Synthesized Research Articles

Microwave and ultrasound-assisted green protocols for 5-methylthiazole induced Betti bases: molecular docking, in-silico pharmacokinetics, and anticancer activity studies

ABSTRACT Herein, we describe an efficient one-pot three-component microwave and ultrasound-endorsed approaches for synthesizing distinct 5-methylthiazole induced Betti bases (5-methyl-thiazol-2-ylamino-aryl-benzylnapthols) employing silica sulfuric acid (SSA, silica-OSO3H) as an active heterogeneous acid catalyst. The title compounds produced in good yields (86–95%) from naphthalen-2-ol, 5-methylthiazol-2-amine, and assorted aryl aldehydes; and structurally characterized by spectral and elemental analyses. A comprehensive comparative study of conventional, ultrasonic, and microwave-irradiated synthetic routes has been achieved by optimizing various reaction parameters. These new protocols provide several advantages, including the use of an inexpensive, non-toxic, and reusable catalyst. Additionally, they benefit from mild reaction conditions, short reaction times, and simple workup and purification procedures, thereby increasing their practicality. Furthermore, the synthesized compounds were evaluated for their anticancer potency against A-549 (lung cancer) and A-498 (kidney cancer) cell lines, with scaffold IVa demonstrating excellent (GI50 < 10 µg/mL) inhibitory activity against A-549. Additionally, molecular docking was performed to investigate potential binding interactions between ligands and proteins. Scaffold IVa exhibited the best docking with cancerous target proteins 1M17 (−8.9 kcal/mol) and 1M14 (−7.2 kcal/mol), thereby supporting our bio-activity studies.

Dual-Functional TiO2/SiO2@Poly(Hexadecyl Methacrylate-co-Butyl Methacrylate-co-Methyl Acrylate) Composites: Nanointegrated Enhancements in Oil Absorption and High-Efficiency Emulsion Interface Demulsification

Our research described in this report introduces a multifunctional composite resin, TiO2/SiO2@poly(hexadecyl methacrylate-co-butyl methacrylate-co-methyl acrylate), synthesized to enhance oil absorption and demulsification for oily wastewater treatment. By incorporating hydrophobically modified nano-titanium dioxide (nano-TiO2) and nano-silicon dioxide (nano-SiO2) into a polyacrylate resin through suspension polymerization, we aimed to overcome the limitations of traditional oil absorbent resins. The resin’s formulation included hexadecyl methacrylate, butyl methacrylate, and methyl acrylate. Characterization was conducted through measurements of contact angle, Fourier-transform infrared spectroscopy, scanning electron microscopy, and Brunauer–Emmett–Teller surface area analyses. The study meticulously optimized the chemical synthesis conditions, focusing on the amount of monomer, initiator and crosslinker, which are crucial for the polymerization reaction. Additionally, the physical parameters, such as the particle size and quantity of the nano-materials, were carefully controlled to achieve the desired material properties. The inclusion of nano-TiO2 and nano-SiO2 significantly enriched the resin’s porous structure, boosting its oil absorption ratios for oil in various solvents, notably enhancing stability and recyclability. The resin exhibited superior oil absorption capacities (e.g. 54.7 g/g for trichloromethane) and improved emulsion separation efficiency (e.g. 98.10% for trichloromethane emulsions), marking a substantial advancement in materials for environmental remediation applications.

Highlighting multicomponent reactions as an efficient and facile alternative route in the chemical synthesis of organic-based molecules: a tremendous growth in the past 5 years

Since Strecker’s discovery of multicomponent reactions (MCRs) in 1850, the strategy of applying an MCR approach has been in use for over a century. Due to their ability to quickly develop molecular diversity and structural complexity of interest, MCRs are considered an efficient approach in organic synthesis. Although MCRs such as the Ugi, Passerini, Biginelli, and Hantzsch reactions are widely studied, this review emphasizes the significance of selective MCRs to elegantly produce organic compounds of potential use in medicinal chemistry and industrial and material science applications, as well as the use of the MCR approach to sustainable methods. During synthesis, MCRs provide advantages such as atom economy, recyclable catalysts, moderate conditions, preventing waste, and avoiding solvent use. MCRs also reduce the number of sequential multiple reactions to one step.

