4-substituted Phenyl Research Articles

Synthesis and investigation of antibacterial activity of 1-(4-substituted phenyl)-5-oxopyrrolidine-3-carbohydrazide derivatives


 
 
 
 Hydrazides are very important precursors for the synthesis of a wide variety of derivatives, including heterocyclic compounds of biological interest in drug design and discovery. Acid hydrazides with a pyrrole, thiophene, furan, quinoline, isoquinoline, isoxazole and benzimidazole core in the structure were found to be used in medicine, pharmacy, agriculture and many other fields.
 In the search for compounds with antibacterial properties, mono- and dihydrazides were used in this study to prepare 1-(4-substituted phenyl)-5-oxopyr-rolidine-3-carbohydrazide derivatives bearing the corresponding hydrazone and azole substituents.
 The formation of the target compounds was performed via condensation reactions with the chosen aromatic aldehydes and isatin, which led to the construction of the appropriate hydrazone-type structures as well as with diketones which afforded compounds with pyrazole and pyrrole nuclei.
 In addition, a preliminary antibacterial evaluation of the synthesised compounds was performed using the gram-positive Bacillus subtilis and the gramnegative Escherichia coli bacterial strains. As it was expected, the evaluation revealed potential antibacterial candidates that can help address the global challenges of antibiotic resistance and infectious disease outbreaks.
 
 
 

Exploration of quinazoline-tethered hydroxamic acid derivatives as HDAC inhibitors for anticancer activity: Design, synthesis, molecular docking, and biological evaluation

In the past two decades, targeted cancer therapy has emerged as a novel class of anticancer therapeutics, besides traditional chemotherapy, surgery, and radiotherapy. Inhibition of HDACs represents a promising avenue for cancer therapeutics and initial success in treating select T-cell lymphomas has led to the FDA approval of four HDAC-targeted agents. The majority of currently available HDAC inhibitors have weak anticancer activity, with significant side effects. To address these drawbacks, in the present work we have designed and synthesized a novel series of histone deacetylase inhibitors combining 2-(4-substituted phenyl) quinazoline bioactive fragment as cap group and N-hydroxycinnamamide/ N-hydroxybenzamide as linker group, and evaluated for their cytotoxic activity against the three cancer cell lines (HeLa, MCF-7 and HCT-116) and HDAC inhibitory activity. All three cancer cell lines were most sensitive to the N-hydroxyacrylamide derivatives (5a-f) as compared to N-hydroxybenzamides (7a-f) derivatives. In particular, compound 5a (0.39, 0.26, 0.41 µM respectively) and 5b (0.27, 0.57, 0.32 µM respectively) were found to be the most potent derivatives among all tested cell lines. For HDAC inhibitory activity, it was found that compounds 5a, 5b, and 5d possessed comparable, even better HDAC inhibitory activity as compared to SAHA. These compounds also tested in vitro heamolytic activity, most of the compounds found biocompatible with human erythrocytes thereby evidencing the lack of haemolytic toxicity of anticancer drugs. In silico ADMET and molecular docking studies further corroborated with the experimental results. Overall, the new synthesized compounds exhibited significant HDAC and cytotoxic activity. Also, the different substituents and unsaturated bond influenced both HDAC inhibitory and cytotoxic activity. The outcome of the current work is that several potential HDAC inhibitors have emerged for further design of more potent HDAC inhibitors with better cytotoxicity.

Synthesis, characterization and biological investigations of some new Oxadiazoles: In-vitro and In-Silico approach

