New pyranosyl cembranoid diterpenes from Sarcophyton trocheliophorum

During our continual searching programme for novel bioactive metabolites from Sarcophyton trocheliophorum, collected from Red Sea, we describe herein the isolation and structural elucidation of further two new pyrane-based cembranoid diterpenes: 9-hydroxy-7,8-dehydro-sarcotrocheliol (1) and 8,9-expoy-sarcotrocheliol acetate (2), along with the well-known sarcotrocheliol acetate (3), (+)-sarcophine (4), (+)-sarcophytoxide (5) and (-)-sarcophytoxide (6). The chemical structures of compounds 1 and 2 were determined on the basis of 1D and 2D NMR (¹H, ¹³C, ¹H–¹H COSY, HMQC, HMBC and NOE), mass spectra (ESI and HR-ESIMS) and by comparison with related structures. The antimicrobial activities of the reported compounds 1–6 were investigated. According to the molecular docking study of compounds 1–6 using 3D structure of α,β tubulin in complex with taxol (PDB code 1JFF) and epothilone A (PDB code 1TVK), sarcophine (4) displayed the highest affinity towards both crystal structures, followed by 5 and 6, meanwhile pyrane-based cembranoid diterpenes (1–3) showed less affinity.     

Synthesis and spectroscopic studies of methoxy-substituted phenylthienylnicotinamidines

Abstract

Five thienylnicotinamidine derivatives 5a–e were prepared from their corresponding nicotinonitriles 3a–e on treatment with lithium trimethylsilylamide [LiN(TMS)₂] followed by hydrolysis using ethanolic/HCl (gas). The nicotinonitriles 3a–e were prepared via Suzuki coupling reaction of bromothienyl derivative 1 with the appropriate phenylboronic acids 2a–e. The DFT calculation was used to optimize the geometric structure of the newly synthesized nicotinamidines. The comparison of DFT/B3LYP calculated spectral data (¹H-NMR and ¹³C-NMR) with the experimental data showed acceptable agreement. Mass fragmentation patterns of 3,4-dimethoxyphenyl, 3,5-dimethoxyphenyl, and 3,4,5-trimethoxyphenyl thienylnicotinamidine derivatives were investigated.     

Rewiring cellular metabolism for heterologous biosynthesis of Taxol

Abstract

Taxol is one of the anticancer drugs synthesized naturally in the evergreen Taxus brevifolia forest tree belonging to the yew family (Taxaceae) growing on the Pacific. There are reportedly evidence for treating ovarian, breast and lung cancers through this drug given its unique structural and functional features. Extraction of this drug from yew trees bark is one of the most common ways of producing this drug, but 3000 trees are needed to obtain a kilogram of Taxol. Hence, further attention has recently been attracted to the metabolic engineering strategies, including, engineering cellular metabolism of microorganisms and their optimization. Accordingly, the present paper article was aimed to review recent advances in elevating the production and commercialization of Taxol through metabolic engineering techniques.     

Baclofen impurities: Facile synthesis and novel environmentally benign chromatographic method for their simultaneous determination in baclofen

An efficient, economic and high yielding method was described for the synthesis of baclofen (BAC) pharmacopoeial impurities (impurity A and impurity B) which can be used for gram‐scale synthesis. Furthermore, a novel ecofriendly thin‐layer chromatographic TLC–densitometric method was established and validated for the determination of BAC and its synthesized impurities. The developed TLC–densitometric method is based on the chromatographic separation using TLC plates (60 F₂₅₄) using a green mobile phase of ethyl acetate–methanol–ammonia solution, 33% (8:2:0.1, by volume) with UV scanning at 220 nm. The proposed method was validated with respect to International Conference on Harmonization guidelines. The validated method was successfully applied for determination of BAC in pure form and in its commercial dosage form. Additionally, the greenness profile of the developed method was evaluated and compared with those of the reported chromatographic methods. The developed method was found to be superior to the published methods, being environmentally benign.     

Spin Selectivity in Electron Transfer in Photosystem I

Photosystem I (PSI) is one of the most studied electron transfer (ET) systems in nature; it is found in plants, algae, and bacteria. The effect of the system structure and its electronic properties on the electron transfer rate and yield was investigated for years in details. In this work we show that not only those system properties affect the ET efficiency, but also the electrons’ spin. Using a newly developed spintronic device and a technique which enables control over the orientation of the PSI monolayer relative to the device (silver) surface, it was possible to evaluate the degree and direction of the spin polarization in ET in PSI. We find high‐spin selectivity throughout the entire ET path and establish that the spins of the electrons being transferred are aligned parallel to their momenta. The spin selectivity peaks at 300 K and vanishes at temperatures below about 150 K. A mechanism is suggested in which the chiral structure of the protein complex plays an important role in determining the high‐spin selectivity and its temperature dependence. Our observation of high light induced spin dependent ET in PSI introduces the possibility that spin may play an important role in ET in biology.     

