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Background: In order to make some progress in discovering the more effective way to eliminate ROS which cause the oxidative stress in organism in humans and bearing in mind the fact that ethyl-2-hydroxy-4-aryl(alkyl)-4-oxo-2-butenoates (β-diketonates) belong to a class of biologically active compounds, series of β-diketonates were synthesized, characterized, and tested to evaluate there antioxidant activity. Further, to investigate how coordination to copper(II) ion affects the activity of β-diketonates, appropriate complexes were synthesized and characterized. Methods: All complexes were characterized by UV-Vis, IR, and EPR spectroscopy, MS spectrometry, and elemental analysis. Fluorescence spectroscopic method was used for investigations of the interactions between biomacromolecules (DNA or BSA) and compound 2E. Viscosity measurements and molecular docking study were performed to confirm the mode of interactions between DNA and BSA and compound 2E. Results: Scavenging activity on DPPH radical revealed that compounds 2A, 2B, and 2E possess largest free radical scavenging, comparable to standard while results of superoxide anion scavenging activities of tested samples showed that maximum scavenging activity (IC50=168.92 μg/mL) was found for 2E, very similar to standard ascorbic acid, followed by 2B and 2G. Results of the interactions between biomacromolecules and 2E indicated that 2E has the affinity to displace EB from the EB-DNA complex through intercalation [Ksv = (3.7 ± 0.1) × 103 M-1], while Ka value obtained via titration of BSA with 2E [Ka = (4.2 ± 0.2) × 105 M-1], support the fact that the significant amount of the drug could be transported and distributed through the cells. Conclusions: All β-diketonates exhibited better scavenging activities than their corresponding copper complexes. Among all the tested compounds, 2E gave the highest reducing power, even higher than standard ascorbic acid, while reducing power for compounds 2A and 2B was also good but lower than standard. DNA and BSA binding study for 2E showed that this compound has the potential to be used as medicament.

Background: In order to discover new agents for chemotherapy with improved properties compared to the existing agents and bearing in mind the fact that some Pd complexes possess better antitumor activity and exhibit less kidney toxicity compared to cisplatin, a series of novel square-planar palladium(II) complexes [Pd (L)2] (3a-f) with O,O bidentate ligands [L = ethyl 2- hydroxy-alkyl(aryl)-4-oxo-2-butenoate] were synthesized. Methods: All complexes were characterized by spectral (UV-Vis, IR, NMR, ESI-MS) and X-ray analysis and examined for their cytotoxic effect on human cancer cell lines HeLa and MDA-MB 231 and normal fibroblasts (MRC-5). Fluorescence spectroscopic method was used for investigations of the interactions between CT-DNA or bovine serum albumin (BSA) and complex 3c. Viscosity measurements and molecular docking study were performed to confirm the mode of interactions between DNA and BSA and complex 3c. Results: Complexes that showed the best results, 3c, 3d, and 3e, were placed under further investigations. Selected complexes induced apoptosis and cell cycle arrest in HeLa and MDA-MB 231 cells. Low concentrations of 3c and 3e showed strong to moderate synergism with low concentrations of cisplatin. The interaction of 3d with cisplatin was antagonistic in all used concentrations, but low IC50 value indicates its usefulness as a single cytotoxic agent. It was also noted that the change of viscosity is more pronounced in DNA solution after addition of complex 3c. Conclusion: Obtained results indicate that the novel palladium(II) complexes have the potential to become candidates for treatment in anticancer therapy.

In order to investigate potential therapeutically agents, novel products of Biginelli reaction (4a-l) were synthesized and exposed to cytotoxic and caspase activities, angiogenesis, cell cycle distribution, gene and microRNA expression levels, lipophilicity assessment and docking study. Among the twelve novel compounds (4a-l) evaluated for the cytotoxic activity, five of them (4c,4d,4f,4kand4l) that showed excellent activity on the tested cell lines (HeLa, LS174 and A549) were selected for further evaluation. Interestingly, compound4fhas up to three times higher selectivity index (SI) towards cancer cells than cisplatin (on HeLa, LS174 and A549 SI = 18.2, 13.5 and 11.2, respectively). The obtained results from cell cycle distribution and caspase activity indicate that tested compounds (4c,4d,4f,4kand4l) promoted caspase-9 activation, implicated in the intrinsic pathway of apoptosis. Lipophilicity of4a-lwas determinate by using reversed-phase high-performance liquid chromatography. Graphical abstract https://ars.els-cdn.com/content/image/1-s2.0-S0045206818312598-ga1_lrg.jpg

The aim of this work is exploration of kinetic, thermodynamic and mechanistic aspects of triethylamine-mediated selenocyclofunctionalization of 4-pentenoic acid by means of phenylselenyl halides (PhSeCl and PhSeBr). The kinetics and mechanism for these reactions have been investigated by the UV–Vis spectrophotometry. The rate constants, as well as thermodynamic parameters (ΔH≠, ΔS≠) have been determined using UV–Vis method at three different temperatures (288, 298 and 308 K) in THF as a solvent. All studied reactions gave negative values for entropy of activation, which is in agreement with the SN2 mechanism of substitution. In addition, obtained values for the rate constants have indicated the higher reactivity of PhSeCl as reagent for cyclization.

