Luminescent Properties of ß-(hydroxyaryl)-butenolides and Fluorescence Quenching in Water.

This work describes the luminescent properties of the new compound ß-(hydroxyaryl)-butenolides recently discovered. The compounds were subjected to UV-Vis absorption and fluorescence analyzes when diluted in different solvents. Through the results, it was possible to observe that the ß-hydroxyarylutenolides have two absorption bands, one at 289-291 nm and the other with higher intensity at 328-354 nm. The emission band between 385-422 nm is observed under excitation at 324-327 nm. The compounds showed solvatochromism as a function of the analyzed solvent. In water, fluorescence quenching of all compounds occurs. Therefore, studies with compound containing the methylenedioxy group attached in phenyl ring were carried at different concentrations of water in DMSO. The decrease in the fluorescence intensity of this compound is linearly proportional to the increase in the amount of water in the DMSO, with a minimum detection volume of 0.028%. Quantum yields of three compounds were evaluated in different solvents, showing that the relationship between the structure of the compound and the solvent is essential for a high value. The fluorescence quantum yield was also measured by Thermal Lens Spectroscopy (TLS) using DMSO as the solvent, confirming the high value for the analyzed samples. Despite being preliminary, the studies revealed that these compounds have luminescent properties that could be applied in the development of chemical sensors for detecting water in DMSO.

Molecular interaction analysis of the lignans from Piper cubeba in complex with Haemonchus contortus phosphomethyltransferase.

In vitro larvicidal assays carried out previously by our research group with cubebin, dihydrocubebin and hinokinin, lignans extracted from the fruits of Piper cubeba, against Haemonchus contortus larvae showed strong action larvicidal these compounds. Hinokinin was the most active (EC50 = 0.34 µg/mL) with strong action on the cuticle of the larvae as observed by scanning electron microscopy of the L3 stage. Therefore, to understand the mechanism of action of these compounds in silico studies were carried out using the enzyme phosphomethyltransferase of Haemonchus contortus that contain PMT-1 and PMT-2 di-domains responsible for phosphocholine synthesis, which is one of the main lipids in nematodes. This pathway is not found in mammals, so this enzyme is an important biological target for the development of new anthelmintics. Results of molecular docking, molecular dynamic and a density functional theory calculations studies with the three lignans show few interactions with PMT-1. However, hinokinin has important interactions with PMT-2, that can deactivate the enzyme and interrupt the phosphocholine synthesis, which is an essential compound for the development and maintenance of the nematode cuticle and its survive. Therefore, the previous results of the in vitro assay allied with in silico results, now realized; suggest that hinokinin may be a possible selective target for the development of new anthelmintics against Haemonchus contortus since the PMT-2 domain is present in this nematode.

The use of molecular electronic structure methods to investigate mechanically interlocked molecules.

Mechanically interlocked molecules (MIMs) show several applications as molecular machines, catalysts, and appear as potential structures for ion recognition. Importantly, the understanding of the nature of the mechanical bonds that support the interaction between the non-interlocked components of MIMs is still a poorly explored topic in the literature. Important discoveries in the field of MIMs have been made using molecular mechanics (MM) and, in particular, molecular dynamics (MD) methods. However, obtaining more accurate geometric and energetic parameters requires the use of molecular electronic structure methods. The present perspective highlights some studies of MIMs using density functional theory (DFT) or ab initio electron correlation methods. We expect that the studies highlighted here will show that such large structures can be studied with more precise approaches by selecting the model system to be studied by chemical intuition or supported by low scaling quantum mechanics methods. This will contribute to the elucidation of important properties to be used in the design of various materials.

Cation recognition controlled by protonation or chemical reduction: a computational study.

To control biochemical processes, non-covalent interactions involving cations are activated by protons or electrons. In the present study, the bonding situation between: (i) carboxylic acid or (ii) ferrocene-functionalized crown ether derivatives and cations (Li+, Na+ or K+) has been elucidated and, mainly, tuned by the substitution of hydrogen atoms by electron donor (-NH2) or acceptor (-NO2) groups. The deprotonation of the carboxyl groups improves the interaction with the cations through more favorable electrostatic O⋯cation interactions. Reducing the ferrocene structures favors cationic recognition supported by a less unfavorable iron⋯cation binding. The receptors preferably interact with smaller cations because of more attractive electrostatic and orbital (σ or π) O⋯cation interactions. The presence of electron donor or acceptor groups in the carboxylic acid-functionalized crown ethers promotes less attractive interactions with the cations, mainly due to the less favorable electrostatic O⋯Na+ interactions. The -H → -NH2 substitution in the ferrocene framework favors the cationic recognition. It is based on the strengthening of the electrostatic and σ O⋯Na+ and H2N⋯Na+ bonds. The (i) absence of repulsive electrostatic iron⋯cation interactions, or (ii) the presence of oxygen atoms with large electron density, ensures carboxylic acid-functionalized crown ethers have more favorable interactions with cations than ferrocene compounds. Therefore, this work has demonstrated how cation recognition can be improved by structural changes in carboxylic acid- or ferrocene-functionalized crown ethers and has shown that the carboxylic acid molecules appear to be better candidates for cation recognition than ferrocene derivatives.