Mentha spicata Mediated Formulation of Iron Oxide Nanoparticles Exhibit Superior Antimicrobial, Antioxidant, and Photodegradation Propensity Compared to Chemically Formulated Counterparts

Introduction: Iron oxide nanoparticles demonstrate tremendous potential in preserving the ecological balance of the environment since they act as antimicrobial agents and efficient photocatalysts. However, environmental sustainability has challenged the synthesis protocols of nanomaterials. Method: This study compares the green synthesis method with the scalable chemical synthesis method. In this work, Iron oxide nanoparticles were fabricated via the green chemistry technique utilizing the leaf extract of Mentha spicata (M-IONP) and also via the chemical co-precipitation method (C-IONP). The synthesized IONPs were analyzed by different characterization methods such as XRD, FTIR, SEM analysis, ZETA potential measurements, and DLS spectroscopy analysis. Results: The biosynthesized and chemically synthesized IONPs were analyzed for their mechanistic action against different applications like antimicrobial, antioxidant, and degradation of harmful dyes. Interestingly, the biosynthesized IONPs (M-IONP) exhibited more effective antimicrobial efficacy towards Gram-positive and Gram-negative organisms than chemically synthesized IONPs. Conclusion: The green synthesized M-IONP also showed significant antioxidant propensity similar to that of the standards taken. Additionally, green-synthesized M-IONP exhibited enhanced degradation efficacies against Methylene blue, chromium, and sulphamethoxazole in comparison to chemically synthesized IONP.

Continuous Flow Microreactors for the High-efficiency Enzymatic Synthesis of 10-Hydroxystearic Acid from Oleic Acid.

Converting fatty acids into specialty chemicals is sustainable but hindered by the low efficiency and thermal instability of current oleic acid hydratases, along with mass transfer limitations in emulsion reactions. This study introduces an optimized continuous flow micro-reactor (CFMR) that efficiently transforms oleic acid at low (15 g·L-1) and high (50 g·L-1) concentrations, improving reaction efficiency and overcoming key conversion barriers. The first CFMR model showed reaction speeds surpassing traditional batch stirred tank reactors (BSTR). Optimizations were performed on three key components: liquid storage, mixer, and reaction section of the CFMR, with each round's best conditions carried into the next. This achieved a space-time yield of 597 g·L-1·d-1 at a 15 g·L-1 oleic acid load. To further enhance the yield, we optimized the emulsifier system to solve incomplete emulsification and developed a two-component feed microreactor (TCFMR) that addressed substrate and product inhibition at high loads, reaching a 91% conversion of 50 g·L-1 oleic acid in 30 minutes, with a space-time yield of 2312 g·L-1·d-1. These advancements represent significant progress in utilizing fatty acids and advancing sustainable chemical synthesis.

Hierarchically structured nanospherical fibrous silica-supported bimetallic catalysts: An enhanced performance in methane decomposition

