derivatives 4e and 4f exhibited good activity, with IC50 values between 7.5 and 11.1 µM against the tested cancer cell lines. Computational studies revealed interesting insights: the docking of the active derivatives (4e and 4f) showed a higher affinity toward the target receptor protein than the control. Molecular dynamic simulations revealed that the active derivatives form stable complexes with the ABL1 kinase protein. Moreover, the ADME and drug-likeness of the derivatives reinforced the potential of the derivatives to be taken up for further development as anticancer agents.

A combined spectroscopic and ab initio study of the transmetalation of a polyphenol as a potential purification strategy for food additives.

Recently, metal exchange (transmetalation) techniques have become popular for the post-synthesis modification of metal organic complexes (MOCs). Here, we have explored the possibility of toxic metal ion (mercury (Hg)) exchange from a model polyphenol, curcumin, which is a very important food additive, using a much less toxic counterpart (copper). While the attachment of different metals on the polyphenol was confirmed using a picosecond resolved fluorescence technique, the surface plasmon resonance (SPR) band of the Ag nanoparticle (NP) was employed as a tool to detect uncoupled Hg ions in aqueous media. Furthermore, a microscopic understanding of the experimental observations was achieved through density functional theory (DFT) based theoretical studies. The presence of Cu ions in the vicinity of Hg-curcumin, upon ground state optimization, was observed to extrude most of the Hg from the curcumin complex and replace its position in the complex. The study may find relevance in the development of a purification strategy for food additives heavily contaminated with toxic metals.

Bioactive fluorenes. Part III: 2,7-dichloro-9H-fluorene-based thiazolidinone and azetidinone analogues as anticancer and antimicrobial against multidrug resistant strains agents.

BACKGROUND: Thiazoles, thiazolidinones and azetidinones are highly ranked amongst natural and synthetic heterocyclic derivatives due to their great pharmaceutical potential. RESULTS: New thiazolidinone and azetidinone class of bioactive agents based on 4-(2,7-dichloro-9H-fluoren-4-yl)thiazole moiety have been successfully synthesized. 4-(2,7-dichloro-9H-fluoren-4-yl)thiazol-2-amine was synthesized and allowed to react with various aryl/heteroaryl aldehydes to afford the corresponding Schiff base intermediates. The target thiazolidinone and azetidinone analogues have derived from Schiff bases by their reactions with thioglycolic acid and chloroacetyl chloride, respectively. The newly synthesized compounds were then evaluated for their antimicrobial activity against some multidrug resistant strains and examined for cytotoxic activity against normal lung fibroblast (WI-38), human lung carcinoma (A549), and human breast carcinoma (MDA-MB-231) cell lines to develop a novel class of fluorene-based bioactive agents. The mode of action and the binding interaction of the synthesized compound with the active sites of dihydrofolate reductase enzyme were well identified by fluorescence-activated cell sorting (FACS) analysis and molecular docking study. CONCLUSION: Some of the synthesized compounds showed remarkable activity against A-549 and MDA-MB-231 when compared to Taxol, which was used as a reference drug. 2,7-dichloro-9H-fluorene-based azetidinones are more efficient as antimicrobial and anticancer agents compared to dichloro-9H-fluorene-based thiazolidinones derivatives.

Combating Essential Metal Toxicity: Key Information from Optical Spectroscopy.

Chelation therapy is one of the most effective and widely accepted methods of treatment to reduce metal toxicity caused by an excess amount of essential metals. Essential minerals play an important role in maintaining healthy human physiology. However, the presence of an excess amount of such essential metals can cause cell injury, which finally leads to severe life-threatening diseases. Chelating complexes can efficiently capture the targeted metal and can easily be excreted from the body. Commonly utilized metal chelators have major side effects including long-term damage to some organs, which has pointed out the need of less harmful biocompatible chelating agents. In this work, we have investigated the iron chelating property of curcumin through various spectroscopic tools by synthesizing and characterizing the iron-curcumin (Fe-Cur) complex. We have also investigated whether the synthesized materials are able to retain their antioxidant activity after the chelation of a substantial amount of metal ion. Our study unravels the improved antioxidant activity of the synthesized chelate complex. We further demonstrate that the proposed complex generates no significant reactive oxygen species (ROS) under dark conditions, which makes it a promising candidate for chelation therapy of iron toxicity. Femtosecond-resolved fluorescence studies further provide insight into the mechanism of activity of the new complex where electron transfer from ligand to metal has been observed prominently. Thus, the Fe-Cur complex has a potential to act as a dual activity medicine for excretion of toxic metal ions via chelation and as a therapeutic agent of oxidative stress caused by the metal ion as well.

