Electron-releasing Substituents Research Articles

Synthesis, structural characterization, DFT and molecular dynamics simulations of dinuclear (μ-hydroxo)-bridged triethanolamine copper(II) complexes: efficient candidates towards visible light-mediated photo-Fenton degradation of organic dyes.

Multinuclear (di/tri) copper(II) complexes bridged through hydroxyl groups are very interesting coordination complexes owing to their potential applications in various fields. In this work, three novel dinuclear (μ-hydroxo)-bridged copper(II) complexes in the crystal form, namely, [Cu2(3,5-DIFLB)2(H2tea)2](H2O) (1), [Cu2(4-ClB)2(H2tea)2](H2O) (2), and [Cu2(4-ETHB)2(H2tea)2](H2O)2 (3) (where DIFLB = difluorobenzoate, CLB = chlorobenzoate, ETHB = ethoxybenzoate, and H3tea = triethanolamine), were isolated at room temperature using methanol and water in a 4 : 1 v/v ratio as a solvent. Furthermore, all three complexes (1-3) were characterised using spectroscopic (UV-vis, DRS, and FT-IR), electrochemical (CV) and single-crystal X-ray diffraction techniques. Structural insights gained by packing analysis revealed the role of steric constraints of substituents and various non-covalent interactions in lattice stabilization, which were indeed supported by theoretical and molecular electrostatic potential illustrations. Hirshfeld surface analysis provided quantitative verification about various non-covalent interactions (interatomic contacts) involved in the packing of molecules. Interestingly, as a potential application, complexes 1-3 all exhibited remarkable visible light-mediated photo-Fenton degradation of approximately 98% for 50 ppm concentration of organic dyes (fuchsin basic (FB) and methyl orange (MO)) in 90 minutes with the optimized conditions of 1 mg mL-1 of dye solution. In all the cases, dye degradation by these materials was ascribed to the symbiotic relations among the molecular structures of complexes 1-3, which were endowed with various electron-withdrawing and electron-releasing substituents and ionic strength, with respect to the structure, shape and interacting patterns of dye molecules. The adsorption mechanism indicates that various weak interactions between the donor and acceptor groups of complexes and dyes, such as electrostatic, hydrogen bonding, and direct coordination to metal sites, play a crucial role, which is confirmed by molecular dynamics (MD) simulations. Theoretical studies by DFT-based descriptors, molecular electrostatic potentials, and band gaps provided deep insights into various electronic and reactivity parameters. For subsequent processes of dye degradation, complexes 1-3 were stable and recoverable. The successful integration of experimental and theoretical approaches sheds light on copper-based dinuclear stable coordination complexes, showcasing a significant step towards the development of novel heterogeneous photo-Fenton catalysts.

Dimeric 3,5-Bis(benzylidene)-4-piperidones: Tumor-Selective Cytotoxicity and Structure-Activity Relationships.

Background: The objective of this study is to find novel antineoplastic agents that display greater toxicity to malignant cells than to neoplasms. In addition, the mechanisms of action of representative compounds are sought. This report describes the cytotoxicity of a number of dimers of 3,5-bis(benzylidene)-4-piperidones against human malignant cells (promyelocytic leukemia HL-60 and squamous cell carcinoma HSC-2, HSC-3, and HSC-4). Methods: Tumor specificity was evaluated by the selectivity index (SI), that is the ratio of the mean CC50 for human non-malignant oral cells (gingival fibroblasts, pulp cells, periodontal ligament fibroblasts) to that for malignant cells. Results: The compounds were highly toxic to human malignant cells. On the other hand, these molecules were less toxic to human non-malignant cells. In particular, a potent lead molecule, 3b, was identified. A QSAR study revealed that the placement of electron-releasing and hydrophilic substituents into the aryl rings led to increases in cytotoxic potencies. The modes of action of a lead compound discovered in this study designated 3b were the activation of caspases-3 and -7, as well as causing PARP1 cleavage and G2 arrest, followed by sub-G1 accumulation in the cell cycle. This compound also depolarized the mitochondrial membrane and generated reactive oxygen species in human colon carcinoma HCT116 cells. In conclusion, this study has revealed that, in general, the compounds described in this report are tumor-selective cytotoxins.

