C10 C11 Research Articles

Antidiabetes and antioxidant potential of Schiff bases derived from 2-naphthaldehye and substituted aromatic amines: Synthesis, crystal structure, Hirshfeld surface analysis, computational, and invitro studies

Three Schiff bases were synthesised by the condensation reaction between 2-napthaldehyde and aromatic amines to afford (E)-N-mesityl-1-(naphthalen-2-yl)methanimine (L1), (E)-N-(2,6-dimethylphenyl)-1-(naphthalen-2-yl)methanimine (L2) and (E)-N-(2,6-diisopropylphenyl)-1-(naphthalen-2-yl)methanimine (L3). The synthesised compounds were characterised using UV–visible, NMR (13C &1H), and Fourier transform infrared spectroscopic methods while their purity was ascertained by elemental analysis. Structural analysis revealed that the naphthalene ring is almost coplanar with the imine functional group as evident by C1–C10–C11–N1 torsion angles of 176.4(2)° and 179.4(1)° in L2 and L3, respectively. Of all the various intermolecular contacts, H⋯H interactions contributed mostly towards the Hirshfeld surfaces of both L2 (58.7 %) and L3 (69.7 %). Quantum chemical descriptors of L1 - L3 were determined using Density Functional Theory (DFT) and the results obtained showed that the energy band gap (ΔE) for L1, L2 and L3 are 3.872, 4.023 and 4.004 eV respectively. The antidiabetic potential of the three compounds were studied using α-amylase and α-glucosidase assay. Compound L1 showed very promising antidiabetic activities with IC50 values of 58.85 μg/mL and 57.60 μg/mL while the reference drug (Acarbose) had 405.84 μg/mL and 35.69 μg/mL for α-amylase and α-glucosidase respectively. In-silico studies showed that L1 docking score as well as binding energies are higher than that of acarbose, which are recognized inhibitors of α-amylase together with α-glucosidase. Further insight from the RMSF, RMSD and RoG analysis predicted that, throughout the simulation L1 showcased evident influence on the structural stability of α-amylase. The antioxidant potential of the compounds was carried out using nitric oxide (NO), ferric reducing ability power (FRAP) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) assays. The compounds exhibited good to fairly antioxidant properties with L1 as well as L3 having IC50 values of 70.91 and 91.21 μg/mL respectively for NO scavenging activities assay, which comparatively outshined acarbose (reference drug) with IC50 value of 109.95 μg/mL. Pharmacology and pharmacokinetics approximations of L1 – L3 showed minimal violation of Lipinski's Ro5 and this projects them to be less toxic and orally bioavailable as potential templates for the design of therapeutics with antioxidant and antidiabetic activities.

High-Contrast and Fast-Removable 19F-MRI Labels with Perfluoro-Tert-Butyl Substituents.

19F MRI is a unique technique for tracking and quantifying the indicator (19F-MRI label) in vivo without the use of ionizing radiation. Here we report new 19F-MRI labels, which are compounds with perfluoro-tert-butyl groups: 1,2-bis(perfluoro-tert-butoxy)ethane (C10F18H4O2) and 1,3-bis(perfluoro-tert-butyl)propane (C11F18H6). Both substances contain 18 equivalent 19F atoms, constituting 68.67% and 71.25% of the molecule, respectively. The emulsions with 19F molecules were prepared and used in 19F MRI studies in laboratory rats in vivo. The substances demonstrated high contrast properties, good biological inertness and the ability to be rapidly eliminated from the body. We showed that at a dose of 0.34 mg/g of body weight in rats, the time for complete elimination of C10F18H4O2 and C11F18H6 is ~30 days. The results turned out to be promising for the use of the presented compounds in 19F MRI applications, especially since they are quite easy to synthesize.

