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.

Cardiovascular Imaging in Women.

Multimodality cardiovascular imaging is a cornerstone diagnostic tool in the diagnosis, risk stratification, and management of cardiovascular diseases, whether those involving the coronary tree, myocardial, or pericardial diseases in general and particularly in women. This manuscript aims to shed some light and summarize the very features of cardiovascular disease in women, explore their unique characteristics and discuss the role of cardiovascular imaging in ischemic heart disease and cardiomyopathies. The role of four imaging modalities will be discussed including nuclear medicine, echocardiography, noninvasive coronary angiography, and cardiac magnetic resonance.

Exploring the untapped pharmacological potential of imidazopyridazines.

Imidazopyridazines are fused heterocycles, like purines, with a pyridazine ring replacing the pyrimidine ring in purines. Imidazopyridazines have been primarily studied for their kinase inhibition activity in the development of new anticancer and antimalarial agents. In addition to this, they have also been investigated for their anticonvulsant, antiallergic, antihistamine, antiviral, and antitubercular properties. Herein, we review the background and development of different imidazopyridazines as potential pharmacological agents. Moreover, the scope of this relatively less charted heterocyclic scaffold is also highlighted.

Investigation of photophysical and electronic properties of aurone derivatives: Insights from spectroscopic techniques and density functional theory calculations.

This paper reports on a study of the photophysical properties, density functional theory (DFT) calculations, infrared (IR), ultraviolet (UV) and nuclear magnetic resonance (NMR) spectroscopic techniques of a series of aurone compounds. The photophysical properties were investigated using UV absorption and fluorescence spectroscopy in a dimethyl sulfoxide (DMSO) solution. Furthermore, the fluorescence quantum yields of the target compounds (1-24) were also investigated. Remarkably, these compounds revealed high quantum yields (Φ = 0.001-0.729) as compared to the already existing aurones in literature. The DFT calculations were performed to elucidate the electronic structure, energy levels and draw a comparison between experimental and theoretical findings. The simulated properties such as molecular frontier orbitals, the density of states, reactivity descriptors (GCRD), electrostatic potential distribution, transition density matrix, electron localization function (ELF) and localized orbital locator (LOL) have been calculated using DFT. The DFT calculations provided insight into the electronic structure and energy levels of the aurone compounds, while the IR and UV spectroscopy results shed light on their functional groups and electronic transitions, respectively. The results of this study contribute to a better understanding of the photophysical properties of aurone compounds and suggest their potential use in technological applications.

Novel Indole-Tethered Chromene Derivatives: Synthesis, Cytotoxic Properties, and Key Computational Insights.

Indole-tethered chromene derivatives were synthesised in a one-pot multicomponent reaction using N-alkyl-1H-indole-3-carbaldehydes, 5,5-dimethylcyclohexane-1,3-dione, and malononitrile, catalysed by DBU at 60-65 °C in a short reaction time. The benefits of the methodology include non-toxicity, an uncomplicated set-up procedure, a faster reaction time, and high yields. Moreover, the anticancer properties of the synthesised compounds were tested against selected cancer cell lines. The derivatives 4c and 4d displayed very good cytotoxic activity, with IC50 values ranging from 7.9 to 9.1 µM. Molecular docking revealed the potent derivatives have good binding affinity towards tubulin protein, better than the control, and the molecular dynamic simulations further demonstrated the stability of ligand-receptor interactions. Moreover, the derivatives followed all the drug-likeness filters.

Flavonoids and related privileged scaffolds as potential urease inhibitors: a review.

Infections caused by bacteria are a significant issue on a global scale, and imperative action is required to discover novel or improved therapeutic agents. Flavonoids are a class of plant-derived compounds that have a variety of potentially useful bioactivities. These activities include immediate antimicrobial properties, synergistic effect with antimicrobials, ferocious repression of pathogenicity, anti-urease activity etc. This review summarizes current studies concerning anti-urease actions of flavonoids as well as structural-activity correlation investigations of the flavonoid core structure. It is possible that if researchers investigate the many structural changes that may be made in flavonoid rings, they'll be able to build up novel compounds that have powerful and effective anti-urease properties.

