A New Family of Benzo[h]Chromene Based Azo Dye: Synthesis, In-Silico and DFT Studies with In Vitro Antimicrobial and Antiproliferative Assessment.

The high biological activity of the chromene compounds coupled with the intriguing optical features of azo chromophores prompted our desire to construct novel derivatives of chromene incorporating azo moieties 4a-l, which have been prepared via a three-component reaction of 1-naphthalenol-4-[(4-ethoxyphenyl) azo], 1, with the benzaldehyde derivatives and malononitrile. The structural identities of the azo-chromene 4a-l were confirmed on the basis of their spectral data and elemental analysis, and a UV-visible study was performed in a Dimethylformamide (DMF) solution for these molecules. Additionally, the antimicrobial activity was investigated against four human pathogens (Gram-positive and Gram-negative bacteria) and four fungi, employing an agar well diffusion method, with their minimum inhibitory concentrations being reported. Molecules 4a, 4g, and 4h were discovered to be more efficacious against Syncephalastrum racemosum (RCMB 05922) in comparison to the reference drugs, while compounds 4b and 4h demonstrated the highest inhibitory activity against Escherichia coli (E. coli) in evaluation against the reference drugs. Moreover, their cytotoxicity was assessed against three different human cell lines, including human colon carcinoma (HCT-116), human hepatocellular carcinoma (HepG-2), and human breast adenocarcinoma (MCF-7) with a selection of molecules illustrating potency against the HCT-116 and MCF-7 cell lines. Furthermore, the molecular modeling results depicted the binding interactions of the synthesized compounds 3b and 3h in the active site of the E. coli DNA gyrase B enzyme with a clear SAR (structure-activity relationship) analysis. Lastly, the density functional theory's (DFTs) theoretical calculations were performed to quantify the energy levels of the Frontier Molecular Orbitals (FMOs) and their energy gaps, dipole moments, and molecular electrostatic potentials. These data were utilized in the chemical descriptor estimations to confirm the biological activity.

Development of Ferromagnetic Materials Containing Co2P, Fe2P Phases from Organometallic Dendrimers Precursors.

The development of synthesis methods to access advanced materials, such as magnetic materials that combine multimetallic phosphide phases, remains a worthy research challenge. The most widely used strategies for the synthesis of magnetic transition metal phosphides (TMPs) are organometallic approaches. In this study, Fe-containing homometallic dendrimers and Fe/Co-containing heterometallic dendrimers were used to synthesize magnetic materials containing multimetallic phosphide phases. The crystalline nature of the nearly aggregated particles was indicated for both designed magnetic samples. In contrast to heterometallic samples, homometallic samples showed dendritic effects on their magnetic properties. Specifically, saturation magnetization (Ms) and coercivity (Hc) decrease as dendritic generation increases. Incorporating cobalt into the homometallic dendrimers to prepare the heterometallic dendrimers markedly increases the magnetic properties of the magnetic materials from 60 to 75 emu/g. Ferromagnetism in homometallic and heterometallic particles shows different responses to temperature changes. For example, heterometallic samples were less sensitive to temperature changes due to the presence of Co2P in contrast to the homometallic ones, which show an abrupt change in their slopes at a temperature close to 209 K, which appears to be related to the Fe2P ratios. This study presents dendrimers as a new type of precursor for the assembly of magnetic materials containing a mixture of iron- and cobalt-phosphides phases with tunable magnetism, and provides an opportunity to understand magnetism in such materials.

Metallopolymers for advanced sustainable applications.

Since the development of metallopolymers, there has been tremendous interest in the applications of this type of materials. The interest in these materials stems from their potential use in industry as catalysts, biomedical agents in healthcare, energy storage and production as well as climate change mitigation. The past two decades have clearly shown exponential growth in the development of many new classes of metallopolymers that address these issues. Today, metallopolymers are considered to be at the forefront for discovering new and sustainable heterogeneous catalysts, therapeutics for drug-resistant diseases, energy storage and photovoltaics, molecular barometers and thermometers, as well as carbon dioxide sequesters. The focus of this review is to highlight the advances in design of metallopolymers with specific sustainable applications.