Synthesis of a novel chloroquinoline, rhodanine encompassed 1,2,3-triazole scaffolds and molecular docking evaluation of their cytotoxicity

A novel series of quinoline-linked rhodanine bearing 1,2,3-triazole analogs (10a-l) have been designed and prepared. All the novel hybrids were analyzed and characterized by spectroscopic performances like 1H-NMR, 13C-NMR, and HR-MS analysis. The anticancer efficiency of final molecules was screened for their in vitro activity against the diverse cancer cells lines like HeLa (cervical carcinoma), MCF-7 (human breast), HT-29 (colon cancer), and Caco-2 (human epithelial). Amongst, compound (10c) exhibited more potent anticancer activity than Combretastatin-A4 as a standard drug against MCF7, Caco-2, HeLa, HT-29, and Caco-2 cancer cells with IC50 values of 3.67, 3.93, 4.92, and 6.83 μM, respectively. The overview of an electron-releasing substituent on the aryl ring exhibited potent anticancer activity. It is the first report to reveal the quinoline-linked rhodanine-bearing 1,2,3-triazole scaffolds as potential antitumor agents with inclusive docking analysis.Graphical abstract

Synthesis, photostability and antibacterial activity of a series of symmetrical α,β-unsaturated ketones as potential UV filters

A series of three symmetrical α,β-unsaturated ketones, namely, (1E,4E)-1,5-bis[4-(methylthio)phenyl]penta-1,4-dien-3-one, 1, (1E,4E)-1,5-bis[4-(dimethylamino)phenyl]penta-1,4-dien-3-one, 2, and (1E,4E)-1,5-bis[4-(ethyl)phenyl] penta-1,4-dien-3-one, 3, were synthesized in excellent yields (above 70%) and within a short reaction time (1 h), via an improved Knoevenagel condensation with acetyl acetone and substituted benzaldehydes. All the compounds were fully characterized by UV/Vis, IR, NMR and mass spectrometry. In addition, compound 1 was characterized by single crystal X-ray diffraction. The photostability of the prepared compounds was investigated in solvents of different polarity and proticity by exposure to simulated solar radiation. Three solvents were used, namely, ethyl acetate, dimethylsulfoxide and methanol. The change in UV absorption was monitored by a standard spectrophotometric method and photodegradation products were identified by 1H NMR. According to the results, 1 and 3 were not photostable, and suffered significant changes in their UV absorption spectra. Compound 2, on the other hand, was observed to be considerably photostable in the polar protic solvent methanol but less photostable in the polar aprotic solvent dimethylsulfoxide. All three compounds (1–3) photodegraded appreciably in the less polar aprotic solvent ethyl acetate. Therefore, their photostability is solvent dependent. The antibacterial activity of 1–3 was evaluated by means of the modified broth microdilution method against both gram-negative and gram-positive bacterial strains. Compounds 2 (methylated amine) and 3 (ethyl) have electron-releasing substituents and they were found to have excellent activity against all the tested bacteria. Thus, compounds 2 and 3 can be further explored as potential leads for the development of cheaper, safer, more effective and potent antibiotics against both gram-positive and gram-negative bacterial strains, and compound 2 is a good candidate for use in sunscreen formulations if dissolved in a polar solvent.

