Symmetrical Analogues Research Articles

Radio-protective effect of some new curcumin analogues

In the present study, novel symmetrical curcumin analogues (2–7) have been synthesized by substituting the phenolic OH of curcumin with different linkers providing additional keto-enol tautomerism, very essential for radioprotective activity. The structures of the synthesized compounds (2–7) were elucidated by elemental analysis, IR, 1H-NMR, 13C-NMR and mass spectral data and were found consistent with the assigned structures. The curative effect of these new compounds, against the oxidative stress due to exposure of rats to the whole body γ-irradiation (7Gy) was investigated. Gamma-irradiated rats exhibited elevations of ALT, AST activities, urea, creatinine, triglycerides, total cholesterol, malondialdehyde (MDA), nitric oxide (NO), Interleukin-6 (IL-6), Tumor Necrosis Factor-α (TNF-α) and Nuclear Factor-kappa B (NF-κB) levels. Contrariwise, the total protein, albumin, total calcium level, SOD, CAT, GSH-Px, GST activities and GSH content were decreased. Treatment of gamma-irradiated rats with the new curcumin analogues (2–7) showed significant amelioration in the in-vivo antioxidant status, liver and kidney functions, as well as the anti-inflammatory markers (IL-6, TNF-α and NF-κB). Inhibition of NF-κB could be responsible for the improvement of the antioxidant and anti-inflammatory status in gamma-irradiated animals, by down-regulation of IL-1β and TNF-α level. In conclusion, the new curcumin analogues (2–7) exhibited post-protective effect on gamma-irradiation, by NF-κB inhibition.

Optical Determination of Electron Transfer Dynamics and Kinetics for Asymmetrical [Mo2]–ph–[Mo2] Systems

We report the study, in terms of electronic coupling (EC) and electron transfer (ET), on three asymmetrical Mo2 dimers [Mo2(DAniF)3]2[μ-(NH)OCC6H4CO2] ([NO–ph–OO]) (DAniF = N,N′-di(p-anisyl)formamidinate), [Mo2(DAniF)3]2[μ-(NH)2CC6H4CO2] ([NN–ph–OO]), and [Mo2(DAniF)3]2[μ-(NH)2CC6H4C(NH)O] ([NN–ph–NO]), which are closely related to the three symmetrical analogues [OO–ph–OO], [NO–ph–NO], and [NN–ph–NN] reported earlier. The mixed-valence (MV) complexes [NO–ph–OO]+, [NN–ph–OO]+, and [NN–ph–NO]+ exhibit metal to ligand and ligand to metal charge transfer bands, along with an intervalence (IV) transition absorption in the Near-IR region. The free energy change (ΔG°) for ET is determined by comparing the redox potential splitting (ΔE1/2) and IV transition energy (EIT) with the data for the symmetrical species. The reorganization energy (λ) is estimated from the Hush model (Δν1/2 = [16ln(2)λRT]1/2). Significantly, electrochemical and optical analyses verify EIT = ΔG° + λ, the core energetic relationship underlying the semiclassical theories. With the electronic coupling parameters calculated from the method suggested by Creutz, Newton and Sutin (HMM′ = ∼ 500 cm–1), the adiabatic ET rate constants ket (f) are determined to be ∼1010 s–1 for [NO–ph–OO]+ and [NN–ph–NO]+, smaller than ket (r) for the backward reaction and ket for the symmetrical analogues by 1 order of magnitude, and ∼109 s–1 for [NN–ph–OO]+. This work illustrates that the redox asymmetry in D–B–A systems controls the ET rate and direction.

Theoretical Studies on F(-) + NH2Cl Reaction: Nucleophilic Substitution at Neutral Nitrogen.

