Increased productivity in quantitative bioanalysis using a monolithic column coupled with high-flow direct-injection liquid chromatography/tandem mass spectrometry

The feasibility of using a monolithic column as the analytical column in conjunction with high-flow direct-injection liquid chromatography/tandem mass spectrometry (LC/MS/MS) to increase productivity for quantitative bioanalysis has been investigated using plasma samples containing a drug and its epimer metabolite. Since the chosen drug and its epimer metabolite have the same selected reaction monitoring (SRM) transitions, chromatographic baseline separation of these two compounds was required. The results obtained from this monolithic column system were directly compared with the results obtained from a previously validated assay using a conventional C18 column as the analytical column. Both systems have the same sample preparation, mobile phases and MS conditions. The eluting flow rate for the monolithic column system was 3.2 mL/min (with 4:1 splitting) and for the C18 column system was 1.2 mL/min (with 3:1 splitting). The monolithic column system had a run time of 5 min and the conventional C18 column system had a run time of 10 min. The methods on the two systems were found to be equivalent in terms of accuracy, precision, sensitivity and chromatographic separation. Without sacrificing the chromatographic separation, sensitivity, accuracy and precision of the method, the reduced run time of the monolithic column method increased the sample throughput by a factor of two.     

Asymmetric synthesis of (–)-leiocarpin A via (–)-(S)-goniothalamin employing Julia–Kocienski olefination

A concise and enantioselective syntheses of antileukemic natural products such as (–)-(S)-goniothalamin and (–)-leiocarpin A has been accomplished in excellent yields. By employing reported conditions on suitable substrates via Julia–Kocienski olefination, intramolecular lactonization, and subsequently dehydroxylative olefination, (–)-(S)-goniothalamin was synthesized. Then Sharpless asymmetric dihydroxylation–intramolecular Michael addition on (–)-(S)-goniothalamin provided (–)-leiocarpin A.     

Effect of cucurbit[n]urils on tropicamide and potential application in ocular drug delivery

The supramolecular interactions of the ocular drug tropicamide (TR) with cucurbit[7]uril (CB7) and cucurbit[8]uril (CB8) were investigated in aqueous solutions by using ¹H NMR, ESI-MS and UV–vis spectroscopic techniques. The results indicate a 1:1 binding stoichiometry of TR with CB7 and CB8. The binding constants of TR in its protonated form were higher (e.g. K = 4 × 10⁶ M^? 1 with CB8) than in its neutral form (e.g. K = 1.4 × 10⁴ M^? 1 with CB8), which led to a complexation-induced increase in its pK _a value of ca. 0.5 and 2 units with CB7 and CB8, respectively. In the presence of about 1% (w/v) CB8, the ionisation degree of 0.1% (w/v) TR was increased from 2% to 62% at neutral pH. The increase in the pK _a value and thus stabilisation of the protonated TR species at neutral pH is discussed in the context of supramolecular drug delivery of ophthalmologic drugs.     

Synthesis and In Vitro Anti-HIV Activity of Some New Schiff Base Ligands Derived from 5-Amino-4-phenyl-4H-1,2,4-triazole-3-thiol and Their Metal Complexes

New Schiff base ligands (6–9) derived from 5-amino-4-phenyl-4H-1,2,4-triazole-3-thiol 1 and substituted benzaldehydes (2–5) as well as their metal complexes with Cu(II), Fe(II), Au(III), and Mn(II) (12–17) have been synthesized. A new benzothiazole derivative (11) was prepared from coupling of 7 with N-(benzothiazol-2-yl)-2-chloroacetamide 10. Their spectral properties were investigated. The newly designed and synthesized Schiff base ligands and the metal complexes were assayed for anti-HIV-1 and HIV-2 activity by examination of their inhibition of HIV-induced cytopathogenicity in MT-4 cells. Compounds 11 and 16 were found to be the most active inhibitors in cell culture (EC₅₀ = 12.2 μg/mL (SI = 4) and > 2.11 μg/mL (SI = > 1), respectively) against HIV-1, whereas 11 showed inhibition against HIV-2 of EC₅₀ > 10.2 μg/mL with SI = 9, which provided a good lead for further optimization.     

Two new zinc(II) and mercury(II) complexes based on N,N′‐(cyclohexane‐1,2‐diylidene)bis(4‐fluorobenzohydrazide): synthesis,crystal structures and antibacterial activities