Dehydroacetic acid hydrazones as potent enzyme inhibitors: design, synthesis and computational studies

The present study offers the work on the hydrazone derivatives of dehydroacetic acid to be considered for computational and synthetic studies. The hydrazone derivatives of dehydroacetic acid were designed with different electron-withdrawing and electron-releasing substituents. The hydrazones and the parent compound (dehydroacetic acid) were subjected to computational studies to evaluate their pharmacologicalproperties. The compounds were assessed by applying Lipinski’s rule followed by ADMET predictions. Among all the derivatives under studies, 4-hydroxy-6-methyl-3-(1-(2-(2-nitrophenyl) hydrazineylidene) ethyl)-2H-pyran-2-one was found to be the most effective derivative which was further evaluated against BSA, trypsin, amylase, lipase and cathepsins (B and H) by using docking studies. The computational results were also verified experimentally by synthesizing the derivative as well as performing enzyme inhibition studies on the synthesized hydrazone and the parent compound.

Electronic Absorption, Emission, and Two-Photon Absorption Properties of Some Extended 2,4,6-Triphenyl-1,3,5-Triazines

We report herein the linear optical properties of some extended 2,4,6-triphenyl-s-triazines of formula 2,4,6-[(1,4-C6H4)C≡C(4-C6H4X)]3-1,3,5-(C3H3N3) (3-X; X = NO2, CN, OMe, NMe2, NPh2) and related analogues 4 and 7-X (X = H, NPh2), before briefly discussing their two-photon absorption (2PA) cross-sections. Their 2PA performance is discussed in relation to 2PA values previously measured for closely related octupoles such as N,N′,N″-triphenylisocyanurates (1-X, 5, and 6-X) or 1,3,5-triphenylbenzenes (2-X). While s-triazines are usually much better two-photon absorbers in the near-IR range than these molecules, especially when functionalised by electron-releasing substituents at their periphery, they present a decreased transparency window in the visible range due to their red-shifted first 1PA peak, in particular when compared with corresponding isocyanurates analogues. In contrast, due to their significantly larger two-photon brilliancy, 2,4,6-triphenyl-s-triazines appear more promising than the latter for two-photon fluorescence bio-imaging purposes. Rationalisation of these unexpected outcomes is proposed based on DFT calculations.

Effect of carbazole and pyrrolidine functionalization of phenanthroline ligand on ground- and excited-state properties of rhenium(I) complexes. Interplay between 3MLCT and 3IL/3ILCT

New rhenium(I) tricarbonyl complexes based on the phenanthroline ligand were designed and synthesized to investigate the role of carbazole (cbz) and pyrrolidine (pyrr) substituents in determining thermal, electrochemical and optoelectronic properties. Both pyrr and cbz are electron-releasing substituents, but they differ in the steric hindrance and electron delocalization ability. The impact of pyrr and cbz on ground- and excited-state properties of [ReCl(CO)3(cbz2-CH3phen)] (1) and [ReCl(CO)3(pyrr2-CH3phen)] (2) were investigated with a range of techniques including cyclic voltammetry, absorbance and emission spectroscopies, transient absorption spectroscopy, and they were discussed in comparison with the model chromophore [ReCl(CO)3(CH3phen)] (3). Experimental results were supported by theoretical calculations. The most striking difference between the pyrr and cbz groups was seen in their impact on the LUMO energy level. While the attached carbazole groups decreased the LUMO energy of 1, the pyrrolidine ones in 2 resulted in the rise of LUMO energy level compared to the model chromophore. For both 1 and 2, the HOMO got energetically destabilized in agreement with electro-donor abilities of pyrr and cbz substituents. Structural modification of phen backbone resulted also in changes of distribution of occupied MOs of 1 and 2 in relation to 3. Experimentally, it was manifested in noticeable changes of electrochemical and photophysical behaviour of the resulting Re(I) complexes in relation to the model chromophore.