The selective synthesis of 5,6-dihydropyrimidin-4(3H)-one scaffold (precursor of dihydrouracil) was a very difficult synthetic challenge that, so far, has not been achieved. For the first time, in this paper, green, selective and high-yields approach to 40 novel 5,6-dihydropyrimidin-4(3H)-ones (DHPMs) by one-pot reaction of aldehydes, Meldrum's acid and isothioureas under solvent-free conditions, in the presence of water, since an additive is presented. In the majority of cases, introduced methodology gave an unprecedented tautomer-selective fashion toward targeted compounds with excellent tautomeric purity (>99.9%), which reached 100% in few cases. The molecular structure of the five compounds has been determined by X-ray crystallography. In each one of them, very short length for the corresponding N2-C1 bond was noticed, making them especially interesting from a structural standpoint. This experimental fact can imply a highly localized electron π density in this part of each heterocyclic ring. The obtained experimental results, which are determined from NMR and ESI-MS study, indicate that this Biginelli-type reaction smoothly proceeds in a one-pot mode, pointing to the three-step tandem process, proceeding via the Knoevenagel, aza-Michael, and retro-Diels-Alder reactions. The presented strategy also had the following advantages: reduction amount of waste, excellent values of green chemistry metrics (cEF, EcoScale and GCIS), and it is the first eco-friendly strategy toward the DHPMs scaffold. © Copyright 2018 American Chemical Society. Supporting data: [http://vinar.vin.bg.ac.rs/handle/123456789/7888]

Nitrogen six-membered heterocyclic compounds, such as pyrimidines, are of synthetic interest because they constitute an important class of natural and synthetic products. 2-oxo-1,2,3,4-tetrahydropyrimidines are important drugs which have shown broad spectrum activities such as inhibitory against human immunodeficiency virus (HIV) replication, antimitotic, antiproliferative, and cytotoxic activities. Their derivatization involves the oxidation of C(sp3)-H bonds and is a major reaction for making double bonds in synthetic chemistry and biological systems. However, actual methods use toxic solvents or require strictly anhydrous conditions. As a consequence, there is a need for new and environmental benign protocols. Here we present water ultrasound oxidation of the benzylic position in 2-oxo-1,2,3,4-tetrahydropyrimidines and benzylic acid salts, into double bond using heterogeneous oxidizing agents Cu(III) or Ag(III). This method has several advantages such as the use of green solvent, broad substrate scope, excellent yields and less amounts of waste with excellent values of green chemistry metrics.

Increased antimicrobial resistance together with the lack of new antimicrobial drugs suggest on an urgent need for new therapeutics in this field. Vanilidene derivatives of Meldrum’s acid present one of the possible approaches. In this work lipophilicity of 13 vanilidene derivatives of Meldrum’s acid as well as their predicted antimicrobial activity towards several characteristic species has been evaluated. 10 vanilidene derivatives have been previously synthesized and 3 new compounds are synthetized afterwards following the same procedure. These selected 13 candidates were examined using thin layer chromatography in two different solvent systems. Gained retention parameters were a starting point for further Quantitative Structure Property Relationships (QSRR) studies in which minimum inhibitory concentration (MIC) for Candida albicans, Trichoderma viride, Penicillium italicum, Fuscarium oxysporum, Pseudomonas aeruginosa and Escherichia coli were determined. Statistically significant QSRR models were established and clustering of the compounds was performed with the help of principal component analysis (PCA) and hierarchical cluster analysis (HCA). Absorption, Distribution, Metabolism, and Excretion (ADME) properties of investigated molecules were subjected to sum of ranking differences (SRD) analysis in order to explore their pharmacokinetic properties. SRD analysis was also performed for the ranking of the established QSRR models. It was shown that compounds 6, 8 and 9 possess a significant antimicrobial activity, satisfied ADME properties and these candidates should be further optimized in order to utilize unexplored potential of Meldrum's acid in synthesis of novel antifungal compounds.