Guttiferone E Displays Antineoplastic Activity Against Melanoma Cells.

Guttiferone E (GE) is a benzophenone found in Brazilian red propolis. In the present study, the effect of GE on human (A-375) and murine (B16-F10) melanoma cells was investigated. GE significantly reduced the cellular viability of melanoma cells in a time-dependent manner. In addition, GE demonstrated antiproliferative effect, with IC50 values equivalent to 9.0 and 6.6 µM for A-375 and B16-F10 cells, respectively. The treatment of A-375 cells with GE significantly increased cell populations in G0/G1 phase and decreased those in G2/M phase. Conversely, on B16-F10 cells, GE led to a significant decrease in the populations of cells in G0/G1 phase and concomitantly an increase in the population of cells in phase S. A significantly higher percentage of apoptotic cells was observed in A-375 (43.5%) and B16-F10 (49.9%) cultures after treatment with GE. Treatments with GE caused morphological changes and significant decrease to the melanoma cells' density. GE (10 µM) inhibited the migration of melanoma cells, with a higher rate of inhibition in B16-F10 cells (73.4%) observed. In addition, GE significantly reduced the adhesion of A375 cells, but showed no effect on B16-F10. Treatment with GE did not induce changes in P53 levels in A375 cultures. Molecular docking calculations showed that GE is stable in the active sites of the tubulin dimer with a similar energy to taxol chemotherapy. Taken together, the data suggest that GE has promising antineoplastic potential against melanoma.

Designing boron and metal complexes for fluoride recognition: a computational perspective.

Fluoride anions (F-) may have beneficial or harmful effects on the environment depending on their concentration. Here, we shed light on F- recognition by compounds containing boron, tellurium and antimony, which were experimentally demonstrated to be capable of interacting with the F- ion in a partially aqueous medium. Boron and metal complexes recognize F- anions primarily using electrostatic energy along with important contributions from orbital interaction energy. The natural orbitals for chemical valence (NOCV) methodology indicates that the main orbital interactions behind fluoride recognition are σ bonds between the receptors and the F- anions. The charged receptors, which provide (i) two B atoms, (ii) one B atom and one Sb atom, or (iii) one B atom and one Te atom to directly interact with the F- ions, appear to be some of the best structures for the recognition of F- anions. This is supported by the combination of favorable electrostatic and σ bond interactions. Overall, the presence of electron donor groups, such as -CH3 and -OH, in the receptor structure destabilizes the fluoride recognition because it decreases the attractive electrostatic energy and increases the Pauli repulsion energy in the receptor⋯F- bonds. Notably, electron acceptor groups, for example, -CN and -NO2, in the receptor structure favor the interaction with the F- ions, due to the improvement of the electrostatic and σ bond interactions. This study opens the way to find the main features of a receptor for F- recognition.

Anti-melanoma effect of ruthenium(II)-diphosphine complexes containing naphthoquinone ligand.

The use of natural products as potential ligands has been explored as a strategy in the development of metal-based chemotherapy. Since ruthenium complexes are promising alternatives to traditional antitumor agents, this study evaluated the anti-melanoma potential of two ruthenium(II) complexes containing the naphthoquinone ligands lapachol (lap), [Ru(lap)(dppm)2]PF6, and lawsone (law), [Ru(law)(dppm)2]PF6, in addition to the bis(diphenylphosphino)methane (dppm) ligand, referred to as complexes (1) and (2), respectively, using a syngeneic murine melanoma model. Activation of the apoptotic pathway by the treatments was assessed by immunohistochemistry in tumor tissue. Additionally, toxicity of the treatments was evaluated by variation in body and organ weight, quantification of biochemical indicators of renal damage, and genotoxicity in bone marrow and hepatocytes. First, the antiproliferative activity of (1) and (2) was observed in B16F10 cells, with IC50 values of 2.78 and 1.68 µM, respectively. The results obtained in mice showed that, unlike complex (1), (2) possesses significant anti-melanoma activity demonstrated by a reduction in tumor volume and mass (88.42%), as well as in mitosis frequency (83.86%). Additionally, complex (2) increased the levels of cleaved caspase-3, inducing tumor cell apoptosis. When compared to the metallodrug cisplatin, complex (2) exhibited similar anti-melanoma activity and lower toxicity considering all parameters evaluated. In silico studies demonstrated no difference in the binding energy of the naphthoquinone complex between complexes (1) and (2). However, the complex containing the lawsone ligand has a lower molar volume, which may be important for interactions with minor DNA grooves. The present results demonstrate the antitumor efficiency of complex (2) and a significantly lower systemic toxicity compared to cisplatin.

The design of anion-π interactions and hydrogen bonds for the recognition of chloride, bromide and nitrate anions.