The SN2 reactions at N center, denoted as SN2@N, has been recognized to play a significant role in carcinogenesis, although they are less studied and less understood. The potential energy profile for the model reaction of SN2@N, chloramine (NH2Cl) with fluorine anion (F(-)), has been characterized by extensive electronic structure calculations. The back-side SN2 channel dominates the reaction with the front-side SN2 channel becoming feasible at higher energies. The minimum energy pathway shows a resemblance to the well-known double-well potential model for SN2 reactions at carbon. However, the complexes involving nitrogen on both sides of the reaction barrier are characterized by NH---X (X = F or Cl) hydrogen bond and possess C1 symmetry, in contrast to the more symmetric ion-dipole carbon analogues. In the F(-) + NH2Cl system, the proton transfer pathway is found to become more competitive with the SN2 pathway than in the F(-) + CH3Cl system. The calculations reported here indicate that stationary point properties on the F(-) + NH2Cl potential energy surface are slightly perturbed by the theories employed. The MP2 and CAM-B3LYP, as well as M06-2X and MPW1K functionals give overall best agreement with the benchmark CCSD(T)/CBS energies for the major SN2 reaction channel, and are recommended as the preferred methods for the direct dynamics simulations to uncover the dynamic behaviors of the title reaction.

PH- and Thiol-Responsive BODIPY-Based Photosensitizers for Targeted Photodynamic Therapy.

A diiodo distyryl boron dipyrromethene (BODIPY) core was conjugated to two ferrocenyl quenchers through acid-labile ketal and/or thiol-cleavable disulfide linkers, of which the fluorescence and photosensitizing properties were significantly quenched through a photoinduced electron-transfer process. The two symmetrical analogues that contained either the ketal or disulfide linkers could only be activated by a single stimulus, whereas the unsymmetrical analogue was responsive to dual stimuli. Upon interaction with acid and/or dithiothreitol (DTT), these linkers were cleaved selectively. The separation of the BODIPY core and the ferrocenyl moieties restored the photoactivities of the former in phosphate buffered saline and inside the MCF-7 breast cancer cells, rendering these compounds as potential activable photosensitizers for targeted photodynamic therapy. The dual activable analogue exhibited the greatest enhancement in intracellular fluorescence intensity in both an acidic environment (pH 5) and the presence of DTT (4 mm). Its photocytotoxicity against MCF-7 cells also increased by about twofold upon preincubation with 4 mm of DTT. The activation of this compound was also demonstrated in nude mice bearing a HT29 human colorectal carcinoma. A significant increase in fluorescence intensity in the tumor was observed over 9 h after intratumoral injection.

On stabilization of scattering resonances in recombination reaction that forms ozone.

Calculations of energy transfer in the recombination reaction that forms ozone are carried out within the framework of the mixed quantum/classical theory and using the dimensionally reduced 2D-model of ozone molecule, with bending motion neglected. Recombination rate coefficients are obtained at room temperature for symmetric and asymmetric isotopomers of singly and doubly substituted isotopologues. The processes of resonance formation, spontaneous decay, collisional dissociation, and stabilization by bath gas (Ar) are all characterized and taken into account within the steady-state approximation for kinetics. The focus is on stabilization step, where the mysterious isotopic η-effect was thought to originate from. Our results indicate no difference in cross sections for stabilization of scatteringresonances in symmetric and asymmetric isotopomers. As practical results, the general and simple analytic models for stabilization and dissociation cross sections are presented, which can be applied to resonances in any ozone molecule, symmetric or asymmetric, singly or doubly substituted. Present calculations show some isotope effect that looks similar to the experimentally observed η-effect, and the origin of this phenomenon is in the rates of formation/decay of scatteringresonances, determined by their widths, that are somewhat larger in asymmetric isotopomers than in their symmetric analogues. However, the approximate two-dimensional model used here is insufficient for consistent and reliable description of all features of the isotopic effect in ozone. Calculations using an accurate 3D model are still needed.

Analysis of Redox Series of Unsymmetrical 1,4-Diamido-9,10-anthraquinone-Bridged Diruthenium Compounds.