The selected quinoxalinones and benzoxazinones derivatives, synthesized in our laboratory earlier, were explored by spectroscopic techniques (UV-Vis, IR, Raman and NMR) and theoretical study (DFT calculations). In order to understand the electronic properties of these compounds, the theoretical UV spectra have been investigated by TDDFT/B3LYP method with 6-311+G(d,p) basis set in ethanol as a solvent. For all compounds, the absorption of UV radiation with a wavelength around 415 nm with an oscillator strength f = 0.90 induces the intramolecular electronic transition (n→π*). The frontiers molecular orbitals are calculated, and contributions of the electronic transitions are determined. Also, we did quantum chemical calculations to investigate the corrosion inhibition properties of these molecules. The vibrational analysis was performed at the B3LYP/6-311+G(d,p) level of theory in vacuo. Obtained results are in very good agreement with experimental data. The calculated 13C NMR shifts in all cases are in good-to-excellent agreement. Also, 1H NMR predicted shifts are comparable with experimental results, but there are some deviations (for N–H shifts) probably as a consequence of intramolecular interactions. The previously synthesized quinoxalinones and benzoxazinones derivatives were explored by spectroscopic techniques (UV-Vis, IR, Raman and NMR) and theoretical study (DFT calculations). UV-Vis, IR, Raman and NMR spectra were calculated and compared with experimental data. The frontiers molecular orbitals are calculated, and contributions of the electronic transitions are determined. Besides that, we investigated the corrosion inhibition properties of these molecules using quantum chemical calculations. Compounds that contain electron donating groups (–OCH3, –NHCOCH3) exhibit better inhibitory efficiency than compounds that contain electron withdrawing groups (–NO2, alkenyl chain).

The reaction of the Δ4-alkenols with PhSeX can follow three possible reaction pathways: two pathways lead to the formation of two regioisomeric cyclic ether products through the process of intramolecular cyclization, while the third represents the addition of the reagent to the double bond of an alkenol. As there are relatively few literature data on the kinetics of these reactions, we have chosen 6-methyl-hept-5-en-2-ol as a substrate of interest in order to obtain valuable results that will enable better understanding of the mechanism of phenylselenoetherification reactions. 6-Methyl-hept-5-en-2-ol is a particularly interesting model-substrate due to its substitution pattern of functional groups involved in the cyclization process. In this research, through synthetic and kinetic studies, we aimed to resolve key questions concerning the influence on kinetics, chemo- and regioselectivity of the reagent's counter ion, steric hindrances in substrate functional groups and the presence of additives.

Innovative, efficient, clean, experimentally simple and environmentally friendly one-pot biocatalytic synthesis of two small libraries of 3,4-dihydro-2(1H)-quinoxalinones (4a–m) and 3,4-dihydro-1,4-benzoxazin-2-ones (5a, 5b, 5f and 5k–o) by heterocyclization of ethyl 2-hydroxy-4-alkyl(aryl)-4-oxo-2-butenoates (1a–o) or their corresponding salts (1a′–o′) with o-phenylenediamine (2) or o-aminophenol (3) in lemon juice as a solvent and a catalyst is presented. In all reactions where esters 1a–o are used for 24 h, very good-to-excellent yields were achieved, but the best yield was realized in the synthesis of 5a (97%) from 3 and 1a. The use of enolate salts (1a′–o′) instead of the corresponding esters 1a–o significantly reduced the reaction time (up to 6 h) and good-to-excellent yields were achieved. Groups with electron-donating or -withdrawing effects at the aromatic ring of the ester did not have significant influences on the yield of targeted products. In addition, several selected 3,4-dihydro-2(1H)-quinoxalinones and 3,4-dihydro-1,4-benzoxazin-2-ones on a gram-scale in the yields up to 92% were synthesized. The presented synthetic strategy has produced smaller amount of waste without by-products and with excellent values of green chemistry metrics (atom efficiency, reaction mass efficiency, E-factor and EcoScale).

Convenient structures such as 2,4-diketo esters have been widely used as an effective pattern in medicinal chemistry and pharmacology for drug discovery. 2,4-Diketonate is a common scaffold that can be found in many biologically active and naturally occurring compounds. Also, many 2,4-diketo ester derivatives have been prepared due to their suitable synthesis. These synthetic drugs and natural products have shown numerous interesting biological properties with clinical potential as a cure for the broad specter of diseases. This review aims to highlight the important evidence of 2,4-diketo esters as a privileged scaffold in medicinal chemistry and pharmacology. Herein, numerous aspects of 2,4-diketo esters will be summarized, including synthesis and isolation of their derivatives, development of novel synthetic methodologies, the evaluation of their biological properties as well as the mechanisms of action of the diketo ester derivates. This paperwork is expected to be a comprehensive, trustworthy, and critical review of the 2,4-diketo ester intermediate to the chemistry community.

