Symmetrical Analogues Research Articles

Environmental pH and a Glu364 to Gln mutation in the chlorophyll-binding CP47 protein affect redox-active TyrD and charge recombination in Photosystem II.

In Photosystem II, loop E of the chlorophyll-binding CP47 protein is located near a redox-active tyrosine, YD , forming a symmetrical analog to loop E in CP43, which provides a ligand to the oxygen-evolving complex (OEC). A Glu364 to Gln substitution in CP47, near YD , does not affect growth in the cyanobacterium Synechocystis sp. PCC 6803; however, deletion of the extrinsic protein PsbV in this mutant leads to a strain displaying a pH-sensitive phenotype. Using thermoluminescence, chlorophyll fluorescence, and flash-induced oxygen evolution analyses, we demonstrate that Glu364 influences the stability of YD and the redox state of the OEC, and highlight the effects of external pH on photosynthetic electron transfer in intact cyanobacterial cells.

Self-assembling behavior of binary mixture of hexa-peri-hexabenzocoronene derivatives with different molecular symmetry

The self-assembly and mesophase behavior of a series of mixtures of hexa-peri-hexabenzocoronene (HBC) derivatives carrying alkyl chains of different lengths at different positions and thus of different molecular symmetry (C1- and D3h-symmetry) were examined by powder X-ray diffractometry, UV–vis spectrometry, photoluminescence, polarizing optical microscopy, and differential scanning calorimetry. Significant reduction of isotropic phase transition temperature/clearing temperature was observed compare to single component symmetric analogues. The chain length modulates the mesophase behavior existed in the mixture. In particular, with long dodecyl groups, the mixture exhibited excimer/exciplex formation as well as aggregation induced emission phenomena in the non-polar solvent of hexane. Formation dynamics of intermolecular excimer/exciplex was studied by nuclear magnetic resonance and UV–vis spectroscopic method.

Evaluation of the photosensitizing properties of zinc and indium tetra cinnamic acid phthalocyanines linked to magnetic nanoparticles on human breast adenocarcinoma cells

This work reports on the synthesis, photophysico-chemical properties and photodynamic therapy activity of novel zinc (1) and indium (2) tetra substituted cinnamic acid phthalocyanine (Pc) complexes linked to amino functionalized magnetic nanoparticles (AMNPs) through an amide bond. Asymmetric ZnPc complex (3) showed better triplet and singlet oxygen quantum yields as compared to its symmetrical analogues (1 and 2). The AMNPs (1-AMNPs and 2-AMNPs) linked conjugates depicted increased triplet quantum yields in comparison to their unlinked Pcs, while 3-AMNPs showed a decrease compared to 3. The complexes showed increased in-vitro photo-cytotoxic effect against MCF-7 cells with an increase in drug concentration. At 80 µg/mL, 2 and 3, 2-AMNPs and 3-AMNPs with higher singlet oxygen quantum yields caused more cytotoxic effect on the cancer cells in the presence of light as compared to 1 and 1-AMNPs respectively.

Amine Boranes Dehydrogenation Mediated by an Unsymmetrical Iridium Pincer Hydride: (PCN) vs (PCP) Improved Catalytic Performance

The IrIII hydride (tBuPCN)IrHCl (1) containing the tridendate unsymmetrical pincer ligand tBuPCN– {tBuPCN(H) = 1-[3-[(di-tert-butylphosphino)methyl]phenyl]-1H-pyrazole} has been exploited as ammonia borane (NH3BH3, AB) and amine boranes dehydrogenation catalyst in THF solution at ambient temperature. 1 releases one H2 equivalent per AB equivalent, with concomitant cyclic poly(aminoboranes) formation [B-(cyclotriborazanyl)-amine-borane (BCTB) and cyclotriborazane (CTB)] as the final “spent fuel”. 1 has been found to have superior catalytic activity than its symmetrical analogue (tBuPCP)IrHCl, with recorded TOF values of 580 h–1 (AB in THF) and 401 h–1 (DMAB in toluene) at ambient temperature. The reaction has been analyzed experimentally through multinuclear [11B, 31P{1H}, 1H] NMR and IR spectroscopy, kinetic rate measurements, and kinetic isotope effect determination with deuterated AB isotopologues. The hydride/borohydride intermediate (tBuPCN)IrH(η2-BH4) (2) is the catalyst resting state formed during t...