A series of new oxadiazole derivatives, namely 1-{2-substituted phenyl −5-[2-tifluoromethyl)-1H-indol-3-yl]-3-(2H)-ylethanone 1,3,4-oxadiazoles were synthesized and investigated in this research. Using AutoDockVina 4.2, the new compounds VIb and VIc were extensively investigated for their ADMET characteristics and in-silico drug receptor interactions with the target enzyme, GlcN-6-P synthase (PDB ID: 2FV5). The existence of an electron-withdrawing group and a lipophilic functional group substituted at the phenyl ring was observed to be more active than in other molecules. The new molecules drug ability was investigated using ADMET experiments performed by Swiss ADME software, and the newly synthesized compounds qualified for ADME characteristics and followed Lipinski’s rule of five. FTIR, 1H NMR, 13CNMR, and mass spectrometry tools were used to characterize the prepared substances. The prepared substances were screened for antibacterial activity against gram-positive (Bacillus subtilis, Staphylococcus aureus) and gram-negative microbes (Pseudomonas aeruginosa and Escherichia coli) using cup plate and MIC techniques. These substances were also screened for antifungal activity against Aspergillus niger and Candida albicans, with Ampicillin and Amphotericin B serving as standard references. The compounds VIb and VIc have more antibacterial action than antifungal activity among the synthesized substances. Compounds VIa to VIf were examined for in vitro antioxidant activity and compounds VIb and VIc has displayed significant antioxidant potentials with IC50 values 45.16 and 38.14 in DPPH assay. The compounds VIa–f were tested for anticancer activity using MDA-MB 361 cell lines using MTT assays, and the IC50 values were recorded, out of which VIb and VIc displayed the lowest IC50 values. In-silico drug receptor interactions with the target enzyme, phosphoinositide-3-kinase (PI3K), with PDB ID: 3MJW were predicted as supportive evidence for the anticancer properties of the synthesized scaffolds.

Synthesis, characterization, crystal structures and cytotoxic activity of Pt(II) complexes with N,N-donor ligands in tumor cell lines

Cisplatin is one of the most used chemotherapeutic agents nowadays. However, it presents several and severe side effects. For that, the synthesis of new analogues of cisplatin is crucial to improve the current therapies. In this work, two squared-planar Pt(II) analogues of cisplatin were presented. These analogues included a bidentate ligand molecule with a 3,5-dimethyl-pyrazole ring and a thiazine (DMPzTz) or thiazoline (DMPzTn) ring. The chemical characterization covered single-crystal X-ray diffraction, infrared spectroscopy (IR) and elemental analysis. Their potential anticarcinogenic ability was studied in three different human tumor cell lines, i.e., histiocytic lymphoma (U-937), promyelocytic leukemia (HL-60) and epithelial cervix carcinoma (HeLa) via cytotoxicity assay. The results showed moderate cytotoxic effect of the complexes on leukemic cell lines, with scarce effect on solid tumor cell line HeLa. Lower IC50 values were found for U-937 cell line, being 32.3 ± 1.2 µmol/dm3 for PtDMPzTn and 43.0 ± 1.4 µmol/dm3 for PtDMPzTz. The comparison with previously synthesized analogues with phenyl substitutions or no substitutions in the pyrazole ring, allows to conclude that the presence of ligands with methyl substituted-pyrazole ring did not improve the effect of the complexes. In addition, the main effect of these potential chemotherapeutic agents is produced by the presence of platinum(II) as metal center, since the free ligands do not show any significant activity.

Catalyst-Free Synthesis of Novel 4-(Benzofuran-2-yl)-N-phenylthiazol-2(3H)-imines, Crystal Structure Elucidation, and the Effect of Phenyl Substitution on Crystal Packing

A one-pot reaction of an equimolar mixture of 4-methoxyaniline, phenyl isothiocyanate, and 2-bromoacetylbenzofuran in absolute ethanol in the absence of any catalysts afforded 4-(benzofuran-2-yl)-3-(4-methoxyphenyl)-N-phenylthiazol-2(3H)-imine with an 83% yield. Under similar conditions, 4-flouroaniline provided a mixture of the expected 4-(benzofuran-2-yl)-3-(4-fluorophenyl)-N-phenylthiazol-2(3H)-imine and unexpected 4-(benzofuran-2-yl)-N-(4-fluorophenyl)-3-phenylthiazol-2(3H)-imine at an overall 73% yield. The structures of the synthesized heterocycles were confirmed using NMR spectroscopy. The products were recrystallized from dimethylformamide to afford samples suitable for structural determination via single-crystal diffraction. The molecules of the products share a common backbone and have similar conformations. They also display some common intermolecular interactions, including C–H···X (X = N, O, π) and π···π contacts. The molecules differ due to the methoxy and fluoro substituents on their phenyl rings, resulting in variations in the extended network in the crystals. Electron density maps and Hirshfeld surfaces have been used to rationalize the intermolecular contacts.

