The first catalytic enantioselective [3+2] cyclization between 4-amino-isoxazoles and quinone monoimines was achieved by using a chiral phosphoric acid catalyst. This transformation afforded a series of isoxazoline fused dihydrobenzofuran derivatives with two sequential chiral centers in high yields and outstanding enantioselectivities. The absolute configuration of the title compounds was determined by X-ray crystal structure analysis. The subsequent application of the obtained products displayed good antifungal activity against five plant pathogenic fungi further demonstrates the versatility of this transformation.This approach provided an excellent alternative strategy for the synthesis of corresponding bioactive molecules containing an isoxazoline fused dihydrobenzofurans skeleton.

Three novel tetra substituted p‑tert-butylthiacalix[4]arene derivatives (3, 4, and 5) with five coordinating carbonyl groups at the lower rims were synthesized. Accordingly, diethyl tetra-t‑butyl‑trihydroxy-tetrathia-tetrabenzenacyclooctaphanyl)oxy)malonate react with ethyl bromoacetate, phenacyl bromide and 2‑chloro-N-(p-tolyl)acetamide, to produce new p‑tert-butylthiacalix[4]arenes in of 60, 90, and 80% yields, respectively. The molecular structures of the products were verified using FT-IR, 1H NMR, and 13C NMR spectroscopy. Metal ions such as Na+, K+, Cs+, Hg2+, Cd2+, Pb2+, Ni2+, Co2+, Cu2+, and Ag+ are easily chelated by the new thiacalixarene derivatives using liquid-liquid extraction technique. These compounds surprisingly show high efficiency in liquid-liquid extraction of alkali, heavy, and transition metal ions. Uptake efficiencies of 71.00% (for Co(II)), 46.00% (for Cu(II), and 15.00% (for Hg(II)) were attained by thiacalixarene 3, 4, and 5. These derivatives were subjected to DFT-based computational analysis with the aim of increasing the efficiency with which thiacalixarene (as a nucleophilic) interacts with the metal ion (3, 4, and 5 in the role of electrophile).

In this current investigation, structural and spectroscopic characteristics of the Lawsone (2-hydroxy-1,4-napthoquinone) molecule was examined by density functional theory (DFT) calculations. Lawsone's anti-cancer abilities against breast cancer proteins was investigated using molecular docking analysis. The optimization was performed through 6-311++G (d,p) basis set to determine the molecular geometry of lawsone. The vibrational frequencies of Lawsone were theoretically generated and compared to analytically determined FTIR and FT-Raman spectra. In this study, a theoretical UV-visible spectrum was generated, and experimental absorption was validated. The reactive potential of lawsone was explored further using a molecular electrostatic potential surface. The HOMO-LUMO energies and energy gap were used to evaluate the stability and molecular reactivity of the lawsone molecule. The charge distribution across the lawsone atoms was found via Mulliken and natural population analyses. The weak interactions of the lawsone molecule were analysed through RDG analysis. The topology of the lawsone molecule was explored through ELF and LOL analysis. The antioxidant potential was validated using the DPPH test. The drug-like features of lawsone were confirmed by physicochemical and pharmacokinetic tests, and molecular docking simulations revealed lawsone's binding affinity against breast cancer proteins, with the greatest affinity of -7.4 Kcal/mol observed against AKT1.