Design of Organoiron Dendrimers Containing Paracetamol for Enhanced Antibacterial Efficacy.

Paracetamol (acetaminophen) is a common painkiller and antipyretic drug used globally. Attachment of paracetamol to a series of organoiron dendrimers was successfully synthesized. The aim of this study is to combine the benefits of the presence of these redox-active organoiron dendrimers, their antimicrobial activities against some human pathogenic Gram-positive, and the therapeutic characteristics of paracetamol. The antimicrobial activity of these dendrimers was investigated and tested with a minimum inhibitory concentration and this has been reported. Some of these newly synthesized dendrimers exhibited the highest inhibitory activity against methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus faecium (VRE), and Staphylococcus warneri compared to reference drugs. The results of this study indicate that the antimicrobial efficacy of the dendrimers is dependent on the size of the redox-active organoiron dendrimer and its terminal functionalities. The best result has been recorded for the fourth-generation dendrimer 11, which attached to 48 paracetamol end groups and has 90 units composed of the η6-aryl-η5-cyclopentadienyliron (II) complex. This dendrimer presented inhibition of 50% of the growth (IC50) of 0.52 µM for MRSA, 1.02 µM for VRE, and 0.73 µM for Staphylococcus warneri. The structures of the dendrimers were characterized by elemental analysis, Fourier transform infrared (FT-IR), nuclear magnetic resonance (1H-NMR), and 13C-NMR spectroscopic techniques. In addition, all synthesized dendrimers displayed good thermal stability in the range of 300-350 °C following the degradation of the cationic iron moieties which occurred around 200 °C.

Synthesis, Biological Assessment, and Structure Activity Relationship Studies of New Flavanones Embodying Chromene Moieties.

Novel flavanones that incorporate chromene motifs are synthesized via a one-step multicomponent reaction. The structures of the new chromenes are elucidated by using IR, 1H-NMR, 13C-NMR, 1H-1H COSY, HSQC, HMBC, and elemental analysis. The new compounds are screened for their in vitro antimicrobial and cytotoxic activities. The antimicrobial properties are investigated and established against seven human pathogens, employing the agar well diffusion method and the minimum inhibitory concentrations. A majority of the assessed derivatives are found to exhibit significant antimicrobial activities against most bacterial strains, in comparison to standard reference drugs. Moreover, their cytotoxicity is appraised against four different human carcinoma cell lines: human colon carcinoma (HCT-116), human hepatocellular carcinoma (HepG-2), human breast adenocarcinoma (MCF-7), and adenocarcinoma human alveolar basal epithelial cell (A-549). All the desired compounds are subjected to in-silico studies, forecasting their drug likeness, bioactivity, and the absorption, distribution, metabolism, and excretion (ADME) properties prior to their synthetic assembly. The in-silico molecular docking evaluation of all the targeted derivatives is undertaken on gyrase B and the cyclin-dependent kinase. The in-silico predicted outcomes were endorsed by the in vitro studies.

Advances in Light-Emitting Dendrimers.

The design of dendrimers with various chromophores has attracted significant attention in light of the dual effect of the luminescence of the chromophores and the morphology of the synthesized dendrimers. Recent developments in this field stem from their wide potential applications, including organic light-emitting diodes, photonic switches and upconversion lasers, as well as sensors and electronic devices. The focus of this comprehensive review is on the design and properties of various classes of light-harvesting dendrimeric materials.

Anti-inflammatory drug approach: Synthesis and biological evaluation of novel pyrazolo[3,4-d]pyrimidine compounds.