Antiplasmodial activity of hydroxyethylamine analogs: Synthesis, biological activity and structure activity relationship of plasmepsin inhibitors

Malaria, particularly in endemic countries remains a threat to the human health and is the leading the cause of mortality in the tropical and sub-tropical areas. Herein, we explored new C2 symmetric hydroxyethylamine analogs as the potential inhibitors of Plasmodium falciparum (P. falciparum; 3D7) in in-vitro cultures. All the listed compounds were also evaluated against crucial drug targets, plasmepsin II (Plm II) and IV (Plm IV), enzymes found in the digestive vacuole of the P. falciparum. Analog 10f showed inhibitory activities against both the enzymes Plm II and Plm IV (Ki, 1.93 ± 0.29 µM for Plm II; Ki, 1.99 ± 0.05 µM for Plm IV). Among all these analogs, compounds 10g selectively inhibited the activity of Plm IV (Ki, 0.84 ± 0.08 µM). In the in vitro screening assay, the growth inhibition of P. falciparum by both the analogs (IC50, 2.27 ± 0.95 µM for 10f; IC50, 3.11 ± 0.65 µM for 10g) displayed marked killing effect. A significant growth inhibition of the P. falciparum was displayed by analog 12c with IC50 value of 1.35 ± 0.85 µM, however, it did not show inhibitory activity against either Plms. The hemolytic assay suggested that the active compounds selectively inhibit the growth of the parasite. Further, potent analogs (10f and 12c) were evaluated for their cytotoxicity towards mammalian HepG2 and vero cells. The selectivity index (SI) values were noticed greater than 10 for both the analogs that suggested their poor toxicity. The present study indicates these analogs as putative lead structures and could serve as crucial for the development of new drug molecules.

Cytoskyrin C, an unusual asymmetric bisanthraquinone with cage-like skeleton from the endophytic fungus Diaporthe sp.

Cytoskyrin C (1), a new bisanthraquinone with asymmetrically cytoskyrin type skeleton, together with a known symmetrical analogue (+)-epicytoskyrin (2), were isolated from an endophytic fungus ARL-09 (Diaporthe sp.). Cytoskyrin C (1) featured an asymmetrically cage-like structural motif arising from the dimerization of anthraquinone monomers by three carbon‑carbon bonds 9a/3′, 3/9a′ and 1/1′. The structure and absolute configuration of compound 1 were determined by spectroscopic analyses, ECD calculation and exciton chirality methods. Moreover, a plausible biogenetic pathway of 1-2 was predicted. Their cytotoxicities against SMMC-7721 cell as well as effects on NF-κB signaling pathway were evaluated.2009 Elsevier Ltd. All rights reserved.

A small molecular electron acceptor based on asymmetric hexacyclic core of thieno[1,2-b]indaceno[5,6-b′]thienothiophene for efficient fullerene-free polymer solar cells

A novel A-D-A (acceptor-donor-acceptor) type non-fullerene small molecule, A201, consisting of an asymmetric thieno[1,2-b]indaceno[5,6-b′]thienothiophene (TITT) unit as middle D part and 2-(3-oxo-2,3-dihydroinden-1-ylidene) malononitrile (IC) groups as end-capped A parts was designed and synthesized. The asymmetric TITT building block showed a higher dipole moment of 0.85 Debye (1 Debye = 3.33564 × 10−30 cm) compared with the symmetric analogues of indacenodithiophene (IDT) and indacenodithieno[3,2-b]thiophene (IDTT) of 0.098 and 0.13 Debye, respectively. The solution-processed bulk heterojunction solar cells using a benzotriazole (BTA)-based polymer of J71 as donor and A201 as acceptor, showed a power conversion efficiency (PCE) of 9.36% with an open-circuit voltage (Voc) of 0.88 V, a short-circuit current (Jsc) of 13.15 mA cm−2, and a fill factor (FF) of 0.67, under the illumination of AM 1.5G at 100 mW cm−2. The high PCE of this material combination could be attributed to its broad absorption spectrum and the high hole mobility (μh) and electron mobility (μe) of 9.56 × 10−4 and 5.17 × 10−4 cm2 V−1 s−1, respectively. These results indicate that the asymmetric electron-donating segments are promising to construct A-D-A type small molecular acceptors, which could largely enhance the diversity of building blocks to design photovoltaic materials.

Asymmetrical Ladder-Type Donor-Induced Polar Small Molecule Acceptor to Promote Fill Factors Approaching 77% for High-Performance Nonfullerene Polymer Solar Cells.

In this work, an effectual strategy of constructing polar small molecule acceptors (SMAs) to promote fill factor (FF) of nonfullerene polymer solar cells (PSCs) is first reported. Three asymmetrical SMAs of IDT6CN, IDT6CN-Th, and IDT6CN-M, which own large dipole moments, are designed and synthesized. The PSCs based on three polar SMAs exhibit apparently higher FFs compared with their symmetrical analogues. The asymmetrical design strategy accompanied with side chain and end group engineering makes IDT6CN-Th- and IDT6CN-M-based nonfullerene PSCs achieve high power conversion efficiency with FFs approaching 77%.