Hydrogen production by methane catalytic decomposition is a promising method that also allows the formation of valuable carbon nanomaterials which can be utilized in transportation fuels, chemical synthesis, and fuel cell technology. In this study, bimetallic 3d transition metal (Ni, Fe, Co) catalysts supported on spherical mesoporous nanofibrous silica (KCC1) were successfully synthesized using a hydrothermal method followed by sono co-impregnation. The catalysts were evaluated for their performance in the catalytic decomposition of methane. Comprehensive characterization of the catalysts was conducted utilizing XRD, FTIR, SEM, TEM, STEM, XPS, H2-TPR, and BET techniques. XRD and TEM analyses confirmed the formation of Ni–Fe, Ni–Co, and Co–Fe bimetallic alloys on the nanofibrous silica without compromising its dendrimeric hierarchical structure. STEM HAADF imaging revealed a uniform dispersion of bimetallic nanoparticles within the spherical fibrous framework. Catalytic tests demonstrated that all bimetallic catalysts showed high stability and activity for methane cracking at 700 °C over 180 min of time on stream (TOS). Among them, Fe-based catalysts Ni–Fe/KCC1 and Co–Fe/KCC1 achieved the highest hydrogen yields of 80% and 60%, respectively. Methane conversion was 1.56 and 2.23 times higher in Ni–Fe/KCC1 compared to Co–Fe/KCC1 and Ni–Co/KCC1, respectively. Post-reaction characterization of the spent catalysts was performed using XRD, Raman spectroscopy, SEM, TEM, and TGA. XRD and Raman spectroscopy were used to evaluate the degree of graphitization and crystallinity in the carbon nanotubes (CNTs) produced on the catalysts, enabling a correlation with the catalyst properties. TEM examination was used to investigate the structural morphology and growth methods of the CNTs, including tip or base growth and chain-like or parallel-wall types. TGA results revealed that all bimetallic catalysts exhibited no amorphous carbon during methane cracking reaction.

Boron-Nitrogen-Containing Benzene Valence Isomers.

Benzene is one of the most ubiquitous structural motifs in chemistry. The valence isomers of benzene have also attracted synthetic chemists' attention due to their unique structures, bonding, and reactivity. We have been investigating boron-nitrogen-containing benzene valence isomers via photoisomerization of 1,2-azaborines. In this contribution, we summarize recent developments of these highly strained BN-heterocyclic compounds including their synthesis, characterization, proposed mechanism of formation, and their potential applications.

The Progress of Reductive Coupling Reaction by Iron Catalysis.

The transition metal catalyzed coupling reaction has revolutionized the strategies for forging the carbon-carbon bonds. In contrast to traditional cross-coupling methods using pre-prepared nucleophilic organometallic reagents, reductive coupling reactions for the C-C bonds formation provide some advantages. Because both coupling partners are reduced in the final products using a stoichiometric amount of a reductant, this approach not only avoids the need to use sensitive organometallic species, but also provides an orthogonal and complementary access to classical coupling reaction. Notably, the reductive coupling reactions feature readily available fragments, promote good step economy, exhibit high functional group tolerance and unique chemoselectivity, which have propelled their increasingly popular in the organic synthesis. In recent years, due to the low price, minimal toxicity, and environmentally benign character, iron-catalyzed carbon-carbon coupling reactions have garnered significant attention from the organic synthetic chemists and pharmacologists, especially the iron-catalyzed reductive coupling. This review aims to provide an insightful overview of recent advances in iron-catalyzed reductive coupling reactions, and to illustrate their possible reaction mechanisms.

Coherent Phonon Dynamics in Plasmonic Gold Tetrahedral Nanoparticle Ensembles.

Coherent phonon modes supported by plasmonic nanoparticles offer prospective applications in chemical and biological sensing. Whereas the characterization of these phonon modes often requires single-particle measurements, synthetic routes to narrow size distributions of nanoparticles permit ensemble investigations. Recently, the synthesis of highly monodisperse gold tetrahedral nanoparticles with tunable edge lengths and corner sharpnesses has been developed. Herein, we characterize a size series of these nanoparticles in colloidal dispersion via transient absorption spectroscopy to examine their mechanical and plasmonic responses upon photoexcitation. Oscillations of transient absorption signals are observed in the plasmon resonance and correspond to the lowest-order radial breathing modes of the nanoparticles, the frequencies of which are affected by the edge length and truncation of the corners. Homogeneous quality factor values ranging from 24 to 34 are observed for the oscillations that convey potential utility in mass-sensing and plasmon-exciton-coupling photonics schemes. Finite-difference time domain and finite element analysis calculations establish specific optically relevant phonon modes.