Nano-MOFs as targeted drug delivery agents to combat antibiotic-resistant bacterial infections.

The drug resistance of bacteria is a significant threat to human civilization while the action of antibiotics against drug-resistant bacteria is severely limited owing to the hydrophobic nature of drug molecules, which unquestionably inhibit its permanency for clinical applications. The antibacterial action of nanomaterials offers major modalities to combat drug resistance of bacteria. The current work reports the use of nano-metal-organic frameworks encapsulating drug molecules to enhance its antibacterial activity against model drug-resistant bacteria and biofilm of the bacteria. We have attached rifampicin (RF), a well-documented antituberculosis drug with tremendous pharmacological significance, into the pore surface of zeolitic imidazolate framework 8 (ZIF8) by a simple synthetic procedure. The synthesized ZIF8 has been characterized using the X-ray diffraction (XRD) method before and after drug encapsulation. The electron microscopic strategies such as scanning electron microscope and transmission electron microscope methods were performed to characterize the binding between ZIF8 and RF. We have also performed picosecond-resolved fluorescence spectroscopy to validate the formation of the ZIF8-RF nanohybrids (NHs). The drug release profile experiment demonstrates that ZIF8-RF depicts pH-responsive drug delivery and is ideal for targeting bacterial disease corresponding to its inherent acidic nature. Most remarkably, ZIF8-RF gives enhanced antibacterial activity against methicillin-resistant Staphylococcus aureus bacteria and also prompts entire damage of structurally robust bacterial biofilms. Overall, the present study depicts a detailed physical insight for manufactured antibiotic-encapsulated NHs presenting tremendous antimicrobial activity that can be beneficial for manifold practical applications.

Large scale validation of a new non-invasive and non-contact bilirubinometer in neonates with risk factors.

The study was aimed to evaluate the performance of a newly developed non-invasive and non-contact bilirubin measurement device (AJO-Neo) as an alternative to the conventional invasive biochemical method of total serum bilirubin (TSB) estimation in preterm and term neonates suffering from hyperbilirubinemia associated with risk factors, and/or undergoing phototherapy. The safety and efficacy of the device were assessed in 1968 neonates with gestational ages ranging from 28 to 41 weeks and suffering from incidences of hyperbilirubinemia. Linear regression analysis showed a good correlation between AJO-Neo and the conventional method of TSB (Pearson's coefficient, r = 0.79). The small bias (0.27 mg/dL) and limits of agreements (- 3.44 to 3.99 mg/dL) were within the range of clinical acceptance. The device was also precise in the measurement of bilirubin levels in all subgroups of the study. The receiver operator curve (ROC), that takes account of both sensitivity and specificity of a device showed high efficacy of the device (area under the curve, AUC = 0.83) in the detection of bilirubin. While monitoring the bilirubin level during phototherapy, the device indicated promising results showing good agreement with TSB. Specificities and sensitivities of the device indicated a much higher accuracy in neonates with associated risk factors for hyperbilirubinemia. Hence, the newly developed device (AJO-Neo) is reliable in measuring bilirubin level in preterm, and term neonates irrespective of gestational or postnatal age, sex, risk factors, feeding behavior or skin color.

Synthesis of stable ligand-free gold-palladium nanoparticles using a simple excess anion method.

We report a convenient excess anion modification and post-reduction step to the impregnation method which permits the reproducible preparation of supported bimetallic AuPd nanoparticles having a tight particle size distribution comparable to that found for sol-immobilization materials but without the complication of ligands adsorbed on the particle surface. The advantageous features of the modified impregnation materials compared to those made by conventional impregnation include a smaller average particle size, an optimized random alloy composition, and improved compositional uniformity from particle-to-particle resulting in higher activity and stability compared to the catalysts prepared using both conventional impregnation and sol immobilization methods. Detailed STEM combined with EDX analyses of individual particles have revealed that an increase in anion concentration increases the gold content of individual particles in the resultant catalyst, thus providing a method to control/tune the composition of the nanoalloy particles. The improved activity and stability characteristics of these new catalysts are demonstrated using (i) the direct synthesis of hydrogen peroxide and (ii) the solvent-free aerobic oxidation of benzyl alcohol as case studies.