Correlation studies in the oxidation of Vanillin Schiff bases by acid bromate - A kinetic and semi-empirical approach

Kinetics and mechanistic aspects of oxidation of Vanillin Schiff bases (obtained from Vanillin and p-substituted anilines) by bromate in acid medium has been studied at 313 ​K. The reaction exhibited first order in [bromate] and less than unity order each in [Vanillin Schiff base] and [acid]. The increase in the rate of reaction with decrease in dielectric constant of the medium is observed with all the studied substrates. The reaction failed to induce the polymerization of acrylonitrile. Electron withdrawing substituents in the aniline ring moiety of Vanillin Schiff base accelerate the rate of oxidation to a large extent and electron releasing substituents retard the rate. The order of reactivity is found to be p-nitro ​> ​p-bromo ​> ​p-chloro ​> ​–H ​> ​p-fluoro ​> ​p-methyl ​> ​p-methoxy ​> ​p-ethoxy and the sensitivity of the substrates towards the reaction rate is further supported by the semi-empirical calculation of electronic properties and global descriptors of the substrates (Vanillin Schiff bases) with different substituents in the aniline ring moiety. The observed trend in the reactivity of the substrates was correlated with the calculated descriptors like electronegativity, chemical potential, electrophilicity index, chemical hardness and frontier molecular orbitals. The linear free-energy relationship is characterized by a straight line in the Hammett's plot of log k versus σ. The ρ values are positive and increase with increase in temperature. From the Exner and Arrhenius plots, the isokinetic relationship is discussed. Oxidation products identified are p-substituted azobenzene and vanillic acid. Based on the experimental observations, a plausible mechanism is proposed and rate law is derived.

Mechanistic exploration of Rh(III)-catalyzed C-H allylation of benzamides with allyl bromide

The allylation of various benzamides under the catalysis of transition metal by the C-H activation is an attractive tool for the functionalization of aromatic system. One such reaction under the catalysis of Rh(III)-complex using allyl bromide as the allylating reagent was studied theoretically by employing density functional theory (DFT) to find out the plausible mechanistic path. The metal mediated allylation of various benzamides includes six steps – coordination of substrate with the catalyst, N-H metalation, C-H metalation, addition of allyl bromide, proton transfer and demetalation. Our calculations reveal that, the path involving the insertion of allyl bromide is energetically favorable compared to that of oxidative addition of allyl bromide. The effect of electron withdrawing and electron releasing substituents was also explained which nicely agrees with the experimental report.

Synthesis and electronic properties of transition metal complexes containing sulfonamidoquinoline ligands

The coordination chemistry of 4-nitro-N-(quinolin-8-yl)benzenesulfonamide has been expanded. Crystal structures of bis[4-nitro-N-(quinolin-8-yl)benzenesulfonamidato-κ2N,N′]cobalt(II) (2), diaqua-bis[4-nitro-N-(quinolin-8-yl)benzenesulfonamidato-κ2N,N′]nickel(II) (3), and bis[4-nitro-N-(quinolin-8-yl)benzenesulfonamidato-κ2N,N′]zinc(II) (4) containing this ligand in ML2 stoichiometry were obtained. The nickel complex is isolated as a dihydrate. The degree of tetrahedrality for the four coordinate copper, cobalt, and zinc complexes was quantitatively compared by calculating the τ4 geometric parameters. Zinc complex 4 was found to be the most tetrahedral, while copper complex 1-NO2 deviated most from tetrahedral geometry. The magnetic moment calculated for 1-NO2 showed inconsistencies when measured in solution and in the solid state. Only a Cu+2 center exists in solution, while a possible mixed spin state of Cu+2 and Cu+3 is proposed in the solid state. With a more electron releasing substituent on the ligand of the copper complex as seen in complex 1-Me, this behavior is not observed and Cu+2 exists in solution and solid state. A reversible reduction at the same potential (−1.5 V vs. ferrocene) for both the ligand and the complex suggests possible redox activity of this class of ligand.