Air Quality Assessment in the Central Mediterranean Sea (Tyrrhenian Sea): Anthropic Impact and Miscellaneous Natural Sources, including Volcanic Contribution, on the Budget of Volatile Organic Compounds (VOCs)

The results of air pollution assessment during a 2017 cruise of the research ship “Minerva Uno” in the Tyrrhenian Sea are reported. Volatile Organic Compounds (VOCs), Oxygenated Volatile Organic Compounds (OVOCs), and pollutants such as nitrogen oxides, ozone, and sulphur dioxide were monitored throughout the cruise. The shallow waters at ten sites of the investigated area were also analyzed. Organic compounds such as n-alkanes showed a bimodal distribution with a maximum at C5–C6 and C10–C11 at sites the most affected by anthropic impact, whereas remote sites showed a unimodal distribution with maximum at C10–C11. The most abundant atmospheric OVOC was acetone (3.66 μg/m3), accounting for 38%; formaldehyde (1.23 μg/m3) and acetaldehyde (0.99 μg/m3) made up about 22–29% of the total. The influence of some natural sources as volcanoes, in the southern part of the Tyrrhenian Sea near the Aeolian arc was studied. This source did not induce any noticeable effect on the total amount of hydrocarbons nor on the levels of trace gases such as CFCs, whereas the trends of sulphur dioxide seemed to confirm a possible contribution. The impact of underwater emissions was observed near the Panarea and Vulcano islands, where lower pHs, high levels of Fe and Mn, and diagnostic of vent activity, were measured.

Dual emissive dinuclear Iridium(III) azomethine complexes: Synthesis, luminescence, thermal stability and antibacterial studies

A set of three novel dinuclear Ir(III) azomethine complexes was effectively synthesized from Schiff bases namely N,N-bis-(3,4-dihydroxybenzaldehyde)-4,4-diaminodiphenylsulphide (HL1), N,N-bis-(2-hydroxy-5-nitrobenzaldehyde)-4,4-diaminodiphenylsulphide (HL2) and N,N-bis-(2-hydroxy-5-chlorobenzaldehyde)-4,4-diaminodiphenylsulphide (HL3). Structural elucidation was carried out through (CHNS) elemental analysis, FT-IR, NMR, energy dispersive X-ray diffraction (EDX), powder X-ray diffraction (PXRD), UV–Visible and photoluminescence spectroscopy. The FTIR and NMR spectra showed that the ligands contain dioxygen-dinitrogen donor atom system, forming dinuclear complexes IrHL1, IrHL2 and IrHL3 upon coordination with Ir(III) ion. X-ray analysis of a single crystal HL2 confirmed the [NNOO] donor system and demonstrated a bending geometry with the torsion angle of 50.98° for C10–C11–S1–C14 linkage as the result of a significant twist at the central sulphur. The low molar conductivity values revealed the absence of electrolytic anions and cations in the complexes. The powder X-ray diffraction studies indicated the presence of crystalline phase in all the Ir(III) complexes. Photophysical characteristics of the compounds were thoroughly investigated in solid as well as liquid states at ambient conditions. The solid complexes manifested two strong emissions in the visible and near infra-red (NIR) regions. Primarily, at the visible region of 610–615 nm, the emission peak is assigned to ligand centered photoluminescence. The secondary emission peak was detected in the NIR region at 1119–1177 nm, ascribed to the triplet excited state emission of the iridium center. All the synthesized complexes were subjected to thermogravimetric analysis revealing thermal stability exceeding 230 °C before undergoing decomposition. Remarkable solid state photoluminescence activities of IrHL3 and IrHL2, in that order, was exhibited through the Stoke's Shift (Δλ) values of 285 and 289 nm, respectively, consequently merit the complexes as promising keystone for luminescent materials in solid state. The bactericidal activity of the test compounds was investigated on three Gram-positive and three Gram-negative bacteria, unveiling mild to moderate antibacterial activity. The IrHL2 complex with p-nitro substituent showed the highest activity against Streptococcus mutant, Staphylococcus aureus and Pseudomonas aeruginosa, succeeded by IrHL3 complex with p-chloro substituent for Streptococcus mutant.