In order to make a progress in discovering a new agents for chemotherapy with improved properties and bearing in mind the fact that substituted 3-hydroxy-3-pyrrolin-2-ones belong to a class of biologically active compounds, series of novel 1,5-diaryl-4-(2-thienylcarbonyl)-3-hydroxy-3-pyrrolin-2-ones were synthesized and characterized by spectral (UV–Vis, IR, NMR, ESI-MS), X-ray and elemental analysis. All compounds were examined for their cytotoxic effect on human cancer cell lines HeLa and MDA-MB 231 and normal fibroblasts (MRC-5). Four compounds, 3-hydroxy-1-(p-tolyl)-4-(2-thienylcarbonyl)-5-(4-chlorophenyl)-2,5-dihydro-1H-pyrrol-2-one (D10), 3-hydroxy-1-(3-nitrophenyl)-4-(2-thienylcarbonyl)-5-(4-(benzyloxy)phenyl)-2,5-dihydro-1H-pyrrol-2-one (D13), 3-hydroxy-1-(4-nitrophenyl)-4-(2-thienylcarbonyl)-5-(4-(benzyloxy)phenyl)-2,5-dihydro-1H-pyrrol-2-one (D14), and 3-hydroxy-1-(4-chlorophenyl)-4-(2-thienylcarbonyl)-5-(4-(benzyloxy)phenyl)-2,5-dihydro-1H-pyrrol-2-one (D15), that showed the highest cytotoxicity against malignant cells and the best selectivity towards normal cells were selected for further experiments. Results obtained by investigating mechanisms of cytotoxic activity suggest that selected 3-hydroxy-3-pyrrolin-2-one derivatives in HeLa cells induce apoptosis that is associated with S phase arrest (D13, D15, and D10) or unrelated to cell cycle distribution (D14). Additionally, to better understand their suitability for potential use as anticancer medicaments we studied the interactions between biomacromolecules (DNA or BSA) and D13 and D15. The results indicated that D13 and D15 have great affinity to displace EB from the EB-DNA complex through intercalation [K sv = (3.7 ± 0.1) and (3.4 ± 0.1) × 10 3 M −1 , respectively], an intercalative mode also confirmed through viscosity measurements. K a values, obtained as result of fluorescence titration of BSA with D13 and D15 [K a = (4.2 ± 0.2) and (2.6 ± 0.2) × 10 5 M, respectively], support the fact that a significant amount of the tested compounds could be transported and distributed through the cells. In addition, by DNA and BSA molecular docking study for D13, D14 and D15 is determined and predicted the binding mode and the interaction region. © 2019 Elsevier Inc. This is peer-reviewed version of the article Joksimović, N., Petronijević, J., Janković, N., Baskić, D., Popović, S., Todorović, D., ... & Bugarčić, Z. (2019). Synthesis, characterization, anticancer evaluation and mechanisms of cytotoxic activity of novel 3-hydroxy-3-pyrrolin-2-ones bearing thenoyl fragment: DNA, BSA interactions and molecular docking study. Bioorganic chemistry, 88, 102954. [http://dx.doi.org/10.1016/j.bioorg.2019.102954] Published version: [https://vinar.vin.bg.ac.rs/handle/123456789/8173]

A series of novel O-alkyl vanillidene derivatives containing Meldrum's acid scaffold under solvent-free conditions were synthesized. The antimicrobial activity was estimated by determination of the minimal inhibitory concentration (MIC) using the broth microdilution. The most active compounds were 5-(4′-hydroxy-2′-iodo-3′-methoxybenzylidenyl)-2,2-dimethyl-1,3-dioxane-4,6-dione (3a), 5-(4′-acetoxy-3′-methoxybenzylidenyl)-2,2-dimethyl-1,3-dioxane-4,6-dione (3f), and 5-(4′-bromopropoxy-3′-methoxybenzylidenyl)-2,2-dimethyl-1,3-dioxane-4,6-dione (3h) with the MIC values ranging from 0.039 to 10 mg mL−1. Antioxidant activity was evaluated by DPPH free radical scavenging activity. 3h showed the largest scavenging activity with an IC50 value of 55.61 μg mL−1 (0.14 mmol L−1). The interaction of 3a and 3h with DNA and bovine serum albumin (BSA) were investigated by the fluorescence spectroscopic method. The results achieved in competitive experiments with ethidium bromide (EB) indicated that 3a and 3h have an affinity to displace EB from the EB–DNA complex through intercalation. Fluorescence spectroscopy data show that the fluorescence quenching of BSA is a result of the formation of the 3a- and 3h-BSA complex species, and indicate that 3a-BSA is more stable, suggesting that 3h-BSA is less suitable for drug–cell interactions.

