Ethyl Moiety Research Articles

DFT Study of The Interaction between the Ni2+ and Zn2+ Metal Cations and The 1,2-Dithiolene Ligands: Electronic, Geometric and Energetic Analysis

Density functional theory (DFT) (B3LYP/6-311++G(d,p)) calculations of the interacting strength 1,2-dithiolene anionic ligands with the [M(OH2)4]2+ and [M(OH2)2]2+ complexes (M = Ni and Zn) were performed. Three series of ligands were studied: compounds with an aromatic ring, with an ethylene moiety and with a heterocyclic ring. The ligands have substituents electron donors and acceptors by induction and resonance. Two substitution reactions were studied: the first is the substitution of two water molecules from the [M(OH2)6]2+ by a dithiolene anionic ligand (L2-) and the second is the substitution of two water molecules from the [M(OH2)4L] by another dithiolene anionic ligand. Geometric, electronic and energetic properties of the substituted aquacations are correlated with the metal-ligand affinity. All the substitution processes for both metal cations are spontaneous and are modulated by the electronic effect of each substituent of the ligand. Geometric parameters and chelation angle are correlated with the interaction strength. The energy decomposition analysis (EDA) results show that the electrostatic component is the main stabilizing term for the monosubstituted complexes, while for the disubstituted complexes the covalent term is the main stabilizing component. The polarization term is the main one to describe the covalent character. Natural bond orbital (NBO) shows the acid-base interaction nature of the metal-ligand bond.

Crystal structure and Hirshfeld surface analysis of N,N'-[ethane-1,2-diylbis(-oxy)]bis-(4-methyl-benzene-sulfonamide).

In the mol-ecule of the title compound, C16H20N2O6S2, the mid-point of the C-C bond of the central ethane moiety is located on a twofold rotation axis. In the crystal, mol-ecules are linked by N-H⋯O hydrogen bonds into supra-molecular chains propagating along the [101] direction. Hirshfeld surface analysis and two-dimensional fingerprint plots indicate that the most important contributions to the crystal packing are from H⋯H (43.1%), O⋯H/H⋯O (40.9%), C⋯H/H⋯C (8.8%) and C⋯C (5.5%) inter-actions.

Correlations between metabolism and structural elements of the alicyclic fentanyl analogs cyclopropyl fentanyl, cyclobutyl fentanyl, cyclopentyl fentanyl, cyclohexyl fentanyl and 2,2,3,3-tetramethylcyclopropyl fentanyl studied by human hepatocytes and LC-QTOF-MS

Recently, a number of fentanyl analogs have been implicated in overdose deaths in Europe and in the US. So far, little is known of the molecular behavior of the structurally related subgroup; the alicyclic fentanyls. In this study, reference standards of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and 2,2,3,3-tetramethylcyclopropyl fentanyl (TMCPF) at a final concentration of 5 µM were incubated with cryopreserved human hepatocytes (1 × 106 cells/mL) for 0, 1, 3 and 5 h. The metabolites formed were identified by liquid chromatography–quadrupole time-of-flight mass spectrometry analysis. The most abundant biotransformation found was N-dealkylation (formation of normetabolites) and oxidation of the alicyclic rings. As ring size increased, the significance of N-dealkylation decreased in favor of alicyclic ring oxidation. An example of this was cyclopropyl fentanyl, with a three-carbon ring, whose normetabolite covered 82% of the total metabolic peak area and no oxidation of the alicyclic ring was observed. In contrast, TMCPF, with a seven-carbon ring structure, rendered as much as 85% of its metabolites oxidized on the alicyclic ring. Other biotransformations found included oxidation of the piperidine ethyl moiety and/or the phenethyl substructure, glucuronidation as well as amide hydrolysis to form metabolites identical to despropionyl fentanyl. Taken together, this study provides a base for understanding the metabolism of a number of structurally related fentanyl analogs formed upon intake.

Modified carbazoles destabilize microtubules and kill glioblastoma multiform cells

Small molecules that target microtubules (MTs) represent promising therapeutics to treat certain types of cancer, including glioblastoma multiform (GBM). We synthesized modified carbazoles and evaluated their antitumor activity in GBM cells in culture. Modified carbazoles with an ethyl moiety linked to the nitrogen of the carbazole and a carbonyl moiety linked to distinct biaromatic rings exhibited remarkably different killing activities in human GBM cell lines and patient-derived GBM cells, with IC50 values from 67 to >10,000 nM. Measures of the activity of modified carbazoles with tubulin and microtubules coupled to molecular docking studies show that these compounds bind to the colchicine site of tubulin in a unique low interaction space that inhibits tubulin assembly. The modified carbazoles reported here represent novel chemical tools to better understand how small molecules disrupt MT functions and kill devastating cancers such as GBM.