Synthesis, Antimicrobial Capability and Molecular Docking of Heterocyclic Scaffolds Clubbed by 2-Azetidinone, Thiazole and Quinoline Derivatives

A new set of molecules was designed and synthesized by compilation of pharmacologically potential segments thiazole and quinoline bridged by 2-azetidinone as a linker in a single molecular skeleton. Structural analysis of synthesized molecules (5a-p) was executed by IR, 1H NMR, 13C NMR, and mass spectroscopy techniques. Aforesaid compounds were analyzed for investigation of their antimicrobial capability against several bacterial and fungal strains. The synthesized compounds 5b, 5f, 5h, 5i, 5k, and 5l were active against bacterial strains while compounds 5j and 5k were active against fungal strains. Synthesized compounds were found to be potential inhibitors against gram-negative bacterial strains Escherichia coli and Pseudomonas aeruginosa, while the same were not effective against gram-positive strains of Staphylococcus aureus and Streptococcus pyogenes. Compounds with electron-releasing substituents were active molecules against all fungal strains used in screening. Also, the influence of substituents on the antimicrobial activity of target molecules (5a-p) was discussed. Molecular docking study against crucial microbial target β-Ketoacyl-acyl carrier protein (ACP) synthase III (FabH) could provide valuable insights into their plausible mechanism of action.

Regioselective iodination of activated arenes using KI-DMSO in aqueous hydrochloride

The KI-DMSO in aqueous hydrochloride has been utilized for selective iodination of activated arenes. The iodination of substrate such as hydroxyacetophenones, amines, phenols, anisole and toluene took place with high regioselectivity and mono-iodination was found to occur. The electron releasing substituents (–CH3, –OCH3, –OH, –NH2) exclusively form para substituted product while ortho-iodination occurred only when para-position was blocked by other substituents. The method is simple and noteworthy for reactive arenes with comprises some advantages as easy reaction procedure, short reaction time (5–12 min.) and fair to good yield of aryl iodides (65–90%). The structure of aryl iodide was established on the basis of spectral and elemental data.

Synthesis and Antiplatelet Activity Evaluation of a Group of Novel Ethyl Acetoacetate Phenylhydrazone Derivatives.

A group of Novel phenylhydrazone derivatives of ethyl acetoacetate was synthesized and evaluated for their antiplatelet activities. Fourteen ethyl acetoacetate phenylhydrazone derivatives were synthesized using the diazonium salt of various aromatic primary amines with good yields and purity. The structure of the final compounds was confirmed and approved by spectroscopic techniques such as 1HNMR, FTIR, and ESI-Mass. We examined the antiplatelet activity of the derivatives against Arachidonic Acid (AA) and Adenosine Diphosphate (ADP) as platelet aggregation inducers. The final results indicated the acceptable potency for different derivatives. In this regard, the para-hydroxyphenylhydrazine derivative of ethyl acetoacetate has the best activity among all derivatives, both on AA and ADP pathways. It seems that the derivatives with electron-releasing substituents (hydroxyl, methoxy, and methyl group) have better inhibition activities against the aggregation induced by AA. In contrast, those with an electron-withdrawing group showed a significant decrease in their potency. Based on the results of this study, we would proceed with further assessments both in-vitro and in-vivo to get success in introducing some new antiplatelet agents to the clinic.

Synthesis, Characterization and Biological Activity of (E)-9-Benzylidene-5-phenyl-5,6,7,8,9,10-hexahydro-[1,2,4]triazolo[3,4-ɑ]quinazoline

Abstract: Novel quinazoline derivatives were synthesized viathe reaction of unsaturated carbonyl compound subsidiaries with 3-aminotriazole. These compounds are convenient and important intermediates for the synthesis of a rangeof useful and novel heterocyclic compounds. The structures of these compounds were characterized using elemental analysis and IR, 1H NMR and mass spectroscopic methods.They were also tested with respect to their anti-bacterial activity against two types of bacteria,Staphylococcus aureusand Pseudomonas aeruginosa. Significant anti-bacterial activity was observed,and the results indicate the favorable effect of electron-releasing substituents on anti-bacterial activity

Deep-Red Luminescence from Platinum(II) Complexes of N^N-^N-Amido Ligands with Benzannulated N-Heterocyclic Donor Arms.