The synthesis, spectroscopic and structural characterization, optical and electrochemical properties and theoretical studies of a family of four new copper(II) complexes supported by a ferrocene-containing N2O2-tetradentate chiral Schiff base ligand derived from enantiomerically pure (1R,2R)-(−)-1,2-diaminocyclohexane are reported. The push-pull Cu(II) complexes were prepared following a one-pot three-component reaction involving the chiral half-unit (1R,2R)-Fc-C(=O)CH=C(CH3)NH-c-C6H10-NH2, copper acetate monohydrate and the appropriately 3-R,5-R’-substituted salicylaldehyde derivative in a 1:1:1 ratio (Fc = ferrocenyl; 3: R = H, R’ = Cl; 4: R = H, R’ = Br; 5: R = R’ = F; 6: R = R’ = NO2), and isolated in 65-97 % yields as brown microcrystalline products. The characterization of the synthesized compounds were investigated through CHN elemental analysis, UV–vis, FT-IR, high-resolution mass spectrometry, and X-ray diffraction analysis in the case of the difluoro substituted complex 5 that was obtained in the form of single crystals. It crystallizes in the orthorhombic non-centrosymmetric space group P212121, with two (R,R)-(−)-chiral carbon atoms in the structure. The four-coordinate Cu(II) metal ion adopts a slightly distorted square planar geometry. Magnetic properties of powdered samples have been investigated (2-300 K) and found consistent with a single isolated copper(II) ion (s=1/2). Cyclic voltammetry showed that the stronger the electron withdrawing effect of the 3,5-substituents, the more anodically shifted the oxidation potential (E1/2) of the ferrocenyl moiety, following the order: 5-Cl < 5-Br < 3,5-F2 < 3,5-(NO2)2. This trend is similar when considering the values of the second-order polarizabilities β of these compounds as measured using Harmonic Light Scattering (HLS) at 1.9 µm, confirming the increasing electron withdrawing effect evidenced by electrochemical studies as well as the conjugation between the electron donor ferrocenyl moiety and the different halogen or nitro substituents through the square planar copper Schiff base framework. Finally, DFT and TD-DFT calculations allow to rationalize the structure and properties of the complexes.

The structures of the adsorbed water molecules in AlPO4-5, their structural evolutions and changes of Al-O-P angles between tetrahedra upon water adsorption were investigated by infrared spectroscopy. The results indicate that Al-H2O coordination is present in the channels and the adsorbed water molecules are in low, intermediate and strong hydrogen-bonded environments. The population of the water species varies with a sudden enhancement from 70-140min, showing similarity to the reported abnormal isotherm due to the increase of host-guest interaction sites. This large-scale uptake of water accelerates structural transformations of water from intermediate to strong hydrogen-bonded structures. Moreover, the water-framework interaction facilitates the closure of Al-O-P angles and thus results in the framework contraction. This study opens the door to a good knowledge of the hydrogen-bonded structures of H2O and framework deformation in hydrated AlPO4-5 from the viewpoint of infrared spectroscopy.

In this study, new chalcone-isoxazole-based hybrid derivatives (12, 13, 18, and 21) and chalcone-triazole hybrid molecules (26) were synthesized using the click chemistry approach. Among these hybrid molecules, 12, 13, 21, and 26 were obtained by combining azole pharmacophore groups such as thiazole, isoxazole, and 1,2,3-triazole. In addition, a new bioactive hybrid molecule (E)-3-(2-(1-((4- (3-(4-((3-(4-(benzyloxy) phenyl) isoxazol-5-yl) methoxy) phenyl)–3–oxoprop-1-en-1-yl) phenoxy)methyl)-1H-1,2,3-triazol-4-yl)thiazol-4-yl)-2H-chromen-2-one (18), which is a chalcone-isoxazole hybrid derivative with azido thiazole coumarin substitution, was synthesized. The chemical structures of synthesized compounds were characterized by spectroscopic techniques such as 1H NMR, 13C NMR, FT-IR, and MALDI-TOF MS (18, 21, and 26). These novel chalcone-azole hybrids (12, 13, 18, 21, and 26) were investigated for their in-vitro anticancer activity against A549 cells, Capan-1 cell lines, and a healthy L929 fibroblast cell line, as well as the apoptotic and necrotic effects of these compounds on Capan-1 cell lines. Among the compounds tested, hybrid 18 showed the best activity in the A549 cell line, while it showed moderate activity in the Capan-1 cell line.