8-benzimidazolyl coumarin-3-oxadiazoles – Synthesis, docking studies and Anti-proliferative evaluation against breast cancer

A series of 8-benzimidazolyl-coumarin-3-oxadiazoles (10a-j) were synthesized and evaluated their anti-cancer activity against breast cancer using MCF-7 cell lines. Out of 10 tricore hybrids synthesized, the compound 10b with 2,4-dimethyl phenyl substitution on the oxadiazole ring is emerged as most potent compound with the IC50 value of 9.26 μg/mL compared to the IC50 value of the standard drug doxorubicin 7.54 μg/mL. The compound 10g with 2,6-difluoro phenyl substituted, 10c with 3‑methoxy benzyl substituted and 10e with 4‑chloro phenyl substitution on the oxadiazole ring are the other analogues with significant anti-cancer activity. The molecular docking studies using Autodock Vina tool revealed that the tested ligands have lower binding energy with the receptor protein quinone reductase-2 (PDB ID - 4ZVM) than the standard drug doxorubicin and exhibited similar amino acid interactions.

Efficient zinc extraction with novel phenyl phosphate PTOPP in sulfuric acid system

Traditional acidic phosphate extractants (D2EHPA and HEH/EHP) exhibit poor extraction performance under high-acid conditions and require saponification pretreatment to maintain the pH stability of the aqueous phase during the solvent extraction. However, saponification pretreatment produces a large amount of saline wastewater, resulting in high treatment costs and difficulty of the industrial waste salts utilization. Thus, we synthesized an efficient p-tert-octyl phenyl phosphate (PTOPP) extractant suitable for a high-acid system based on phenyl substitution and carbon-chain design. The structure and content of the synthesized products were confirmed to be [(CH3)3CCH2C(CH3)2C6H4O]2P(O)OH (diphenyl phosphate, P10B4, 88.26%) and (CH3)3CCH2C(CH3)2C6H4OP(O)(OH)2 (monophenyl phosphate, DHP10B4, 10.68%) via HRMS, LCMS, and NMR characterization combined with potentiometric titration. After three-stage countercurrent extraction and two-stage countercurrent stripping, the zinc extraction efficiency of PTOPP reached 85%, and the zinc concentration of aqueous phase increased from 20 g/L to 66.53 g/L with a 3.3 enrichment multiple. In comparison, the enrichment multiples of D2EHPA and HEH/EHP under the same conditions were only 1.5 and 1.1, respectively. The zinc extraction mechanism with PTOPP was determined by the slope method and structural characterization of the extracted compound (PTOPP-Zn). During the zinc extraction process, the P-OH and P=O groups in PTOPP interacted with Zn2+ to form Zn–O bonds through proton exchange and coordination reactions, and the molecular formula of the extracted compound was ZnA2·HA. The novel PTOPP significantly improves the zinc extraction performance and achieves a remarkable enrichment effect without saponification pretreatment, thereby avoiding the consumption of NaOH and the discharge of Na2SO4 wastewater. It has promising applications in the fields of low-grade zinc mineral resource recovery and heavy-metal wastewater disposal.

Novel indole derivatives of dihydropyrimidinone: Synthesis, characterization, molecular docking and antimicrobial activity

