Derivatives 3a Research Articles

Non-food bioactive products as pesticide candidates: Preparation and agrochemical activities of novel nonivamide ether derivatives containing the isoxazole fragment

To explore non-food natural products as pesticide candidates for agricultural application, a series of nonivamide ether derivatives (3a–3q) containing the isoxazole fragment were constructed from an alkaloid nonivamide isolated from Capsicum annuum L. Against Mythimna separata Walker, the final corrected mortality rate (FCMR) of 3b at 1.0 mg/mL was 62.9 %, which was 2.0 times of that of nonivamide. Against Aphis citricola Van der Goot, the median lethal dose (LD50) value of 3d was 0.049 μg/nymph, which was 12.4 times of that of nonivamide. Against Plutella xylostella Linnaeus, the median lethal concentration (LC50) value of compound 3b was 0.793 mg/mL, which was 9.2-fold of that of nonivamide. Furthermore, the enzymes activity changes of carboxylesterase (CarE), glutathione S-transferase (GST), and mixed function oxidase (MFO) over time in P. xylostella treated with 3b were evaluated. We hope that this study will establish a robust groundwork for structural modification of nonivamide derivatives and their potential utilization as plant-based insecticides.

New pyrano-pyridine conjugates as potential anticancer agents: design, synthesis and computational studies.

New pyrano[3,2-c]pyridine 4a-h, 5-8 and pyrano[2,3-d]pyrimidin 9a,b series were designed and chemically synthesized. Using the standard drug doxorubicin, the novel chemical entities have been assessed in vitro as potential anticancer prospects on cell lines from liver, breast, colon, and lung cancer along with examining their inhibitory behaviors upon both EGFR and VEGFR-2 kinases. Compared to erlotinib (IC50 = 0.18 µM), compounds 8a and 8b demonstrated the highest anticancer activity with IC50 Values 0.23 and 0.15 µM, respectively). Further, derivative 8a illustrated encouraging inhibitory characteristics against EGFR and VEGFR-2 (IC50 = 1.21 and 2.65 μM, respectively). A computational study was used to estimate the physicochemical and pharmacokinetic properties to afford insightful information about the newly synthesized agents.

Design, Synthesis and Preliminary In‐vitro Activity of 6‐Hydroxyalkyl β‐Carboline Derivatives for the Development of Drug Conjugates Targeting MDM2

The mouse‐double‐minute‐2 (MDM2) protein, the main downregulator of the tumor suppressor p53 protein, represents a promising target for the development of novel anticancer therapies. However, the lack of selectivity and poor effectiveness in tumors bearing mutated‐p53 impaired the approval of several MDM2 inhibitors for the market. In this context, the possibility of generating drug‐conjugates within a MDM2 inhibitor is a growing research area aimed to overcome these drawbacks. Considering the promising MDM2 inhibition by the β‐carboline‐based 1, in this work we explored the introduction of a new functionalization on it for a future conjugation while preserving its anticancer properties. Based on preliminary docking studies, we synthesized derivatives 2a‐d having linear hydroxyalkyl chains with different lengths at the 6‐position of the β‐carboline core, which effectively preserved the submicromolar IC50 on wild‐type‐p53‐U87MG glioblastoma cell line observed with 1. Candidates 2a,d showed the functionalization was tolerated with respect of bioactivity also on mutated‐p53‐U138MG glioblastoma cell line, and their hydroxyl groups proved to be easily accessible when coupled to 4‐pentynoic‐N,N’‐dimethylethylenediamine affording derivatives 10a,d with high yields. In summary, our results led to generating novel 6‐hydroxyalkyl‐β‐carboline compounds displaying a suitable hydroxyl‐site useful to improve the efficacy and/or the tumor specificity of 1 through conjugation strategies.