A systematic examination of ligand basicity effects on bonding in palladium(0)- and palladium(II)-ethylene complexes

The impact of ancillary ligand basicity on the binding and activation of ethylene in a series of [(L)Pd0(C2H4)] and [(L)PdII(C2H4)]2+ complexes (where L = substituted 1,10-phenanthroline ligands) has been studied with density functional theory using natural bond orbital (NBO) analysis, energy decomposition analysis (EDA-NOCV), and molecular orbital (MO) analysis. With palladium(0), metrics of ethylene CC bond activation are strongly correlated with increasing ligand basicity, including the CC bond length and vibrational frequency, the magnitude of Pd(0) → ethylene(π∗) NBO donation, and the Wiberg CC bond index. In contrast, ethylene(π) → Pd(0) donation is not strongly influenced by ligand basicity, which is manifested in strong correlations between Pd(0) → ethylene(π∗) donation and both CC bond length and ν(CC). EDA-NOCV results show that the [(L)Pd0]-(C2H4) interaction energy is dominated by Coulombic attraction and enhanced slightly with more electron-donating ligands. MO analysis demonstrates that a linear increase in the energy of the filled [(L)Pd0] HOMO with ligand pKa is directly correlated with the enhanced [(L)Pd0] → ethylene(π∗) donation. For the [(L)PdII(C2H4)]2+ adducts, CC bond lengthening and weakening is roughly half the amount observed with Pd0, with ligand substitution having a negligible impact. NBO analysis confirms that ethylene activation is dominated by ethylene(π) → PdII donation, which is enhanced with electron-withdrawing ligands while PdII → ethylene(π∗) donation decreases with less basic ligands. EDA-NOCV results show that the [(L)PdII]2+-(C2H4) interaction energy is also dominated by Coulombic attraction and is enhanced by more electron-withdrawing ligands, largely as a result of a concurrent increase in ethylene(π) → [(L)PdII]2+ stabilization and a decrease in Pauli repulsion. Finally, MO analysis indicates an electrophilic ethylene moiety due to substantial stabilization of both the alkene π- and π∗-orbitals through interaction with the [(L)PdII]2+ fragment.

Unprecedented alkylation of carboxylic acids by boron trifluoride etherate

The alkylation of carboxylic acids by an ethyl moiety of boron trifluoride etherate in the absence of ethyl alcohol from the reaction system is unexpected and novel. Both aromatic and aliphatic carboxylic acids were clearly alkylated affording good yields in short reaction times with the exception of nicotinic acid that necessitated an overnight reaction. It was noted that while ortho -substituted hydroxyl groups of carboxylic acids investigated were not affected by alkylation, those of meta - and para -substituted carboxylic acids were partially etherified. Furthermore, the alkylation reaction was found to be compatible with a range of functional groups such as halogens, amino and nitro groups except for the alkene function of undecylenic acid that underwent polymerisation with concomitant alkylation of its carboxylic acid function. KEY WORDS : Carboxylic acids, Alkylation, Etherification, Functional groups, Boron trifluoride etherate Bull. Chem. Soc. Ethiop. 2018 , 32(2), 387-392. DOI: https://dx.doi.org/10.4314/bcse.v32i2.16

Enantiopure sulfoximines-catalyzed 1, 4-additions to 2-en-ketone

An efficient chiral catalyst procedure for the preparation of β-chiral ketone via the 1, 4-additions reaction of 2-en-ketone has been developed using enantiopure sulfoximines modified with functional groups as ligands. The carefully design and synthesized functional enantiopure sulfoximines could be used as linker. In this system the formation of new chiral centers occurs with the regioselective addition of the ethyl moiety at the terminal carbon of the 2-en-ketone. In addition, aromatic substituents in the substrate promote the addition reaction.

Mesoporous Silica and Organosilica Nanomaterials as UV-Blocking Agents.