Effect of an asymmetry of branching on structural characteristics of dendrimers revealed by Brownian dynamics simulations

Dendrimers in dilute solution with asymmetry of branching were simulated by the Brownian dynamics method. In this simulation a coarse-grained dendrimer model and athermal solvent conditions were implemented, extending previous work to a wider range of branch asymmetries at fixed average spacer lengths and high generation numbers close to the theoretical limit. We considered both global and local structural characteristics of dendrimers. The global ones, such as the average distance of ends from the center, the radius of gyration, the hydrodynamic radius and the dendrimer shape anisotropy, are practically insensitive to the asymmetry of branching. The effect of the spacer asymmetry is revealed mainly in the local structure of dendrimers. In particular the radial density profile changes its shape from a convex to a concave one with an increase of the asymmetry. As compared to symmetrical case, the distribution of terminal monomer units in asymmetrical dendrimers shifts towards the dendrimers periphery. The terminal monomers in an asymmetrical dendrimer are on average in a denser environment compared to their symmetrical analogs. The shorter spacers are less stretched and more turned back to the core than the longer ones located at the same topological distance from the dendrimer periphery. The simulations also demonstrated that the asymmetry of branching leads to a smaller radial overlap of dendron fragments inside the dendrimer as compared to the symmetrical case. However, the total overlap was found to be independent of the asymmetry of branching.

Synthesis of Analogues of Dicoumarol and Their Biological Evaluation

Both symmetrical (1a-f) and asymmetrical (2a-f) analogues of dicoumarol were synthesized in 20 – 86% yield by using microwave assisted one-pot protocol. Their ability to inhibit NAD (P)H:oxidorectase quinone 1 (NQO1) and cytotoxicity towards A549 small lung cancer cell line were evaluated. Interestingly, (E)-3-(2-hydroxynaphthalen-1-y)chroman-2,4-dione (2d) showed not only moderate inhibitory potency (IC50 = 20 ± 6 nM) towards NQO1 but also was toxic (IC50 = 9.2 ± 0.2 µM) towards the A549 small lung cancer cell line.

Symmetric dimeric adamantanes for exploring the structure of two viroporins: influenza virus M2 and hepatitis C virus p7.

BackgroundAdamantane-based compounds have been identified to interfere with the ion-channel activity of viroporins and thereby inhibit viral infection. To better understand the difference in the inhibition mechanism of viroporins, we synthesized symmetric dimeric adamantane analogs of various alkyl-spacer lengths.MethodsSymmetric dimeric adamantane derivatives were synthesized where two amantadine or rimantadine molecules were linked by various alkyl-spacers. The inhibitory activity of the compounds was studied on two viroporins: the influenza virus M2 protein, expressed in Xenopus oocytes, using the two-electrode voltage-clamp technique, and the hepatitis C virus (HCV) p7 channels for five different genotypes (1a, 1b, 2a, 3a, and 4a) expressed in HEK293 cells using whole-cell patch-clamp recording techniques.ResultsUpon testing on M2 protein, dimeric compounds showed significantly lower inhibitory activity relative to the monomeric amantadine. The lack of channel blockage of the dimeric amantadine and rimantadine analogs against M2 wild type and M2-S31N mutant was consistent with previously proposed drug-binding mechanisms and further confirmed that the pore-binding model is the pharmacologically relevant drug-binding model. On the other hand, these dimers showed similar potency to their respective monomeric analogs when tested on p7 protein in HCV genotypes 1a, 1b, and 4a while being 700-fold and 150-fold more potent than amantadine in genotypes 2a and 3a, respectively. An amino group appears to be important for inhibiting the ion-channel activity of p7 protein in genotype 2a, while its importance was minimal in all other genotypes.ConclusionSymmetric dimeric adamantanes can be considered a prospective class of p7 inhibitors that are able to address the differences in adamantane sensitivity among the various genotypes of HCV.

Synthesis and DNA‐Binding Studies of A New Cyclic Dimeric Symmetrical Pseudo‐Turn Mimetic

AbstractA new dimeric cyclic 24 member symmetrical turn analogue was synthesized efficiently by an intramolecular Heck reaction. This facile reaction has produced selectively a single dimeric product having two sets of intramolecular hydrogen bonds (IHB) at the two ends of it. Different experimental studies have unambiguously proved the presence of a pseudo‐turn like structure. Furthermore, it was shown that this molecule binds to the minor groove of DNA just like a known minor groove binder, DAPI (4′,6‐diamidino‐2‐phenylindole).