Natural benzofuran derivatives as promising scaffold for alleviating Alzheimer symptoms: acetylcholinesterase inhibition, structure activity relationship and in silico studies

Three isolated natural benzofuran compounds 1a-c and four semi-synthesized benzofuran derivatives 2a,b and 3a,b were evaluated for their in vitro acetylcholinesterase inhibition assay. Most of the tested compounds showed moderate activity with IC50 ranged from 102.4 ± 5.72 µM to 565.75 ± 4.17 µM, the most potent compound was kellin 1a with IC50 102.4 ± 5.72 µM. The kellin derivatives 1a, 2a and 3a bearing additional methoxyl group showed more inhibition activity than its analogues of visnagin derivatives 1b,c, 2b and 3b. The in silico investigation on the seven benzofuran derivatives matched our in vitro acetylcholinesterase results and explains the similarity in structures between the benzofuran compounds and donepezil drug. khellin had the best pharmacophore features among the studied compounds, the best fit score 1.862 and best dock score −9.135. In addition, our in silico study showed clearly that compounds carrying additional hydrophobic group had more potent activity through matched more ligand features.

Discovery of New Immunomodulatory Anticancer Thalidomide Analogs: Design, Synthesis, Biological Evaluation and In Silico Studies.

New thalidomide analogs have been designed and synthesized by hybridizing the immunomodulatory gutarimide moiety with three antiproliferative nuclei: quinazolinedione, phthalazinedione, and quinoxalinone. The biological results revealed the strong impact of quinazoline derivatives 7a and 28, and phthalazine based 20a against HepG-2, MCF-7, PC3, and HCT-116 cell lines, compared to thalidomide. In particular, compound 20a was the most promising as it had far better biological activity than thalidomide with regard to inhibition of TNF-α, IL-6, caspase 3, COX-I/II, and VEGFR-2, as well as cell cycle arrest, and apoptosis rate enhancement in MCF-7 cells, the most sensitive cell line to the current new molecules. Compound 20a caused reduction in levels of TNF-α and IL-6 by 75.22% and 82.51%, respectively. It elevated the caspase-3 level by 7.21-fold. Furthermore, IC50 against COX-I, COX-II, and VEGFR-2 were 0.65 μM, 0.33 μM, and 232 nM, respectively. In addition, it raised the apoptosis rate from 65.65% to 99.89%. Moreover, 20a was further examined through a docking study and a 200 ns molecular dynamics simulation for its complex with VEGFR-2, along with computational ADME properties. This work suggests the high significance of compounds 20a, 7a and 28, as lead compounds for development of new effective immunomodulatory antitumor drugs.

The charge transport properties of dicyanomethylene-functionalised violanthrone derivatives.

The study of organic small molecule semiconductor materials as active components of organic electronic devices continues to attract considerable attention due to the range of advantages these molecules can offer. Here, we report the synthesis of three dicyanomethylene-functionalised violanthrone derivatives (3a, 3b and 3c) featuring different alkyl substituents. It is found that the introduction of the electron-deficient dicyanomethylene groups significantly improves the optical absorption compared to their previously reported precursors 2a-c. All compounds are p-type semiconductors with low HOMO-LUMO gaps (≈1.25 eV). The hole mobilities, measured from fabricated organic field-effect transistors, range from 3.6 × 10-6 to 1.0 × 10-2 cm2 V-1 s-1. We found that the compounds featuring linear alkyl chains (3b and 3c) displayed a higher mobility compared to the one with branched alkyl chains, 3a. This could be the result of the more highly disordered packing arrangement of this molecule in the solid state, induced by the branched side chains that hinder the formation of π-π stacking interactions. The influence of dicyanomethylene groups on the charge transport properties was most clearly observed in compound 3b which has a 60-fold improvement in mobility compared to 2b. This study demonstrates that the choice of the solubilising group has a profound effect on the hole mobility on these organic semiconductors.

