Modified-Hydroxyapatite-Chitosan Hybrid Composite Interfacial Coating on 3D Polymeric Scaffolds for Bone Tissue Engineering

Three dimensional (3D) scaffolds have huge limitations due to their low porosity, mechanical strength, and lack of direct cell-bioactive drug contact. Whereas bisphosphonate drug has the ability to stimulate osteogenesis in osteoblasts and bone marrow mesenchymal stem cells (hMSC) which attracted its therapeutic use. However it is hard administration low bioavailability, and lack of site-specificity, limiting its usage. The proposed scaffold architecture allows cells to access the bioactive surface at their apex by interacting at the scaffold's interfacial layer. The interface of 3D polycaprolactone (PCL) scaffolds has been coated with alendronate-modified hydroxyapatite (MALD) enclosed in a chitosan matrix, to mimic the native environment and stupulate the through interaction of cells to bioactive layer. Where the mechanical strength will be provided by the skeleton of PCL. In the MALD composite's hydroxyapatite (HAP) component will govern alendronate (ALD) release behavior, and HAP presence will drive the increase in local calcium ion concentration increases hMSC proliferation and differentiation. In results, MALD show release of 86.28 ± 0.22. XPS and SEM investigation of the scaffold structure, shows inspiring particle deposition with chitosan over the interface. All scaffolds enhanced cell adhesion, proliferation, and osteocyte differentiation for over a week without in vitro cell toxicity with 3.03 ± 0.2 kPa mechanical strength.     

Development of sodium alginate-xanthan gum based nanocomposite scaffolds reinforced with cellulose nanocrystals and halloysite nanotubes

Sodium alginate (Alg) and xanthan gum (XG) based nanocomposite scaffolds reinforced with various amounts of cellulose nanocrystals (CNCs) and/or halloysite nanotubes (HNTs) were prepared by freeze-casting/drying method. In this study, the structure-property-performance relationship was mainly focused and analysed. Morphological analysis showed high porosity and pore-interconnectivity (pore channels) in all obtained scaffolds. Structural analysis demonstrates the good interfacial interactions and uniform dispersion of the CNCs and HNTs, involving partial orientation within the polymeric network. The water uptake capacity (from 14.73.7 ± 0.46 g/g to 11.34 ± 0.32 g/g) and porosity (from 91.7 ± 0.81% to 88.5 ± 0.64%) were reduced. The compressive strengths (in dry state from 91.1 ± 1.2 kPa to 114.4 ± 0.6 kPa and in wet state from 9.0 ± 0.8 kPa to 10.6 ± 0.8 kPa), thermal stability, cytocompatibility (MC3T3-E1 osteoblastic cells) of the nanocomposite scaffolds improved as compared to Alg and AlgX scaffolds without CNCs and/or HNTs. The obtained scaffolds may be appropriate as scaffolding material in bone tissue engineering.     

Hydrogel Nanocomposite as a Synthetic Intra-Ocular Lens Capable of Accommodation

A hydrogel nanocomposite was designed, synthesized, and evaluated for use as an auto-focusing intra-ocular lens. The hydrogel scaffold was composed of a monomer-free, thiol that contained polyacrylamide (5%), which was allowed to gel in the presence of nanoparticles at pH 7.4, 25°C. The nanoparticles consisted of a proteo-mimetic polyacrylamide nanogel (∼42 nm), bovine serum albumin (BSA) (∼6 nm), and hydrophilized silica (∼3 nm). The extent of nanoparticle loading increased with decreasing particle size. The elastic modulus increased with increasing loading of the proteo-mimetic nanogels and BSA, and it decreased with hydrophilized silica. In this investigation, the hydrogel that contained silica was the most promising class of nanocomposite hydrogels with properties comparable to that of a young porcine lens. A nanocomposite that consisted of 10% hydrogel scaffold and 24% hydrophilized silica (elastic [E] modulus of ∼1.0 kPa and refractive index [RI] of 1.42) was injected into a pre-evacuated porcine lens capsular bag. The composite lens was evaluated in a custom-designed four-arm radial stretcher, and its force-time spectrum was characterized by time constants of 60 ± 8.9 and 800 ± 32 ms. These results were comparable to a young porcine lens (E Modulus of 1.2 kPa; RI of 1.4105; time constants of 48.3 ± 0.58 and 668 ± 24.6 ms, respectively)     