In this study, the acid chlorides of pyrazolo[3,4-d]pyrimidine compounds were prepared and reacted with a number of nucleophiles. The novel compounds were experimentally tested via enzyme assay and they showed cyclooxygenase-2 inhibition activity in the middle micro molar range (4b had a COX-1 IC50 of 26 µM and a COX-2 IC50 of 34 µM, 3b had a COX-1 IC50 of 19 µM and a COX-2 IC50 of 31 µM, 3a had a COX-2 IC50 of 42 µM). These compounds were analyzed via docking and were predicted to interact with some of the COX-2 key residues. Our best hit, 4d (COX-1 IC50 of 28 µM, COX-2 IC50 of 23 µM), appears to adopt similar binding modes to the standard COX-2 inhibitor, celecoxib, proposing room for possible selectivity. Additionally, the resultant novel compounds were tested in several in vivo assays. Four compounds 3a (COX-2 IC50 of 42 µM), 3d, 4d and 4f were notable for their anti-inflammatory activity that was comparable to that of the clinically available COX-2 inhibitor celecoxib. Interestingly, they showed greater potency than the famous non-steroidal anti-inflammatory drug, Diclofenac sodium. In summary, these novel pyrazolo[3,4-d]pyrimidine analogues showed interesting anti-inflammatory activity and could act as a starting point for future drugs.

A novel synthetic chemical entity (UPEI-800) is neuroprotective in vitro and in an in vivo rat model of oxidative stress.

In this study, we tested a novel synthetic pyrazole-containing compound, 5-amino-1-phenyl-1H-pyrazole-4-carbonitrile (APPC), as an antioxidant in both in vitro and in vivo models of oxidative stress. In addition, the utility of covalently combining APPC with another well-established antioxidant, lipoic acid (LA), was also tested in both models. The in vitro results demonstrated that pretreatment with APPC in a mixed neuronal-glial culture exposed to oxygen-glucose deprivation (OGD) followed by reoxygenation-refeeding, resulted in significant neuroprotection at concentrations between 2.5 to 25 µmol/L. In contrast, LA was not neuroprotective following OGD alone or following reoxygenation-refeeding. However, the synthetic covalent combination of APPC with LA, named "UPEI-800", resulted in significant neuroprotection at concentrations between 0.027 and 2.7 µmol/L (100-fold more potent than APPC alone), an effect shown to be correlated with increased cellular antioxidant capacity. Further, in an in vivo model of ischaemia-reperfusion injury following transient occlusion of the middle cerebral artery (tMCAO), both APPC (0.1 and 1.0 mg/kg) and UPEI-800 (1×10-3  mg/kg) provided significant neuroprotection. Consistent with the in vitro findings, the in vivo results following tMCAO also demonstrated a 100-fold increase in the potency of the covalently linked compound UPEI-800 compared to APPC alone.

Photoinduced Synthesis of Dual-Emissive Tetraphenylethene-Based Dendrimers with Tunable Aggregates and Solution States Emissions.

Photoactive materials are actively researched, piloting breakthroughs that have enriched fundamental understanding of science, and have led to real applications. Tetraphenylethene, a photoactive molecule that is of interest from fundamental and applied perspectives, features photochemical properties that are not exploited in the design of photoactive, dual-emissive materials. Here, tetraphenylethene-based, dual-emissive dendrimers are constructed via a synthetic approach that involves a photochemical reaction that exploits the photochemistry of tetraphenylethene. These dendrimers are emissive in solution and in the aggregate state with tunable dual emissions at 368 and 469 nm. The photochemical reaction also tunes the size of the aggregates, increasing the size after UV irradiation. The reported synthetic strategy is a direct and facile approach to accessing dual-emissive macromolecules, especially tetraphenylethene-based systems for real applications.

Antimicrobial Organometallic Dendrimers with Tunable Activity against Multidrug-Resistant Bacteria.

Multidrug-resistant pathogens are an increasing threat to public health. In an effort to curb the virulence of these pathogens, new antimicrobial agents are sought. Here we report a new class of antimicrobial organometallic dendrimers with tunable activity against multidrug-resistant Gram-positive bacteria that included methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium. Mechanistically, these redox-active, cationic organometallic dendrimers induced oxidative stress on bacteria and also disrupted the microbial cell membrane. The minimum inhibitory concentrations, which provide a quantitative measure of the antimicrobial activity of these dendrimers, were in the low micromolar range. AlamarBlue cell viability assay also confirms the antimicrobial activity of these dendrimers. Interestingly, these dendrimers were noncytotoxic to epidermal cell lines and to mammalian red blood cells, making them potential antimicrobial platforms for topical applications.

Sandwich complex-containing macromolecules: property tunability through versatile synthesis.