Critical behavior of light in mode-locked lasers

Light is shown to exhibit critical and tricritical behavior in passively mode-locked lasers with externally injected pulses. It is a first and unique example of critical phenomena in a one-dimensional many-body light-mode system. The phase diagrams consist of regimes with continuous wave, driven parapulses, spontaneous pulses via mode condensation, and heterogeneous pulses, separated by phase transition lines that terminate with critical or tricritical points. Enhanced non-Gaussian fluctuations and collective dynamics are present at the critical and tricritical points, showing a mode system analog of the critical opalescence phenomenon. The critical exponents are calculated and shown to comply with the mean field theory, which is rigorous in the light system.     

Interaction in the geometro-differential conception of extended particles and the Galilei semigroup of trajectories

Along the lines of a previous work, the geometrical structure of Hibert bundles describing extended quantum free particles is repeated with Galilei external and internal independent symmetries. Then, in order to introduce the interaction, this structure is extended by replacing configuration and momentum spaces by the socelled spaces of trajectories and extended velocity boosts, respectively. These provide representations giving the probability amplitudes for the particle to follow certain trajectories. The interaction can be introduced in the transformation law from functions on the space of trajectories (free dynamics) to functions on spacetime (intracting dynamics). This transformation law, which makes use of a universal distribution, is seen as a functional in our work according to a quantum functional theory which generalizes the ideas of de Broglie. Intertwining of induced representations gives the free propagator in the space of trajectories and, henceforth, the propagator with interaction in space-time for the extended particle.     

Chromatographic analysis of ledipasvir and sofosbuvir: New treatment for chronic hepatitis C infection with application to human plasma

Sofosbuvir (SOF) and ledipasvir (LED) are recently approved and coformulated as directly acting antiviral agents used for treatment of hepatitis C virus (HCV). A reversed phase high performance liquid chromatography - diode array detector (RP-HPLC/DAD) method was developed and validated for the first time for the analysis of newly formulated anti-HCV combination, in pure form, pharmaceutical formulation and in human plasma. In the developed method, separation was performed on Zorbax® Eclipse C18 column using a gradient mixture of acetonitrile–water as a mobile phase and scanning was performed at 260?nm (for SOF) and 330?nm (for LED). The two drugs were completely separated from each other and from plasma, where plasma peak appeared at 2.76?±?0.05?min, SOF at 4.25?±?0.05, and LED at 7.35?±?0.05. The developed method showed high sensitivity, the drugs showed linearity in the range of 1–45?µg/mL for both pure form and spiked human plasma. Three freeze–thaw cycles were performed separately at two different temperatures, ?8 and ?20°C. No significant loss of the studied drugs were observed during repeated thawing and freezing. Validation parameters such as accuracy, precision, robustness, and ruggedness were tested in compliance with USP recommendations, where acceptable results were obtained. Applying to pharmaceutical formulation showed no interference from tablet excipients.     

Invariant measures for the horocycle flow on periodic hyperbolic surfaces

We classify the ergodic invariant Radon measures for the horocycle flow on geometrically infinite regular covers of compact hyperbolic surfaces. The method is to establish a bijection between these measures and the positive minimal eigenfunctions of the Laplacian of the surface. Two consequences arise: if the group of deck transformations G is of polynomial growth, then these measures are classified by the homomorphisms from G ₀ to ℝ where G ₀ ≤ G is a nilpotent subgroup of finite index; if the group is of exponential growth, then there may be more than one Radon measure which is invariant under the geodesic flow and the horocycle flow. We also treat regular covers of finite volume surfaces. The first author was supported by NSF grant 0500630. The second author was supported by NSF grant 0400687.     

Experimental study of the stability and optimization of multipulse passive mode locking

We present an experimental study of the stability of passively mode-locked pulses against noise in multipulse operation of an erbium-doped fiber laser. The laser properties are determined by two dimensionless combinations of the laser parameters. Measurements of the pulses' destabilization threshold as a function of those laser parameters show the optimal regions that maximize the mode-locked pulse stability. We find good agreement between the experimental observations and the theoretical predictions.