Light-Based 3D Printing of Gelatin-Based Biomaterial Inks to Create a Physiologically Relevant In Vitro Fish Intestinal Model

To provide prominent accessibility of fishmeal to the European population, the currently available, time- and cost-extensive feeding trials, which evaluate fish feed, should be replaced. The current paper reports on the development of a novel 3D culture platform, mimicking the microenvironment of the intestinal mucosa in vitro. The key requirements of the model include sufficient permeability for nutrients and medium-size marker molecules (equilibrium within 24 h), suitable mechanical properties (G' < 10 kPa), and close morphological similarity to the intestinal architecture. To enable processability with light-based 3D printing, a gelatin-methacryloyl-aminoethyl-methacrylate-based biomaterial ink is developed and combined with Tween 20 as porogen to ensure sufficient permeability. To assess the permeability properties of the hydrogels, a static diffusion setup is utilized, indicating that the hydrogel constructs are permeable for a medium size marker molecule (FITC-dextran 4 kg mol⁻¹). Moreover, the mechanical evaluation through rheology evidence a physiologically relevant scaffold stiffness (G' = 4.83 ± 0.78 kPa). Digital light processing-based 3D printing of porogen-containing hydrogels results in the creation of constructs exhibiting a physiologically relevant microarchitecture as evidenced through cryo-scanning electron microscopy. Finally, the combination of the scaffolds with a novel rainbow trout (Oncorhynchus mykiss) intestinal epithelial cell line (RTdi-MI) evidence scaffold biocompatibility.     

Developing a Novel Platelet-Rich Plasma-Laden Bioadhesive Hydrogel Contact Lens for the Treatment of Ocular Surface Chemical Injuries

Permanent injury to corneal limbal stem cells after ocular surface chemical and thermal injuries is a major cause of corneal blindness. In this study, a PRP-laden GelMA hydrogel contact lens is manufactured which is aimed to support the limbal niche after ocular surface insults thereby preventing limbal stem cell failure. GelMA with varying platelet-rich plasma (PRP) concentrations (5%, 10%, and 20%) is photopolymerized using a visible light crosslinking system followed by characterizations of mechanical properties, growth factor release, enzymatic degradation, and in vitro cytotoxicity. The addition of 10% PRP into 10% GelMA hydrogel precursor solution results in the highest tensile and compressive modulus (38 and 110 kPa, respectively) and burst pressure (251±37.66 mmHg). Degradation time varies according to the concentration of the collagenase enzyme tested (0, 2.5, 5, and 40 µg/mL) and is most prolonged with 20% PRP. EGF and TGF-β release profiles suggest an initial burst release followed by sustained release, most consistent in the 10% PRP sample. Although cell viability decreases on day 1, rapid recovery is observed and is approximately 120% after day 21. PRP-laden GelMA in the form of a contact lens may be a promising biomaterial-based treatment approach for the maintenance of limbal epithelial stem cells after ocular surface insults.     