Self-assembly is the organization of molecular units into ordered structures using non-covalent interactions like hydrogen bonding, Van der Waals forces, π-π stacking, capillarity, entropy, and others. The most widely reported interactions in self-assembly are hydrogen bonding and π-π stacking interactions. Self-assembly can be employed in the synthesis of bidentate ligands and their complexes using the hydrogen bond interaction of monodentate ligands. These self-assembled bidentate ligands and their metal complexes have found applications in hydrogenation, hydroformylation, hydrocyanation, and hydration reactions with excellent yields and good catalytic properties. In two of the reports, complexes derived from self-assembled bidentate ligands had catalytic activities better than t-Bu-XANTPHOS (22) and BIPHEPHOS (23), special ligands, used for catalyzing the hydroformylation of alkenes. In addition to the self-assembly of bidentate ligands from monodentate ligands, bidentate ligands have also been used as linkers, spacers, inter-lockers, and ligands in the construction of supramolecular complexes. In this work, (i) the structure and application of self-assembly in the synthesis of bidentate ligands, (ii) the structure and application of these self-assembled bidentate ligands and their metal complexes in catalysis and (iii) the structure and application of bidentate ligands in the construction of molecular knots, catenanes, molecular rotors, and other supramolecules were studied. While catenanes and rotaxanes consist of two or more molecular components interlocked, molecular knots are a single entwined macrocycle. Structural features like steric restriction, surface cavity, surface area, porosity, and flexibility of the molecules determined their applications as catalysts.

This study presents a modeling of hydrophobic tetrapeptides acting in a competitive manner against 3-hydroxy-3-methylglutaryl coenzyme A reductase. This enzyme catalyzes the reductive deacylation of 3-hydroxy-3-methylglutaryl coenzyme A to mevalonate, using two molecules of nicotinamide adenine dinucleotide phosphate as cofactors, and this reaction represents the rate-limiting step in cholesterol biosynthesis. Thus, it is a target of many investigations in order to control a cholesterol level because the elevated cholesterol level is known as a risk factor of hypercholesterolemia. In previous studies, the two hypocholesterolemic peptides were isolated from soy glicinin. Based on these sequences, a number of the tri-, tetra-, hexa- and heptapeptides were designed in order to improve their inhibitory activities. The peptide fragmentation was applied as a main tool in design. Using the developed design method, a new recognized motif in the designed tetrapeptides was identified. According to the design parameter, the IIIP peptide possessed the most rigid structure among the new designed tetrapeptides. The circular dichroism study confirmed that the observed predominant conformation of the IIIP peptide was close to the type I of a β-turn. The IIIP peptide was determined as the strongest inhibitor among the new designed tetrapeptides. The kinetic study revealed the competitive HMGR inhibition by the peptide, which acted as a bisubstrate blocking an access of HMG-CoA and NADPH to their binding sites. The correlation coefficient (r2) between the predicted and observed peptide activities of 0.91 suggests wide possibilities of the proposed approach to design new peptides that may differ from the previously designed peptides in the recognized motif, sequences, lengths and structural preferences.

This study focuses on the synthesis, the structural studies of four new divalent metal coordination complexes of (1-methyl-1H-imidazol-2-yl)methanol (Hmim), and the assessment of their antimicrobial activity against five pathogenic microorganisms as well as their antioxidant potential. M(II) complexes were prepared by condensation of Hmim with Zn(OAc)2, Cu(OAc)2, NiCl2.6H2O, or CuCl2 in dry 1,2-dimethoxyethane at rt.. The ligand and its complexes have been characterized systematically by elemental analysis, FT-IR and UV-Vis spectroscopy, and single-crystal X-ray diffraction. In [Zn(Hmim)2(OAc)2] (1)four donor atoms surround the metal ion displaying tetra-coordinated compound in distorted tetrahedral geometry, while in [Cu(Hmim)3OAc].AcOH (2), the Cu(II) ion is coordinated by three Hmim ligands and one acetate ligand displaying a tetragonally distorted octahedral environment. In [Ni(Hmim)2(H2O)2]Cl2 (3), and [Cu(Hmim)3]Cl2 (4), the ligand is coordinated to M(II) ions in bidentate fashion exhibiting a distorted octahedral environment, the chloride anions act only as counter ions. The free ligand and its complexes 1-4 were tested in vitro for their antimicrobial activity against the growth of five strains including Gram (+) and Gram (-) bacteria, a Gram (+) phytopathogenic bacteria, a yeast and a fungus using the agar diffusion method. The SAR study of the antibacterial activity revealed significant differences in their inhibition activity profile, where 1 gave the best results displaying significant inhibition effects with a broad spectrum. The free-radical scavenging activity of synthesized compounds was investigated through their DPPH radical scavenging capacity, and has shown moderate to interesting antioxidant potential.