Comparative study of the antioxidant properties of monocarbonyl curcumin analogues C66 and B2BrBC in isoproteranol induced cardiac damage

AimTo test the antioxidant properties of the newly synthesized (2E,6E)-2,6-bis(2-bromobenzylidene)cyclohexanone (B2BrBC) in parallel with C66 in rats with cardiac hypertrophy. Materials and methodsThe protective effects of both C66 and B2BrBC against oxidative stress in rats with cardiac hypertrophy, was studied by evaluating the activity of antioxidant enzymes, the relationship between the ratio of the activities of the antioxidant enzymes R = SOD/(GPx + CAT) and levels of thiols and lipid peroxidation in the heart. In order to gain better understanding of the antioxidant properties of the studied compounds, computational methods were utilized. The properties of selected structurally related derivatives were obtained on optimized geometries for ground states, using semi-empirical PM3 quantum mechanical calculations. Key findingsThe ratio R shows disequilibrium in rats with induced hypertrophy (p < 0.001). Coextending changes were detected in total and free sulfhydryl group content (p = 0.011 for t-SH and p = 0.008, for free SH, respectively). The results with the B2BrBC, indicated strong thiol prevention reflected in the levels of both t-SH and f-SH. Taking into account the HOMO energies of B2BrBC (−9.398 eV) and C66 (−9.667), it can be concluded that B2BrBC has lower HOMO energy, which makes it a better electron donor and a better antioxidant. SignificanceThe obtained results indicated that the antioxidant ability of B2BrBC is positively associated with the catalytic SOD and GPx activities expressed through preserved t-SH levels. It seems plausible that for a compound to exhibit antioxidant activity, as most of the 2,6-bis(benzylidene)cyclohexanones do, they should be good electron donors. Impact statementUnderstanding the relationship between cardiac hypertrophy induced oxidative injuries and supporters of endogenous reparatory machinery will help in establishing the beneficial role of adequate antioxidant supplementation. In this study reliable data on the preventive effects of newly synthesized symmetric monocarbonyl curcumin analogue B2BrBC and its role in the prevention of oxidative injuries on three levels (enzymatic, protein and lipid), in the heart hypertrophic onset, were obtained.

The extent of charge transfer: A qualitative computational study on electronic transitions of unsymmetrical squarylium dyes

The nature of lowest energy electron transitions of unsymmetric squarylium (USQ) dyes has been studied through ab initio and DFT methods with Le Bahers’s diagnosing indexes. Soliton structure of atomic charge alternation and bond length alternation data indicates the asymmetric nature of charge distribution with respect to geometry. Unlike in symmetrical counterparts, occurrence of ground state dipole moment along with large transition dipole moments associated with electron transitions point up to the experimentalist’s hypothesis of greater charge-transfer (CT) character in USQ derivatives. However, poor net charge transferred (∼0.5e), negligible CT distance (0–1.2Å), maximum ratio of charge increment and depletion barycenters (above 90%) and large H-index illustrates the poor CT behavior of lowest energy electron transitions in USQ derivatives. No correlation has been seen for net charge transferred and charge transfer distance with lowest energy electron transition. The present work offers a design principle that instead of USQ derivatives, symmetrical analogs which are easy to synthesize and workup, and hence low cost derivatives can be preferred as sensitizers in DSSC.

Asset Pricing with Downside Liquidity Risks

We develop a parsimonious liquidity-adjusted downside capital asset pricing model to investigate whether phenomena such as downward liquidity spirals and flights to liquidity impact expected asset returns. We find strong empirical support for the model. Downside liquidity risk (sensitivity of stock liquidity to negative market returns) has an economically meaningful return premium that is 10 times larger than its symmetric analogue. The expected liquidity level and downside market risk are also associated with meaningful return premiums. Downside liquidity risk and its associated premium are higher during periods of low marketwide liquidity and for stocks that are relatively small, illiquid, volatile, and have high book-to-market ratios. These results are consistent with investors requiring compensation for holding assets susceptible to adverse liquidity phenomena. Our findings suggest that mitigation of downside liquidity risk can lower firms’ cost of capital. This paper was accepted by Lauren Cohen, finance.

Synthesis of 1,4-Oxazepane-2,5-diones via Cyclization of Rotationally Restricted Amino Acid Precursors and Structural Reassignment of Serratin.