Effect of the Maillard reaction on properties of casein and casein films

The use of biodegradable natural polymers has increased due to the over-solid packaging waste. In this study, a chemical modification of the casein molecule was performed by Maillard reaction, and the modified polymer was evaluated by polyacrylamide gel electrophoresis (PAGE), thermogravimetry/derivative thermogravimetry (TG/DTG), FT-IR, and ¹H-NMR spectroscopy. Subsequently, films based on the modified casein were obtained and characterized by mechanical analysis, water vapor transmission, and erosion behavior. The PAGE results suggested an increase of molecular mass of the modified polymer, and FT-IR spectroscopy data indicated inclusion of C–OH groups into this molecule. The TG/DTG curves of modified casein presented a different thermal decomposition profile compared to the individual compounds. Mechanical tests showed that the chemical modification of the casein molecules provided higher elongation rates (45.5%) to the films, suggesting higher plasticity, than the original molecules (13.4%). The modified casein films presented higher permeability (0.505 ± 0.006 μg/h mm³) than the original polymer (0.387 ± 0.006 μg/h mm³) films at 90% relative humidity (RH). In pH 1.2, modified casein films presented higher erosion rates (32.690 ± 0.692%) than casein films (19.910 ± 2.083%) after 8 h, suggesting an increased sensibility for erosion of the modified casein films in acid environment. In water (pH 7.0), the films erosion profiles were similar. Those findings indicate that the modification of molecule by Maillard reaction provided films more plastic, hydrophilic, and sensitive to erosion in acid environment, suggesting that a new polymer with changed properties was founded.     

Dynamic elastomers based on bio-derived crosslinker

Petroleum-derived monomers are the most common building blocks for ester-based thermosets. Bio-derived thermoset elastomers are becoming viable alternatives to conventional thermosets. Herein, we developed a biobased vitrimer-type thermoset elastomers using abundant and sustainable raspberry ketone as feedstock. We utilize raspberry ketone to create building blocks for dynamic oxime chemistry and crosslinked these through free radical polymerization with poly(ethylene glycol) methyl ether methacrylate as a comonomer. In contrast to other dynamic networks based on ester bonds, which need catalysts, this is undesirable since catalyst deactivation or leaching lowers its effect over time and may impair reuse. This network incorporates catalyst-free bond exchange reactions in catalyst-dependent polyester networks by substituting oxime-esters for typical ester linkages. The elastomer exhibits stress relaxation, a low glass transition temperature (T_g) (−55 to −40.2°C) and tensile strength up to 5.2 ± 3.0 kPa. Furthermore, the dynamic oxime transesterification exchange mechanism allows elastomers to be reprocessed using a hot press at 160°C and 8 × 10³ kPa pressure. After reprocessing, the tensile strength of elastomers can be recovered up to 78.1 ± 10.9%. This work integrates the principles of catalyst-free dynamic exchange process and mechanical recycling coupled with biobased components to provide a rational solution towards conventional elastomers. In the future, these elastomers can be exploited for the development of hydrogels, recyclable elastomers, and commodity plastics.     

Microtopography based on inverse opal structures regulates the behavior of bone marrow‐derived mesenchymal stem cells

Physical cues from the extracellular microenvironment play an important role in regulating cell behavior, such as adhesion, migration, and differentiation. Many studies have shown that different physical parameters (eg, stiffness and topography) could modulate the in vitro differentiation of mesenchymal stem cells (MSCs), which had multilineage differentiation potential and could be easily isolated from various tissues such as bone marrow, adipose tissue, and the umbilical cord. However, the underlying mechanism of the topographical influence on MSCs and the detailed cell‐substrate interaction remain unclear. Here, we present oriented elliptical inverse opal structures for regulating the morphology and alignment of bone marrow‐derived MSCs. The inverse opal structures were made through a convenient bottom‐up approach of self‐assembly, which is facile and cost effective. MSCs cultured on the oriented structures were highly aligned and extended highly oriented thick lamellipodia. Moreover, the oriented substrates cracked along the lateral boundary of the cells, suggesting that a strong cell‐substrate interaction was induced by the response of MSCs to the oriented topography. These features of the oriented elliptical topography indicated their promising value in stem cell research and tissue engineering.     

