Electrochemical Detection of Artemisinin Using Cobalt Sulphide/Reduced Graphene Oxide Nanocomposite

Solvothermally synthesized cobalt sulphide/reduced graphene oxide (CoS/rGO) was used to fabricate an electrochemical sensor for detection of artemisinin. Microscopic techniques were used to characterize CoS/rGO nanocomposite. The electrochemical sensor was fabricated by modifying the surface of glassy carbon electrode with CoS/rGO nanocomposite. [Fe(CN)6]^3−/4− was used as a mediator to aid oxidation of artemisinin. Differential pulse voltammetric technique was used for the detection of artemisinin. A linear range of 30–100 μM was used. Experimentally, a detection limit of 0.5 μM was obtained. Therefore, the developed sensor can be used for quality control of artemisinin.     

Catalytic metathesis of carbon dioxide with heterocumulenes mediated by titanium isopropoxide

The insertion of an isopropoxide ligand of titanium isopropoxide into heterocumulenes gives a product that carries out metathesis at elevated temperatures by undergoing insertion of a second heterocumulene in a head to head fashion, followed by an extrusion reaction.     

Application of complex-lag distributions for estimation of arbitrary order phase derivatives in digital holographic interferometry

This Letter proposes a method to estimate phase derivatives of arbitrary order in digital holographic interferometry. Based on the desired order, the generalized complex-lag distribution is computed from the reconstructed interference field. Subsequently, the phase derivative is estimated by tracing the peak of the distribution. Simulation and experimental results are presented to validate the method's potential.     

AgNO3 Catalyzed Regio‐Selective Synthesis of 3‐Alkyl/Aryl‐idene‐3,4‐dihydro‐4‐tosyl‐2H‐1,4‐Benzoxazine: Novel Anti‐Tubercular Scaffolds

A facile and efficient method for the construction of 3‐alkyl/aryl substituted 1,4‐benzoxazine and benzoxazepine via AgNO₃ catalyzed cyclization of propargyloxy sulfonamides and their anti‐tubercular activity against Mycobacterium tuberculosis H₃₇R_V is described. This cyclization proceeds through 6‐exo‐dig manner to generate the products in moderate to good yields.     

Dimerization of alkynes promoted by a pincer-ligated iridium complex. C-C reductive elimination inhibited by steric crowding

The pincer-ligated species (PCP)Ir (PCP = kappa3-C6H3-2,6-(CH2PtBu2)2) is found to promote dimerization of phenylacetylene to give the enyne complex (PCP)Ir(trans-1,4-phenyl-but-3-ene-1-yne). The mechanism of this reaction is found to proceed through three steps: (i) addition of the alkynyl C-H bond to iridium, (ii) insertion of a second phenylacetylene molecule into the resulting Ir-H bond, and (iii) vinyl-acetylide reductive elimination. Each of these steps has been investigated, by both experimental and computational (DFT) methods, to yield unexpected conclusions of general interest. (i) The product of alkynyl C-H addition, (PCP)Ir(CCPh)(H) (3), has been isolated and, in accord with experimental observations, is calculated to be 29 kcal/mol more stable than the analogous product of benzene C-H addition. (ii) Insertion of a second PhCCH molecule into the Ir-H bond of 3 proceeds rapidly, but with a 1,2-orientation. This orientation gives (PCP)Ir(CCPh)(CPh=CH2) (4) which would yield the 1,3-diphenyl-enyne if it were to undergo C-C elimination; however, the insertion is reversible, which represents the first example, to our knowledge, of simple beta-H elimination from a vinyl group to give a terminal hydride. The 2,1-insertion product (PCP)Ir(CCPh)(CH=CHPh) (6) forms more slowly, but unlike the 1,2 insertion product it undergoes C-C elimination to give the observed enyne. (iii) The failure of 4 to undergo C-C elimination is found to be general for (PCP)Ir(CCPh)(vinyl) complexes in which the vinyl group has an alpha-substituent. Thus, although C-C elimination relieves crowding, the reaction is inhibited by increased crowding. Density-functional theory (DFT) calculations support this surprising conclusion and offer a clear explanation. Alkynyl-vinyl bond formation in the C-C elimination transition state involves the vinyl group pi-system; this requires that the vinyl group must rotate (around the Ir-C bond) by ca. 90 degrees to achieve an appropriate orientation. This rotation is severely inhibited by steric crowding, particularly when the vinyl group bears an alpha-substituent.     

Alkaloids with Anti-Onchocercal Activity from Voacanga africana Stapf (Apocynaceae): Identification and Molecular Modeling

A new iboga-vobasine-type isomeric bisindole alkaloid named voacamine A (1), along with eight known compounds—voacangine (2), voacristine (3), coronaridine (4), tabernanthine (5), iboxygaine (6), voacamine (7), voacorine (8) and conoduramine (9)—were isolated from the stem bark of Voacangaafricana. The structures of the compounds were determined by comprehensive spectroscopic analyses. Compounds 1, 2, 3, 4, 6, 7 and 8 were found to inhibit the motility of both the microfilariae (Mf) and adult male worms of Onchocerca ochengi, in a dose-dependent manner, but were only moderately active on the adult female worms upon biochemical assessment at 30 μM drug concentrations. The IC₅₀ values of the isolates are 2.49–5.49 µM for microfilariae and 3.45–17.87 µM for adult males. Homology modeling was used to generate a 3D model of the O. ochengi thioredoxin reductase target and docking simulation, followed by molecular dynamics and binding free energy calculations attempted to offer an explanation of the anti-onchocercal structure–activity relationship (SAR) of the isolated compounds. These alkaloids are new potential leads for the development of antifilarial drugs. The results of this study validate the traditional use of V. africana in the treatment of human onchocerciasis.     