Sandwich complexes feature unique properties as the physical and electronic properties of a hydrocarbon ligand or its derivative are integrated into the physical, electronic, magnetic, and optical properties of a metal. Incorporation of these complexes into macromolecules results in intriguing physical, electrical, and optical properties that were hitherto unknown in organic-based macromolecules. These properties are tunable through well-designed synthetic strategies. This review surveys many of the synthetic approaches that have resulted in tuning the properties of sandwich complex-containing macromolecules. While the past two decades have seen an ever-growing number of research publications in this field, gaps remain to be filled. Thus, we expect this review to stimulate research interest towards bridging these gaps, which include the insolubility of some of these macromolecules as well as expanding the scope of the sandwich complexes.

Recent developments in the synthesis and applications of terpyridine-based metal complexes: a systematic review.

Terpyridine-based metal complexes have emerged as versatile and indispensable building blocks in the realm of modern chemistry, offering a plethora of applications spanning from materials science to catalysis and beyond. This comprehensive review article delves into the multifaceted world of terpyridine complexes, presenting an overview of their synthesis, structural diversity, and coordination chemistry principles. Focusing on their diverse functionalities, we explore their pivotal roles in catalysis, supramolecular chemistry, luminescent materials, and nanoscience. Furthermore, we highlight the burgeoning applications of terpyridine complexes in sustainable energy technologies, biomimetic systems, and medicinal chemistry, underscoring their remarkable adaptability to address pressing challenges in these fields. By elucidating the pivotal role of terpyridine complexes as versatile building blocks, this review provides valuable insights into their current state-of-the-art applications and future potential, thus inspiring continued innovation and exploration in this exciting area of research.

Study on Regio- and Diastereoselectivity of the 1,3-Dipolar Cycloaddition Reaction of Azomethine Ylide with 2-(Benzo[d]thiazol-2-yl)-3-(aryl)acrylonitrile: Synthesis, Spectroscopic, and Computational Approach.

An unprecedented and efficient three-component 1,3-dipolar cycloaddition reaction using (E)-2-(benzo[d]thiazol-2-yl)-3-(aryl)acrylonitriles 4a-g and an in situ generated azomethine ylide 3 from isatin and N-methylglycine is described. The reaction exhibits exclusive regioselectivity, resulting in the formation of 3'-(benzo[d]thiazol-2-yl)-1'-methyl-2-oxo-4'-(aryl)spiro[indoline-3,2'-pyrrolidine]-3'-carbonitriles regioisomers through exo/endo approaches. The diastereoselectivity of the reaction is highly dependent on the substitution pattern of the phenyl ring in dipolarophiles 4a-g, leading to the formation of exo-/endo-cycloadducts in varying ratios. To understand the stereoselectivity, the transition state structures were optimized using the TS guess geometry with the QST3-based method. The reaction mechanism and regioselectivity were elucidated by evaluating global and local electrophilicity and nucleophilicity descriptors at the B3LYP/cc-pVTZ level of theory, along with considerations based on the HSAB principle. The analysis of global electron density transfer (GEDT) showed that the reactions are polar and electron density fluxes from azomethine ylide 3 toward dipolarophile 4a-g. It was found from the molecular electrostatic potential map (MESP) that at the more favorable transition state, approach of reactants locates the oppositely charged regions over each other resulting in attractive forces between the two fragments. The computational results are consistent with the experimental observations, confirming that the reactions proceed through an asynchronous one-step mechanism.

Dibenzyl ferrocene-1,1'-dicarboxyl-ate.

In the title compound, [Fe(C(13)H(11)O(2))(2)], there are markedly different orientations of the two phenyl-meth-oxy-carbonyl substituents [O-C-C-C torsion angles = 84.5 (3) and 139.6 (2)°]. These orientations are mediated by a number of inter-molecular C-H⋯O inter-actions, which result in a one-dimensional hydrogen-bonded network of mol-ecules.

Pharmacological Evaluation of Novel Organoiron Dendrimers as Antimicrobial and Anti-Inflammatory Agents.