Sequential-Flow Synthesis of Donepezil: A Green and Sustainable Strategy Featuring Heterogeneous Catalysis and Hydrogenation.

An atom-economical sequential-flow synthesis of donepezil, a widely prescribed drug for Alzheimer's disease, was accomplished using inexpensive, commercially available precursors. This achievement was made possible by reconfiguring the synthetic route to include only heterogeneous catalytic addition and condensation reactions, with a particular emphasis on skeletal transformation and bond formation through hydrogenation processes. Notably, water was the sole byproduct in this synthesis. A crucial aspect of this work was the development of appropriate continuous-flow processes to achieve a one-flow synthesis. This was accomplished by implementing in-line treatments of the main reaction stream to eliminate inhibitory factors that could affect catalyst performance in the hydrogenation steps.

Development of Two Synthetic Routes to 4‐(N‐Boc‐N‐methylaminomethyl)benzaldehyde: A Versatile Starting Material in Pharmaceutical Synthesis

AbstractTwo novel synthetic routes to 4‐(N‐Boc‐N‐methylaminomethyl)benzaldehyde, an important pharmaceutical starting material, were developed using terephthaloyl chloride and terephthalaldehyde. In the first approach, terephthaloyl chloride was converted to an ester amide. The treatment of the ester amide with LiAlH4 followed by protection of the resulting amine with tert‐butoxycarbonyl anhydride yielded the corresponding benzyl alcohol. The benzyl alcohol was oxidized to the aldehyde completing the first‐generation synthesis. The second approach utilized a one‐step protocol mono‐selective reductive amination of terephthalaldehyde with N‐Boc‐methylamine using chlorodimethylsilane. Both methods were scalable to 50 mmol and provided the desired aldehyde in a synthetically useful yield, demonstrating their practicality.

Electrochemical Hydrogenation of N‐Heterocycles and Related Substrates: A Mini‐Review

ABSTRACTCatalytic hydrogenation refers to the (often) metal‐mediated addition of dihydrogen (H2) equivalents to unsaturated compounds to form new element‐hydrogen bonds. This conceptually simple reaction is ubiquitous in the production of a vast number of essential chemicals. Despite a growing recognition of the importance of sustainability in manufacturing, the use of fossil‐derived hydrogen gas and precious metal catalysts in hydrogenation remains widespread. Electrochemical variants of these processes are an appealing alternative, especially those that can make use of sustainable Brønsted acids, more abundant electrode materials and renewable electricity. In this mini‐review, we give a selective overview of electrochemical hydrogenation methodologies for N‐heterocycles and some related substrates from the specific perspective of the synthetic chemistry made possible by this increasingly popular approach.

Application of Biotechnology and Chiral Technology Methods in the Production of Ectoine Enantiomers

Natural ectoine, (+)-(4S)-2-methyl-1,4,5,6-tetrahydropyrimidine-4-carboxylic acid, is an extremely important small biomolecule belonging to the class of osmolytic/osmoprotective compounds. It stabilizes biomacromolecules such as DNA and proteins and protects them from denaturation by heat, dehydration, and UV radiation. The rapidly growing interest in this compound resulted in currently exclusive biotechnological production, while a chemical process along with enantioseparation as an alternative has not yet been established. An improved chemical synthesis of racemic ectoine starting from γ-butyrolactone in very good yield is described. Regioselective monoacetylation is achieved by the complexation of a copper(II)-ion with two molecules of 2,4-diamonobutyric acid in the key synthetic step. The racemic ectoine was synthesized with the aim of being successfully enantioseparated for the first time by high-performance liquid chromatography (HPLC) using a teicoplanin-based Chiral-T column in different solvent systems. The presence of (+)-ectoine was determined and quantified using an HPLC protocol on the Synergy Polar-RP column in fermentation broths inoculated with different strains of Streptomyces sp. bacteria isolated from the Adriatic Sea and grown on different NaCl concentrations.