The enaminone was reacted with substituted aldehyde and urea in glacial acetic acid. The indole derivatives of dihydropyrimidinone were obtained in good yield. Spectroscopic methods were employed to confirm and characterize the structures of all novel synthesized compounds. All the compounds were screened for antimicrobial activity against Gram-positive, Gram-negative, and Candida albicans. Most of the synthesized compounds were active against all tested trains. Enaminone was found to be highly active against all strains except P. aeruginosa and S. typhi. Enaminone presented (MIC = 64 µg/mL) against S. pneumonia, (MIC = 16 µg/mL) against B. anthracis, and (MIC = 32 µg/mL) against S. aureus as compared to positive control erythromycin (MIC = 8 µg/mL), gentamycin (MIC = 2 µg/mL) and ciprofloxacin (MIC = 4 g/L) respectively. A molecular docking study was performed at the active site of E. coli DNA gyrase, K. pneumonia DNA gyrase, and topoisomerase IV. The results showed that the compound with phenyl substitution exhibited an inhibition zone of 18 mm against E. coli and presented the highest binding energy S = -9.83 kcal/mol. It showed three π−bonds with (DA20, and DT15), aromatic rings in the molecule, and the carboxyl groups of the urea ring chelated Mg2+. Compound with 4-nitrophenyl exhibited an inhibition zone of 13.6 mm against K. pneumoniae. It also presented the highest binding energy S = -9.55 kcal/mol. LYS444 and DC315 were predicted to form an H-bond donor with hydrogen in phenyl and urea rings. All the compounds followed Lipinski's rule of five without any violation.

Multi-stimuli responsive carbazole-imidazole derivatives: Effect of phenyl substitution and UV light-oxygen induced photochemical transformation

New carbazole-imidazole derivatives, (3-(4,5-diphenyl-1H-imidazole-2-yl)-9-(3-methoxyphenyl)-9H-carbazole (Cz-DPIM)) and 9-(3-methoxyphenyl)-3-(1,4,5-triphenyl-1H-imidazole-2-yl)-9H-carbazole (Cz-TPIM) are synthesized and investigated the effect of phenyl substitution on the fluorescence and stimuli-induced fluorescence properties. Cz-DPIM exhibited relatively strong fluorescence in solution compared to Cz-TPIM (Quantum yield (Φf, compared to quinine sulphate standard) = 0.28 (Cz-DPIM) and 0.09 (Cz-TPIM)). In contrast, Cz-DPIM is weakly fluorescence in solid-state but Cz-TPIM showed strong fluorescence (Φf = 1.3% (Cz-DPIM) and 18.2% (Cz-TPIM)). Cz-TPIM displayed mechanoresponsive reversible fluorescence switching upon crushing and solvent fuming. Both Cz-DPIM and Cz-TPIM exhibited reversible halofluorochromsim upon exposure of trifluoroacetic acid (TFA) and ammonia (NH3). Interestingly, Cz-DPIM and Cz-TPIM exhibited photocleavage upon UV light irradiation in presence of oxygen in CH3CN and produced green emissive fluorescence product. The controlled studies revealed that the presence of oxygen is important for exhibiting photocleavage by UV light exposure and suggest potential use for oxygen sensing application. The UV light and oxygen induced photocleavage of Cz-DPIM and Cz-TPIM also demonstrated in thin films.

Mechanistic Insight into Anion-Binding Catalytic Living Cationic Polymerization.

Exploiting non-covalent interactions to catalyze challenging ionic polymerizations is an ambitious goal but is in its infancy. We recently demonstrated non-covalent anion-binding catalysis as an effective methodology to enable living cationic polymerization (LCP) of vinyl ethers in an environmentally benign manner. Here, we further elucidate the structure-reactivity relationships of the elaborately designed seleno-cyclodiphosph(V)azanes catalysts and the roles of anion-binding interactions by a combined theoretical DFT study and experimental study. The investigation suggests that the distinct cis-cyclodiphosph(V)azane framework combined with "selenium effect" and electron-withdrawing 3,5-(CF3 )2 -Phenyl substitution pattern in catalyst enables a critical contribution to accessing excellent stability, anion affinity and solubility under polymerization conditions. Thus, the catalyst could leverage anion-binding interactions to precisely control reversible and transient dormant-active species equilibrium, allowing it to dynamically bind, recognize and pre-organize propagating ionic species and monomer, thereby facilitating efficient chain propagation and minimizing irreversible chain transfer events under mild conditions. The more in-depth understanding of the mechanism for anion-binding catalytic LCP reported herein should help to guide future catalyst design and to extend this concept to broader polymerization systems where ionic species serve as crucial intermediates.