The role of anions in several biochemical processes has given rise to enormous interest in the identification/exploration of compounds with the potential ability to recognize anions. Here, an anthracene-squaramide conjugated compound, O2C4[NH(C14H10)][(NH(C6H6)], has been modified through the substitutions (i) H → F and (ii) H → OH at the anthracene and benzene rings to improve the capabilities of these structures for recognizing chloride, bromide, and nitrate anions. Through an energy decomposition analysis method, the recognition of the anions is chiefly identified as a non-covalent process. H → F substitutions at the benzene ring and, principally, the anthracene ring favor anion recognition, since H → F substitutions create a π-acid region in the aromatic ring, as indicated based on the molecular electrostatic potential surfaces. Similarly, H → OH substitutions also improve the recognition of anions, which is related to the establishment of partly covalent chemical bonds of the form O-H(Cl-, Br- and O-), which are verified based on the quantitative analysis of the maximum and minimum values of the molecular electrostatic potential surfaces and the quantum theory of atoms in molecules method. The presence of large electron density has a key role in the recognition of Cl- anions, and the more favorable electrostatic interactions between the anthracene structure and Br- anions, relative to NO3- anions, mean that receptorBr- interactions are more attractive than receptorNO3- ones. These data can contribute to the design of structures with the relevant abilities to interact with anions.

The simultaneous recognition mechanism of cations and anions using macrocyclic-iodine structures: insights from dispersion-corrected DFT calculations.

The recent development of compounds for recognizing ions highlights the applicability of this area. In this work, the simultaneous recognition of cations (Li+, Na+ and K+) and anions (F-, Cl- and I-) using a macrocycle comprising a simple crown ether and an iodine-triazole unit is investigated. The roles of the (i) cation radius, (ii) anion radius, and (iii) electron withdrawing (-CN) and donor (-OH) groups of the receptor in ionic recognition were evaluated. Energy decomposition analysis (EDA) shows that the ion-receptor interactions are attractive and predominantly electrostatic. Molecular electrostatic potential plots and EDA analysis reveal that a decreasing cation radius favors interactions with the oxygen atoms present in the crown ether. A decreasing anion radius increases the σ-hole interactions with the iodine atoms present in the receptors. In compounds containing -CN and -OH groups, the oxygen atoms in the crown ether show lower ability to interact with the Na+ cation. Nevertheless, in the receptor-OH structure, the Na+OH interactions counterbalance the lower ability of the crown ether oxygens to interact with the Na+ cation. I- recognition is enhanced by the presence of -OH and, more strongly, -CN groups, occurring due to the increased σ-hole area in the receptor-CN structure, as supported by a C-HI- interaction in the receptor-OH compound. The reported results are useful for the design of compounds with improved capabilities for both cation and anion recognition prior to engaging in exploratory synthesis efforts.

(±)-Licarin A and its semi-synthetic derivatives: In vitro and in silico evaluation of trypanocidal and schistosomicidal activities.

This paper reports the synthesis of (±)-licarin A 1, a dihydrobenzofuran neolignan, resultant of an oxidative coupling reaction of isoeugenol and horseradish peroxidase (HRP) enzyme. Following, three semi-synthetic derivatives from this compound were obtained: benzylated (±)-licarin A 2, methylated (±)-licarin A 3 and acetylated (±)-licarin A 4. After structural elucidation and assignment by Nuclear Magnetic Resonance of 1H, 13C and DEPT, all compounds were evaluated in vitro against Trypomastigote forms of Trypanosoma cruzi (T. cruzi), the etiologic agent of Chagas disease, and Schistosoma mansoni (S. mansoni) worms, the etiologic agent of schistosomiasis. Compound (4) was the most active against S. mansoni adult worms, displaying worm viability reduction at 25 µM and mortality of all worms at 100 and 200 µM within 24 h. Compound 1 was the second most active, showing worm viability reduction at 50 µM and mortality of 25% and 100% of worms in 24h at concentrations of 100 and 200 µM, respectively. In addition, theoretical calculations aiming at finding molecular properties that showed the correlation for schistosomicidal and trypanocidal activities of (±)-licarin A and three of its semi-synthetic derivatives were also performed.

How computational methods and relativistic effects influence the study of chemical reactions involving Ru-NO complexes?

Two treatments of relativistic effects, namely effective core potentials (ECP) and all-electron scalar relativistic effects (DKH2), are used to obtain geometries and chemical reaction energies for a series of ruthenium complexes in B3LYP/def2-TZVP calculations. Specifically, the reaction energies of reduction (A-F), isomerization (G-I), and Cl- negative trans influence in relation to NH3 (J-L) are considered. The ECP and DKH2 approaches provided geometric parameters close to experimental data and the same ordering for energy changes of reactions A-L. From geometries optimized with ECP, the electronic energies are also determined by means of the same ECP and basis set combined with the computational methods: MP2, M06, BP86, and its derivatives, so as B2PLYP, LC-wPBE, and CCSD(T) (reference method). For reactions A-I, B2PLYP provides the best agreement with CCSD(T) results. Additionally, B3LYP gave the smallest error for the energies of reactions J-L. © 2017 Wiley Periodicals, Inc.