Superquantiles at Work: Machine Learning Applications and Efficient Subgradient Computation

Set-Valued and Variational Analysis - R. Tyrell Rockafellar and his collaborators introduced, in a series of works, new regression modeling methods based on the notion of superquantile (or...     

A rapid and sensitive bioanalytical LC–MS/MS method for the quantitation of a novel CDK5 inhibitor 20–223 (CP668863) in plasma: Application to in vitro metabolism and plasma protein-binding studies

A rapid, selective, and sensitive liquid chromatography coupled with tandem mass spectrometry (MS/MS) method was developed and validated for the quantitation of the novel CDK5 inhibitor ‘20–223' in mouse plasma. Separation of analytes was achieved by a reverse-phase ACE Excel C₁₈ column (1.7 μm, 100 × 2.1 mm) with gradient elution using 0.1% formic acid (FA) in methanol and 0.1% FA as the mobile phase. Analytes were monitored by MS/MS with an electrospray ionization source in the positive multiple reaction monitoring mode. The MS/MS response was linear over the concentration range 0.2–500 ng/mL for 20–223. The within- and between-batch precision were within the acceptable limits as per Food and Drug Administration guidelines. The validated method was successfully applied to plasma protein binding and in vitro metabolism studies. Compound 20–223 was highly bound to mouse plasma proteins (>98% bound). Utilizing mouse S9 fractions, in vitro intrinsic clearance (CL_int) was 24.68 ± 0.99 μL/min/mg protein. A total of 12 phase I and II metabolites were identified with hydroxylation found to be the major metabolic pathway. The validate method required a low sample volume, was linear from 0.2 to 500 ng/mL, and had acceptable accuracy and precision.     

Deciphering Internal and External π-Conjugation in C3-Symmetric Multiple Azobenzene Connected Systems in Self-Assembly

Two tripodal C₃-symmetric photoswitchable molecular systems T1 and T2 are reported that have extended conjugation at external and internal positions using an acryl group. The influence of the extended π-bonds in their absorption properties, thermal relaxation of the photoisomers and their propensities in forming supramolecular self-assemblies have been explored through spectroscopy, and microscopic studies. In particular, the investigations on the self-assembly have been carried out using scanning electron microscopy (SEM), transmission electron microscopy (TEM), polarized optical microscopy (POM), X-ray diffraction studies (XRD) and atomic force microscopy (AFM). Remarkably, the position of the acryl group influences the behaviour of the two target molecules in supramolecular assembly, and also in the formation of photoresponsive organic hydrogels or microcrystals.     

Excited-State Dynamics of Thienoguanosine,an Isomorphic Highly Fluorescent Analogue of Guanosine

Thienoguanosine (^thG) is an isomorphic analogue of guanosine with promising potentialities as fluorescent DNA label. As a free probe in protic solvents, ^thG exists in two tautomeric forms, identified as the H1, being the only one observed in nonprotic solvents, and H3 keto–amino tautomers. We herein investigate the photophysics of ^thG in solvents of different polarity, from water to dioxane, by combining time-resolved fluorescence with PCM/TD-DFT and CASSCF calculations. Fluorescence lifetimes of 14.5–20.5 and 7–13 ns were observed for the H1 and H3 tautomers, respectively, in the tested solvents. In methanol and ethanol, an additional fluorescent decay lifetime (≈3 ns) at the blue emission side (λ≈430 nm) as well as a 0.5 ns component with negative amplitude at the red edge of the spectrum, typical of an excited-state reaction, were observed. Our computational analysis explains the solvent effects observed on the tautomeric equilibrium. The main radiative and nonradiative deactivation routes have been mapped by PCM/TD-DFT calculations in solution and CASSCF in the gas phase. The most easily accessible conical intersection, involving an out-of plane motion of the sulfur atom in the five-membered ring of ^thG, is separated by a sizeable energy barrier (≥0.4 eV) from the minimum of the spectroscopic state, which explains the large experimental fluorescence quantum yield.     