Exploration of Indolo[3,2c]isoquinoline derived triazoles as potential antimicrobial and DNA cleavage agents: Synthesis, DFT calculations, and molecular modeling studies

Indole and its derivatives are well-known assorted motif in drug design and development. We here in reporting synthesis of new 9-chloro-1-(4-substituted phenyl)-12H-indolo[2,3-c][1,2,4]triazolo[3,4-a]isoquinolines 7 (a-h). Structures of the newly synthesized compounds were confirmed by making use of spectroscopic techniques like IR, NMR and Mass. The DFT calculations were taken for the selected molecules using CAM-B3LYP hybrid functional with a 6–31 + g(d) all-electron basis set using the Gaussian 09 package. The drug-likeness predictions were described for the synthesized derivatives. The In vitro antimicrobial and DNA cleavage activities were reported for all compounds 7 (a-h). The compounds 7a, 7b, and 7h showed excellent microbial inhibition and DNA cleavage activity as compared to standard drugs. Furthermore, the docking studies for the newly synthesized molecules were carried out by Auto dock software with two molecular targets Epidermal Growth Factor Receptor tyrosine kinase (1 M17) and C-kit Tyrosine Kinase (1 T46) exhibited better binding affinity of all synthesized compounds. In addition, the docking results were observed to be in full agreement with the in vitro DNA cleavage assay suggesting the potential of synthesized metal complexes in biological applications. Lastly, the protein stability, fluctuations of APO-Protein, and protein–ligand complexes were investigated through Molecular Dynamics (MD) simulations studies using Desmond Maestro 11.3 and potential lead molecules were identified.

Naphtho[2,1-b]furan derived triazole-pyrimidines as highly potential InhA and Cytochrome c peroxidase inhibitors: Synthesis, DFT calculations, drug-likeness profile, molecular docking and dynamic studies

Napthofuran and its fused heterocyclic derivatives evaluated with varied biological activity functional groups comprise an important class of compounds for new chemical entities. We here in reporting synthesis of new 3-(4-substituted phenyl)naphtho[1′,2′:4,5]furo[2,3-e][1,2,4]triazolo[4,3-c]pyrimidines 6(a-f). Structures of the newly synthesized compounds were confirmed by making use of spectroscopic techniques like IR, NMR and Mass. The DFT calculations were taken for the selected molecules using B3LYP hybrid functional with a 6–31+G (d, p) all-electron basis set using the Gaussian 09 package. The bioactivity predictions were evaluated for the synthesized compounds. The In vitro biological activities were reported for the all compounds 6(a-f). The compound 6a showed high activity of anti-TB and antioxidant activity with at MIC 1.6 μg/ml and at percentage of inhibition (72.54±0.21) at 10μg/ml respectively. The compound 6f (73.21±0.11) showed antioxidant activity better than standard drug BHA (71.32±0.13) at 10 μg/ml. Furthermore, the docking studies for the newly synthesized molecules were carried out by Auto dock software with proteins InhA (4TZK),Cytochrome c peroxidase (2 × 08) and protease (Mpro) of SARS-CoV-2 Omicron (PDB ID: 7TOB). All the compounds showed a strong binding affinity for the docked proteins. The outcome of docking results showed that compound 6ahad excellent binding energies -10.8, -9.4, and -9.0 kcal/mol with 4TZK, 2 × 08, and 7TOB respectively. Lastly, the protein stability, fluctuations of APO-Protein, protein-ligand complexes were investigated through Molecular Dynamics (MD) simulations studies using Desmond Maestro 11.3 and potential lead molecules were identified.

Improving the efficiency of dye-sensitized solar cells based on BODIPY dye and its analogous: The synergistic effect of benzo fusion and phenyl substitution

The facile structural modification and excellent photophysical properties of boron-dipyrromethene (BODIPY) make them potential photosensitizers in dye-sensitized solar cells (DSSCs). This study focuses on improving the photophysical properties of BODIPY and a series of its analogous such as BOPHY and BOPPY via phenyl substitution and benzene fusing. The structural, electronic, optical, and photovoltaic properties of the parent and modified dyes were theoretically calculated in the THF solvent. While extending the conjugation length via individual benzene fusing or phenyl substitution improves the power conversion efficiency, incorporating both modifications result in a synergistic effect through direct inductive and indirect spatial effects. Compared to the parent dye, phenyl substituted and benzene fused dyes exhibit an increased power conversion efficiency by about 5 and 10%, respectively. The synergistic effect of both modifications significantly improves the hole and electron mobilities and promotes the efficiency of DSSC by up to 20%. These findings suggest a possible strategy for further experimental research on BODIPY analogous and screening new photosensitizers for solar cell applications.