Reaction of N,N′‐(cyclohexane‐1,2‐diylidene)bis(4‐fluorobenzohydrazide), C₂₀H₁₈F₂N₄O₂, ( L^F ), with zinc chloride and mercury(II) chloride produced different types and shapes of neutral coordination complexes, namely, dichlorido[N,N′‐(cyclohexane‐1,2‐diylidene)bis(4‐fluorobenzohydrazide)‐κ²N,O]zinc(II), [ZnCl₂(C₂₀H₁₈F₂N₄O₂)], ( 1 ), and dichlorido[N,N′‐(cyclohexane‐1,2‐diylidene)bis(4‐fluorobenzohydrazide)‐κ⁴O,N,N′,O′]mercury(II), [HgCl₂(C₂₀H₁₈F₂N₄O₂)], ( 2 ). The organic ligand and its metal complexes are characterized using various techniques: IR, UV–Vis and nuclear magnetic resonance (NMR) spectroscopies, in addition to powder X‐ray diffraction (PXRD), single‐crystal X‐ray crystallography and microelemental analysis. Depending upon the data from these analyses and measurements, a typical tetrahedral geometry was confirmed for zinc complex ( 1 ), in which the Zn^II atom is located outside the bis(benzhydrazone) core. The Hg^II atom in ( 2 ) is found within the core and has a common octahedral structure. The in vitro antibacterial activities of the prepared compounds were evaluated against two different bacterial strains, i.e. gram positive Bacillus subtilis and gram negative Pseudomonas aeruginosa bacteria. The prepared compounds exhibited differentiated growth‐inhibitory activities against these two bacterial strains based on the difference in their lipophilic nature and structural features.     

Design and synthesis of new series of 3-cyanopyridine and pyrazolopyridine derivatives

Reaction of 3-cyano-4,6-dimethyl-2-pyridone with ethyl chloroacetate afforded ethyl 2-([3-cyano-4,6-dimethylpyridin-2-yl]oxy)acetate 2 and ethyl 2-(3-cyano-4,6-dimethyl-2-oxopyridin-1[2H]-yl)acetate 3 , the reaction product yield depend on the reaction condition (potassium carbonate concentration and reaction time). These compounds used as precursors to synthesize pyridine derivatives 4 , 6-10 , 15, 17-20 , furopyridines 5, 16 , pyrazolopyridine 12 , pyridopyrazolopyrimidines 14a,b . The structure of the newly synthesized compounds was confirmed by spectral data (IR, NMR, and mass spectra) and elemental analysis.     

The Kinetics of Tenoxicam Photodegradation in Solution

Photodegradation of tenoxicam was investigated under different reaction conditions. After 60 min of exposure to UV light, the photodegradation was extensive, and the maximum and minimum in the UV-visible spectrum were shifted to shorter and longer wavelengths, respectively. Ethanol exerted a photostabilizing effect on tenoxicam. Tenoxicam is more stable in acidic and basic media than in neutral solution. Increasing light intensity or temperature causes an increase in the rate of photodegradation. The photodegradation of tenoxicam was found to follow first-order kinetics under all these conditions.     

Molecule-Responsive Fluorescent Sensors of α-Helix Peptides Bearing α-Cyclodextrin, Pyrene and Nitrobenzene Units in Their Side Chains

-Helix peptides bearing one unit of -cyclodextrin (-CD), one unit of pyrene and one unit of nitrobenzene (NB) in their side chains have been designed and synthesized as novel molecule-responsive devices.In both the CD-peptides, -PR17 and -PL17, the NB unit is separated from the CD unit by two turns of the helix. Two reference peptides (PL17, and -P17,) have also been synthesized. The circular dichroism studies in the peptide absorption region (200–250 nm)of -PR17 and -PL17 suggestthat the CD-peptides form stable-helixstructures (83–77%), which was destabilized by accommodating guest molecules (e.g., n-pentanol) into the CD cavity. It suggests that formation of intramolecular host–guest(CD–NB) complex stabilized thehelical structure and exogenous guest molecule excluded the appending NB moiety from inside to outside of the CD cavity, thereby causing destabilization of the helical structure and increasing the random coil content. The ICD spectra of the peptides in the pyrene and nitrobenzene absorption region (250–40 nm) suggest that NB forms inclusion complex with CD. The fluorescence studies revealed that the fluorescence of the pyrene unit is quenched by the NB unit in -PR17 and -PL17. The fluorescence intensity increases with increasing guest concentration for the CD-peptides.This guest-responsiveenhancement in the fluorescence intensity can be explained in terms of increased distance between the pyrene and NB moieties, which is caused by exclusion of the NB moiety from the CD cavity by guest accommodation. Using the guest-responsive fluorescence quenching properties of the CD-peptides, we have obtained binding constants for various short chain alkanols. -PL17 has higher binding affinity to the guest molecules than its isomer, -PR17, indicating that the location of functional groups on the peptide scaffold is important in molecule detection.     

Efficient One‐Pot Four‐Component Synthesis and X‐ray Crystallographic Structure of 2‐Pyridone Derivatives

A series of 3‐cyano‐2‐pyridone derivatives were synthesized by one‐pot four‐component condensation reaction involving a benzaldehyde derivative, alkyl cyanoacetate, acyclic or cyclic ketones, and ammonium acetate in reflux condition. The X‐ray structure of the products 5a and 5d confirm symmetric dimers via hydrogen bonding interactions between individual pyridine molecules showing, in addition, also π–π stacking interactions.