The synthesis of a novel and attractive class of nonsteroidal anti-inflammatory and antimicrobial organoiron dendrimers attached to the well-known drug ibuprofen is achieved. The structures of these dendrimers are established by spectroscopic and analytical techniques. The antimicrobial activity of these dendrimers is investigated and tested against five human pathogenic Gram-positive and Gram-negative bacteria, and minimum inhibitory concentrations are reported. Some of these synthesized dendrimers exhibit higher inhibitory activity against methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecium, and Staphylococcus warneri compare to the reference drugs. As well, the in vitro and in vivo anti-inflammatory activities of these dendrimers are evaluated. The results of in vivo anti-inflammatory activity and histopathology of inflamed paws show that all dendrimers display considerable anti-inflammatory activity; however, second-generation dendrimer (G2-D6) shows the best anti-inflammatory activity, which is more potent than the commercial drug ibuprofen at the same tested dose. Results of the toxicity study reveal that G2-D6 is the safest drug on biological tissues.

Aspirin-Based Organoiron Dendrimers as Promising Anti-Inflammatory, Anticancer, and Antimicrobial Drugs.

Designing nanocarriers with actions directed at a specific organ or tissue is a very promising strategy since it can significantly reduce the toxicity of a bioactive drug. In this study, an organometallic dendrimer was used to synthesize a biocompatible drug delivery system by attaching aspirin to the periphery of the dendrimer. Our goal is to enhance the bioavailability and anticancer activity of aspirin and reduce its toxicity through successive generations of organoiron dendrimers. The biological activity of aspirin-based dendrimer complexes was evaluated. The result of antimicrobial activity of the synthesized dendrimers also demonstrated an increase in their antimicrobial activity with increased generation of the dendrimers for most types of microorganisms. This study reveals for the first time that organoiron dendrimers linked with aspirin exhibit an excellent Gram-negative activity comparable to the reference drug Gentamicin. All synthesized dendrimers were tested for their anticancer activity against breast cancer cell lines (MCF-7), hepatocellular cell lines (Hep-G2), and a non-cancer cell line, Human Embryonic Kidney (HEK293), using the MTT cell viability assay and compared against a standard anticancer drug, Doxorubicin. Compounds G3-D9-Asp and G4-D12-Asp exhibited noticeable activity against both cell lines, both of which were more effective than aspirin itself. In addition, the in vivo anti-inflammatory activity and histopathology of swollen paws showed that the designed aspirin-based dendrimers displayed significant anti-inflammatory activity; however, G2-D6-Asp showed the best anti-inflammatory activity, which was more potent than the reference drug aspirin during the same period. Moreover, the coupling of aspirin to the periphery of organoiron dendrimers showed a significant reduction in the toxicity of aspirin on the stomach.

Synthesis and biological evaluation of novel pyrazole compounds.

A novel dipyrazole ethandiamide compound and acid chloride of pyrazolo[3,4-d]pyrimidine 4(5H)-one were prepared and reacted with a number of nucleophiles. The resultant novel compounds were tested in several in vitro and in vivo assays. Three compounds inhibited the secretion of neurotoxins by human THP-1 monocytic cells at concentrations that were not toxic to these cells. They also partially inhibited both cyclooxygenase-1 and -2 isoforms. In animal studies, two compounds were notable for their anti-inflammatory activity that was comparable to that of the clinically available cyclooxygenase-2 inhibitor celecoxib. Modeling studies by using the molecular operating environment module showed comparable docking scores for the two enantiomers docked in the active site of cyclooxygenase-2.

Polynorbornenes Containing Ferrocene Derivatives and Alkyne-bis(tricarbonylcobalt).

Coordination of dicobalt hexacarbonyl to the alkyne moiety of norbornene complexes containing either ferrocene or η(6) -chlorobenzene-η(5) -cyclopentadienyliron hexafluorophosphate, gave two unique trimetallic complexes available for ROMP. Polymerization of each monomer using Grubbs second generation catalyst gave organoiron/organocobalt polynorbornenes with weight average molecular weights between 55 300 and 69 000 with PDIs between 1.2 and 1.9. Cyclic voltammetric studies of the monomers and polymers at -40 °C showed a reversible reduction for cationic complexes containing η(6) -benzene-η(5) -cyclopentadienyliron and for the dicobalt hexacarbonyl moieties while, a reversible oxidation for the ferrocene containing complex was observed. Thermal analysis showed that the cobalt carbonyl moiety of the polymers degraded near 130 °C; however, the polymeric backbone was stable up to 350 °C. Scanning electron microscopy (SEM) and SEM-EDS indicated that the polymers possessed a fine globular morphology and that the distribution of iron and cobalt atoms was homogenous on the macro-scale.