Discovery of triphenylphosphonium (TPP)-conjugated N-(1,1'-biphenyl)-2-yl aliphatic amides as excellent fungicidal candidates.

Succinate dehydrogenase inhibitors (SDHIs) are the fastest growing agricultural fungicides at present, but their rapidly growing resistance is a serious problem for their application. Previously, we screened out a fungicidal lead compound CBUA-TPP (1) through triphenylphosphonium (TPP)-driven mitochondrial-targeting strategy. The targeting led to the rapid accumulation of 1 in mitochondria and the saturation inhibition of complex II in a short time, resulting in electron leakage and the explosion of reactive oxygen species (ROS). However, the contribution of biphenyl-2-amines to the activity of these compounds and their structure-activity relationship are still unknown. Two series of CBUA-TPP (1) analogues (series 2 and 3) were designed and synthesized. The bioassay results indicated that series 2 compounds generally showed much higher fungicidal activities than series 3, suggesting the crucial contribution of the biarylamine module in these targeted molecules and the pyridinyl substitution of phenyl is unfavorable to their activities. Interestingly, these two series of compounds displayed almost opposite substituent effects. Several compounds showed excellent fungicidal activities in vitro, among which compound 2-1 exhibited excellent field control efficacy on potato late blight. By optimizing the lead compound, the contribution of biarylamine in CBUA-TPP (1) analogs to the fungicidal activity is clarified. Several compounds, represented by 2-1, have great potential as fungicide candidates. They exhibit high and broad-spectrum fungicidal activities and are highly effective against common pathogenic fungi infecting vegetables and fruits both in vitro and field control. It not only provided a new choice for controlling these diseases, but its low resistance tendency also provided a better scheme for resistance management. © 2023 Society of Chemical Industry.

Synthesis, Anticancer, Antimicrobial and Antioxidant Potential of Novel 4-(Substituted phenyl-1,3,4-oxadiazol/thiadiazol-2-yl)-4-(4-substituted phenyl) Azetidin-2-One Derivatives.

By exploiting the ample biological potential of 1,3,4-oxadiazole/thiadiazole ring, 4-substitutedphenyl-1,3,4-oxadiazol/Thiadiazol-2-yl)-4-(4-substitutedphenyl) azetidin-2-one derivatives were prepared. Various substituted azetidin-2-one derivatives have been identified as immunostimulating and antimicrobial, as well as their antioxidant activity. 2-amino 1,3,4 oxadiazole/thiadiazole conjugates were synthesized by mixing semi/thio carbazides and sodium acetate with water and stirring well, followed by adding aldehydes in methanol at room temperature. Acetate (glacial) was used as the catalyst to produce Schiff's bases (intermediates) by treating substituted aldehydes with 2-amino 1,3,4 oxadiazole/thiadiazole(s). Using the mixture of triethylamine (dropwise) and chloroacetylchloride with vigorous stirring, 4-substitutedphenyl-1,3,4-oxadiazol/Thiadiazol-2-yl)-4-(4-substitutedphenyl) azetidin-2-one derivatives were prepared. The newly synthesized conjugates were evaluated for their anticancer potential using MCF-7 cell lines. Amoxicillin and fluconazole were used as reference drugs to determine their antimicrobial activity. Synthesized derivatives were evaluated for their antioxidant properties using 2-diphenyl-1-picrylhydrazyl (DPPH). In vitro cytotoxicity screening (MTTS assay) revealed that derivatives AZ-5, 9, 10, 14 and 19 demonstrated high efficacy with the percentage of inhibition at different concentration ranges (0.1 μM, 0.5 μM, 1 μM, 2 μM) of 89% to 94% μM as compared to doxorubicin as standard drug. The antimicrobial study indicated that compounds AZ-10, 19, and AZ-20 were found to have significant antimicrobial potential with MIC ranges of 3.34 µM to 3.71 µM in comparison to reference drugs having 4.29 µM to 5.10 µM. Based on antioxidant screening, most of the synthetic derivatives showed greater stability and effectiveness than the standard drug. According to the antioxidant screening, compounds AZ-5 and AZ-15 (IC50 = 45.02 μg/mL and 42.88 μg/mL, respectively) showed the greatest potency, as compared to ascorbic acid (IC50 = 78.63 μg/mL). Structure-activity relationship (SAR) studies of synthesized novel derivatives revealed that para-substituted halogen and nitro derivatives have remarkable potential against MCF-7 cancer cell lines and different microbial strains. Current evidence indicates that the synthesized derivatives may be promising candidates for use in the prevention and treatment of these infections. These synthesized compounds require further mechanism-based research to understand how they interact with the cells.