Mechanistic and kinetic aspects, as well as quantum chemical calculations, for the formation of a tetrahydrofurane ring by cyclization of the highly substituted alcohol–2,6-dimethyl-hept-5-en-2-ol with phenylselenohalides (PhSeCl and PhSeBr), in the presence of various Lewis bases (piperidine, triethylamine, pyridine and quinoline) and Lewis acids (CoCl2, SnCl2) as additives were studied. The substituted tetrahydrofuran ring is common motif in many natural products, especially in bioactive marine macrolides. Due to the presence of additives in reactions, the high regioselectivity was achieved, and the tetrahydrofuran type of ether in all studied reactions was obtained in excess in regard to the six-membered cyclic ether. In addition, kinetic aspects of reactions mediated by Lewis bases were studied by UV–Vis spectroscopy (in THF, at 288 K), as reactions of pseudo-first-order. Obtained values for rate constants proved catalytic role of additives and indicated that the reaction rate depends on pKa values of used base as well as on their ability for formation of hydrogen bond with OH–alcohols group.

An innovative route for the construction of 2-oxo and thioxo-1,2,3,4-tetrahydropyrimidines was delineated through a multicomponent reaction under Biginelli conditions, starting from different aromatic aldehydes, β-ketoesters and urea or thiourea. Proper choice of copper complex (PhNH3)2CuCl4, as a novel homogeneous catalyst, enables facile, efficient, and inexpensive reaction under mild experimental conditions. Moreover, we present the first application of this complex salts in organic synthesis ever. The obtained products are of high purity, and can be easily isolated from the reaction mixture in good to excellent yields. Also, compared to the classical Biginelli reaction conditions, the present method has the advantages in higher yields and experimental and work-up simplicity. To illustrate the joint catalytic action of the Cu2+ and phenylammonium ions, two key steps of Biginelli reaction were examined using the M06 functional. [Projekat Ministarstva nauke Republike Srbije, br. 172011 i br. 172016]

The pyridine-mediated reactions of nerolidol with both PhSe+ and PhSeCl were investigated using two DFT methods. Comparison of the obtained results provides a description of the counterion influence for the first time. As a consequence of very low solvation free energy of the neutral reactants, addition of the phenylselenyl group to the double bond of nerolidol is an endergonic process, and occurs via a transition state to yield an intermediate that undergoes cyclisation. Due to the influence of the counteranion on the positively charged moiety of the reaction system, the activation free energies in the reaction with PhSeCl are significantly larger than those in the reaction with PhSe+. Thus, only the anti pathway is favoured. The lower activation energy required for the formation of less stable cis-5-ethenyl-5-methyl-2-[6-methyl-2-(phenylseleno)hept-5-en-2-yl]tetrahydrofuran confirms that the examined reaction is kinetically controlled.

A systematic study of the mechanism of phenylselenoetherification of a naturally occurring alcohol linalool with PhSe+ was performed at the B3LYP/6-311+G(d,p) level of theory, in conjunction with the CPCM solvation model. The syn and anti reaction pathways were examined in the absence and presence of some Lewis bases (quinoline, piperidine, pyridine, and triethylamine) as catalysts. It was found that the reaction occurs via the phenylseleniranium intermediate, which further suffers a nucleophilic attack of the oxygen to two olefinic carbon atoms. This intramolecular cyclization yields 5-ethenyl-5-methyl-2-[2-(phenylseleno)-prop-2-yl]tetrahydrofuran as the major product and 6-ethenyl-2,2,6-trimethyl-3-phenylselenotetrahydropyran as the minor product. Lewis bases facilitate the reaction by strong hydrogen bonds between the alcoholic hydrogen and nitrogen of an additive moiety, and they stabilize the product complexes. Since the formation of the tetrahydrofuran derivative requires higher activation energy, but is thermodynamically more stable than the tetrahydropyran, it was concluded that the phenylselenoetherification reaction of linalool is thermodynamically controlled.

The mechanism of the phenylselenoetherification of some naturally occurring alcohols linalool and nerolidol in the presence of some bases (piperidine, pyridine, triethylamine, quinoline) as catalysts was examined through the kinetic study of the cyclization under pseudo-first order conditions by UV–Vis spectrophotometry. It was demonstrated that the intramolecular cyclization is facilitated in the presence of some bases caused by the hydrogen bond between base and OH-group of the alkenol. The obtained values for the rate constants show that there is a good agreement between those constants and the basicity of the catalyst. The fastest reaction is the one using the strongest base (piperidine) and the smallest rate constant corresponded to the use of the weakest base (quinoline).