Mesoporous silica nanoparticles (MSN) and periodic mesoporous organosilica nanoparticles containing bridging benzene (PMOBTB) and ethane (PMOBTE) moieties are synthesized, characterized, and evaluated for application in skin protection from UVA/UVB sun irradiation. Furthermore, the influence of surface functionalization with chelating 3-(2-aminoethylamino)propylsilane and Zn2+ ions on the UV-blocking ability of MSN is evaluated, along with the photostability and capability of the synthesized nanomaterials to carry avobenzone, a known UV-absorbing agent. The obtained results reveal promising characteristics of MSN and PMO materials with regard to their potential for sunscreen applications, which could be beneficial in terms of alleviating concerns about health and environmental hazards of sunscreen ingredients.

Structure‐Activity Relationship of Novel Compounds Based on Tamoxifen with Proposed Sigma‐2 Receptor Activity

Sigma‐2 receptors are overexpressed in several different types of human cancer cells and are regarded as potential therapeutic targets. Ligands for sigma‐2 receptors have been shown to elicit anticancer properties including growth arrest and apoptosis. While much research has been devoted to designing sigma‐2 receptor ligands for therapeutic benefits, none have stood up to rigorous testing and clinical trials needed for approval in human patients. In an attempt to provide more literature on the potential usefulness of sigma‐2 receptor ligands for anticancer activity, we synthesized a series of analogs based upon the known sigma‐2 receptor ligand tamoxifen that lack estrogen receptor binding properties.We previously reported on the first molecule in this series, SP‐1, with IC50 activity ranging from 30–60 μM against several dissimilar cell lines. To further elucidate structurally important regions of the molecule and ascertain a structure‐activity relationship (SAR) for anticancer activity, six additional molecules were synthesized and tested. These molecules included modifications to both the terminal phenyl and nitrogen moieties of SP‐1 (N,N‐dimethyl‐2‐(4‐(1‐(p‐tolyl) vinyl)phenoxy)ethan‐1‐amine). The XTT cell viability assay was then used to screen these compounds for anticancer activity in four diverse human cancer cell lines including A‐172 human glioblastoma, A375 human malignant melanoma, HT‐29 human colorectal adenocarcinoma, and MCF7 human breast adenocarcinoma. Interestingly, hydration of the ethylene moiety attached to the carbon linker between the two phenyl rings markedly reduced anticancer activity of SP‐2, SP‐3, SP‐7 and SP‐8. Substantial anticancer activity was not observed at concentrations less than 90 μM regardless of structural modifications made to the periphery of these molecules. However, SP‐5 and SP‐6, which conserved the nonpolar central linker present in SP‐1, demonstrated moderately potent anticancer activity against the four cancer cell lines. SP‐5, which only differs from SP‐1 by the addition of one carbon to the peripheral phenyl ring, was found to have nearly the same potency as SP‐1. However, SP‐6, which includes the addition of a morpholine ring to the periphery of the molecule, demonstrated slightly less potent activity than that of SP‐1 and SP‐5. However IC50 values were still found to range from 45–90 μM in all four cells lines. While the changes made to these analogs failed to improve the efficacy of our parent molecule SP‐1, the information regarding the SAR will help guide the synthesis of further analogs. Additional studies investigating the mechanisms of death and putative targets are ongoing for these lead molecules.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Synthesis and Photophysical Properties of Dibenzobarrelene‐Incorporated 1,4‐Diphenyl‐1,3‐pentadienes and a 5‐Sila Derivative Having High Fluorescence Efficiency

Two dibenzobarrelene‐incorporated 1,3‐pentadienes and a 5‐sila derivative have been synthesized by intramolecular cycloaddition reactions between (9‐anthryl)methyl, (9‐anthryl)hydroxymethyl, or (9‐anthryl)dimethylsilyl groups and a phenylethynyl group linked by an ethene moiety with a cis conformation. The three compounds exhibit blue luminescence (λem = 432–445 nm) in CH2Cl2 with high quantum yields (ΦF = 0.83–0.92). In the solid state, the methylene and dimethylsilyl derivatives luminesce (λem = 442 and 438 nm, respectively) with narrow full‐width at half‐maxima (FWHM, 40 and 37 nm, respectively), whereas the hydroxymethylene compound shows a broad and slightly redshifted emission (λem = 488 nm, FWHM = 112 nm) due to intermolecular hydrogen bonding. The fluorescence intensity of the dimethylsilyl compound was decreased by desilylation with Bu4NF. The structures of the compounds were characterized unambiguously by NMR spectroscopy and X‐ray crystallography, and their photophysical properties were elucidated both experimentally as well as by TD‐DFT calculations.