A synthetic methodology for accessing narrow-band, deep-red phosphorescence from mononuclear Pt(II) complexes is presented. These charge-neutral complexes have the general structure (N^N-^N)PtCl, in which the Pt(II) centers are supported by benzannulated diarylamido ligand scaffolds bearing substituted quinolinyl and/or phenanthridinyl arms. Emission maxima ranging from 683 to 745 nm are observed, with lifetimes spanning from 850 to 4500 ns. In contrast to the corresponding proligands, benzannulation is found to counterintuitively but markedly blue-shift emission from metal complexes with differing degrees of ligand benzannulation but similar substitution patterns. This effect can be further tuned by incorporation of electron-releasing (Me, tBu) or electron-withdrawing (CF3) substituents in either the phenanthridine 2-position or quinoline 6-position. Compared with symmetric bis(quinoline) and bis(phenanthridine) architectures, "mixed" ligands incorporating one quinoline and one phenanthridine unit present a degree of charge transfer between the N-heterocyclic arms that is more pronounced in the proligands than in the Pt(II) complexes. The impact of benzannulation and ring-substitution on the structure and photophysical properties of both the proligands and their deep-red emitting Pt(II) complexes is discussed.

An efficient microwave accelerated three component reaction of phenacyl azides and pyridinium phenacyl salts: A facile greener approach to 2-amino-2-ene-1,4-diones/pyrrolidin-2-ones

A mild and efficient base promoted, microwave assisted, green synthesis of 2-amino-2-ene-1,4-diones has been described by the decomposition of phenacyl azides followed by treatment with pyridinium salts of phenacyl bromides in aqueous media. A diverse range of substrates bearing electron-releasing and electron-withdrawing substituents were well tolerated and delivered corresponding 2-amino-2-ene-1,4-diones in good yields. Synthesized 2-amino-2-ene-1,4-diones have been further explored in the synthesis of various substituted 4-hydroxypyrrolidin-2-ones.

Experimental and theoretical evaluation of new piperidine and oxaquinuclidine core containing derivatives as an efficient corrosion inhibitor for copper in nitric acid medium

The inhibition efficiency of copper corrosion in 1 M HNO3 by five piperidine and oxaquinuclidine core containing compounds namely 2,4,6,11-tetraphenyl-9-oxa-1,5-diazatricyclo [5.3.1.03.8] undecane (OX1), 2,4,6,11-tetraaryl (4-methoxyphenyl)-9-oxa-1,5-diazatricyclo [5.3.1.03.8] undecane (OX2), 2,4,6,11-tetraaryl (4-chlorophenyl)-9-oxa-1,5-diazatricyclo [5.3.1.03.8] undecane (OX3), 2,4,6,11-tetraaryl-p-tolyl-9-oxa-1,5-diazatricyclo [5.3.1.03.8] undecane (OX4), and 2,4,6,11-tetraaryl (4-fluorophenyl)-9-oxa-1,5-diazatricyclo [5.3.1.03.8] undecane (OX5) has been investigated using gravimetric method, electrochemical studies, FT-IR, scanning electron microscopy (SEM), energy dispersive X-ray analysis (EDX), DFT and Monte Carlo simulation techniques. Inhibitors are chosen based on electron donating and accepting ability to the metal surface. These compounds differentiated in phenyl ring containing electron withdrawing (Cl, F) and electron releasing (OCH3, CH3) substituents. Experimental and computational studies showed that methoxy (OCH3) substituent exhibit more efficiency compared to other compounds and it is due to more electron donating nature of the OCH3 group. The adsorption of the inhibitors on copper surface obeyed Langmuir adsorption isotherm. Polarization results show that OXs are acting as a mixed type of inhibitors. In the surface characterization studies, change in frequency (FT-IR), change in surface roughness (SEM) and appearance of additional element peaks (EDX) before and after film formation confirmed the protective layer formation. Quantum chemical parameters and Monte Carlo simulation studies further evidenced by the inhibitor adsorption of the copper surface.