Design, Synthesis, and Structural Characterization of Thioflavones and Thioflavonols as Potential Tyrosinase Inhibitors: In Vitro and In Silico Studies.

To find new potential tyrosinase inhibitors, a diverse range of 2-arylchromone-4-thione derivatives (2a-2p) were designed and synthesized by employing a multistep strategy, and the newly synthesized compounds, for the first time, were screened in vitro for their tyrosinase inhibitory activity. In this context, the newly synthesized compounds (2a-2p) were characterized using a combination of several spectroscopic techniques including Fourier transform infrared, UV-vis, 1H NMR, and 13C NMR spectroscopies and electron ionization-mass spectrometry. All the target compounds were potent against tyrosinase as compared to the standard inhibitor kojic acid (half-maximal inhibitory concentration (IC50) = 12.6 ± 0.6 µM). The compounds (2a-2p) produced IC50 values in the range from 1.12 ± 0.04 to 5.68 ± 0.13 µM. Among the synthesized 4-thioflavones and 4-thioflavonols, the compound 2n exhibited excellent tyrosinase inhibitory activity with the lowest IC50 of 1.12 ± 0.04 µM that could be recommended as potential lead candidates to cure tyrosinase-mediated hyperpigmentation in the future. A kinetic study of compound 2n revealed that compound 2n inhibited tyrosinase in a competitive mode. Furthermore, the nontoxic performance of the most beneficial compounds ranging from 1 to 25 g/mL was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test method for A375 human melanoma cells for the highly efficient target compounds (2m, 2n, 2o, and 2p). Moreover, a molecular modeling study was performed against tyrosinase enzyme (2Y9X) to check the binding interactions of the synthesized compounds (2a-2p) against the target protein. Furthermore, quantitative structure-activity relationship studies were conducted based on an antityrosinase assay. The value of the correlation coefficient (R 2) 0.9997 shows that there was a good correlation between (2a-2p) structures and selected properties. The geometry optimization of all complexes was performed by using Gaussian 09. Additionally, a drug-likeness research was used to establish the potent analogues' positive action as a new antityrosinase agent (2n, 2o, and 2p).

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

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

Distinctive tunable photophysical properties of versatile environmentally-sensitive tribranched cyanopyridine fluorophores.

In the present work, twenty-four environmentally-sensitive cyanopyridine fluorophores bearing pyrene and/ or fluorene with different para-substituted-phenyl moieties that have been previously designed and synthesized by us are studied in depth for their photophysical properties. Initially, the optical performances of the compounds were investigated by employing UV-visible and fluorescence spectroscopic tools in various aprotic and protic solvents. All the compounds exhibited absorption bands between 310 and 452 nm, and emission bands between 454 and 633 nm. High sensitivity emission spectra with solvents of different polarities were recorded and studied. The fluorescence quantum yield (ϕf) increased in solvents of low polarity and decreased on increasing the polarity of solvents. On the other hand, in case of strong electron donating (-NMe2) and strong electron attracting (-CN) substitution, a pronounced increase in Stokes shifts (up to 252 nm, 14250 cm-1) were recorded. Lippert-Mataga and Reichardts correlations, applied for estimating the variation in dipole moments (Δµ), suggested that the emissive state of designed fluorescence 3-cyanopyridine derivatives is of strong ICT character. The aprotic and protic solvents gave a linear plot for the Stokes shifts in a Lippert-Mataga plot, which appeared as two distinct domains in ET(30) scales indicating the presence of hydrogen bondings. It was observed that for compounds 5b - 8b, with (-NMe2) group on the skeleton of phenyl ring, the Lippert-Mataga and Reichardt-Dimroth's plots deviated from linearity signifying that 5b - 8b molecules were involved in specific interaction with protic solvents.