Several natural products containing a 1,4-oxazepane-2,5-dione-core are known. One example is serratin, isolated from Serratia marcescens. Because of the presence of a carboxylic amide, which has a preference for a trans-conformation, and the presence of a labile lactone in this core, many synthetic methodologies commonly used for the cyclization toward medium-sized heterocycles cannot be applied. As N-acyl amino acids lacking a third substituent at nitrogen failed to undergo ring-closure, several N-protecting groups were evaluated. With the use of the removable PMB-group, an N-unsubstituted 1,4-oxazepane-2,5-dione was synthesized. Via the application of pseudoprolines (i.e. serine-derived oxazolidines as another type of protecting group), a compound with the presumed structure of the natural product serratin was obtained. As a result of the differences in spectral data, the incorrect structural assignment of the natural product serratin was identified. Instead of the predicted seven-membered heterocycle, a symmetrical serratamolide analogue is proposed to be the correct structure of serratin.

Well-Designed Unsymmetrical Salphen-Al Complexes: Synthesis, Characterization, and Ring-Opening Polymerization Catalysis

The unsymmetrical salphen ligand (3,5-tBu-1-OH-C6H2)CH═N-C6H4-N═CH(3-Ph-1-OH-C6H3) (tBu-PhLH2) was designed and synthesized to support aluminum complexes. Its symmetric analogues, (3,5-tBu-1-OH-C6H2)CH═N-C6H4-N═CH(3,5-tBu-1-OH-C6H2) (tBuLH2) and (3-Ph-1-OH-C6H3)CH═N-C6H4-N═CH(3-Ph-1-OH-C6H3) (PhLH2), were also explored and compared. The methane elimination reactions between ligands and AlMe3 resulted in formation of tBu-PhLAlMe (1), tBuLAlMe (2), and PhLAlMe (3) in high yields, which were characterized by elemental analysis, 1H and 13C NMR. The coordination geometries of unsymmetrical and symmetric ligands in 1 and 2 were studied by X-ray diffractions, which revealed a five-coordinated distorted square-pyramidal geometry around Al centers. The aluminum methyl compounds 1–3 reacted with BnOH at 70 °C to give tBu-PhLAlOBn (4), tBuLAlOBn (5), and PhLAlOBn (6), respectively, which existed as monometallic species in solution as indicated by NMR studies. However, the aluminum isopropoxide prepared by the reacti...

Synthesis and SAR studies of potent H+/K+-ATPase and anti-inflammatory activities of symmetrical and unsymmetrical urea analogues

A sequence of symmetrical and unsymmetrical urea derivatives 1–24 were synthesized and characterized by standard spectroscopic techniques. The synthesized analogues were tested for their in vitro H+/K+-ATPase and anti-inflammatory activities. The majority of the compounds showed outstanding activity, compared to that of omeprazole and indomethacin, usual standard drugs of antiulcer and anti-inflammatory, respectively. In particular, hydroxy, methyl, and methoxy derivatives 13–24 were the most active compounds possessing a significant amplify for diverse substituents on the benzene ring thus, contributing positively to gastric ulcer inhibition. Compounds 1–3 and 22–24 showed excellent anti-inflammatory activity due to the presence of electron-withdrawing groups (Cl and F) on the molecule.

The role of the capping bond effect on pyclen natY3+/90Y3+ chelates: full control of the regiospecific N-functionalization makes the difference.

Thanks to a smart regiospecific N-functionalization, a pyclen based ligand bearing one picolinate and two acetate arms organized in a dissymmetric manner was synthesized for Y3+ complexation, and compared to its symmetric analogue. The nature of the capping bonds around the metal coordination environment has a dramatic effect on the properties of the chelate, the natY3+ and 90Y3+ dissymmetric derivatives presenting enhanced thermodynamic stability and kinetic inertness.

Amide rotation trajectories probed by symmetry.

Amide rotation of peptidyl-prolyl fragments is an important factor in backbone structure organization of proteins. Computational studies have indicated that this rotation preferentially proceeds through a defined transition-state structure (syn/exo). Here, we complement the computational findings by determining the amide bond rotation barriers for derivatives of the two symmetric proline analogues, meso and racemic pyrrolidine-2,5-dicarboxylic acids. The rotations around these residues represent syn/exo-syn/exo and anti/endo-syn/exo hybrid transition states for the meso and racemic diastereomer, respectively. The rotation barriers are lower for the former rotation by about 9 kJ mol-1 (aqueous medium), suggesting a strong preference for the syn/exo (clockwise) rotation over the anti/endo (anticlockwise) rotation. The results show that both hybrid rotation processes are enthalpically driven but respond differently to solvent polarity changes due to the different transition state dipole-dipole interactions.