New 2-hydrazinothiazole derivatives as potential MAO-A, MAO-B, AChE, and BChE inhibitors

The incidence of neurodegenerative Alzheimer’s and Parkinson’s diseases is increasing worldwide every day, and treatment options are currently very limited. There is no definitive cure for these diseases, and the drugs available in clinical practice only provide symptomatic relief without halting the progression of neurodegeneration. One commonly employed strategy in the treatment of Alzheimer’s and Parkinson’s diseases is to return neurotransmitter levels by inhibiting enzymes like cholinesterase (ChE) and monoamine oxidase (MAO). In this research, we focused on investigating the therapeutic potential of 2-[2-(substituted benzylidene)hydrazinyl]-4-(substituted phenyl)thiazole derivatives (2a–2h) by incorporating hydrazine, known for its inhibitory effects on monoamine oxidases, into the structure of molecules that inhibit acetylcholinesterase. Thiazole ring was included in these derivatives due to its reported inhibitory activity against both cholinesterases and monoamine oxidase enzymes. When the enzyme inhibition activities were evaluated, it was determined that compounds 2c, 2d, and 2h showed the highest inhibitory activity against AChE, while compounds 2f and 2h expressed the highest activity against MAO-B. It was determined that compound 2h had the highest inhibitory activity on both AChE (0.030 ± 0.001 μM) and MAO-B (0.048 ± 0.002 μM) and compound 2h was the only compound with conspicuous dual inhibitory activity. Furthermore, molecular docking calculations and molecular dynamics simulations were found to agree with experimental results.

Exploring 5-Nitro-N-phenyl-3-(phenylamino)-1H-indazole-1-carboxamide (5-NPIC) Derivatives as Anticancer Agents: Synthesis, Docking and Molecular Dynamics Insights

The synthesis and characterization of a series of 5-nitro-[Formula: see text]-phenyl-3-(phenylamino)-1[Formula: see text]-indazole-1-carboxamide 5-NPIC derivatives (5a– 5v) have been reported as anticancer agents in this study. These derivatives were synthesized by reacting 3-chloro-5-nitro-[Formula: see text]-phenyl-1[Formula: see text]-indazole-1-carboxamide (4) with a variety of aniline derivatives in isopropanol. FT-IR, 1H-NMR, 13C-NMR and mass spectral methods were employed to confirm the structures of analogues (5a– 5v). The anticancer activity evaluation of compounds 5a– 5v revealed that 3-((3-methoxyphenyl) amino)-5-nitro-[Formula: see text]-phenyl-1[Formula: see text]-indazole-1-carboxamide (5j) exhibited good efficacy. The stability of ligand–protein complexes was systematically evaluated using molecular dynamics simulations (MDS), which demonstrated a consistent and robust binding of the most potent compound within the binding sites of target proteins. The results confirmed the anticancer activity, which was further substantiated by comprehensive molecular docking analyses that revealed complex interactions involving hydrophobic contacts, electrostatic forces and hydrogen bonds. Our results would collectively provide invaluable insights into the intricate molecular structure and dynamics of receptor target sites, thereby establishing a solid foundation for the development of novel and potent anticancer agents with optimistic pharmaceutical implications in near future.

Novel s-triazine derivatives as potential anticancer agents: Synthesis, DFT, DNA binding, molecular docking, MD simulation and in silico ADMET profiling

The ongoing challenge of cancer in modern medicine highlights the urgent need for targeted therapeutic strategies, particularly against the EGFR/PI3K/AKT/mTOR signalling pathways, which are pivotal in tumorigenesis. This study presents the design, synthesis, characterization, DNA binding studies and computational evaluation of a novel series of trisubstituted s-triazine derivatives 3a–n as potential anticancer agents. The synthetic methodology utilized the reaction of various oxygen-containing nucleophiles with cyanuric chloride via nucleophilic aromatic substitution, yielding the corresponding target products with high yield and purity. Density Functional Theory (DFT) calculations utilizing the B3LYP level provided insights into the electronic properties of the compounds, with derivatives 3f, 3n, and 3l displaying the lowest energy gaps and highest electrophilicity indices, indicative of their enhanced reactivity. DNA binding results from UV–Vis absorption spectroscopy confirmed the groove mode of binding for the most potent compound 3f with the binding constant (Kb) value of 6.75 × 104 M−1. Molecular docking studies against DNA (PDB ID: 3EY0) and EGFR (PDB ID: 6V6O) revealed strong binding affinities, with compound 3f (R1= ethoxy, R2= 3-CF3) exhibiting a notable binding energy of -8.9 kcal/mol and −9.1 kcal/mol respectively. Additionally, these compounds showed significant binding interactions with PI3K (PDB ID: 5HJB) and mTOR (PDB ID: 4JSV), suggesting their potential as dual inhibitors of the PI3K/AKT/mTOR pathway. The drug-likeness and ADMET profiles further support the therapeutic promise of compound 3f bearing a 3-trifluoromethyl substituent.