Functionalization and Properties of Tetrahydronaphtho[2,1‐a]azulene Photoswitches

AbstractHere we present a synthetic procedure for regioselectively functionalizing the tetrahydronaphtho[2,1‐a]azulene (THNA) photoswitch in its seven‐membered ring (position C10). Bromination of the C10–C11 positions occurred with excellent selectivity when using carbondisulfide as solvent at room temperature. Elimination of HBr provided a C10 bromo‐substituted THNA that could be arylated by Suzuki cross‐coupling reactions. A series of arylated compounds was prepared and subjected to switching studies. Upon irradiation, the five‐membered ring underwent ring‐opening to a product that at room temperature underwent almost instantaneous ring‐closure. By following the conversion at low temperature by UV/Vis absorption spectroscopy, we could elucidate the influence of aryl donor and acceptor groups. Thus, with a donating methoxyphenyl substituent, the ultrafast ring‐closure reaction was even further enhanced.

Total Synthesis of the Bis-silyl Ether of (+)-15-epi-Aetheramide A.

Synthesis of the macrolactone depsipeptide aetheramide A was attempted by three different approaches. The first approach to form the macrolactone involving macrolactonization to form the C1-C21 bond and the second approach using a ring-closing metathesis (RCM) strategy to form the C10-C11 olefinic bond failed. The third approach starting from R-mandelic acid, involving the RCM reaction to install the C18-C19 ring junction, was successful in assembling the macrolactone.

Bayesian inference in a class of partially identified models

This paper develops a Bayesian approach to inference in a class of partially identified econometric models. Models in this class are characterized by a known mapping between a point identified reduced‐form parameter μ and the identified set for a partially identified parameter θ. The approach maps posterior inference about μ to various posterior inference statements concerning the identified set for θ, without the specification of a prior for θ. Many posterior inference statements are considered, including the posterior probability that a particular parameter value (or a set of parameter values) is in the identified set. The approach applies also to functions of θ. The paper develops general results on large sample approximations, which illustrate how the posterior probabilities over the identified set are revised by the data, and establishes conditions under which the Bayesian credible sets also are valid frequentist confidence sets. The approach is computationally attractive even in high‐dimensional models, in that the approach avoids an exhaustive search over the parameter space. The performance of the approach is illustrated via Monte Carlo experiments and an empirical application to a binary entry game involving airlines. Partial identification identified set criterion function Bayesian inference C10 C11

Synthesis of the polyketide moiety of the jamaicamides

▪Isolated from the Jamaican cyanobacterium Lyngbya majuscula, the jamaicamides are unique, mixed polyketide-peptides reported to be sodium channel blockers. The polyketide moiety contains an (E)-chloroolefin, an undetermined methyl stereocenter (C9), and an (E)-olefin (C10–C11). Herein we report the stereo- and regioselective synthesis of the polyketide moiety of the jamaicamides via a Julia–Kocienski coupling as the key step.

A late Quaternary sedimentary record of steryl alkyl ethers from offshore southeastern Australia

Steryl alkyl ethers (SAEs) have been reported from marine sediments ranging from Holocene to Lower Cretaceous and their production has been linked to upwelling of cold, nutrient-rich water. However, the lack of continuous stratigraphic records for them has complicated validation of the precise connection of their production, sedimentary distribution and survival to climatic conditions. Here, we report an SAE record that spans the last ca. 135ka from a core taken offshore southeastern Australia in the Murray Canyons Group region. The SAEs are composed predominantly of C27–C30 steroid moieties with one or two double bonds, ether-bound to C10–C11 alkyl moieties. Some of the SAEs are identical to those reported in marine sediments, whereas others have not been identified previously. They do not exhibit any systematic change in distribution over the past 110ka but sediments older than 110ka possess a different assemblage, with a higher amount of constituents containing a C11 alkyl moiety. The SAE accumulation rate increases rapidly during glacial episodes and for intervals characterized by a sharp decline in sea-surface temperature. The results suggest that SAEs may be related to marine eukaryotes that thrive when there is an influx of cold, deep waters in the Murray Canyons Group region, likely triggered by stronger westerlies over southeastern Australia forcing deeper water to reach the surface during glacials.