A simple route to interpenetrating network hydrogel with high mechanical strength

A simple two-step method was introduced to improve the hydrogel mechanical strength by forming an interpenetrating network (IPN). For this purpose, we synthesized polyacrylate/polyacrylate (PAC/PAC), polyacrylate/polyacrylamide (PAC/PAM), polyacrylamide/polyacrylamide (PAM/PAM) and polyacrylamide/poly(vinyl alcohol) (PAM/PVA) IPN hydrogels. The PAC/PAC IPN and PAC/PAM IPN hydrogels showed compressive strength of 70 and 160 kPa, respectively. For the PAM/PAM IPN and PAM/PVA IPN hydrogels, they exhibited excellent tensile strength of 1.2 and 2.8 MPa, and elongations at break of 1750% and 3300%, respectively. A strain relaxation was also observed in the case of PAM series IPN hydrogels. From FTIR, TGA and SEM measurements, we confirmed that physical entanglement, hydrogen bonds and chemical crosslinking played major roles in improving hydrogel strength and toughening. The two-step technique contributes to the understanding of ideal networks, provides a universal strategy for designing high mechanical strength hydrogels, and opening up the biomedical application of hydrogels.     

Polarity guided extraction,HPLC based phytochemical quantification,and multimode biological evaluation of Otostegia limbata (Benth.) Boiss

Purpose of studyOtostegia limbata (Benth.) Boiss. (Family: Lamiacae) is an important underexplored ethnomedicinal plant that has been used as antinflammatory, anticancer and antibacterial herbal remedy previously. The present work was aimed to evaluate the antioxidant, antimicrobial, antileishmanial, and anticancer prospective of O. limbata stem and leaf extracts.ResultsThe highest amount of phenolic and flavonoid content was obtained in the methanol-acetone and methanol stem extracts i.e., 53.29 ± 1.33 and 28.64 ± 1.16, respectively with highest DPPH scavenging in MeH stem extract (IC₅₀ = 34.5 ± 1.34 μg/ml). Significant amount of catechin, gallic acid, apigenin and rutin was quantified. A moderate antibacterial and substantial antifungal activity was observed. Cytotoxicity against brine shrimps categorized 21% of stem (3 out of 14 extracts) and 57% (8 out of 14 extracts) of leaf extracts as potent. Substantial cytotoxicity against THP-1 cell line (IC₅₀ = 3.46 ± 0.25 μg/ml) and Leishmania (IC₅₀ = 1.50 ± 0.23 μg/ml) was exhibited by methanol-distilled water leaf extract while noteworthy antiproliferative activity against Hep-G2 (IC₅₀ = 0.44 ± 0.45 μg/ml) was manifested by n-hexane stem extract. Absence of hemolysis in normal RBCs signified plant’s selective cytotoxicity. Methanol-distilled water and chloroform stem extracts displayed prominent protein kinase inhibition and antidiabetic potential of plant.ConclusionThe results of present study recommend O. limbata as a potential source of antifungal, antileishmanial, anticancer, and α-amylase inhibitory agents.     

Generation and characterization of integration-free induced pluripotent stem cells from patients with autoimmune disease

Autoimmune diseases (AIDs), a heterogeneous group of immune-mediated disorders, are a major and growing health problem. Although AIDs are currently treated primarily with anti-inflammatory and immunosuppressive drugs, the use of stem cell transplantation in patients with AIDs is becoming increasingly common. However, stem cell transplantation therapy has limitations, including a shortage of available stem cells and immune rejection of cells from nonautologous sources. Induced pluripotent stem cell (iPSC) technology, which allows the generation of patient-specific pluripotent stem cells, could offer an alternative source for clinical applications of stem cell therapies in AID patients. We used nonintegrating oriP/EBNA-1-based episomal vectors to reprogram dermal fibroblasts from patients with AIDs such as ankylosing spondylitis (AS), Sjögren''s syndrome (SS) and systemic lupus erythematosus (SLE). The pluripotency and multilineage differentiation capacity of each patient-specific iPSC line was validated. The safety of these iPSCs for use in stem cell transplantation is indicated by the fact that all AID-specific iPSCs are integrated transgene free. Finally, all AID-specific iPSCs derived in this study could be differentiated into cells of hematopoietic and mesenchymal lineages in vitro as shown by flow cytometric analysis and induction of terminal differentiation potential. Our results demonstrate the successful generation of integration-free iPSCs from patients with AS, SS and SLE. These findings support the possibility of using iPSC technology in autologous and allogeneic cell replacement therapy for various AIDs, including AS, SS and SLE.     