Synthesis, In Vivo, ADME Determination, and Molecular Docking Studies of 1,3,4‐Oxadiazoles Containing Pyridine and Piperazine Moieties as New Diuretic Agents

AbstractA series of 1‐(piperazin‐1‐yl)‐2‐((5‐(pyridin‐4‐yl)‐1,3,4‐oxadiazol‐2‐yl)thio)ethan‐1‐one derivatives (9a–l) were prepared using a multistep reaction between 2‐chloro‐1‐(piperazin‐1yl)ethan‐1‐one derivatives (4a–l) and 5‐(pyridine‐4‐yl)‐1,3,4‐oxadiazole‐2‐thiol (8) and studied their diuretic potential by following established in vivo and in silico protocols. The data obtained from the experimental rat animal model in vivo diuretic studies indicated that synthesized derivatives 9d, 9e, 9g, 9i, and 9j possess excellent diuretic potential. The results obtained from in vivo study were also reinforced by the data of in silico studies performed using AutoDock (1.5.7) software. The molecular docking involved interactions of synthesized molecules with two target proteins, that is, human carbonic anhydrase II protein (hCA‐II, PDB ID: 3HS4) and human NKCCl K289NA492E protein (NKCCl, PDB ID: 7S1Y). The ADME properties of the synthesized molecules have also been determined using pkCSM software that established that the synthesized molecules are good candidates for oral absorption. All the data of in vivo and in silico studies synergized the results that state that the diuretic activity of all synthesized compounds is greater than that of the standard drug (furosemide), whereas compounds 9d, 9e, 9g, 9i, and 9j show excellent activity with values of 1.32, 1.33, 1.35, 1.39, and 1.35, respectively.

Facile Synthesis of (S)‐2‐Aryl‐N‐(1‐phenylethylisonicotinamides) Derivatives via SMC Reaction: Their Thermodynamic and Spectroscopic Features via DFT Approach

AbstractIn this study, 2‐bromoisonicotinic acid and (S)‐1‐phenylethaneamine were reacted in the presence of pyridine and TiCl4 to produce 2‐bromo‐N‐(1‐phenylethyl)isonicotinamide (3). The derivatives (5a–f) of (S)‐2‐bromo‐N‐(1‐phenylethyl)isonicotinamide were then created by a Suzuki–Miyaura cross‐coupling process catalyzed by palladium (0) and K3PO4 as a base. The reactivity and electronic features of the compounds were investigated using DFT molecular electrostatic potential investigations, reactivity descriptors, and frontier molecular orbital analysis.

Synthesis and Molecular Docking Study of Hydrazone Schiff Bases of α‐Naphthalene‐Containing Alkyl Phenyl Ether Fragment as Potent α‐Amylase and α‐Glucosidase Inhibitors

AbstractIn this study, new Schiff base derivatives of α‐naphthalene acetic acid containing alkyl phenyl ether fragment have been effectively synthesized through multistep reaction process, characterized by 1H‐NMR and 13C‐NMR spectroscopy. These derivatives have been tested for their in vitro α‐amylase and α‐glucosidase inhibitory activities. In the series, 8 compounds (2j, 2f, 2e, 2m, 2a, 2b, 2l, and 2c) exhibited promising α‐amylase inhibition with IC50 values from 5.38 ± 0.36 to 14.59 ± 0.64 µg/mL. Similarly, in the case of α‐glucosidase inhibitory activity, 10 derivatives (2e, 2f, 2j, 2m, 2b, 2c, 2i, 2d, 2a, and 2l) exhibited excellent activity having IC50 values from 6.96 ± 0.39 to 16.27 ± 0.31 µg/mL, wheras the remaining derivatives exhibited good‐to‐least antidiabetic potential. The ADME properties were calculated for all Schiff base derivatives using Swiss‐ADME web tool. Furthermore, the docking studies identified the binding modes of the compounds.