Structure optimization and preliminary bioactivity evaluation of N-hydroxybenzamide-based HDAC inhibitors with Y-shaped cap

Histone deacetylase inhibitors (HDACIs) are effective small molecules in the treatment of human cancers. In our continuing efforts to develop novel N-hydroxyterephthalamide-based HDACIs, herein we report the design and development of a new class of N-hydroxybenzamide-based HDACIs. In this new class of analogs, we inserted an ethylene moiety in the linker and used indole as a part of the Y-shaped cap group. Biological characterization identified compounds 4o, 4p, 4q and 4t to show improved HDAC inhibition, while no isoform selectivity for HDACs was observed. These compounds also exhibited improved anti-proliferative activity against multiple cancer cell lines when compared to their parent compound and positive control SAHA.

Phototriggered Growth and Detachment of Polymer Brushes with Wavelength Selectivity.

Both phototriggered growth and removal of polymer chains from surfaces are efficient ways to finely tune interface properties. Combining these two capabilities in one system with independent control can significantly increase the feasibility of photoregulation on surface modification but has not been reported yet. Herein we describe a novel approach to control both the growth and the detachment of polymer brushes independently by light with different wavelengths. The approach is based on a nitrodopamine-based initiator (NO2-BDAM) which contains a catechol structure for surface modification, alkyl bromide group for radical polymerization, and o-nitrophenyl ethyl moiety for photolysis. When dimanganese decacarbonyl (Mn2(CO)10) was applied together with NO2-BDAM as an initiating system, visible light (460 nm) can be used to trigger the site-specific growth of polymer brushes. Resulting polymer brushes can be selectively removed by UV light (360 nm). This method is suitable for different monomers on various substrates, suggesting a facile and robust method to regulate surface properties.

Rhodium-Catalyzed Enantioposition-Selective Hydroarylation of Divinylphosphine Oxides with Aryl Boroxines.

The rhodium-catalyzed hydroarylation of divinylphosphine oxides (RP(O)(CH=CH2 )2 ) with aryl boroxines ((ArBO)3 ) gives the corresponding monoarylation products (RP(O)(CH=CHAr)CH2 CH3 ) in high yields. One of the two vinyl groups in the phosphine oxide undergoes oxidative arylation while the other one is reduced to an ethyl moiety. These reactions proceed with high selectivity in terms of the enantiotopic vinyl groups in the presence of (R)-DTBM-segphos/Rh to give the P-stereogenic monoarylation products with high enantioselectivity.

Rhodium‐Catalyzed Enantioposition‐Selective Hydroarylation of Divinylphosphine Oxides with Aryl Boroxines

AbstractThe rhodium‐catalyzed hydroarylation of divinylphosphine oxides (RP(O)(CH=CH2)2) with aryl boroxines ((ArBO)3) gives the corresponding monoarylation products (RP(O)(CH=CHAr)CH2CH3) in high yields. One of the two vinyl groups in the phosphine oxide undergoes oxidative arylation while the other one is reduced to an ethyl moiety. These reactions proceed with high selectivity in terms of the enantiotopic vinyl groups in the presence of (R)‐DTBM‐segphos/Rh to give the P‐stereogenic monoarylation products with high enantioselectivity.

Solid-state self-inclusion complexation behaviour of a pillar[5]arene-based host–guest conjugate

A host–guest conjugate consisting of a pillar[5]arene and an ethylene moiety containing a triazole group at one end and a perfluorooctyl group at the other end displayed unusual real-time scale solid-state self-inclusion complexation behaviour.

High-performance FDTE-based polymer semiconductors with F⋯H intramolecular noncovalent interactions: Synthesis, characterization, and their field-effect properties

Herein, we report two novel donor-acceptor copolymers, PFDTE1 and PFDTE2, based on (E)-1,2-bis(3-fluorothiophen-2-yl)ethene (FDTE) moiety. X-ray diffraction crystallography indicated that F⋯H hydrogen bonds exist in single FDTE unit. Theoretical simulation results revealed that the FDTE unit owns increased torsional potential due to the presence of fluorine-induced intramolecular noncovalent interactions. The two copolymers exhibited ambipolar carrier transport characteristics, with hole/electron mobilities of 4.24/0.30 cm2 V−1 s−1 for PFDTE1 and 5.42/0.36 cm2 V−1 s−1 for PFDTE2. The complementary-like inverters based on PFDTE2 were also successfully fabricated and showed high gain values of 104 and 115, respectively, providing potential in ambipolar complementary-like inverters. AFM and 2D-GIXRD analyses revealed that the two copolymers formed lamellar, edge-on molecular packing, and crystalline thin films with small π–π stacking distances down to 3.55 Å.