The influence of dielectric layer on the thermal boundary resistance of GaN-on-diamond substrate

The cooling behavior of GaN-on-diamond substrate can be enhanced by reducing the thermal boundary resistance (TBR), which is mainly determined by the nature of interlayer. Although SiN film is considered as the primary candidate of dielectric layer, it is still needed to be optimized. In order to facilitate the understanding of the influence of dielectric layer on the TBR of GaN-on-Diamond substrate, aluminum nitride (AlN), and silicon nitride (SiN) film were compared systematically, both of which are 100 nm. The time-domain thermoreflectance (TDTR) measurements, adhesion evaluation, and microstructural analysis methods were adopted to analyse these two interlayers. The results show the TBR of SiN interlayer is as low as 38.5 ± 2.4 m²K GW⁻¹, comparing with the value of 56.4 ± 5.5 m²K GW⁻¹ for AlN interlayer. The difference of TBR between these two interlayers is elucidated by the diamond nucleation density, and the adhesion between the diamond film and GaN substrate, both of which are affected by the surface charge and chemical groups of the dielectric layer.     

Thermodynamic properties of CO2 absorption in hydroxyl ammonium ionic liquids at pressures of (100–1600) kPa

Solubility of CO₂ in six hydroxyl ammonium ionic liquids 2-hydroxyethanaminium acetate [hea], bis(2-hydroxyethyl)ammonium acetate [bheaa], 2-hydroxy-N-(2-hydroxyethyl)-N-methylethanaminium acetate [hhemea], 2-hydroxyethanaminium lactate [hel], bis(2-hydroxyethyl)ammonium lactate [bheal], 2-hydroxy-N-(2-hydroxyethyl)-N-methylethanaminium lactate [hhemel] at temperatures (298.15, 313.15, and 328.16) K and pressures ranging from (100 to 1600) kPa was determined. From the experimental solubility data, the Henry’s constant of CO₂ for each hydroxyl ammonium ionic liquids was estimated and reported as a function of temperature. Furthermore, enthalpy and entropy of absorption were obtained from estimated Henry’s constant. The results showed that the solubility increase with increasing pressure and decrease with increasing temperature and the solubility of CO₂ in these six hydroxyl ammonium ionic liquids was in sequence: [hea] > [bheaa] > [hel] > [bheal] > [hhemel] > [hhemea].     

Drug‐Loaded Elastin‐Like Polypeptide–Collagen Hydrogels with High Modulus for Bone Tissue Engineering

Emphasizing the role of hydrogel stiffness and cellular differentiation, this study develops collagen and elastin‐like polypeptide (ELP)–based bone regenerative hydrogels loaded with recombinant human bone morphogenetic protein‐2 (rhBMP‐2) and doxycycline with mechanical properties suitable for osteogenesis. The drug‐incorporated collagen–ELP hydrogels has significantly higher modulus of 35 ± 5 kPa compared to collagen‐only hydrogels. Doxycycline shows a bi‐phasic release with an initial burst release followed by a gradual release, while rhBMP‐2 exhibits a nearly linear release profile for all hydrogels. The released doxycycline shows anti‐microbial activity against Pseudomonas aeruginosa, Streptococcus sanguinis, and Escherichia coli. Microscopic observation of the hydrogels reveals their interconnected, macroporous, 3D open architecture with pore diameters between 160 and 400 µm. This architecture supports human adipose–derived stem cell attachment and proliferation from initial days of cell seeding, forming a thick cellular sheath by day 21. Interestingly, in collagen and collagen–ELP hydrogels, cell morphology is elongated with stretched slender lamellipodial formation, while cells assemble as spheroidal aggregates in crosslinked as well as drug‐loaded hydrogels. Osteogenic markers, alkaline phosphatase and osteocalcin, are expressed maximally for drug‐loaded hydrogels compared to those without drugs. The drug‐loaded collagen–ELP hydrogels are thus promising for combating bacterial infection and promoting guided bone regeneration.     