About 130–150 million people worldwide are chronically infected with the hepatitis C virus (HCV), and this infection can lead to serious liver problems such as cirrhosis, hepatocellular carcinoma, or liver cancer. One of the most well researched therapeutic targets for HCV is the NS5B protein, which is used to find novel treatment candidates to supplement currently approved combinations or multiple combinations of medications. As a result, NS5B has been the focus of numerous intriguing medicinal chemistry projects over the past several years, which has led to the appearance of promising preclinical therapeutic compounds. For all those medicinal chemist researchers dealing with HCV research programs, specifically pointing on NS5B and setting broad spectrum identification of creative anti-HCV compounds, the discussion described in this particular review will undoubtedly be beneficial and essential which describes the recent synthesized NS5B inhibitors including patents, structure-activity relationship and docking studies.

Reductive functionalization of carbon dioxide is an important approach which not only reduces CO2 concentration but also functionalized it for the formation of value added chemicals. In this perspective, a hexadentate mononuclear cobalt (III) complex [CoIIIL] of non-Schiff base ligand (H4L) was synthesized and structurally characterized by single crystal X-ray diffraction. The electronic spectra of the complex showed two bands at 448 and 561 nm corresponds to the LMCT and d-d transitions respectively. The derived inexpensive [CoIIIL] complex was very much effective as catalyst in carbon dioxide functionalization reaction. The catalytic synthesis of mono selective N-formamide product from amines was produced through diagonal transformation of carbon dioxide in presence of polymethylhydrosiloxane (PMHS) as reducing agent and [CoIIIL] complex as catalyst. The effects of various reaction parameters were examined. Broad range of substrates (aromatic as well as aliphatic amines) smoothly produced good percentage of respective N-formamides product (72-94%) under mild reaction condition utilizing 1 atmospheric CO2. The high TON (1540-2000) and TOF value (192.5-400.0 h−1) for the catalytic reactions strongly depicted the productive nature of the [CoIII(L)] catalyst. The probable mechanestics studies clearly reveals that the [CoIIIL] complex activated the Si−H bond of PMHS to react with carbon dioxide in order to form the silyl formates intermediate for activation of N–H bonds in amines, thus leading to the excellent performance of the catalytic reaction.

Diabetes mellitus (DM), especially type 2 diabetes mellitus (T2DM), is the most disruptive metabolic disorder globally affecting human health. To effectively manage this medical condition, the quest for a new medication to treat T2DM continues. The emergence of medication resistance to the insulin and leptin receptors leads to significant concerns. The compounds which can tackle this resistance issue may be helpful in the therapeutic management of T2DM. Protein tyrosine phosphatase 1B (PTP1B) is a promising therapeutic target for treating T2DM. Diverse natural bioactive and synthetic molecules have offered great opportunities for developing lead molecules with significant inhibitory action in in vitro and in vivo against PTP1B. Numerous PTP1B inhibitors have recently been found from natural sources or synthesized by organic synthesis and shown effectiveness for treating T2DM. This review comprehensively updates the latest research findings in developing potent natural and synthetic PTP1B inhibitors over the past six years, including structural features of PTP1B, classification of inhibitors, biological effects, and protein-inhibitors interaction modalities. These studies will be highly helpful for the medicinal chemists working in this field to design and develop novel selective PTP1B inhibitors as anti-diabetic agents in the future.

A novel series of 21 chromone-3-acrylic acid ester analogues (5aa-5cm) were designed, synthesized and evaluated for PL inhibitory activity. The molecular docking study indicate that all the designed chromone analogues have the good binding ability (MolDock score: -115.86 to -160.07 kcal/mol) in the active site of PL enzyme (PDB ID: 1LPB), showing interactions with essential amino acid residues (Phe77, Tyr114, Ser152, Phe215, Arg256). Also, all the analogues were checked for in silico drug likeness property and all were found to have drug like properties, obeying Lipinski rule of 5, with no PAINS alerts. Analogue 5am, with the best docking score, was stable in molecular dynamics simulation for 100 ns (maximum RMSD of 6.4 Å), showing crucial amino acid interactions for more than 60% of the simulation time. The structure of the synthesized analogues were then confirmed by NMR, HRMS and IR spectroscopy. Among the synthesized analogues, 5am and 5ad exhibited potent PL inhibition with IC50 of 5.16 ± 0.287 & 5.82 ± 0.933 µM, respectively, as compared with orlistat (IC50 = 0.86 ± 0.09 µM). The inhibition kinetics and in silico studies confirmed competitive type of inhibition of analogue 5am. The current work highlights the importance of chromone analogues as potential PL inhibitors. Further, the lead optimization may lead to much more potential PL inhibitors.