Admission Rate of Patients With Major Psychiatric Disorders to the Intensive Care Unit.

BACKGROUND: Major psychiatric disorders such as major depression and schizophrenia interfere with patients' life activities and ability to function. These disorders correlate with a higher prevalence of medical and psychiatric comorbidities. OBJECTIVE: To compare the admission rate of patients with major psychiatric disorders between the intensive care unit and other departments in a tertiary care center. METHODS: In a retrospective study of records of 238 721 patients, data were collected from admission files and the intensive care unit computer system. The study group was 245 patients with psychiatric disorders admitted to the intensive care unit. Control groups were 9226 psychiatric patients in other hospital departments and 3032 nonpsychiatric patients in the intensive care unit. RESULTS: A major psychiatric disorder was diagnosed twice as often in the 3277 patients admitted to the intensive care unit as in patients admitted to other departments (7.5% vs 3.8%, P < .001). The study group had fewer male patients than did the nonpsychiatric intensive care unit group (52% vs 66%, P < .001); the age distribution was similar. Patients with a psychiatric disorder required longer stays than other intensive care unit patients. However, their mortality rate was significantly lower (8.57% vs 17.1%, P = .001). A direct correlation between the admission and a psychiatric condition was found in one-third of admissions in the study group. CONCLUSIONS: Psychiatric patients' admission rate to the intensive care unit was significantly higher than their admission rate to other departments. Their intensive care unit stays were also longer, which may increase resource use.

Unprecedented Regio- and Stereoselective Synthesis of Pyrene-Grafted Dispiro[indoline-3,2'-pyrrolidine-3',3″-indolines]: Expedient Experimental and Theoretical Insights into Polar [3 + 2] Cycloaddition.

A series of dispiro[indoline-3,2'-pyrrolidine-3',3″-indolines] was synthesized via a multicomponent polar [3 + 2] cycloaddition (32CA) reaction of isatin derivatives, sarcosine and (E)-3-(2-oxo-2-(pyren-1-yl)ethylidene)indolin-2-one derivatives. The regio- and stereochemistries of the cycloadducts were established on the basis of one-dimensional (1D) (1H-, 13C-, 13C-CRAPT NMR) and two-dimensional (2D) homonuclear and heteronuclear correlation NMR spectrometry experiments (1H-1H gDQFCOSY, 13C-1H-HSQCAD, 13C-1H-HMBCAD, 1H-1H-ROESYAD). The molecular mechanism and regio- and stereoselectivities of the cycloaddition (CA) reaction have been investigated utilizing a density functional theory (DFT) method and were thoroughly explained based on the transition-state stabilities and global/local electrophilicity/nucleophilicity reactivity indices of the reactants.

Development a spectrofluorometric micellar supported encapsulated method for micro determination of silver ion using new 2,6-disubstituted pyridine derivatives.

Herein, the presented manuscript provides for an extensive spectrofluorimetric method for micro determination of silver ion. This established method based on the use of the three synthesized 2,6-disubstituted pyridine derivatives (R1, R2 and R3) through exploiting their high fluorescence emission property. A noticeable effect on the fluorescence emission of the reagents after chelation with Ag (I) was monitored. Its noteworthy that the sensitivity and stability of this method was increased by using micellar medium. After chelation with Ag(I), the fluorescence emission of the ligands R1 and R2 were effectively quenched in a regular manner by increasing Ag(I) concentration. In contrast, an increase of the fluorescence intensity for reagent R3 after addition of Ag (I) was observed. The solvatochromism for all reagents under investigation was examined in different solvent. Furthermore, the chelation between Ag(I) and the and designed pyridine reagents was assessed spectrophotometrically. The optimum conditions for the most stable complexes which give a high signal difference were explored and well-determined. The linear range for determination of silver ion were determined and found to be 0.18-1.16, 0.06-0.59 and 0.18-1.43 µg mL-1 for R1, R2 and R3, respectively. The statistical analytical parameters such as LOD, LOQ, SD of slope, SD of intercept and RDS were calculated. In addition, the developed methods were efficaciously applied for determination of Ag(I) in some water samples. These selective complexation methods found to be in good precision compared to official and reported method as revealed F-test.