Unveiling Novel Hybrids Quinazoline/Phenylsulfonylfuroxan Derivatives with Potent Multi‐Anticancer Inhibition: DFT and In Silico Approach Combining 2D‐QSAR, Molecular Docking, Dynamics Simulations, and ADMET Properties

AbstractIn this work, the biological activities of 29 novel quinazoline/phenylsulfonylfuroxan derivatives (1a–z, 1aa, 1ab, 2a, 2b, 2d, and 2f) were computationally investigated as potential anti‐cancer inhibitors against five cell lines, i.e., H1975, MCF‐7, Eca‐109, MGC‐803, and A549, which are involved in various diseases, including lung, breast, esophageal squamous carcinoma, and gastric cancer. The 2D‐QSAR predictive approach, exploiting multiple linear regression (MLR) models and rigorous internal and external cross‐validation, showed a correlation factor R2 of range: 0.68−0.82. Moreover, the MLR‐derived R2test and Y randomization (R2rand) values for the five cell lines are higher than 0.60 and less than 0.3, respectively, indicating a strong alignment with the internal and external validation data. New 70 quinazoline hybrids based on the most effective in vivo 1q inhibitor were designed, and their pIC50 activity was predicted. The best‐scoring 15 (N1–N15) compounds were further evaluated using molecular docking and dynamics simulations (100 ns) with the VEGFR‐2 kinase target (PDB code: 3U6J). All the data sets accurately predict the strongest binding affinity for the selected (N6, N7, N9, and N11) molecules, as evidenced by the highest docking score, hydrogen bond energy, and significant amino acid steric interactions. Furthermore, the RMS/RMSF/Rg dynamics parameters show that the formed complexes are satisfactorily stable. The ADMET properties indicate that the selected new ligands have shown a promising drug‐like profile and can be considered potential candidates for future anti‐cancer therapies, with perspective validating their anticancer activity by in vitro and in vivo studies.

Designing 1,2,3‐Triazole Derivatives for Targeted Inhibition of Proteolytic and Coagulant Activities in Bothrops Jararaca and Bothrops neuwiedi Snake Venoms

AbstractSnakebites inflict significant injuries on humans and animals, posing a severe global public health challenge due to high mortality and morbidity rates. This study presents results against the venoms of Bothrops jararaca and Bothrops neuwiedi using sixteen synthetic hybrid molecules containing thiophene and triazoles, designated as 6a–h and 7a–h. The compounds were assessed for their ability to inhibit proteolytic and plasma coagulant activities induced by the snake venoms, and their toxicity was analyzed. Most derivatives demonstrated nontoxicity through in silico analysis with the Osiris Property Explorer tool and in vitro cytotoxic hemocompatibility on red blood cells. Notably, only derivative 6e exhibited toxicity to erythrocytes, while 6b, 6d, 7c, and 7f displayed mutagenic, tumorigenic, or adverse effects on the reproductive system. Derivatives 6a, 6c–h, 7c–e, 7g, or 7h effectively inhibited the coagulating activity of B. jararaca venom, while 6a–b, 6d–e, 6h, or 7a–f inhibited coagulation induced by B. neuwiedi venom. All derivatives demonstrated inhibition of the proteolytic activity caused by B. jararaca venom, and derivatives 6a–d and 7e–f inhibited the activity of B. neuwiedi venom. Consequently, these derivatives exhibited varying degrees of efficacy in countering two crucial toxic effects of B. jararaca or B. neuwiedi venoms, suggesting their potential as antivenoms against both species.

β-Carboline-3-carboxamide Antimalarials: Structure-Activity Relationship, ADME-Tox Studies, and Resistance Profiling.