QM/MM Trajectory Surface Hopping Approach to Photoisomerization of Rhodopsin and Isorhodopsin: The Origin of Faster and More Efficient Isomerization for Rhodopsin

The photoinduced cis-trans isomerization dynamics of rhodopsin and isorhodopsin are studied using a newly developed hybrid QM/MM trajectory surface hopping MD scheme based on the Zhu-Nakamura theory for nonadiabatic transitions. Rhodopsin and isorhodopsin have 11-cis and 9-cis forms of retinal as chromophore and the two proteins are isomerized to bathorhodopsin enclosing the all-trans form. The simulation reproduced faster and more efficient isomerization in rhodopsin than in isorhodopsin. In the excited state, rhodopsin shows a straightforward dynamics, whereas isorhodopsin dynamics is rather complicated and in a back-and-forth manner. The latter complicated dynamics would be mainly due to a narrow space near the active dihedral angle ═C8-C9═C10-C11═ (ϕ9) created by Thr 118 and Tyr 268 in opsin. Rhodopsin gives bathorhodopsin only while isorhodopsin yields a byproduct. The rigorous selectivity in rhodopsin would be another reason why rhodopsin is selected biologically. Comparison with our previous opsin-free investigations reveals that opsin tends to confine the twist of the active dihedral to only one direction and funnels transitions into the vicinity of minimum energy conical intersections (MECI). The twist-confinement totally blocks simultaneous twisting of ϕ9 and ϕ11 (═C10-C11═C12-C13═) and enhances the quantum yields. The opposite rotation of ϕ9 and ϕ11 ("wring-a-wet-towel" motion) takes place upon photoexcitation, which also does without opsin. The wring-a-wet-towel motion is dynamically enhanced in comparison with the one expected from locations of the MECI. The present simulation reveals that the Weiss-Warshel model for cis-trans photoisomerization is not applicable for rhodopsin because the branching ratio after transition is crucial.

Experimental and theoretical studies of the molecular structure of 4-(3-(1 H-imidazol-1-yl)propyl)-5- p-tolyl-2 H-1,2,4-triazol-3(4 H)-one

The triazol–imidazol compound, 4-(3-(1 H-imidazol-1-yl)propyl)-5- p-tolyl-2 H-1,2,4-triazol-3(4 H)-one ( 3), (C 15H 17N 5O), was prepared and characterized by 1H NMR, 13C NMR, IR and single-crystal X-ray diffraction. By using the density functional theory (DFT) method with 6-31G(d) basis set, the molecular geometry, vibrational frequencies and gauge including atomic orbital (GIAO) 1H and 13C NMR chemical shift values of the title compound ( 3) in the ground state were calculated and compared with the experimental data. The calculated results are show that the optimized geometry can well reproduce the crystal structure. X-ray, FT-IR and NMR spectral results of the title compound ( 3) indicate that the compound exists as keto form. To determine most favorable conformation as theoretically, molecular energy profile of the title compound ( 3) were obtained as a function of the selected torsion angles T(N1 C8 C7 C6), T1 and T(C8 N1 C10 C11), T2, which is varied from −180° to +180° in every 10 by semi-empirical (PM3) calculations. In addition, DFT calculations of the title compound ( 3), molecular electrostatic potential and frontier molecular orbitals were performed at B3LYP/6-31G(d) level of theory.