The Prominence of Facilitatorπ-Holes: The Classic N←N Pnictogen Bonding in Nitrobenzene-Ammonia Dimer with its Structural Elucidation and Experimental Characterization at Low Temperatures.

The nitrogen of nitro group is a paradigmatic pnictogen due the presence of aπ-hole and a number of studies have been performed recently on prototypical nitromethane (NM). Homodimers and heterodimers of NM are sustained byπ-hole driven pnictogen bonds hosted by nitrogen. To understand the effect of substitution on this π-hole and thus the pnictogen bond, heterodimers of nitrobenzene (NB; phenyl substitution in place of methyl) with ammonia (AM) have been probed, as a test case, using matrix isolation infrared spectroscopy andab initiocomputations. Of the four structures optimized on the potential energy surface the energetically dominant global minimum, stabilized by π-hole driven O=N←N pnictogen bonding with co-operative N-H←O hydrogen bonding, was experimentally identified at low temperatures. A comparison of the pnictogen bonding of NB-AM dimers with NM counterpart (NM-AM dimers) divulged the dominance of electrostatic origin of pnictogen bonding in both the class of dimers. The reduced strength of pnictogen bonding in NB-AM dimers in comparison to NM-AM dimers was discerned, which has been established to be a consequence of the reduced electrostatic potential at the π-hole of NB relative to that in NM. The strength ofπ-hole driven pnictogen bond was directly correlated with the binding energy and the infrared shifts in the signature vibrational bands of the NB, NM and AM submolecules due to dimerization under matrix isolated conditions at low temperatures.

Design, synthesis and characterization of novel substituted pyrazol-azetidin-2-one derivatives for their antimicrobial activity

A novel method is elucidated herein, describing the synthesis of novel 3-chloro-4-(2-substituted phenyl)-1-( 4'-((1-(5-( 4-substituted phenyl)-3-phenyl-4, 5-dihydro-1H-pyrazol-1-yl) ethylidene) amino)-[1,1'-biphenyl]-4-yl) azetidin-2-one, consisting of a pyrazol motif (prepared from chalcone) and a lactam ring ( synthesized from Schiff base of aromatic aldehyde) as a potential antimicrobial agent. The structural elucidation of the synthesized compounds have been confirmed from the elemental analysis, UV-Vis absorption spectroscopy, IR, 1H NMR and mass spectral studies. The novel compounds have been subjected to in vitro antimicrobial screening against certain gram positive (S. aureus, B. subtilis) and gram negative (P. aeruginosa, E. coli) bacterial species. Compounds Vb, Vd and Ve are the most potent amongst all the synthesized compounds against the tested microbes.

Multicolor Iridium(III) Complexes with Host-Guest Recognition Motifs for Enhanced Electrochemiluminescence and Modular Labeling.