The mechanism of phenylselenoetherification of (Z)- and (E)-hex-4-en-1-ols using some bases (triethylamine, pyridine, quinoline, 2,2'-bipyridine) as catalysts and some solvents [tetrahydrofuran (THF) and CCl4] as reaction media was examined through studies of kinetics of the cyclization by UV-vis spectrophotometry. It was demonstrated that the intramolecular cyclization is facilitated in the presence of bases as a result of the hydrogen bond between the base and the alkenol's OH group. The rate constants in the base-catalyzed reactions are remarkably influenced by the bulkiness and basicity of the base used and the nature of the considered nitrogen donors. The obtained values for rate constants show that the reaction with triethylamine is the fastest one. THF with higher polarity and higher basic character is better as a solvent than CCl4. Quantum-chemical calculations [MP2(fc)/6-311+G**//B3LYP/6-311+G** + ZPE(B3LYP/6-311+G**] show that the cyclization of (Z)-hex-4-en-1-ol to a tetrahydrofuranoid five-membered ring is kinetically controlled, while the cyclization of (E)-hex-4-en-1-ol to the tetrahydropyranoid six-membered ring is thermodynamically controlled. This is in accordance with previous experimental findings.

Studies on the phenylselenoetherification of some D 4 -alkenols in the presence of pyridine and some Lewis acids are described. All alkenols underwent intramolecular cyclization yielding corresponding tetrahydrofuran or tetrahydropyran derivatives. Yield and diastereomeric ratio of the cyclic products depend on counterion of selenylating reagent used. We found that external additives, such as pyridine and some Lewis acids coordinating to the electrophilic and/or nucleophilic species are used to control the course of cyclizations with high degrees of efficiency and improve the level of stereoinduction.

Δ 4 -Primary alkenols (Z)- and (E)-hex-4-en-1-ols underwent facile cyclization to the corresponding phenyl selenoethers using PhSeX (X = Cl, Br) in high yields and in good to excellent selectivities in the presence of some catalysts (Lewis acids and bases). The reaction succeeded in complete control of stereo- and regioselectivity. The best results were obtained with triethylamine and tin(II) chloride. Triethylamine as an additive in the reaction with (Z)-hex-4-en-1-ol gives only erythro-2-[1-(phenylseleno)ethyl]tetrahydrofuran, while the E-isomer gives cis-2-methyl-3-(phenylseleno)tetrahydropyran in large excess. Tin(II) chloride as an additive in the reaction with (Z)-hex-4-en-1-ol gives threo-2-[1-(phenylseleno)ethyl]tetrahydrofuran and with the E-isomer gives trans-2-methyl-3-(phenylseleno)tetrahydropyran. The reactions were performed under very mild experimental conditions, and the obtained yields were almost quantitative.

A fast and efficient method for intramolecular heterocyclization of (Z)- and (E)-hex-4-en-1-ols was developed. The method does not cause side reactions of the substrates and provides the cyclic phenylselenoethers in high yields after only few minutes. A catalytic amount of SnCl2 increased the yield, but in the presence of an equimolar amount of SnCl2, formation of corresponding cyclic ethers were almost quantitative and reaction occurred instantaneously under extremely mild experimental conditions.

The kinetics and mechanism of the reaction of phenylselenenyl halides (PhSeX, X = Cl, Br) and some primary unsaturated alcohols (pent-4-en-1-ol and hex-5-en-1-ol) in tetrachloromethane media have been studied, under the pseudo -first order conditions, in the presence and absence of pyridine as catalyst by variable temperature UV–vis spectrophotometry. Under the kinetic conditions, both the slower uncatalyzed and faster catalyzed (by pyridine) paths give the change of absorbance of the reaction mixture at some wavelength. The obtained values for rate constants have shown that the reactions with phenylselenenyl bromide are slower. Also, the reactions of both phenylselenenyl halides with hex-5-en-1-ol are faster than those with pent-4-en-1-ol. The negative values for entropy of activation for all studied reactions confirm the S N 2 mechanism of substitution.

A serie of novel square pyramidal copper(II) complexes [Cu(L)(2)H2O] (3a-d) with O,O-bidentate ligands [L = ethyl-2-hydroxy-4-aryl-4-oxo-2-butenoate; aryl = 3-methoxyphenyl-2a, (E)-2-phenylvinyl-2b, (E)-2-(4-hydroxy-3-methoxyphenyl)vinyl-2c, 3-nitrophenyl-2d, 2-thienyl-2e] were synthesized and characterized by spectral (UV-Vis, IR, ESI-MS and EPR), elemental and X-ray analysis. The antimicrobial activity was estimated by the determination of the minimal inhibitory concentration (MIC) using the broth micro-dilution method. The most active antibacterial compounds were 3c and 3d, while the best antifungal activity was showed by complexes 3b and 3e. The lowest MIC value (0.048 mg mL(-1)) was measured for 3c against Proteus mirabilis. The cytotoxic activity was tested using the MTT method on human epithelial carcinoma HeLa cells, human lung carcinoma A549 cells and human colon carcinoma LS174 cells. All complexes showed extremely better cytotoxic activity compared to cisplatin at all tested concentrations. Compound 3d expressed the best activity against all tested cell lines with IC50 values ranging from 7.45 to 7.91 mu g mL(-1). The type of cell death and the impact on the cell cycle for 3d and 3e were evaluated by flow cytometry. Both compounds induced apoptosis and S phase cell cycle arrest. The interactions between selected complexes (3d and 3e) and CT-DNA or bovine serum albumin (BSA) were investigated by the fluorescence spectroscopic method. Competitive experiments with ethidium bromide (EB) indicated that 3d and 3e have a propensity to displace EB from the EB-DNA complex through intercalation suggesting strong competition with EB [K-sv = (1.4 +/- 0.2) and (2.9 +/- 0.1) x 10(4) M-1, respectively]. K-sv values indicate that these complexes bind to DNA covalently and non-covalently. The achieved results in the fluorescence titration of BSA with 3d and 3e [K-a = (2.9 +/- 0.2) x 10(6) and (2.5 +/- 0.2) x 10(5) M, respectively] showed that the fluorescence quenching of BSA is a result of the formation of the 3d- and 3e-BSA complexes. The obtained K-a values are high enough to ensure that a significant amount of 3d and 3e gets transported and distributed through the cells.