The Cross-Adaptation of Green and Citrus Odorants

In 1998, a set of straight chain aldehydes ranging in carbon chain length from seven to ten carbons were identified for their ability to excite olfactory receptor I-7 (OR-I7; Zhao et al. 1998). Several studies have examined the differences in physiological response to these odorants in mammals as well as the different psychophysical properties of these odorants. Octanal (C8) is the primary agonist of OR-I7 while hexanal, C6, does not excite OR-I7. The primary psychophysical difference between these two odorants is their perceptual quality, C8 is characterized as citrus and C6 is described as green (Kittel et al. 2008). Because ligands with similar odor qualities have been shown to cross-adapt, while those with differing odor qualities do not, one would predict C6 would not cross-adapt with C8, decanal (C10), and undecanal (C11) but C8, C10, and C11 would cross-adapt with each other. This study uses squeeze bottle sensory tests to examine the cross-adaptation and self-adaptation of hexanal, octanal, C10, and C11. Individuals evaluated the intensity of each odorant before and after smelling an adapting stimulus. Self-adaptation was measured for all four odorants. The strongest observed cross-adaptation occurred between odorant pairs C10–C11 while C10–C8, and C10–C11 showed slightly less cross-adaptation. Most importantly, cross-adaptation occurred between C6 and the three other stimuli to a significantly lesser degree. As predicted, C6 did not cross-adapt with any of the three other odorants; however, the three citrus odorants did readily cross-adapt suggesting adaptation is a peripheral process.

Study of interaction between tiagabine HCl and 2-HPβCD: investigation of inclusion process

Tiagabine (TGB) is an antiepileptic agent enhancing the activity of GABA at neuronal and glial region. It has recently been shown that enhancement of TGB chemical stability was improved by complexation with 2-hydroxypropyl-beta-cyclodextrin (2-HPβCD). The aim of this project is to explain the improvement of the chemical stability of complexed TGB by studying the inclusion properties and factors affecting the complexation selectivity between 2-HPβCD and TGB. Analysis of the interaction between 2-HPβCD and TGB and the effect of 2-HPβCD on TGB solubility was performed by phase solubility method described by Higuchi and Connors; the complexation was followed by characterization using DSC, FTIR and NMR spectroscopy. In aqueous media, the analysis of NMR proton shift change continuous variation method (Job’s plot) and the NMR diffusion-ordered spectroscopy (DOSY) measurements clearly show that TGB form 1:1 inclusion complex with 2-HPβCD with an association constant (K a) of 3396 M−1. More detailed information about the inclusion mode and the geometry of the complex was obtained by the analysis of 2D NMR NOESY experiment and molecular modelling calculations. The inclusion process indicates that A-ring, C10–C11 double bond and the half of the B-ring of TGB molecule were located inside the cavity while the nipecotic acid part of TGB (Ring C) was exposed towards the outside of the 2-HPβCD cavity. These results suggest that the inclusion of the C10–C11 double bond in the 2-HPβCD cavity may possibly the reason of improvement of TGB chemical stability.

Total synthesis of (4 S,10 R)-4-hydroxy-10-methyl-11-oxododec-2-en-1,4-olide and related bioactive marine butenolides

Marine-derived microorganisms produce structurally diverse butenolides possessing a variety of bioactivities. Described here is the total synthesis of (4 S,10 R)-4-hydroxy-10-methyl-11-oxododec-2-en-1,4-olide and a related butenolide containing anti stereochemistry at C10–C11. A three-module coupling strategy has been established for synthesis of the stereoisomers of the naturally occurring butenolides by assembling the C3–C7 and C9–C12 fragments via double alkylation of a 1,3-dithiane. The C10–C11 stereochemistry could be easily controlled by an asymmetric aldol condensation, while the butenolide unit was efficiently constructed according to the ring-closing metathesis protocol.