Load‐bearing biodegradable polycaprolactone‐poly (lactic‐co‐glycolic acid)‐ beta tri‐calcium phosphate scaffolds for bone tissue regeneration

A biodegradable scaffold with tissue ingrowth and load‐bearing capabilities is required to accelerate the healing of bone defects. However, it is difficult to maintain the mechanical properties as well as biodegradability and porosity (necessary for bone ingrowth) at the same time. Therefore, in the present study, polycaprolactone (PCL) and poly (lactic‐co‐glycolic acid) (PLGA5050) were mixed in varying ratio and incorporated with 20 wt.% beta tri‐calcium phosphate (βTCP). The mixture was shaped under pressure into originally nonporous cylindrical constructs. It is envisioned that the fabricated constructs will develop porosity with the time‐dependent biodegradation of the polymer blend. The mechanical properties will be sustained since the decrease in mechanical properties associated with the dissolution of the PLGA, and the formation of the porous structure will be compensated with the new bone formation and ingrowth. To prove the hypothesis, we have systematically studied the effects of samples composition on the time‐dependent dissolution behavior, pore formation, and mechanical properties of the engineered samples, in vitro. The highest initial (of as‐prepared samples) values of the yield strength (0.021 ± 0.002 GPa) and the Young's modulus (0.829 ± 0.096 GPa) were exhibited by the samples containing 75 wt.% of PLGA. Increase of the PLGA concentration from 25 to 75 wt.% increased the rate of biodegradation by a factor of 3 upon 2 weeks in phosphate buffered saline (1 × PBS). The overall porosity and the pore sizes increased with the dissolution time indicating that the formation of in situ pores can indeed enable the migration of cells followed by vascularization and bone growth.     

The calorimetric study of some guanidine derivatives involved in living bodies nitrogen metabolism

The energies of combustion of creatine (anhydrous and monohydrate), creatinine, and arginine were measured in a static bomb adiabatic calorimeter, in pure oxygen at 3,040 kPa. The derived standard enthalpies of formation in solid state of the above-mentioned compounds are, respectively, −520.4 ± 4.3, −809.7 ± 1.3, −204.2 ± 7.0, and −634.8 ± 2.3 kJ mol⁻¹ . The data of enthalpy of formation are compared with literature values and with estimated values by means of group additivity. The dehydration of creatine monohydrate and the processes occurring in the three guanidine derivatives at temperatures exceeding 200 °C were investigated by means of DSC.     

Antibacterial,Adhesive, and Conductive Hydrogel for Diabetic Wound Healing

Diabetic mellitus is one of the leading causes of chronic wounds and remains a challenging issue to be resolved. Herein, a hydrogel with conformal tissue adhesivity, skin-like conductivity, robust mechanical characteristics, as well as active antibacterial function is developed. In this hydrogel, silver nanoparticles decorated polypyrrole nanotubes (AgPPy) and cobalt ions (Co²⁺) are introduced into an in situ polymerized poly(acrylic acid) (PAA) and branched poly(ethylenimine) (PEI) network (PPCA hydrogel). The PPCA hydrogel provides active antibacterial function through synergic effects from protonated PEI and AgPPy nanotubes, with a tissue-like mechanical property (≈16.8 ± 4.5 kPa) and skin-like electrical conductivity (≈0.048 S m⁻¹). The tensile and shear adhesive strength (≈15.88 and ≈12.76 kPa, respectively) of the PPCA hydrogel is about two- to threefold better than that of fibrin glue. In vitro studies show the PPCA hydrogel is highly effective against both gram-positive and gram-negative bacteria. In vivo results demonstrate that the PPCA hydrogel promotes diabetic wounds with accelerated healing, with notable inflammatory reduction and prominent angiogenesis regeneration. These results suggest the PPCA hydrogel provide a promising approach to promote diabetic wound healing.     