The development of parasite resistance to both artemisinin derivatives and their partner drugs jeopardizes the effectiveness of the artemisinin combination therapy. Thus, the discovery of new antimalarial drugs, with new mechanisms of action, is urgently needed. We recently disclosed that β-carboline 1a was orally efficacious in Plasmodium berghei-infected mice and that it showed low cross-resistance between susceptible Plasmodium falciparum and four different drug-resistant strains. In this report, we describe the synthesis and in vitro antimalarial evaluation of 91 new derivatives of 1a. The asexual blood stage growth inhibition data show a clear preference for a 3,4-dihalogenated, 3,5-dihalogenated, 3,4,5-trichloro-, or 4-trifluoromethyphenyl ring at the C1-position. The most potent compound, 3,4,5-trichlorophenyl-substituted 42a, is twice as potent as 1a. Six potent analogues were assessed for their drug-like properties, and four of these were subjected to in vitro barcoded cross-resistance profiling. Compounds 1a, 1m, 42a, and 42m showed no cross-resistance to 32 resistance mutations on the Dd2 genetic background and 10 resistance mutations on the 3D7 genetic background. These data suggest that compounds in this scaffold possess a novel mechanism of antimalarial action.

Synthesis, Antibacterial, Anti-Biofilm Properties, and Docking Study of Indeno[1,2-b]Pyridin-5-One Derivatives

In this context, we designed and synthesized a series of hydrazonal and their related indeno[1,2-b]pyridin-5-one derivatives to investigate their antibacterial and anti-biofilm properties. Several of the synthesized compounds exhibited significant efficacy against all microorganism species tested. Most of the compounds demonstrated favorable results when tested against Gram-positive bacteria. The derivatives 4a, 4f, 6c, and 6f exhibit the highest antimicrobial efficacy, as indicated by their minimum inhibitory concentration (MIC) values ranging from 4 to 512 μg/mL. We conducted additional investigations on 4a, 6c, and 6f for the purpose of examining their synergy using Checkerboard assay. Compound 6c demonstrated a synergistic impact against methicillin-sensitive Staphylococcus aureus (MSSA) and Pseudomonas aeruginosa, while exhibiting moderate synergistic activity against methicillin-resistant Staphylococcus aureus (MRSA). In addition, the simultaneous use of gentamycin with compounds 4a and 6f demonstrates a synergistic impact in fighting against methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa, respectively. Three chosen compounds were evaluated for their antibiofilm efficacy. Application of 4a, 6c, and 6f effectively reduced the production of biofilms in MRSA, MSSA, and Pseudomonas aeruginosa, resulting in a significant decrease compared to the untreated samples. In addition, ADME and pharmacokinetic analyses were conducted for the three most potent derivatives, namely 4a, 6c, and 6f. Compounds 4a and 6c were subjected to docking in the LasR Quorum-Sensing Receptor, whereas compounds 6c and 6f were docked in the sortase enzyme.

Facile and Metal‐Free Synthesis of Isoflavones Using α‐Aryl‐β,β‐Ditosyloxy Ketones

AbstractConsidering the drawbacks associated with available synthetic methodologies of isoflavones, herein we have reported a metal‐free and eco‐friendly approach to these natural products. In the present study, we have carried out the synthesis of eight isoflavone derivatives 7a–7h using α‐aryl‐β,β‐ditosyloxy ketone protocol. Initially, we have protected the 2’‐hydroxy group of respective chalcone moiety in order to remove its interference under reaction conditions. The protected chalcones were then subjected to 1,2‐aryl migration by being treated with hydroxy(tosyloxy)iodobenzene (HTIB) reagent in a non‐nucleophilic solvent (CH2Cl2). This migration furnished the formation of α‐aryl‐β,β‐ditosyloxy ketones via C−C bond formation from their corresponding chalcones in moderate to good yields (55–82 %). The ambiguity regarding the exact molecular structure of the α‐aryl‐β,β‐ditosyloxy ketones was examined through the single crystal X‐ray diffraction data. At last, the synthesis of isoflavones was carried out in moderate to good yields (50–80 %) by performing the reaction of α‐aryl‐β,β‐ditosyloxy ketones with sodium hydroxide in aqueous methanol.