Total Synthesis and Evaluation of Cytostatin, Its C10—C11 Diastereomers, and Additional Key Analogues: Impact on PP2A Inhibition.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Total synthesis and stereochemical reassignment of (+)-dolastatin 19, a cytotoxic marine macrolide isolated from Dolabella auricularia

Using conformational analysis and biogenetic considerations, a revised configurational assignment for the cytotoxic marine macrolide dolastatin 19 is proposed, together with its validation by completion of the first total synthesis. Key features of the highly stereocontrolled route include an asymmetric vinylogous Mukaiyama aldol reaction to simultaneously install both the remote C13 stereocenter and the C10–C11 ( E)-trisubstituted olefin, two sequential 1,4- syn boron-mediated aldol reactions, and a late-stage, α-selective Mukaiyama glycosylation to append the l-rhamnose-derived pyranoside.

Synthesis of model BC bicycles of taxol using C10–C11 ring-closing metathesis strategy

Model BC ring-systems of taxol 23b and 28b, which lack an oxygenated substituent at C7, have been efficiently synthesized. The key step is a ring-closing metathesis (RCM) to form the 8-membered B ring between C10 and C11. Comparison of the metathesis reaction in this route with the RCM used in a previous study with similar substrates is highlighted.

Stereoselective Synthesis of the Monomeric Unit of SCH 351448

AbstractThe monomeric unit of the macrodiolide SCH 351448 has been synthesized from three building blocks. Strategic disconnections were chosen between C21–C22 (Wittig) and C10–C11 (stereoselective aldol). The cis configuration of both 2,6‐disubstituted tetrahydropyran rings was established by a stereoselective cationic reduction. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

Matched and mismatched pairings in B-secotaxane construction: a structure elucidation study

The synthesis of the basic B-seco taxoid skeleton was achieved through a C10–C11 coupling of the A-ring segment (14 S)- 1 with the C-ring segments (10 S) and (10 R)-α-alkoxyorganolithium reagents, prepared in situ from 2 and 6 through nBuLi mediated transmetallation. The matched reactions of (14 S)- 1 with (10 S)- 2 and (10 S)- 6 displays an outstanding diastereoselectivity providing 12 and 34, respectively, as single isomers and hence allowing a convenient entry to highly functionalized taxoid diterpene frameworks. Significant mismatching was observed with the (10 R)-epimer of 2 and 6 yielding little, if any, diastereoselectivity. The structures of B-secotaxanes were assigned on the basis of spatial proximity effects in the proton NMR spectrum. Assignment of the C10/C11 stereochemistry was made possible through conversion of the B-secotaxoid frameworks, derived from the matched and mismatched adducts, to the corresponding cyclic acetals. Configurational stability of α-alkoxyorganolithium derivatives was verified in all the cases investigated. Structure elucidation of these adducts was essential for the successful C1–C2 bonding via an intramolecular aldol reaction, given the fact that adducts containing a β-MOM substituent at C10 would be disfavored for such an endeavor.

Preparation of Intact Hexahydrobenzofuran Subunits of Ivermectin by Selective Ozonolysis of the Δ3,4‐Intermediate Secoester

AbstractAvermectins, and especially their semi‐synthetic partial hydrogenation adduct Ivermectin, constitute a potent endectocide family of worldwide veterinary use that has been known for more than twenty years and has also demonstrated a great efficacy in the treatment of various human filariasis diseases. In a program to design new access to cost‐effective analogues with a new or optimised medical profile, we decided to develop a practical synthetic strategy starting from southern subunits cut from commercial Ivermectin, which is now easily available at a reasonable price. We describe here the first process for preparing intact hexahydrobenzofuran subunits by controlled degradation of Ivermectin in a basically three‐step process that totally preserves the integrity of the Δ3 unsaturated pattern of the unit, which is a requisite feature for the biological activity of this family of molecules. The two crucial steps of the sequence, developed here on a gram scale, involve a transesterification reaction in the presence of titanium(IV) alkoxide that allows the macrolactone opening without isomerisation in 55–70 % yields, followed by the selective ozonolysis of the C10–C11 double bond in the presence of different reducting agents to afford the expected southern unit in reasonable yields. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)