The unsymmetrical diruthenium complexes [(bpy)2Ru(II)(μ-H2L(2-))Ru(III)(acac)2]ClO4 ([3]ClO4), [(pap)2RuII(μ-H2L(2-))Ru(III)(acac)2]ClO4 ([4]ClO4), and [(bpy)2Ru(II)(μ-H2L(2-))Ru(II)(pap)2](ClO4)2 ([5](ClO4)2) have been obtained by way of the mononuclear precursors [(bpy)2Ru(II)(H3L(-))]ClO4 ([1]ClO4) and [(pap)2Ru(II)(H3L(-))]ClO4 ([2]ClO4) (where bpy = 2,2′-bipyridine, pap = 2-phenylazopyridine, acac(-) = 2,4-pentanedionate, and H4L = 1,4-diamino-9,10-anthraquinone). Structural characterization by single-crystal X-ray diffraction and magnetic resonance (nuclear magnetic resonance (NMR), electron paramagnetic resonance (EPR)) were used to establish the oxidation state situation in each of the isolated materials. Cyclic voltammetry, EPR, and ultraviolet-visible-near-infrared (UV-vis-NIR) spectroelectrochemistry were used to analyze the multielectron transfer series of the potentially class I mixed-valent dinuclear compounds, considering the redox activities of differently coordinated metals, of the noninnocent bridge and of the terminal ligands. Comparison with symmetrical analogues [L2′Ru(μ-H2L)RuL2′](n) (where L′ = bpy, pap, or acac(-)) shows that the redox processes in the unsymmetrical dinuclear compounds are not averaged, with respect to the corresponding symmetrical systems, because of intramolecular charge rearrangements involving the metals, the noninnocent bridge, and the ancillary ligands.

Small Molecule Inhibitors of Ca(2+)-S100B Reveal Two Protein Conformations.

The drug pentamidine inhibits calcium-dependent complex formation with p53 ((Ca)S100B·p53) in malignant melanoma (MM) and restores p53 tumor suppressor activity in vivo. However, off-target effects associated with this drug were problematic in MM patients. Structure-activity relationship (SAR) studies were therefore completed here with 23 pentamidine analogues, and X-ray structures of (Ca)S100B·inhibitor complexes revealed that the C-terminus of S100B adopts two different conformations, with location of Phe87 and Phe88 being the distinguishing feature and termed the "FF-gate". For symmetric pentamidine analogues ((Ca)S100B·5a, (Ca)S100B·6b) a channel between sites 1 and 2 on S100B was occluded by residue Phe88, but for an asymmetric pentamidine analogue ((Ca)S100B·17), this same channel was open. The (Ca)S100B·17 structure illustrates, for the first time, a pentamidine analog capable of binding the "open" form of the "FF-gate" and provides a means to block all three "hot spots" on (Ca)S100B, which will impact next generation (Ca)S100B·p53 inhibitor design.

T(T,2n)4He and3He(3He,2p)4He: The Reaction Mechanism from Solar Energies to 10 MeV

We have studied the energy dependence of the reaction mechanism of the T(t,2n)4 He reaction at stellar energies and of its charge symmetric analog reaction 3 He(3 He,2p)4 He at energies up 10 MeV. We find that the reaction mechanism changes dramatically over this energy range in part due to the interference of the two identical fermions in the three-body final state.

Development of molecular photoswitch with very fast photoresponse based on asymmetrical bis-azospiropyran

To study the effects of an extended bis-azo conjugated bridge with two different photochemical functions on a molecule in photochromic responses, a novel asymmetrical bifunctional bis-azo spiropyran photochromic dye was designed and synthesized. The obtained photoresponses were compared with symmetrical bifunctional bis-azo spiropyran analogues, and relative mono-azo and simple spiropyrans. Colourimetric behaviour, luminescence, and switching kinetics of all the dyes were studied. The largest molar absorption coefficient in merocyanine form, quickest response to light, and highest fluorescence quantum yield of the spiropyran form with a superior ratio of emission intensities of spiropyran to merocyanine form were achieved for the asymmetric bis-azospiropyran. Solvatochromic effect was studied to observe the solvent effects on non-irradiation colouration of the photochromic dyes. Furthermore, The molecular energy levels for optimized geometries of the synthesized bis-azospiropyrans and their probable photochemical products were obtained at the B3LYP/6-31G(d) level of theory.

Exploring the Effects of Glycosylation and Etherification of the Side Chains of the Anticancer Drug Mitoxantrone.

