Selective and rapid water transportation across a self-assembled peptide-diol channel via the formation of a dual water array

Achieving superfast water transport by using synthetically designed molecular artifacts, which exclude salts and protons, is a challenging task in separation science today, as it requires the concomitant presence of a proper water-binding site and necessary selectivity filter for transporting water. Here, we demonstrate the water channel behavior of two configurationally different peptide diol isomers that mimic the natural water channel system, i.e., aquaporins. The solid-state morphology studies showed the formation of a self-assembled aggregated structure, and X-ray crystal structure analysis confirmed the formation of a nanotubular assembly that comprises two distinct water channels. The water permeabilities of all six compounds were evaluated and are found to transport water by excluding salts and protons with a water permeability rate of 5.05 × 10⁸ water molecules per s per channel, which is around one order of magnitude less than the water permeability rate of aquaporins. MD simulation studies showed that the system forms a stable water channel inside the bilayer membrane under ambient conditions, with a 2 × 8 layered assembly, and efficiently transports water molecules by forming two distinct water arrays within the channel.

A 1,2-diol-linked peptide forms a self-assembled channel in the lipid bilayer membrane. The channel allows rapid transport of water by excluding proton and salts.     

Total Synthesis of Aculeatins A and B from L‐Malic Acid

An efficient total synthesis of the cytotoxic spiroketal natural products aculeatin A and B is described. The synthesis of the 1,3,5‐triol moiety with appropriate configuration was accomplished from the commercially available L ‐malic acid. The key steps in this synthesis are the Barbier allylation, LiAlH₄/LiI‐mediated syn‐stereoselective 1,3‐asymmetric reduction, and phenyliodine bis(trifluoroacetate) (=[bis(trifluoroacetoxy)iodo]benzene; PIFA) mediated oxidative spirocyclization.     

The Stereoselective Total Synthesis of (6S)‐5,6‐Dihydro‐6‐[(2R)‐2‐hydroxy‐6‐phenylhexyl]‐2H‐pyran‐2‐one via Prins Cyclization

The stereoselective total synthesis of an antiproliferative and antifungal α‐pyrone natural product (6S)‐5,6‐dihydro‐6‐[(2R)‐2‐hydroxy‐6‐phenylhexyl]‐2H‐pyran‐2‐one is described. The key steps involved are the Prins cyclization, Mitsunobu reaction, and ring‐closing metathesis reaction.     

High-performance liquid chromatographic assay of alpha-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazine butanol (BMY 14802), a potential antipsychotic drug, in monkey and rat plasma

A high-performance liquid chromatographic-fluorescence method was developed for the quantitative analysis of BMY-14802 (I) in monkey and rat plasma. After the addition of the internal standard (BMY-14853 I.S.), 250 microliters of plasma were made basic by the addition of 2 ml of saturated sodium carbonate buffer. Compound I and the I.S. were then extracted into 5 ml of methyl tert.-butyl ether. The organic phase was evaporated and the resulting residue was reconstituted in mobile phase. Final separation and quantitation of I was achieved on an octadecyl column with a 0.05 M potassium phosphate-acetonitrile-triethylamine-85% phosphoric acid (650:350:0.1:0.05, v/v) mobile phase. Fluorescence detection was used to monitor the eluent at an excitation wavelength of 240 nm and an emission wavelength of 400 nm. The limit of detection was 0.5 ng/ml. The standard curve was linear over the range 5.0-1000 ng/ml. Intra-assay and inter-assay precision values were less than 4.0% relative standard deviation and accuracy was within 12% of nominal values. Compound I was shown to be stable in monkey and rat plasma for at least six months when stored at -20 degrees C.     

A comparison between analytical approaches for molecular weight estimation of proteins with variable levels of glycosylation

Biotherapeutics, such as mAbs and fusion proteins, are a major and rapidly growing class of pharmaceuticals. Majority of the biopharmaceuticals are glycoproteins, wherein about 1 to 30% of their molecular weight (MW) are contributed by the glycans. Determination of MW of heavily glycosylated proteins, such as Fc-fusion proteins, is seriously hampered by the physicochemical characteristics and heterogeneity of the attached carbohydrates. Glycosylation influences the expected size of the glycoprotein, which leads to disproportionate MW estimation, in size-dependent methods. Hence, in this study, we have demonstrated the advantages and limitations of four widely used MW estimation techniques for three proteins having varying levels of glycosylation. It was proven that glycosylation had least impact on MW determination by SEC-MALS and SV-AUC. However, MW estimation by LC-MS and SDS-PAGE was extensively hampered by the degree of glycosylation. It is, thus, essential to consider the structural characteristics of proteins while selecting a technique for determining their MW.     

Coreflooding Studies to Evaluate the Impact of Salinity and Wettability on Oil Recovery Efficiency

In this work, coreflood studies were carried out to determine the recovery benefits of low salinity waterflood compared to high salinity waterflood and the role of wettability in any observed recovery benefit. Two sets of coreflood experiments were conducted; the first set examined the EOR potential of low salinity floods in tertiary oil recovery processes, while the second set of experiments examined the secondary oil recovery potential of low salinity floods. Changes in residual oil saturation with variation in wettability, brine salinity and temperature were monitored. All the coreflood tests gave consistent increase in produced oil, corresponding to reduction in residual oil saturation and increase in water-wetness (for the second set of experiments) with decrease in brine salinity and increase in brine temperature.     

Determination of belfosdil, a new calcium channel blocker, in human plasma by capillary gas chromatography with nitrogen-phosphorus detection

Belfosdil and the internal standard were extracted from human plasma by a double liquid-liquid extraction. After a concentration step, gas chromatographic analysis of the sample was performed using a capillary fused-silica column and a nitrogen-phosphorus detector. The limit of detection of belfosdil was 0.025 ng/ml and the standard curve was linear over the range 0.05-100 ng/ml. The intra-assay and inter-assay precisions were within 7% (relative standard deviation) and the intra-assay and inter-assay accuracy values deviated by less than 5%. The extractability of belfosdil was 79%. The assay method was successfully used for the analysis of plasma samples from clinical studies with dose ranges of 5-100 mg of belfosdil.     

Reductive Studies on 3-Oxidopyrylium-alkene [5 + 2] Cycloadducts: Access to Some Hydroxy Cycloheptenoids

The scope of nickel boride as a versatile reducing reagent is extended to the 3-oxidopyrylium-alkene [5 + 2] cycloadducts. In this report, we demonstrate that nickel boride is capable of one-pot 1,2- and 1,4-reduction of enones present in the cycloadducts in good yields. Subsequent elaboration of the cycloadducts towards synthesis of functionalized cycloheptenoid derivatives devoid of the oxa-bridge is also explored.