An Entry to Enantioenriched 3,3-Disubstituted Phthalides through Asymmetric Phase-Transfer-Catalyzed γ-Alkylation.

A novel asymmetric phase-transfer-catalyzed γ-alkylation of phthalide 3-carboxylic esters has been developed, giving access to 3,3-disubstituted phthalide derivatives, which present a chiral quaternary γ-carbon in good to excellent yields and good enantioselectivities (74–88% ee). The enantiomeric purity could be substantially enhanced to 94–95% ee by recrystallization. Both electron-withdrawing and electron-releasing substituents are well tolerated on the phthalide core as well as on the aromatic moiety of the alkylating agent. This methodology, enabling the introduction of an unfunctionalized group at the phthalide γ-position, fully complements previously reported organocatalytic strategies involving functionalized electrophiles, thus expanding the scope of accessible 3,3-disubstituted products. The high synthetic value of this asymmetric reaction has been proven by the formal synthesis of the naturally occurring alkaloid (+)-(9S,13R)-13-hydroxyisocyclocelabenzine.

Design, synthesis, in vitro and in vivo biological evaluation of 2-amino-3-aroylbenzo[b]furan derivatives as highly potent tubulin polymerization inhibitors

A new class of inhibitors of tubulin polymerization based on the 2-amino-3-(3′,4′,5′-trimethoxybenzoyl)benzo[b]furan molecular scaffold was synthesized and evaluated for in vivo and in vitro biological activity. These derivatives were synthesized with different electron-releasing or electron-withdrawing substituents at one of the C-4 through C-7 positions. Methoxy substitution and location on the benzene part of the benzo[b]furan ring played an important role in affecting antiproliferative activity, with the greatest activity occurring with the methoxy group at the C-6 position, the least with the substituent at C-4. The same effect was also observed with ethoxy, methyl or bromine at the C-6 position of the benzo[b]furan skeleton, with the 6-ethoxy-2-amino-3-(3′,4′,5′-trimethoxybenzoyl)benzo[b]furan derivative 4f as the most promising compound of the series. This compound showed remarkable antiproliferative activity (IC50: 5 pM) against the Daoy medulloblastoma cell line, and 4f was nearly devoid of toxicity on healthy human lymphocytes and astrocytes. The potent antiproliferative activity of 4f was derived from its inhibition of tubulin polymerization by binding to the colchicine site. The compound was also examined for in vivo activity, showing higher potency at 15 mg/kg compared with the reference compound combretastatin A-4 phosphate at 30 mg/kg against a syngeneic murine mammary tumor.

Triarylisocyanurate-Based Fluorescent Two-Photon Absorbers.

The synthesis and characterization of six triarylisocyanurates, featuring 2,7-fluorenyl or 9,10-anthracenyl groups incorporated in their peripheral arms are reported. Photophysical studies reveal that these new octupolar derivatives are more fluorescent (ΦF ≥0.60 for all new compounds except for 1,3,5-tri(9H-fluoren-2-yl)-1,3,5-triazinane-2,4,6-trione 3) and present a red-shifted lowest absorption and emission compared to their known phenyl analogues of comparable size. Depending on the nature of the terminal substituent, fast intramolecular energy transfer among the three arms or localization of the excitation on a single branch occurs after population of their first singlet excited state. The latter effect was only observed in the presence of strongly electron-releasing substituents in polar media. These new chromophores are also better two-photon absorbers than the 1,4-phenylene-based isocyanurates reported so far, with cross sections σ2 ≥500 GM at 770 nm for 4-NPh2 the fluorenyl group containing (13) and the anthracenyl group containing (14) chromophores. All these spectroscopic features, analyzed with the help of quantum chemical calculations, are crucial for the design of new biphotonic fluorescent dyes.