Enantioselective sulfa-Michael addition of thioacids to α,β-unsaturated ketones with bifunctional organocatalyst

Organocatalytic conjugate addition of thioacids to α,β-unsaturated ketones has been studied in the presence of cinchona alkaloid derived urea catalyst. Both the enantiomers of products are accessible with the same level of enantioselectivity using pseudoenantiomeric quinine/quinidine derived catalysts. The catalytic process provides optically active thioesters with high chemical yields (up to 99%) and useful enantioselectivity (up to 83% ee). The reaction was performed with 1 mol % of catalyst in toluene at room temperature. A transition state model has been proposed to explain the stereochemical outcome of the reaction.     

Combined experimental and computational studies on carbon-carbon reductive elimination from Bis(hydrocarbyl) complexes of (PCP)Ir

The reductive elimination of carbon-carbon bonds is one of the most fundamentally and synthetically important reaction steps in organometallic chemistry, yet relatively little is understood about the factors that govern the kinetics of this reaction. C-C elimination from complexes with the common d (6) six-coordinate configuration generally proceeds via prior ligand loss, which greatly complicates any attempt to directly measure the rates of the specific elimination step. We report the synthesis of a series of five-coordinate d (6) iridium complexes, ( (tBu)PCP)Ir(R)(R'), where R and R' are Me, Ph, and (phenyl-substituted) vinyl and alkynyl groups. For several of these complexes (R/R' = Ph/Vi, Me/Me, Me/Vi, Me/CCPh, and Vi/CCPh, where Vi = trans-CHCHPh) we have measured the absolute rate of C-C elimination. For R/R' = Ph/Ph, Ph/Me, and Ph/CCPh, we obtain upper limits to the elimination rate; and for R/R' = CCPh/CCPh, a lower limit. In general, the rates decrease (activation barriers increase) according to the following order: acetylide < vinyl approximately Me < Ph. Density functional theory (DFT) calculations offer significant insight into the factors behind this order, in particular the slow rates for elimination of the vinyl and, especially, phenyl complexes. The transition states are calculated to involve rotation of the aryl or vinyl group around the Ir-C bond, prior to C-C elimination, such that the group to which it couples can add to the face of the aryl or vinyl group. This rotation is severely hindered by the presence of the phosphino -t-butyl groups that lie above and below the plane of the aryl/vinyl group in the ground state. Accordingly, calculations predict dramatically different relative rates of elimination from the much less sterically hindered complexes ( (H)PCP)Ir(R)(R'). For example, the barrier to elimination from ( (H)PCP)Ir(Me) 2 is 20 kcal/mol, which is 2 kcal/mol greater than from the ( (tBu)PCP)Ir analogue. In contrast, the activation enthalpies calculated for vinyl-vinyl and phenyl-phenyl elimination from ( (H)PCP)Ir are remarkably low, only 2 and 9 kcal/mol, respectively; these values are 16 and 22 kcal/mol less than those of the corresponding ( (tBu)PCP)Ir complexes. Moreover, since these eliminations are very nearly thermoneutral, the barriers are calculated to be equally low for the reverse reactions [C-C oxidative addition to ( (H)PCP)Ir]. The absence of differences in intraligand CC bond lengths in the transition states relative to the ground states, combined with a comparison of calculated "face-on" and "planar" transition states for C-C coupling, suggests that the critical importance of the aryl/vinyl rotation is based on geometric or steric factors rather than electronic ones. Thus there is no evidence for participation of the pi or pi* orbitals of the aryl or vinyl groups in the formation of the C-C bond, although a small pi effect cannot be rigorously excluded. Likewise, the results do not support the hypothesis that the degree of directionality of the carbon-based orbital used for bonding to iridium (sp (3) > sp (2) > sp) plays an important role in this system in determining the barrier to reductive elimination.     

Synthesis and NMR elucidation of pentacycloundecane-derived hydroxy acid peptides as potential anti-HIV-1 agents

The synthesis and NMR elucidation of eight novel peptides incorporating the pentacycloundecane (PCU)-derived hydroxy acid are reported. The PCU cage amino acids were synthesized as racemates and the incorporation of the PCU-derived hydroxy acid with natural (S)-amino acids produced inseparable diastereomeric peptides. A series of overlapping signals from the cage and that of the peptide side chain was observed in the ¹H- and ¹³C-NMR spectra, complicating the elucidation thereof. Two-dimensional NMR techniques proved to be a very useful tool in overcoming these difficulties. These compounds are potential HIV protease inhibitors.