An efficient protocol for the preparation of phenylselenoethers from unsaturated alcohols using phenylselenenyl halides at room temperature was developed. The procedure employs phenylselenenyl chloride and bromide, some Δ 4- and Δ 5-alkenols and Ag2O, as an additive, to generate the tetrahydropyrans or tetrahydrofurans. This method permits the preparation of cyclic phenylselenoethers in high yields and under extremely mild conditions.

An innovative route for intramolecular cyclization of alkenols has been delineated through a ring closing reaction of suitably alkenols functionalized cyclic ethers tetrahydropyran or tetrahydrofuran type by reaction with phenylselenyl halides, in good yield. Proper choice of some 4 and 5 -alkenols and pyridine as catalyst enables fast and facile cyclization. Catalytic amount of pyridine increased the yield, but in the presence of equimolar amount of pyridine, formation of corresponding cyclic ethers were quantitative and reaction were achieved instantaneously under extremely mild experimental conditions. It is possible that aromatic–aromatic ring stacking provides such role of pyridine. The effect of the steric hindrance in the starting alkenols, and halide ion of the selenenylating reagent is not significant, all halides generally giving equal results, and primary, secondary, tertiary and more substituted alkenols also giving quantitative yields. © 2007 Elsevier B.V. All rights reserved.

The reactions of Pt(II) complexes, cis -[Pt(NH 3 ) 2 Cl 2 ], [Pt(terpy)Cl] + , [Pt(terpy)( S -cys)] 2+ , and [Pt(terpy)(N7-guo)] 2+ , where terpy = 2,2′:6′,2″-terpyridine, S -cys = l -cysteine, and N7-guo = guanosine, with some biologically relevant ligands such as guanosine-5′-monophosphate (5′-GMP), l -cysteine, glutathione (GSH) and some strong sulfur-containing nucleophiles such as diethyldithiocarbamate (dedtc), thiosulfate (sts), and thiourea (tu), were studied in aqueous 0.1 M Hepes at pH of 7.4 using UV–vis, stopped-flow spectrophotometry, and 1 H NMR spectroscopy.

A small library of novel 2-oxo-1,2,3,4-tetrahydropyrimidines was synthesized via a one-pot multicomponent Biginelli reaction. Copper complex [Formula: see text] which was used for the first time as a homogeneous and heterogeneous catalyst, makes this a facile and efficient reaction at room temperature. All the obtained products fall out of the solution in pure form and are easily isolated via filtration in good-to-excellent yields. The molecular structure of one of the products, ethyl 6-methyl-2-oxo-4-(4[Formula: see text]-isopropoxy-3[Formula: see text]-methoxyphenyl) - 1,2,3,4 - tetrahydropyrimidine-5- carboxylate, has been determined by X-ray crystallography. All non-hydrogen atoms in the heterocyclic, six-membered ring are determined to be approximately coplanar.

An improved procedure for intramolecular cyclization of some Δ5-alkenols, using PhSeX (X = Cl, Br) has been developed. We found that cyclization can be facilitated in the presence of pyridine, Ag2O, and some Lewis acids as catalysts. Thus catalytic amount of additives (pyridine and Ag2O) influences higher yields but equimolar amount achieves almost quantitative yield under extremely mild experimental conditions. In the presence of Lewis acids (ZnCl2 and FeCl3) high yields of cyclic ether products are obtained with catalytic amounts. © 2004 Wiley Periodicals, Inc. Heteroatom Chem 15:146–149, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10227

An improved procedure for intramolecular cyclization of some Δ5-alkenols using PhSeX (X=Cl, Br) was developed. We found that cyclization can be facilitated in the presence of pyridine, Ag2O, and AgOAc as additives. Thus, a catalytic amount of additive influenced higher yields and equimolar amounts achieved almost quantitative yields under extremely mild experimental conditions. The effect of the halide ion of the selenylating reagent was not significant.