The wide range of pharmalogical activity exhibited by quinoline derivatives, due to its fused benzene ring with pyridine structure, has made them a popular framework for medicinal chemistry. The single crystal X-ray diffraction and quantum computational studies revealed the crystal packing of the novel saturated quinoline derivative, 6-bromo-N-pyridin-4-yl-2-thiophen-2-ylquinoline-4-carboxamide. The structural examination of titled molecule unveiled the involvement of carboxyl functional group and N-heterocyclic pyridine rings in various intermolecular interactions that are responsible for upholding the crystal stability, which was validated by the Hirshfeld surface analysis. Furthermore, in silico studies were performed to scrutinize the antioncogenic properties of entitled molecule. Topoisomerase, a vital enzyme involved in DNA replication and repair which regulates DNA topical structure makes it a prime candidate for targeted anticancer therapies. The ligand's acceptable binding affinity to the targeted protein was identified through molecular docking, and dynamic simulation was carried out to monitor and analyze the fluctuations of ligand-protein complex for a simulation period of 100ns. Eventually, the novel molecule exhibited the most favourable interaction and stability within the substrate-binding pocket of targeted protein.

Mechanically robust composites prepared via interfacial hydrogen bonding interactions are crucial in biological tissue engineering and protective materials. However, few reports have studied the effect of different hydrogen bonding interactions on the properties of composites. To remedy these limitations, polyvinyl alcohol/modified glass fiber composites were obtained based on different hydrogen bonding interactions. Glass fibers were modified via introducing with amino, carboxyl and hydroxyl groups. The modified glass fiber was chosen as the reinforcement, which introduced into polyvinyl alcohol (PVA) to achieve interface modification and different hydrogen bonding interactions. The results showed that PVA molecular chains, crystals and modified glass fibers arranged in a directional and orderly manner inside the composites. The strength and toughness of PVA/modified glass fiber composites were effectively improved due to the combination of the orientation and hydrogen bonding interactions. Especially, the carboxylated glass fiber possesses more active groups, which can provide rich interaction sites for hydrogen bonding interactions, indicating better comprehensive properties of the PVA/modified glass fiber composites. This work provides valuable research foundation for further investigating the mechanism of hydrogen bonding interactions on the mechanical properties of composites.

Rational design of lanthanide metal-organic frameworks (Ln-MOFs) with high stability is of great significance for multifunctional applications. Ln-MOFs have attracted extensive attention in the field of photocatalysis due to their large specific surface area and strong visible light efficiency. In this paper, two 2D/3D Ln-MOFs with different spatial configurations have been successfully synthesized under solvothermal conditions, namely [La(HL)(H2O)]n·3H2O (1), [Er(HL)·3/2(H2O)]n·3/2H2O (2), where H4L = 5-(bis(3-carboxybenzyl)amino)isophthalic acid. Their structures were determined by X-ray single crystal diffraction analysis, and further characterized by XRD analysis and IR spectroscopy. The complex 1 shows layered structure, which extends into a three-dimensional (3D) supramolecular network by π-π interactions, the complex 2 exhibit 3D network structures with a Schläfli symbol of 412·63 topologies, respectively. BET test results showed that there were carboxylic acid groups without coordination in the structure of complex 1, with abundant active sites and higher adsorption activity than complex 2, which would promote the effective contact and reaction between the photocatalyst and tetracycline (TC), thus improving the photocatalytic efficiency of complex 1. Under visible light irradiation, complex 1 showed good photocatalytic degradation of TC, and the degradation rate of TC could reach 75.54% under 120 min. This can be attributed to the effective separation of photogenerated electron-hole pairs and adsorption properties of complex 1. This study provides a new idea for MOFs as an efficient photocatalyst to degrade antibiotic pollutants.

