Imidazo[1,2-a]pyrazine inhibitors of phosphoinositide 3-kinase alpha (PI3Kα): 3D-QSAR analysis utilizing the Hybrid Monte Carlo algorithm to refine receptor-ligand complexes for molecular alignment

Phosphoinositide 3-kinase alpha (PI3Kα) is a lipid kinase involved in several cellular functions such as cell growth, proliferation, differentiation and survival, and its anomalous regulation leads to cancerous conditions. PI3Kα inhibition completely blocks the cancer signalling pathway, hence it can be explored as an important therapeutic target for cancer treatment. In the present study, docking analysis of 49 selective imidazo[1,2-a]pyrazine inhibitors of PI3Kα was carried out using the QM-Polarized ligand docking (QPLD) program of the Schrödinger software, followed by the refinement of receptor–ligand conformations using the Hybrid Monte Carlo algorithm in the Liaison program, and alignment of refined conformations of inhibitors was utilized for the development of an atom-based 3D-QSAR model in the PHASE program. Among the five generated models, the best model was selected corresponding to PLS factor 2, displaying the highest value of Q²_test (0.650). The selected model also displayed high values of r²_train (0.917), F-value (166.5) and Pearson-r (0.877) and a low value of SD (0.265). The contour plots generated for the selected 3D-QSAR model were correlated with the results of docking simulations. Finally, this combined information generated from 3D-QSAR and docking analysis was used to design new congeners.     

2,4‐Dinitrophenol‐Catalyzed α‐C(sp3)−H and C(sp)−H Bond Functionalization of Cyclic Amines and Alkynes: Highly Regio‐/Diastereoselective Synthesis of α‐Alkynyl‐3‐Amino‐2‐Oxindoles

A transition‐metal‐ and oxidant‐free DNP (2,4‐dinitrophenol)‐catalyzed atom‐economical regio‐ and diastereoselective synthesis of monofunctionalized α‐alkynyl‐3‐amino‐2‐oxindole derivatives by C?H bond functionalization of cyclic amines and alkynes with indoline‐2,3‐diones has been developed. This cascade event sequentially involves the reductive amination of indoline‐2,3‐dione by imine formation and cross coupling between C(sp³)?H and C(sp)?H of the cyclic amines and alkynes. This reaction offers an efficient and attractive pathway to different types of α‐alkynyl‐3‐amino‐2‐oxindole derivatives in good yields with a wide tolerance of functional groups. The salient feature of this methodology is that it completely suppresses the homocoupling of alkynes. To the best of our knowledge, this is the first example of a DNP‐catalyzed metal‐free direct C(sp³)?H and C(sp)?H bond functionalization providing biologically active α‐alkynyl‐3‐amino‐2‐oxindole scaffolds.     

Chiral Bent-Shaped Molecules Exhibiting Unusually Wide Range of Blue Liquid-Crystalline Phases and Multistimuli-Responsive Behavior

Recently, an unprecedented observation of polar order, thermochromic behavior, and exotic mesophases in new chiral, bent-shaped systems with a −CH₃ moiety placed at the transverse position of the central core was reported. Herein, a homologous series of compounds with even-numbered carbon chains from n=4 to 18 were synthesized, in which −Cl was substituted for −CH₃ at the kink position and a drastic modification in the phase structure of the bent-shaped molecule was observed. An unusual stabilization of the cubic blue phase (BP) over a wide range of 16.4 °C has been witnessed. Two homologues in this series ( 1 -12 and 1 -14) exhibit an interesting phase sequence consisting of BPI/II, chiral nematic, twist grain boundary, smectic A, and smectic X (SmX) phases. The higher homologues ( 1 -16 and 1 -18) stabilize the SmX phase enantiotropically over the entire temperature range. Crystal structure analysis confirmed the bent molecular architecture, with a bent angle of 148°, and revealed the presence of two different molecular conformations in an asymmetric unit of compound 1 -4. A DFT study corroborated that the −Cl moiety at the central core of the molecule led to an increase in the dipole moment along the transverse direction, which, in turn, facilitated the unusual stabilization of frustrated structures. Crystal polymorphism has been evidenced in three homologues ( 1 -10, 1 -12, and 1 -14) of the series. On the application of mechanical pressure through grinding, compound 1 -10 transformed from a bright yellow crystalline solid to a dark orange–green amorphous solid, which reversed upon dropwise addition of dichloromethane, indicating reversible mechanochromism in this class of compounds. In addition, excellent thermochromic behavior has been observed for compound 1 -10 with a controlled temperature–color combination.     

Impact of fibre nonlinearities in optical DWDM transmission systems at different data rates

The impact of major fibre nonlinearities, like stimulated Raman scattering (SRS) and four wave mixing (FWM), in cascaded amplifier dense wavelength division multiplexing (DWDM) transmission system, has been studied at different data rates. SRS has been calculated considering pulse walk off effect. Analysis has been carried out to evaluate signal to noise ratio (SNR) considering the combined effect of SRS and FWM in the presence of amplified spontaneous emission (ASE) noise to achieve minimum noise at different data rates.     

A Convenient One Step Synthesis of 1,3-Diaryl-6-methyl-4-oxo-1,2,3,4-tetrahydro-2-thioxofuro [2,3-d] Pyrimidines

1,3-Diaryl-6-methyl-4-oxo-1,2,3,4-tetrahydro-2-thioxofuro (2,3-d) pyrimidines have been synthesised in one step in good yield by the reaction of 1,3-diaryl-1,3-dihydro-2-thioxo-2H,5H-pyrimidine-4,6-diones with chloroacetone in presence of triethylamine.     

Structure factor of amorphous TiO2 nanoparticle; Molecular Dynamics Study

Three samples of amorphous TiO₂ of 3 nm size are prepared by molecular dynamics simulations using different heating and quenching rates and open boundary conditions. Matsui–Akaogi force field is used to calculate the correlation functions. It is found that atomic distribution in these samples differ within the limit of 4%. The calculated coordination numbers suggest that 52–54% Ti atoms are 6-fold coordinated, 31–32% Ti atoms are 5-fold coordinated, 7–10% are 4-fold coordinated and few Ti atoms even 7-fold coordinated through vertex and edge sharing in these samples. On the other hand 66–68% oxygen atoms remain 3-fold coordinated, 25–28% are 2-fold coordinated and 5–6% oxygen atoms become 4-fold coordinated. Most of the over coordinated and under coordinated strained structures are in the core and surface regions respectively. The agreement between the calculated and measured reduced structure factors suggests that atomic arrangements in the laboratory samples prepared by sputtering and sol-gel methods may be similar to those predicted by molecular dynamics simulations.     

Synthetic Strategies Applicable in the Synthesis of Privileged Scaffold: 1,4-Benzodiazepine

The development of new synthetic approaches to the 1,4-benzodiazepine ring system and their further elaboration have provided access to a broad range of functionalized derivatives. In this review an attempt has been made to summarize those synthetic strategies involved for the synthesis of privileged scaffold 1,4-benzodiazepine over time.     

A review report on medical imaging phosphors

The present review deals with the synthesis and characterization of different phosphors used in medical imaging. A comparative study of different synthesis methods and characterization is presented. The best method for synthesized phosphor is the solid state method because the morphology of the sample is very good. The photostimulated luminescence of the prepared sample has been represented by different authors. The best phosphor used in medical imaging is BaBrCl:Eu²⁺.