An innovative route for intramolecular cyclization of pent- 4-en-1-ol has been delineated through a ring closing reaction with phenylselenyl halides, in good yield. Several catalysts (triethylamine, quinoline, 2,2ʹ-bipyridine, pyridine, CoCl2 and SnCl2) enable fast, facile and efficient cyclization.

Two novel Pd(II) complexes with 2-(phenylselanylmethyl)oxolane and 2-(phenylselanylmethyl)oxane as ligands were synthesized. The crystal and molecular structure of the complexes has been determined by single crystal X-ray diffraction. It turned out for both complexes that the two ligands are coordinated to Pd via Se atoms in a trans-fashion and the other two trans-positions are occupied by Cl ions. Detailed 1D- and 2D-NMR analyses revealed the existence of equilibrating trans-diastereomeric species differing in the configuration at four chiral centers (selenium and carbon) in the solution of the complexes. A computational study was also undertaken to assess the relative stabilities of the mentioned stereoisomeric species. The antimicrobial properties of the complexes were investigated against a series of human pathogenic bacterial and fungal strains. The complexes were shown to possess promising broad spectrum moderate antimicrobial activity that is more pronounced against fungal organisms. The noted activity could be completely attributed to the Pd(II) center, whereas the ligands probably mediate the transportation of a Pd(II) species across cell membranes.

The procedure employs phenylselenyl chloride or bromide, pent-4-en-1-ol, and additives, like pyridine and silver(I) salts, to generate the cyclic ether of tetrahydrofuran type in high yields. A catalytic amount of additive leads to higher yields, but equimolar amounts achieved almost quantitative yields under extremely mild experimental conditions. The effect of the halide ion of the selenylating reagent is not significant.

A convenient two-step protocol prepa-ration of cineol (1-isopropyl-4-methyl-7-oxabicyclo-[2,2,1]heptane) from -terpineol (p-menth-1-en-8-ol)is reported. The phenylselenoetherification of -ter-pineol with PhSeX (X = Cl, Br, I) as a key step isdescribed. -Terpineol reacts with PhSeX to form thecorresponding phenylselenoether in short reactiontime and in quantitative yield. A subsequent reduc-tion with Bu 3 SnH to cineol proceeds in high yield(98%) C 2004 Wiley Periodicals, Inc. Heteroatom Chem15:468–470, 2004; Published online in Wiley InterScience(www.interscience.wiley.com). DOI 10.1002/hc.20044 INTRODUCTION Cyclofunctionalization of unsaturated alcohols is avery popular reaction providing easy access to cyclicether products [1–6]. In many respects, selenocy-clofunctionalization has the advantage that the in-troduction of the heteroatom, the manipulation ofthe obtained product, and the removal of the func-tion are facilitated by simple and mild condition re-quired [5–7]. This methodology has been extendedto more complex system having alcohol and doublebond functions.Cyclization of unsaturated alcohols leading tocyclic ethers is well documented in the literature

Primary and secondary alcohols, e.g. (I), react to give tetrahydropyrans whereas tertiary alcohols such as (IV) yield tetrahydrofurans.

Vitamin B12-catalyzed allylic dimerization of some γ- and δ-bromoalkanols with activated Zn-dust in mixture ethanol/water (1:1) has been studied. Investigated bromoalkanols were prepared from corresponding tertiary Δ4- and Δ5-alkenols by means of benzeneselenyl bromide and subjected to chemical reduction with vitamin B12. All investigated bromoalkanols, after dehydrobromination, underwent to oxidative allylic coupling and hydratation in the presence of protic solvents to give predominantly polyhydroxy alkanols.

The mechanism of phenylselenoetherification of pent-4-en-1-ol using some bases (pyridine, triethylamine, quinoline, 2,2'-bipyridine) as catalyst was examined through studies of kinetics of the cyclization, by UV-VIS spectrophotometry. It was demonstrated that the intramolecular cyclization is facilitated in the presence of bases caused by the hydrogen bond between base and alkenol's OH-group. The obtained values for rate constants have shown that the reaction with triethylamine is the fastest one. Quantum chemical calculations (MP2(fc)/6-311+G**//B3LYP/6-311+G**) show, that the transition state of the cyclisation is S(N)2 like.

The regioselectivity in cyclofunctionalization of some acyclic olefinic alcohols with benzeneselenenyl halides (PhSeCl and PhSeBr) at different temperatures (−78°C, O°C and room temperature) is investigated. It has been found that Δ4- and Δ5- alkenols are converted into five- and/or six-membered cyclic phenyl selenoethers, the yield of which decreases with increasing reaction temperature. PhSeCl has been found to be more efficient than PhSeBr in the cyclization reactions.