Coenzyme B12-dependent enzymes catalyze complex radical-mediated reactions initiated by homolytic cleavage of the organometallic Co-C bond of the cofactors upon substrate binding. Herein, we synthesize new 2,3-diaminomaleonitrile (DAMN) based Schiff base probe for an investigation of binding interaction with coenzyme B12-dependent enzymes by molecular docking approach. The formulated compound has been well characterized by elemental analysis, NMR (1H and 13C), Mass spectrometry and UV–visible spectroscopy. Moreover, the complete structure elucidation of Schiff base probe was achieved via X-ray crystallography. Docking study reveals that the newly synthesized Schiff base compound confers good binding response towards glutamate mutase and methionine synthase as supported by calculated docking score and binding energies -7.7 kcal/mol and -8.9 kcal/mol, respectively. The results indicate significant binding effect of synthesized Schiff base on the catalysis of B12-dependent enzymes. We hope that the present information can be utilized to develop potent therapeutic drugs.

A new coordination complex, CoCl2(NNH)2, was synthesized by complexation of the pyrazole (NNH) ligand with CoCl2 in less than 5 minutes with a high yield (>85%). The synthesis was done using microwave radiation in water solvent where no side products were detected. The complexation was confirmed using UV-visible, CHN-analysis, and FT-IR analysis and compared to theoretical IR, DFT and TD-DFT calculations. CoCl2(NNH)2 crystallizes in a C2/c space group with distorted tetrahedral center as shown by single-crystal X-ray diffraction, two types of heteromeric [N-H···Cl] synthons have been recorded, such interactions type and ratios were confirmed also via Hirsfield surface analysis (HSA). The desired complex was evaluated for its antibacterial activity against four classes of gram-positive and gram-negative bacteria, and its antifungal activity against four types of fungi. The complex's physio-chemical properties, toxicity risk, lipophilicity, and pharmacophore sites were studied using the POM (Petra-Osiris-Molinspiration) bio-computational theory.

Herein two novel ionic cuprous complexes [Cu(POP)(Pytzb)]BF4 (Cu1, POP = bis(2-diphenylphosphinophenyl)ether, Pytzb = 2-(1-(benzyl)-1H-1,2,3-triazol-4-yl)pyridine) and [Cu(Xantphos)(Pytzb)]BF4 (Cu2, Xantphos = 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene) have been synthesized in reasonable yields, and their crystal structure, UV absorption and photoluminescent properties, as well as electrochemical behaviors were investigated. At 300 K, both Cu1 and Cu2 in solid state exhibit outstanding green luminescence peaked at 533 and 526 nm, respectively, with significantly high photoluminescent quantum yields (PLQYs, 47.5 and 60.5%, respectively). Detailed exploration of emission decay times for Cu1 and Cu2 in dependence of temperature demonstrates that the two complexes are typical thermally activated delayed fluorescence (TADF) materials at ambient temperature with TADF proportions of 83 and 80%, respectively. The two complexes were employed as dopants in solution-processed electroluminescent devices.

One new homologous series of mesogenic bromoalkoxy terminated naphthyl derivatives containing flexible spacers as well as azo and ether linkages was synthesized by the etherification of an azo dye (E)-4-(naphthalen-2-yldiazenyl) phenol with various α, ω-dibromo-alkanes, respectively. Compounds in the present work were convinced with respective right structures confirmed with various spectroscopic techniques. Thermotropic properties of the compounds were investigated. Among all the compounds, compounds with flexible spacer (n = 4, 5, 6) exhibited excellent liquid crystalline nature. Structure–property relationships, the influence of different flexible spacers, the mesophase ranges and the photo-isomerization of liquid crystalline compounds were studied. The photophysical behavior was gained by UV–visible spectroscopy and optical properties were determined with a spectroscopic ellipsometer. Computational studies of all molecular structures were performed with satisfactory explanation to attribute mesogenic and optical properties. It's worth noting that synthesized mesogenic materials are excellent dielectrics making them suitable for electronic and industrial applications, as well as having a suitable refractive index making them suitable for light-guiding phenomena.