Quantitative analysis of enasidenib in dried blood spots of mouse blood using an increased‐sensitivity LC–MS/MS method: Application to a pharmacokinetic study

A simple, sensitive and rapid assay method has been developed and validated as per regulatory guidelines for the estimation of enasidenib on mouse dried blood spots (DBS) using liquid chromatography coupled to tandem mass spectrometry with electrospray ionization in the positive‐ion mode. The method employs liquid extraction of enasidenib from DBS disks of mouse whole blood followed by chromatographic separation using 0.2% formic acid–acetonitrile (25:75, v/v) at a flow rate of 1.0 mL/min on an Atlantis dC₁₈ column with a total run time of 2.0 min. The MS/MS ion transitions monitored were m/z 474.0 → 267.1 for enasidenib and m/z 309.2 → 251.3 for the internal standard (warfarin). The assay was linear in the range of 1.01 – 3044 ng/mL. The within‐run and between‐run precisions were in the range of 3.18 – 9.06 and 4.66 – 8.69%, respectively. Stability studies showed that enasidenib was stable on DBS cards for 1 month. This novel method has been applied to analyze the DBS samples of enasidenib obtained from a pharmacokinetic study in mice.     

Self‐emulsion polymerization of amphiphilic monomers—a green route to synthesis of polymeric nanoscaffolds

Self‐emulsion polymerization (SEP), a green route developed by us for the polymerization of amphiphilic monomers, does not require any emulsifier or an organic solvent except that the water‐soluble initiators such as 2,2′‐azobis[2‐(2‐imidazolin‐2‐yl)propane]dihydrochloride (VA‐044) and potassium persulfate (KPS) are only used. We report here the polymer nanoscaffolds from a number of amphiphilic monomers, which can be used for in situ encapsulation of a variety of nanoparticles. As a demonstration of the efficacy of these nanoscaffolds, the synthesis of a biocompatible hybrid nanoparticle (nanohybrid), prepared by encapsulating Fe₃O₄ magnetic nanoparticle (Fe₃O₄ MNPs) in poly(2‐hydroxyethyl methacrylate) in water, for MRI application is presented. The nanohybrid prepared following the SEP in the form of an emulsion does not involve the use of any stabilizing agent, crosslinker, polymeric emulsifier, or surfactant. This water‐soluble, spherical, and stable nanohybrid containing Fe₃O₄ MNPs of average size 10 ± 2 nm has a zeta potential value of ?41.89 mV under physiological conditions. Magnetic measurement confirmed that the nanohybrid shows typical magnetic behavior having a saturation magnetization (Ms) value of 32.3 emu/g and a transverse relaxivity (r2) value of 29.97 mM^?1 s^?1, which signifies that it can be used as a T2 contrast agent in MRI. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019     

Synthesis,Characterization, and Structure of Quinoline‐based Benzimidazole Derivatives

Quinoline‐based benzimidazole compounds have been successfully synthesized and characterized by various spectroscopic techniques like FT‐IR, ¹H NMR, ¹³C NMR, and mass spectral analysis, and the structures have been authenticated by single crystal X‐ray diffraction method. Here, we report an economical, mild, and efficient procedure that involves condensation of 8‐hydroxyquinoline‐2‐carbaldehyde with various diamines as substrates to give bis‐imines. A systematic study towards both aliphatic and aromatic bis‐imines has been conducted to investigate the ring‐closure reaction that generates the benzimidazole moiety in the heterocyclic compounds discussed in this study. Aliphatic bis‐imines does not undergo cyclization; however, the bis‐imines derived from o‐phenylenediamine and derivatives generates heterocyclic compounds with benzimidazole moiety. In contrast to synthetic procedures reported earlier for benzimidazoles, the reaction conditions herein reported are simpler. Path for reactions holds initial condensation with one equivalent of 8‐hydroxyquinoline‐2‐carbaldehyde to form mono‐imine followed by immediate intramolecular ring closure. The subsequent nupleophilic attack to another equivalent of 8‐hydroxyquinoline‐2‐carbaldehyde and migration of hydride generates the benzimidazole moiety and the active methylene group. The ─CH₂ group was confirmed from ¹H and ¹³C NMR, wherein the two hydrogens appeared at around 6.40–6.52 ppm and the carbon center appeared at 51.54–51.77 ppm. The single crystal X‐ray diffraction also confirmed the formation of benzimidazole moiety and the active methylene group in the heterocyclic compounds discussed in this study.     