Cyclometalated Ir(III) complexes with high electrochemiluminescence (ECL) efficiency and appropriate bioconjugation sites are urgently needed in ECL immunoassays (ECLIA). Herein, we report the synthesis, photophysics, electrochemistry, and ECL of six new Ir(III) complexes bearing naphthyl (nap) or adamantane phenyl (adap) substitutions, four of which emit cyan, green, or red light and display 1.7- to 7.5-fold increases in ECL intensity. In combination with DFT/TDDFT calculations, this enhancement is rationalized to the augmented radiative rate that arises from both the strengthened spin-orbit coupling (SOC) and the increased transition dipole moment. In addition, the adap-based Ir(III) complex shows high binding affinity with β-cyclodextrin (β-CD) due to the strong hydrophobic interaction, which enables us to develop a modular strategy for the labeling of Ir(III) complexes with biomolecules and to use hydrophobic luminophores in the aqueous-phase detection. As demonstrated, a novel ECLIA is built up and exhibits a wide linear range from 1 ng/mL to 10 μg/mL and a detection limit of 72 pg/mL for the determination of C-reactive protein (CRP). These findings provide new insights into the design, synthesis, and bio-labeling of highly emissive Ir(III) complexes and pave the way for the development of novel ECLIA based on host-guest recognition motifs.

Cytotoxic Effects of New Palladium(II) Complexes with Thiazine or Thiazoline Derivative Ligands in Tumor Cell Lines.

The synthesis of analogs of cisplatin, which is a widely used chemotherapeutic agent, using other metal centers could be an alternative for cancer treatment. Pd(II) could be a substitute for Pt(II) due to its coordination chemistry similarity. For that reason, six squared-planar Pd(II) complexes with thiazine and thiazoline ligands and formula [PdCl2(L)] were synthesized and characterized in this work. The potential anticarcinogenic ability of the compounds was studied via cytotoxicity assay in three different human tumor cell lines, i.e., epithelial cervix carcinoma (HeLa), promyelocytic leukemia (HL-60), and histiocytic lymphoma (U-937). Data obtained showed that complexes with methyl substitutions did not modify cell viability, while no-methyl substituted compounds had a moderate cytotoxic effect on all three cell lines. The complexes with phenyl substitutions displayed the lowest IC50 values, which ranged between 46.39 ± 3.99 μM and 62.74 ± 6.45 μM. Moreover, Pd accumulation inside the cell was observed after incubation with any of the four complexes mentioned, and the two complexes with phenyl rings were found to induce an increase in the percentage of apoptotic cells. These results suggested that the presence of bulky substitutions on the ligands such as phenyl groups may influence the cytotoxicity of the chemotherapeutic agents synthesized.

Facile synthesis and in-vitro cytotoxicity study of some 5-(4-substituted phenyl)-7-hydroxy-9-methyl-2-thioxo-2,3-dihydro-1H-dipyrimido[1,2-a:4′,5′-d]pyrimidin-4(5H)-one derivative and their Optoelectronic, DFT, and LFPs applications

A some new 5-(4-Substituted phenyl)-7-Hydroxy-9-methyl-2-thioxo-2,3-dihydro-1H-dipyrimido[1,2-a:4′,5′-d]pyrimidin-4(5H)-one derivative (4a-c) have been synthesized through multicomponent reaction using l-Proline as a catalyst and the structures were confirmed by analytical and spectroscopic techniques. Optical properties were studied in solvent media, absorption and emission bands appeared at ̴ 290 nm to 370 nm of longer wavelength. A cyclic voltammogram was used to study the redox behavior and estimation of experimental HOMO-LUMO of targeted compounds. DFT studies reveal compounds are better photoactivity and kinetic stability at the gaseous phase. Further, LFPs have been developed and visualized by powder dusting method on selected surfaces and clear observation of II and III of LFPs features under UV-Light. In addition, compounds are screened for cytotoxicity study against the A549 cell line, and compound 4c exhibits better selectivity against the cell line with a noticeable IC50 value of 16.74±0.23 µg/mL. As well compounds were analyzed for in-silico docking studies against the target enzyme EGFR Kinase protein and ADME toxicology studies reveal that obtained compounds are nontoxic. From these findings, we conclude that our obtained targets have better optoelectronic behavior and good anti-cancer agents.