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

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

Design, synthesis, and biological evaluation of novel N 4 -substituted sulfonamides: acetamides derivatives as dihydrofolate reductase (DHFR) inhibitors.

BACKGROUND: Sulfonamide derivatives are of great attention due to their wide spectrum of biological activities. Sulfonamides conjugated with acetamide fragments exhibit antimicrobial and anticancer activities. The inhibition dihydrofolate reductase (DHFR) is considered as one of the most prominent mechanism though which sulfonamide derivatives exhibits antimicrobial and antitumor activities. RESULTS: In this study, a new series of 2-(arylamino)acetamides and N-arylacetamides containing sulfonamide moieties were designed, synthesized, characterized and assessed for their antimicrobial activity and screened for cytotoxic activity against human lung carcinoma (A-549) and human breast carcinoma (MCF-7) cell lines. A molecular docking study was performed to identify the mode of action of the synthesized compounds and their good binding interactions were observed with the active sites of dihydrofolate reductase (DHFR). CONCLUSION: Most of the synthesized compounds showed significant activity against A-549 and MCF-7 when compared to 5-Fluorouracil (5-FU), which was used as a reference drug. Some of these synthesized compounds are active as antibacterial and antifungal agents.

Bioactive fluorenes. part I. Synthesis, pharmacological study and molecular docking of novel dihydrofolate reductase inhibitors based-2,7-dichlorofluorene.

In this study, a new series of 2,7-dichloro-4-(2-substituted-amino acetyl)fluorene derivatives were synthesized, characterized and evaluated for their antimicrobial activity and screened for cytotoxic activity against human lung carcinoma (A-549) and human breast carcinoma (MCF-7) cell lines. Most of the synthesized compounds displayed significant activity against A-549 and MCF-7 cell lines when compared to 5-fluorouracil (5-FU), which was used as a reference drug. In addition, some of these reported novel compounds exhibited promising antibacterial and antifungal properties. A molecular docking study was performed to identify the mechanism of action of the synthesized compounds, which suggested binding interactions with the active sites of dihydrofolate reductase (DHFR).

Exploiting a multicomponent domino reaction strategy for the tailoring of versatile environmentally sensitive fluorophore-based nicotinonitriles incorporating pyrene and fluorene moieties.

A simplistic and highly effective protocol for the synthesis of a new class of poly-functionalized innovative nicotinonitriles incorporating pyrene and/or fluorene moieties has been developed through the domino four-component condensation reaction of 1-(pyren-1-yl)ethanone/1-(9H-fluoren-2-yl)ethanone, numerous aromatic aldehydes, and 3-oxo-3-(pyren-1-yl)propanenitrile/3-(9H-fluoren-2-yl)-3-oxopropanenitrile and ammonium acetate in acetic acid as a reaction medium. The advantages of this approach are the short reaction time, excellent yield, and the easy experimental workup that affords substrate diversity and operative competence under metal-free reaction conditions for the formation of C-C and C-N bonds. The substituent effects on the photophysical property-based absorption and the emission of the synthesized compounds in dichloromethane have been well-investigated. Strong absorption quenching of around 100 nm was observed when substitution of the benzene ring at the C4-position of the pyridine moiety occurred with an electron-donating (-N(CH3)2) group. All of the newly synthesized nicotinonitrile derivatives showed strong blue-green fluorescence emission with maxima in the range between 420-630 nm. These highly pronounced emission spectra will help this family of compounds to find application in many areas and the field of materials science.

Facile access to regio- and stereoselective synthesis of highly functionalized spiro[indoline-3,2'-pyrrolidines] incorporating a pyrene moiety: experimental, photophysical and theoretical approach.