Herein we report the synthesis and biological evaluation of symmetric and asymmetric analogues of the DNA intercalating drug mitoxantrone (MTX) in which the side chains of the parent drug were modified through glycosylation or methyl etherification. Several analogues with glycosylated side chains exhibited higher DNA affinity than the parent MTX. The most potent in vitro cytotoxicity was observed for MTX analogue 8 (1,4-dimethoxy-5,8-bis[2-(2-methoxyethylamino)ethylamino]anthracene-9,10-dione) with methoxy ether containing side chains. Treatment of melanoma-bearing mice with MTX or analogue 8 decreased the intraperitoneal tumor burden relative to untreated mice; the effect of 8 was less pronounced than that of MTX. In vitro metabolism assays of MTX with rabbit liver S9 fraction gave rise to several metabolites; almost no metabolites were detected for MTX analogue 8. The results presented indicate that derivatization of the MTX side chain primary hydroxy groups may result in a significant improvement in DNA affinity and lower susceptibility to the formation of potentially toxic metabolites.

Donor-π-acceptor type porphyrins with large two-photon absorption cross section

The third-order nonlinear optical properties of 5-(4-pyrenylalkynylphenyl)-10,15,20-tris(4-octyloxyphenyl)porphyrin (1) and 5-(4-iodophenyl)-10,15,20-tris(4-octyloxyphenyl)porphyrin (2) have been comparatively investigated with symmetrical 5,10,15,20-tetra(4-octyloxyphenyl)porphyrin (3) and pyrene (4) as reference using femtosecond-pulsed Z-scan technique. Due to the D–π–A structure, both A3B type asymmetric porphyrins 1 and 2 were revealed to exhibit larger two-photon absorption (2PA) cross sections over the symmetrical analogue 3 with the largest value of 6.1 × 105 GM revealed for 1 because of the intramolecular energy transfer from the excited pyrene moiety to the porphyrin moiety as indicated by the fluorescence spectroscopic result. The good 2PA properties of these A3B type porphyrins with ultrafast response indicate their good application potential in nonlinear photonic devices.

Synthesis and Anti-Inflammatory Evaluation of Novel C66 Analogs for the Treatment of LPS-Induced Acute Lung Injury.

We previously reported a symmetric monocarbonyl analog of curcumin (MACs), C66, which demonstrated potential anti-inflammatory activity and low toxicity. In continuation of our ongoing research, we designed and synthesized 34 asymmetric MACs based on C66 as a lead molecule. A majority of the C66 analogs effectively inhibited LPS induction of TNF-α and IL-6 expression. Additionally, a preliminary SAR was conducted. Furthermore, active compounds 4a11 and 4a16 were found to effectively reduce theW/D ratio in the lungs and the protein concentration in the bronchoalveolar lavage fluid (BALF). Meanwhile, a histopathological examination indicated that these two analogs significantly attenuate tissue injury in the lungs with LPS-induced ALI rats. 4a11 and 4a16 also inhibited mRNA expression of several inflammatory cytokines, including TNF-α, IL-6, IL-1β, COX-2, ICAM-1 and VCAM-1, in the Beas-2B cellsafter LPS challenge. Altogether, the data exhibit a series of new C66 analogs as promising anti-inflammatory agents for the treatment of LPS-induced ALI.

Synthesis and Characterization of Symmetrical and Unsymmetrical Analogues of 1,2-bis[bis(4-chlorophenyl) Methyl] Diselane

The 'living' species selenide anion Se 2 2- , generated in situ by the reduction of 1,2-bis(bis(4-chlorophenyl)methyl)diselane with sodium borohydride, was treated with various organic halides to afford synthetically important organoselenium compounds including α,ω-diselenoethers and selenides bearing ester functionality, under mild and neutral conditions. These compounds have been characterized analytically with the help of various spectroscopic techniques viz., IR, multinuclear NMR ( 1 H, 13 C, 77 Se) and mass spectrometry.

Design, synthesis and biological activity of novel asymmetric C66 analogs as anti-inflammatory agents for the treatment of acute lung injury

Acute lung injury (ALI) is a leading cause of morbidity and mortality in critically-ill patients. Previously, we reported that a symmetric mono-carbonyl analog of curcumin, (C66), exhibits enhanced stability and was found to have efficacy and be involved in potential cytokines inhibition. In the present study, a series of novel asymmetric C66 analogs were designed and synthesized. A majority of them effectively inhibited the LPS-induced expression of TNF-α and IL-6. Significantly, compound 4b2 was found to effectively reduce LPS-induced pulmonary inflammation, as reflected by reductions in concentration of total protein, inflammatory cell count as well as the lung W/D ratio in bronchoalveolar lavage (BAL) fluid. Furthermore, in vivo administration of 4b2 resulted in remarkable improvement in histopathological changes of lung in rats.