Photoinduced Birefringence and Liquid Crystal Orientation on Polymers with Different Azobenzene Content in the Main Chain.

In this paper, we give an overview of novel main-chain azobenzene-based fluorinated poly(arylene ether)s with different content of azo groups, aiming at providing a better understanding of the link between a number of N═N bonds and the macroscopic response of the material. We discuss chemical synthesis and molecular structure and report on a comprehensive analysis of the polymer properties, thermal behavior, and mechanical strength. We show that a higher content of azobenzene moieties reduces the mechanical strength of the polymer materials. On the other hand, polymers with a higher content of azobenzene demonstrate higher values of induced birefringence due to a larger number of azobenzene in the trans form. The photoisomerization constants of all polymers fall within a very close range. The minor variations are attributed to the number of azobenzene groups in the polymer composition and the conformational arrangements of the polymer chain packing. The developed light-sensitive polymers were employed for dynamic control and manipulation of the liquid crystal orientation by polarization of the incident light. After the double irradiation of the substrates using appropriate photomasks, we made patterned cells that consist of domains with different high-resolution liquid crystal director orientations.

Understanding Cytochrome P450 Enzyme Substrate Inhibition and Prospects for Elimination Strategies.

Cytochrome P450 (CYP450) enzymes, which are widely distributed and pivotal in various biochemical reactions, catalyze diverse processes such as hydroxylation, epoxidation, dehydrogenation, dealkylation, nitrification, and bond formation. These enzymes have been applied in drug metabolism, antibiotic production, bioremediation, and fine chemical synthesis. Recent research revealed that CYP450 catalytic kinetics deviated from the classic Michaelis-Menten model. A notable substrate inhibition phenomenon that affects the catalytic efficiency of CYP450 at high substrate concentrations was identified. However, the substrate inhibition of various reactions catalyzed by CYP450 enzymes have not been comprehensively reviewed. This review describes CYP450 substrate inhibition examples and atypical Michaelis-Menten kinetic models, and provides insight into mechanisms of these enzymes. We also reviewed 3D structure and dynamics of CYP450 with substrate binding. Outline methods for alleviating substrate inhibition in CYP450 and other enzymes, including traditional fermentation approaches and protein engineering modifications. The comprehensive analysis presented in this study lays the foundation for enhancing the catalytic efficiency of CYP450 by deregulating substrate inhibition.

Divergent Synthesis and Antigenicity Evaluation of Core Oligosaccharides of the Lipopolysaccharides from Acinetobacter baumannii SMAL and ATCC 19606.

Acinetobacter baumannii poses a serious threat to human health. Pathogenic bacterial lipopolysaccharides (LPSs) are potent immunogens for the development of antibacterial vaccines. To investigate the antigenic properties of A. baumannii LPS, five well-defined core oligosaccharide fragments from the LPS of A. baumannii SMAL and ATCC 19606 were synthesized. A divergent synthesis strategy based on orthogonally protected α-(2 → 5)-linked Kdo dimer 6 was developed. Selective exposure of different positions in this key precursor and then elongation of sugar chains via stereocontrolled formation of both 1,2-trans and 1,2-cis-2-aminoglycosidic linkages permitted the efficient synthesis of the targets. The synthetic route also highlights a 4-O and then 7-O glycosylation sequence for assembly of the novel 4,7-branched Kdo framework. Antigenicity assay using the glycan microarray technique disclosed that tetrasaccharide 3 featuring both 4,7-branch and α-(2 → 5)-Kdo-Kdo structural elements was a potential antigenic determinant.

From β-Carotene to Retinoids: A Review of Microbial Production of Vitamin A.