PH-Switched fluorescent pseudorotaxane assembly of cucurbit[7]uril with bispyridinium ethylene derivatives

The host-guest properties of cucurbit[7]uril (Q[7]) and bispyridinium ethylene derivatives have been studied by 1H NMR spectroscopy, UV–vis absorption spectra, and fluorescence emission analysis. The proton shifts associated with the guest encapsulated by the host suggested that the Q[7]-based [2]pseudorotaxane behaves like a fast molecular shuttle along the bispyridinium ethylene axle of the guest upon protonation and deprotonation of the terminal carboxylates. In particular, the distinct fluorescent response signals indicated that the bispyridinium ethylene moiety not only behaves as the axle component for the pseudorotaxane system, but also acts as an optical reporting unit during the host–guest complexation.

Anchimerically Activatable Antiviral ProTides.

This work describes the synthesis and biological evaluation of an anchimerically activated proTide of 2'-C-β-methylguanosine as an inhibitor of dengue virus 2 (DENV-2). The proTide incorporates a chemically cleavable 2-(methylthio)ethyl moiety and a HINT1 hydrolyzable tryptamine phosphoramidate. Inhibition of DENV-2 replication by proTide 6 was 5-fold greater than the parent nucleoside while displaying no apparent cytotoxicity. Furthermore, we demonstrate with a HINT1 inhibitor that the anti DENV-2 activity of the proTide correlates with the activity of HINT1. Taken together, these results demonstrate that a phosphoramidate based pronucleotide that undergoes an initial nonenzymatic activation step based on anchimeric assistance followed by P-N bond cleavage by HINT1 can be prepared.

Construction of new fluorophores by Diels-Alder reaction of diacenaphthothiophenes

The Diels–Alder (DA) reaction of diacenaphtheno[1,2-b;1′,2′-d]thiophene (1a) with benzyne affords 1:1 and 1:2 adducts, 7 and 8, in 47 and 11% yields. An X-ray crystallographic analysis reveals that 8 possesses a dibenzobarrelene structure involving a rigid di(1-naphthyl)ethene moiety. Thus, the second DA reaction occurs at the central benzene ring of 7 selectively. The 1:2 adduct 8 emits intense blue fluorescence in CH2Cl2. Moreover, we examined the DA reactions of 1a and tetra-t-butyl derivative 1b with p-benzoquinone to afford acenaphtheno[1,2-j]fluoranthene 10a, and its tetra-t-butyl derivative 10b and a quinone 11b, respectively. Novel fragmentation reaction should occur to produce the acenaphthenofluoranthene frameworks of 10. An X-ray crystallographic analysis reveals a rather planar structure of 11b. The central benzene ring of 11b shows large bond alternation by the Mills-Nixon effect. The compounds 10a and 10b emit sky blue fluorescence with moderate ΦSN values. The electronic properties of new compounds are well consistent with the theoretical predictions.

Toward an ab initio potential energy surface for paclitaxel: A C-13 isoserine side chain conformational study

(S)-3-Methyl-3-butenyl-(2R,3S)-N-benzoyl-3-phenylisoserinate is used as a model of the C-13 side chain, an essential subunit for the cytotoxicity of the diterpenoid paclitaxel, a chemotherapeutic drug used in the treatment of cancer. The potential energy surface (PES), calculated using a density functional theory method (DFT) and refined with MP2 single-point energy calculations, based on B3LYP geometries, was evaluated. Twelve intramolecular hydrogen bond patterns were identified for 103 in vacuo conformers. The most stable subset of these structures was found to have cooperative NH ⋯ OH ⋯ OC(O) motifs and six minima of importance that lie within 1.2kcal/mol of each other. The oxygen atoms of the ester groups effectively compete with the 2′-oxygen as a proton acceptor of NH to form stable internal hydrogen bonded structures. Additionally, the conventional OH ⋯ OC(N) hydrogen bond, which is represented by almost one third of the located minima, donates a number of stable conformers. However, the PES of the conformationally flexible model is highly dependent on the polarity of the environment. For example, the OH ⋯ OC(N) feature dominates over the cooperative motif in water. The side chain of the experimental T-taxol shaped structure agrees nicely with the respective theoretical lowest energy minimum. The π-π interactions of the phenyl rings and ethylene moiety of this structure are also discussed.