Alternative biofuels

This study presents the experimental results for the dimethyl ether (DME) + propane system obtained using the Burnett method. The apparatus was calibrated using helium. PVTx measurements were taken for four isotherms (344, 354, 364, and 375 K), performing 16 Burnett expansions in pressures ranging from about 3,000 to 70 kPa. The second and third virial coefficients were derived from experimental results. The experimental uncertainty in the second and third virial coefficients was estimated to be within ±5 cm³/mol and ±1,000 cm⁶/mol², respectively.     

Kinetic and mechanistic studies on the reaction of thiosemicarbazide with [(H<Subscript>2</Subscript>O)(tap)<Subscript>2</Subscript>RuORu(tap)<Subscript>2</Subscript>(H<Subscript>2</Subscript>O)]<Superscript>2+</Superscript> {tap = 2-(m-tolylazo)pyridine}

The interaction of thiosemicarbazide with the title complex has been studied spectrophotometrically in aqueous medium as a function of [complex], [thiosemicarbazide], pH and temperature at constant ionic strength. At pH 7.4, the reaction shows two distinct paths; both of which are [thiosemicarbazide] dependent. A parallel reaction scheme fits well with the experimental findings. An associative interchange mechanism is proposed for both the paths; the activation parameters calculated from Eyring plots are ΔH₁^≠ = 14.2 ± 0.8 kJ mol⁻¹, ΔS₁^≠ = −241 ± 2 JK⁻¹ mol⁻¹, ΔH₂^≠ = 30.8 ± 1.4 kJ mol⁻¹ and ΔS₂^≠ = −236 ± 4 JK⁻¹ mol⁻¹. From the temperature dependence of the outer sphere association complex equilibrium constants, the thermodynamic parameters calculated are ΔH₁^° = 34.25 ± 1.9 kJ mol⁻¹, ΔS₁^° = 146 ± 6 J K⁻¹ mol⁻¹ and ΔH₂^° = 9.4 ± 1.1 kJ mol⁻¹, ΔS₂^° = 71 ± 3 JK⁻¹ mol⁻¹, which gives a negative ΔG° at all temperatures studied, supporting the spontaneous formation of an outer sphere association complex.     

Hypervalent iodine(III) catalyzed rapid and efficient access to benzimidazoles,benzothiazoles and quinoxalines: Biological evaluation of some new benzimidazole-imidazo[1,2-a]pyridine conjugates

A rapid, simple and highly efficient method for the synthesis of a variety of 2-aryl-benzimidazoles, 2-aryl-benzothiazoles and quinoxalines has been developed using Koser’s reagent [PhI(OH)OTs] as catalyst. The present work highlights the potential of Koser's reagent ([PhI(OH)OTs]) for the synthesis of benzimidazoles, benzothiazoles and quinoxalines, etc. Short reaction time, high yields, importantly low catalyst loading, broad substrate scope and scalability are the salient features of this methodology. Particularly, this method has been employed successfully to synthesize highly structured indole-benzimidazole and quinoxaline-6-carboxamide derivatives as well as biologically important benzimidazole-imidazo[1,2-a]pyridine conjugates in moderate to good yields. These remarkable features make the present methodology a valid contribution to the existing precedents for the synthesis of benzimidazoles, etc. In the MTT assay, benzimidazole-imidazo[1,2-a]pyridine conjugates 3s, 3t and 3v were found to be active on MCF-7 (IC₅₀ values of 5.10 ± 0.10, 8.23 ± 0.02, and 10.75 ± 0.03 µM, respectively) and MDA-MB-231 cell lines (IC₅₀ values of 10.83 ± 0.13, 7.68 ± 0.05, and 7.87 ± 0.24 µM, respectively). Flow-cytometry analysis revealed that the treatment of MCF-7 cells with compound 3s showed moderate effect on the progression of G0/G1 phase of the cell cycle.