Vitamin A (retinoids) is crucial for human health, with significant demand across the food, pharmaceutical, and animal feed industries. Currently, the market primarily relies on chemical synthesis and natural extraction methods, which face challenges such as low synthesis efficiency and complex extraction processes. Advances in synthetic biology have enabled vitamin A biosynthesis using microbial cell factories, offering a promising and sustainable solution to meet the increasing market demands. This review introduces the key enzymes involved in the biosynthesis of vitamin A from β-carotene, evaluates achievements in vitamin A production using various microbial hosts, and summarizes strategies for optimizing vitamin A biosynthesis. Additionally, we outline the remaining challenges and propose future directions for the biotechnological production of vitamin A.

Metal-free alkyne annulation enabling π-extension of boron-doped polycyclic aromatic hydrocarbons.

A C-H functionalizing annulation reaction of boron-doped polycyclic aromatic hydrocarbons (PAHs) with alkynes is described. This metal-free π-extension provides a new synthetic route to fusion atom B-doped polycyclic aromatic hydrocarbons (PAHs) that is demonstrated with the synthesis of a family of new, functionalized, structurally constrained 6a,15a-diborabenzo[tuv]naphtho[2,1-b]picenes. These annulation products exhibit deep LUMO energy levels, strong visible-range absorptions, and sterically accessible π-systems that can adopt herringbone or π-stacked solid-state structures based on choice of substituents. From regioselectivity and DFT calculations, we propose an annulation mechanism involving intramolecular electrophilic aromatic substitution of a zwitterionic intermediate.

Synthesis and band gap determination for 4-phenyl-7-(5-(thiazol-2-yl) thien-2-yl)benzo[c][1,2,5]thiadiazole, a new polyheterocyclic molecule with potential applications as a semiconductor in organic photovoltaic solar cells

Organic photovoltaic (OPV) solar cells are a promising emerging technology for sustainable energy generation. In these cells, the absorbing layer consists of a repeated series of aromatic organic rings with a system of π delocalized electrons, a feature that allows these materials to absorb sunlight and facilitate electron transfer. In the present work, a new tetrameric molecule with high structural complexity, 4-phenyl-7-(5-(thiazol-2-yl) thien-2-yl)benzo[c][1,2,5]thiadiazole, was synthesized by a convergent pathway. The final step of the synthetic route was the Suzuki coupling of two new dimeric molecules, obtained from commercially available raw materials such as thiophene and o-phenylenediamine. The band gap of the final compound was found to be 2.5 eV using an optical methodology and 2.38 eV using an electrochemical methodology. The results suggest that this tetrameric molecule has potential for application in OPV cells.

Polaron-assisted dielectric relaxation processes in donor-doped BaTiO3-based ceramics

Ceramic samples based on the Ba1-xGdxTiO3 system, where x = 0.001, 0.002, 0.003, 0.004 and 0.005, were prepared via the Pechini’s chemical synthesis route. Structural properties, analyzed from X-ray diffraction and Rietveld refinement, revealed the formation of the pure ABO3 perovskite structure with tetragonal symmetry (P4mm) for all the studied compositions. Doping with Gd3+ promoted a reduction in the unit-cell volume, confirming the preferential substitution of the rare-earth cation at the A-site. The dielectric properties have been analyzed over a wide temperature and frequency range, revealing a significant contribution of the conduction mechanisms in the dielectric response of the studied ceramics. In fact, by using the Davidson-Cole formalism, the observed electrical behavior was found to be associated with relaxation processes related to intrinsic defects mobility promoted by a thermally-activated polaronic mechanism. The obtained values of the activation energy for the relaxation processes, estimated from the Arrhenius’ law for the mean relaxation time, revealed a decrease from 0.29 up to 0.21 eV as the Gd-doping concentration increases, which suggests the conduction process to be associated with the polaronic effects due to the coexistence of Ti4+ and Ti3+ ions in the structure. Analysis from the conductivity formalism, by using the Jonscher’s universal power-law, confirmed the polaron-type conduction mechanism for the dielectric dispersion, as suggested by the dielectric analysis, being the nature of the hopping mechanism governed by small polaron hopping (SPH) charge transport in the studied Ba1–xGdxTiO3 ceramics.