The regio- and stereochemical polar [3 + 2] cycloaddition of azomethine ylides, which were generated in situ by the reaction of isatin and sarcosine or benzylamine, with (E)-3-aryl-1-(pyren-1-yl)prop-2-en-1-ones as dipolarophiles, was studied using experimental and theoretical methods. The chemical structures and relative configurations of all products have been fully established by 1D and 2D homonuclear and heteronuclear correlation NMR spectrometry. The effects of the electronic and steric factors of the reactions were discussed. The photophysical properties of the synthesized spiro[indoline-3,2'-pyrrolidin]-2-ones and 5'-phenyl-spiro[indoline-3,2'-pyrrolidin]-2-ones were studied. The mechanism of the reactions was investigated using global and local reactivity indices and frontier molecular orbital (FMO) analysis at the B3LYP/6-31G level of theory. The relationship between the electrophilicity index ω of the dipolarophiles and the Hammett constant σ p has been studied. The theoretical scale of reactivity correctly explains the electrophilic activation/deactivation effects promoted by electron-withdrawing and electron-releasing substituents in the para-position of the dipolarophiles.

Ammonium chloride catalyzed synthesis of novel Schiff bases from spiro[indoline-3,4'-pyran]-3'-carbonitriles and evaluation of their antimicrobial and anti-breast cancer activities.

BACKGROUND: Indolinone and spiro-indoline derivatives have been employed in the preparation of different important therapeutic compounds required for treatment of anticonvulsants, antibacterial, Antitubercular, and anticancer activities. Schiff bases have been found to possess various pharmacological activities such as antitubercular, plant growth inhibiting, insecticsidal, central nerve system depressant, antibacterial, anticancer, anti-inflammatory, and antimicrobial. Mannich bases have a variety of biological activities such as antibacterial and antifungal activities. RESULTS: In this study, a green, rapid and efficient protocol for the synthesis of a new series of Schiff bases from spiro[indoline-3,4'-pyran]-3'-carbonitrile derivatives using ammonium chloride as a very inexpensive and readily available reagent. The prepared compounds were assessed in vitro for their antimicrobial activity. Also, the cytotoxic activity of the prepared compounds was assessed in vitro against human cells line MCF7 breast cancer. CONCLUSION: Good activity was distinguished for Schiff bases from spiro[indoline-3,4'-pyran]-3'-carbonitriles, with some members recorded higher antimicrobial and anti-breast cancer activities.Graphical abstractNovel Schiff bases from spiro[indoline-3,4'-pyran]-3'-carbonitriles.

Efficient synthesis and antimicrobial evaluation of some Mannich bases from 2-arylidine-1-thia-4-azaspiro[4.5]decan-3-ones.

BACKGROUND: Thiazolidinone, has been employed in the preparation of different important drugs required for treatment of inflammations, bacterial infections, and hypertension. Mannich bases have been shown to exhibit diverse biological activities, such as antibacterial, and antifungal activities. Spiroheterocycles including thiazolidine moiety have antimicrobial activity. RESULTS: In this study, a novel, rapid, and efficient protocol is developed for the synthesis of various 2-arylidine-1-thia-4-azaspiro[4.5]decan-3-ones using sodium dodecylbenzene sulfonate (DBSNa) as an inexpensive and readily available reagent in acetic acid at room temperature. High yields, easy work-up, and short reaction times are advantages of this procedure. The synthesized arylidines were undergone Mannich reaction with formaldehyde and secondary amines in absolute ethanol at room temperature to afford the corresponding N-Mannich bases. All prepared Mannich bases were evaluated for their antimicrobial activity. CONCLUSIONS: Good activity was noted for Mannich bases from 2-arylidine-1-thia-4-azaspiro[4.5]decan-3-ones, with some members recorded higher antimicrobial activity. Graphical abstractSynthesis of Mannich bases of 2-arylidine-1-thia-4-azaspiro[4.5]decan-3-ones.