Synthesis and Anticancer Properties of Heterobimetallic Fe(II)/Pd(II) Complexes Bearing Different Butadienyl Fragments

AbstractIn this work, we describe the synthesis of heterobimetallic Fe(II)/Pd(II) complexes bearing different halides and halide‐substituted butadienyl ligands. The synthetic approach involves the preparation of suitable Pd(II)‐butadienyl precursors containing a thioquinoline moiety, followed by the substitution of this relatively labile ligand with dppf (dppf=1,1′‐bis(diphenylphosphino)ferrocene). With the exception of complexes containing at least one iodine atom, all compounds were synthesized in high yields and purity, and thoroughly characterized using spectroscopic and diffractometric methods. The investigation of the antiproliferative activity of the synthesized organometallic complexes against ovarian and breast cancer cell lines revealed that all compounds exhibit noteworthy cytotoxicity, with IC50 values in the micromolar range and generally comparable to those of cisplatin. Interestingly, significant differences of cytotoxicity among the analysed compounds were observed in the case of MRC‐5 normal cells. Of particular interest is the dichloride derivative 3 a, which is essentially inactive towards non‐cancerous cells (IC50>100 μM), thus demonstrating promising in vitro selectivity that we believe warrants further investigation in the future.

Novel phthalocyanines bearing fluoro-methylquinolin substituents: Synthesis, characterization, photophysical and photochemical properties

The novel 4-((6-fluoro-2-methylquinolin-4-yl)oxy)phthalonitrile (3a), 3-((6-fluoro-2-methylquinolin-4-yl)oxy)phthalonitrile (3b), tetra 6-fluoro-2-methylquinolin-4-yl)oxy substituted zinc(II) phthalocyanines (4a and 4b) and their water soluble derivatives (5a and 5b) were prepared. The proposed structures of novel compounds were comfirmed via FT-IR, 1HNMR , UV–Vis and MALDI-TOF mass data. The aggregation tendency, fluorescence quantum yield, singlet oxygen quantum yield and photodegradation measurements were performed to examine the photodynamic therapy potential of both peripherally tetra substituted zinc(II) phthalocyanines (4a and 4b) and the water soluble quaternized tetra substituted zinc(II) phthalocyanines (5a and 5b). The result showed that both the novel tetra 6-fluoro-2-methylquinolin-4-yl)oxy substituted zinc(II) phthalocyanines (4a and 4b) and their water soluble derivatives (5a and 5b) could be used as photosensitizer agents in PDT thanks to their lack of aggregation tendency, having sufficient fluorescence emission for monitoring and produce high amount of singlet oxygen to destroy cancerous tissues and having moderate photostability.

Different Patterns of Pd-Promoted C-H Bond Activation in (Z)-4-Hetarylidene-5(4H)-oxazolones and Consequences in Photophysical Properties

This work aims to amplify the fluorescence of (Z)-4-hetarylidene-5(4H)-oxazolones 1 by suppression of the hula-twist non-radiative deactivation pathway by C^N-orthopalladation of the 4-hetarylidene ring. Different (Z)-4-hetarylidene-2-phenyl-5(4H)-oxazolones, 1a–1c, prepared by the Erlenmeyer–Plöchl method, have been studied. The orthopalladation of (Z)-2-phenyl-4-(5-thiazolylmethylene)-5(4H)-oxazolone (1a) takes place by C-H bond activation of the H4 of the heterocycle and C^N-chelation, giving the dinuclear trifluoroacetate derivative 2a. By further metathesis of bridging ligands in 2a, complexes containing the orthometalated oxazolone and a variety of ligands 3a–5a, were prepared. The study of the photophysical properties of 1a–5a shows that the bonding of the Pd metal to the 4-hetaryliden-5(4H)-oxazolone does not promote, in these cases, an increase in fluorescence. Interestingly, the orthopalladation of (Z)-2-phenyl-4-(4-thiazolylmethylene)-5(4H)-oxazolone (1b) gives orthopalladated 2b, where the incorporation of the Pd to the oxazolone takes place by C-H bond activation of the ortho-H2 of the 2-phenyl group, ring opening of the oxazolone heterocycle and simultaneous N,N-bonding of the N atoms of the thiazole ring and the generated benzamide fragment. This N^N^C-tridentate dianionic bonding mode is obtained for the first time in oxazolones. Despite a similar lock of the hula-twist deactivation, 2b does not show fluorescence.