Design of Organoiron Macromolecules Based on Upper Rim Functionalized Calix[4]arenes.

The versatility of cationic cyclopentadienyliron complexes is demonstrated for the generation of calix[4]arene-based dendrimers and polymers. Dendrimers were prepared from a branched organoiron calix[4]arene through subsequent reactions of azo dyes and organoiron complexes. The resulting azo dye-containing metallocalix[4]arenes were soluble in polar organic solvents and displayed λ(max) ranging between 430 and 456 nm. Upon addition of various acids, the λ(max) shifted to higher wavelengths (513-535 nm). In the solid state and in solution, the azo dye-containing metallocalix[4]arenes reversibly changed colour in the presence of acid and base, indicating their potential use as acid sensors. Cyclic voltammetric studies showed that the iron centres of the metallocalix[4]arenes were reversibly reduced at E(1/2) = -1.49 V. When non-branching organoiron-based calix[4]arene were reacted with dithiols, polymers containing calix[4]arenes either in their side chains or main chains were obtained. The polymers possessed weight average molecular weights between 35 000 and 53 000. The polymers were determined to be thermally stable with backbone decomposition occurring above 500 °C.

Properties of the [M(dppm)2M']2+ building blocks (M, M' = Pd or Pt): site selectivity, emission features, and frontier orbital analysis.

The homodinuclear [ClM(mu-dppm)(2)MCl] complexes 1 (M = Pd) and 2 (M = Pt) react with RNC ligands (R = Ph, xylyl, p-tolyl, p-C(6)H(4)iPr) to provide the A-frame [ClPd(mu-dppm)(2)(mu-C=N-R)PdCl] (R = Ph (5a), xylyl (5b)), [ClPt(mu-dppm)(2)(mu-C=N-R)PtCl] (R = p-tolyl (4a); p-C(6)H(4)iPr (4b)), and the d(9)-d(9) M(2)-bonded [ClPt(mu-dppm)(2)Pt(CN-R)]Cl (R = xylyl (3a); p-C(6)H(4)iPr (3b)) complexes. The heterodinuclear [XPd(mu-dppm)(2)PtX] complexes 6a (X = Cl) and 6b (X = I) react with RNC (R = o-anisyl) to form the A-frame [XPd(mu-dppm)(2)(mu-C=N-R)PtX] (X = Cl (9); I (10a)) and M(2)-bonded [ClPt(mu-dppm)(2)Pt(CN-R)]Cl (10b) complexes. The dangling ligand-containing complex [ClPd(mu-dppm)(2)Pt(eta(1)-dppm=O)](BF(4)) (7) reacts with xylyl-NC stoichiometrically to produce the dicationic salt [(xylyl-NC)Pd(mu-dppm)(2)Pt(eta(1)-dppm=O)](BF(4))(2) (8). Parameters ruling the coordination site terminal versus bridging are discussed. The precursor 10a reacts with RNC (R = o-anisyl, tBu) to form the heterobimetallic bis(isonitrile) [IPd(mu-dppm)(2)(mu-C=N-o-anisyl)Pt(CN-R)]I complexes 11b and 12, respectively, demonstrating the site selectivity of the second CNR ligand coordination, Pd versus Pt. The X-ray structures of 11b and 12 were obtained. Complex 12 is the first example of an A-frame system of the Ni-triad bearing two different isocyanide ligands. Several d(9)-d(9) terminal and d(8)-d(8) A-frame homo- and heterodinuclear complexes in 2-MeTHF at 77 K were studied by UV-vis and luminescence spectroscopy. Assignments for the lowest energy absorption and emission bands are made on the basis of density functional theory and time-dependent density functional theory computations.