Application of Polyphosphoric Acid‐Mediated Acyl Migration for Regiospecific Synthesis of Diverse 2‐Acylpyrroles from Chalcones

A metal‐free approach for the synthesis of 2‐acylpyrroles is reported in this paper. Synthesis of the target molecule started from chalcones and was carried out in two steps. Initial step involved the conversion of chalcones to corresponding 4‐substituted‐3‐acylpyrroles by reaction with TosMIC. In the subsequent step, target molecules were obtained in modest to good yields by polyphosphoric acid‐mediated acyl rearrangement of 3‐acylpyrroles to their 2‐acyl congeners. The crucial final step was amenable to diverse substitutions on pyrrole ring. Preliminary experiment for the determination of mechanism indicated the involvement of acylium ion.     

Pyrazole‐4‐carboxylic Acids from Vanadium‐catalyzed Chemical Transformation of Pyrazole‐4‐carbaldehydes

The conversion of aldehydes into carboxylic acids using oxidizing agents is a common protocol in transformation chemistry. An efficient oxidation strategy of transformation of pyrazole‐4‐aldehydes to the corresponding acids using vanadium catalysts in the presence of 30% H₂O₂ as an oxidant is described. The catalytic technology was successfully applied to a range of various 4‐formylpyrazoles, and plausible mechanism is also discussed.     

Development of biobased polyurethane‐imides from maleinized cottonseed oil and castor oil

An eco‐friendly coating system, which is largely biobased, has been developed from castor and cottonseed oil. Cottonseed oil was functionalized with maleic anhydride by “ene” reaction to give maleinized cottonseed oil (MACSO); the anhydride groups were reacted with isocyanates to yield –NCO terminated polyurethane prepolymer. The prepolymer was further chain extended with hydroxyl groups of castor oil to give polyurethane‐imides (PUIs). The cross‐linked films thus obtained had good mechanical properties, and the imide groups in the backbone improved the corrosion resistance of PUIs as revealed by potentiodynamic polarization study. With increasing content of MACSO, thermal stability, glass transition temperatures (T_g), tensile strength, and corrosion resistance of resulting PUIs significantly increased.     

Stereoselective Insertion of Benzynes into Lawsones: Synthesis of Biologically Important Benzannulated Bicyclo[3.3.0]octanes

An ideal stereoselective insertion of in situ generated benzynes into lawsones through domino formal [2+2]-cycloaddition followed by rearrangement is disclosed. The reaction allowed for the preparation of biologically important benzannulated bicyclo[3.3.0]octanes in good yields and with excellent selectivities by using simple substrates and conditions.     

Ionic Assembly,Anion–π, Magnetic,and Electronic Attributes of Ambient Stable Naphthalenediimide Radical Ions

Organic spin-based molecular materials are considered to be attractive for the generation of functional materials with emergent optoelectronic, magnetic, or magneto-conductive properties. However, the major limitations to the utilization of organic spin-based systems are their high reactivity, instability, and propensity for dimerization. Herein, we report the synthesis, characterization, and magnetic and electronic studies of three ambient stable radical ions ( 1 a^.+ , 1 b^.+ , and 1 c^.+ ). The radical ions 1 b^.+ and 1 c^.+ with BPh₄⁻ and BF₄⁻ counter anions, respectively, were synthesized in excellent yields by means of anion metathesis of 1 a^.+ with Br⁻ as its counter anion. Notably, synthesis of 1 a^.+ was achieved in an ecofriendly, solvent-free protocol. The radical ions were characterized by means of single-crystal X-ray diffraction studies, which revealed the discrete nature of the radical ions and extensive hydrogen-bonding interactions within the radical ions and with the counter anions. Thus, radical ions can be organized to form infinite supramolecular arrays using weak noncovalent interactions. In addition, the Br⁻, BF₄⁻, and BPh₄⁻ anions formed diverse types of anion–π interactions with the naphthalene and imide rings of the radical ions. The radical ions were characterized by means of X-band electron paramagnetic resonance (EPR) spectroscopy in solution and in the solid state. Magnetic studies revealed their paramagnetic nature in the range of 10 to 300 K. The radical ions exhibited high resistivity approaching the gigaohm (GΩ) scale. In addition, the radical ions exhibited panchromism.