On the theory of axisymmetric conical flows and their one-dimensional unsteady analogues

Axisymmetric conical flows (CF) without swirling and their unsteady cylindrically and spherically symmetric self-similar analogues with a self-similarity exponent of unity are considered in the approximation of an ideal (inviscid and non-heat-conducting) perfect gas. In the flows considered, Chapman–Jouguet detonation waves (DWJ) are allowed together with shock waves within the limits of the classical model (heat release is instantaneous, on both sides of a discontinuity of zero thickness there is a perfect gas with dissimilar adiabatic exponents in the general case). The main new elements associated with CF are the introduction of DWJ into known flows and the merge of several CF into one. The construction and analysis of a number of new solutions are prefaced with the merge of unsteady self-similar analogues of CF. All the merges of the unsteady analogues are also original. The systemization of the approaches used and the theoretical analysis based on them are illustrated by examples of the numerical construction of the flows in the planes of their independent variables. The illustrations include streamlines (for CF), particle trajectories (for the unsteady analogues), the C+- and C−- characteristics and their envelope, shock waves and DWJ.

Exchange Interactions in Cobalt(II) and Nickel(II) Complexes Containing M4(μ3-OH)2 Metal Cores with Distorted Rhombic Topology

Antiferromagnetic interactions between the Co2+ or Ni2+ ions were found in complexes [(μ3 ‐ L)2Co 5 II (μ ‐ OH)2(Piv)7(NO3)] and [(μ3 ‐ L)2(HPiv)Ni 4 II (μ3 ‐ OH)2(Piv)4(NO3)2] (Piv– = pivalic acid anion, L = 1,1′-dipyridazinylferrocene) possessing a metal core with distorted rhombic topology M4(μ3-OH)2. In contrast to the case of symmetrical analogs, the signs of all the exchange interaction parameters J were determined unambiguously.

The synthesis of an octasubstituted monohydroxylated phthalocyanine designed to investigate the effect of the presence of active moieties

Filling a lack: monofunctionalized octasubstitution, the missing substitution pattern of phthalocyanines.

One-pot synthesis of symmetrical dinucleoside polyphosphates and analogs via 4,5-dicyanoimidazole-promoted tandem P–O coupling reactions

A novel one-pot protocol for the synthesis of symmetrical dinucleoside tri-, tetra-, and pentaphosphates, and their phosphonate analogs simply from nucleoside 5′-phosphoropiperidates has been developed by utilizing 4,5-dicyanoimidazole-promoted tandem P–O coupling reactions.

Nearly symmetric-indecomposable matrices

We introduce nearly symmetric-decomposable matrices, which are a symmetric analogue of nearly decomposable matrices. The defining matrix property is related to 2-matching covered and minimally 2-matching covered properties of a graph (possibly containing loops). We develop constructions and properties of nearly symmetric-decomposable -matrices, some of which relate to the location and number of nonzero entries on the main diagonal.

Synthesis and properties of new non-symmetric 2,5-bis(4-alkylphenylethynyl)thiophenes

The synthesis and characterisation of new non-symmetric 2,5-bis(4-alkylphenylethynyl)thiophenes are described. Phase transition properties of these non-symmetric homologues are compared to those of the corresponding symmetric analogues. Furthermore, optical, dielectric and elastic data of investigated compounds and nematic mixture are provided. Compounds are characterised by 1H NMR spectroscopy and mass spectrometry (electron ionization) analysis. They show an enantiotropic nematic behaviour in broad temperature ranges, confirmed by a polarising thermomicroscopy and differential scanning calorimetry. Detailed synthetic procedures are attached, showing a great synthetic versatility of the thiophene ring substitution. Synthesised compounds stand as promising components of highly birefringent liquid crystalline mixtures.