Development of a bioanalytical method for the quantification of sinococuline in human plasma and its application in phase I clinical pharmacokinetic study

A selective, highly sensitive, precise, and novel bioanalytical method has been developed and validated to quantify sinococuline, an active constituent present in the phytopharmaceutical drug product containing Cocculus hirsutus plant extract, in vivo. Chromatographic separation was achieved on a Luna Omega Polar-C18 bonded analytical column maintained at 45°C. The isocratic mobile phase consisted of methanol and ammonium formate buffer (60:40, v/v) at acidic pH with a low flow rate of 0.250 mL/min. Detection was performed on an API 4000 mass spectrometer using electrospray ionization in positive polarity and multiple reaction monitoring mode to achieve a lower limit of quantification of 1.50 ng/mL. Excellent accuracy and precision were obtained after extracting the analyte from plasma samples using a chemical analogue as an internal standard in the absence of an isotope-labeled compound. The extraction efficacy was evidenced from recovery study, and the analyte was found to be stable in plasma. Validation study demonstrated linearity with coefficient of correlation, r ≥ 0.99, and minimal matrix effect. This bioanalytical method was successfully applied to evaluate pharmacokinetic parameters of sinococuline from a phase I clinical trial of an aqueous extract of C. hirsutus in healthy human volunteers.     

Visible‐Light‐Driven Halogen Bond Donor Based Molecular Switches: From Reversible Unwinding to Handedness Inversion in Self‐Organized Soft Helical Superstructures

Visible‐light‐driven molecular switches endowing reversible modulation of the functionalities of self‐organized soft materials are currently highly sought after for fundamental scientific studies and technological applications. Reported herein are the design and synthesis of two novel halogen bond donor based chiral molecular switches that exhibit reversible photoisomerization upon exposure to visible light of different wavelengths. These chiral molecular switches induce photoresponsive helical superstructures, that is, cholesteric liquid crystals, when doped into the commercially available room‐temperature achiral liquid crystal host 5CB, which also acts as a halogen‐bond acceptor. The induced helical superstructure containing the molecular switch with terminal iodo atoms exhibits visible‐light‐driven reversible unwinding, that is, a cholesteric–nematic phase transition. Interestingly, the molecular switch with terminal bromo atoms confers reversible handedness inversion to the helical superstructure upon irradiation with visible light of different wavelengths. This visible‐light‐driven, reversible handedness inversion, enabled by a halogen bond donor molecular switch, is unprecedented.     

Designing hierarchical NiCo2S4 nanospheres with enhanced electrochemical performance for supercapacitors

Journal of Solid State Electrochemistry - Hierarchical nanostructure materials have attracted significant attention due to their fascinating structural features for the application of...     

Greener route for microwave enhanced syntheses of bioactive 1,5-benzodiazepines using heterogeneous calcium ferrite/graphene oxide nanocomposite as a novel and sustainable catalyst

In the present paper, a novel and benign protocol for microwave enhanced one pot syntheses of 2,3-dihydro-1,5 benzodiazepine derivatives from substituted acetophenones, aryl-aldehydes and o-phenylene diamine using heterogeneous calcium ferrite/graphene oxide (CF/GO) nanocomposite has been reported. The catalyst was prepared by ultrasonication method and characterized by spectral and analytical techniques. The CF/GO nanocomposite was employed for environmentally benign synthesis of 2,3-dihydro-1,5 benzodiazepines. The synthesized benzodiazepine derivatives were screened for their antimicrobial activities against various bacteria and fungi. The present synthetic strategy offered several advantages such as excellent yields in short span of time, simple modus operandi, ease of isolation and purification of products, simple recovery and reusability of the catalyst. A tentative mechanism for synthesis of 2,3-dihydro-1,5 benzodiazepine using CF/GO nanocatalyst has also been proposed.     

Galactose-Grafted 2D Nanosheets from the Self-Assembly of Amphiphilic Janus Dendrimers for the Capture and Agglutination of Escherichia coli

High aspect ratio, sugar-decorated 2D nanosheets are ideal candidates for the capture and agglutination of bacteria. Herein, the design and synthesis of two carbohydrate-based Janus amphiphiles that spontaneously self-assemble into high aspect ratio 2D sheets are reported. The unique structural features of the sheets include the extremely high aspect ratio and dense display of galactose on the surface. These structural characteristics allow the sheet to act as a supramolecular 2D platform for the capture and agglutination of E. coli through specific multivalent noncovalent interactions, which significantly reduces the mobility of the bacteria and leads to the inhibition of their proliferation. Our results suggest that the design strategy demonstrated here can be applied as a general approach for the crafting of biomolecule-decorated 2D nanosheets, which can perform as 2D platforms for their interaction with specific targets.     

Synthesis and biological evaluation of some new class of benzothiazole–pyrazole ligands containing arene ruthenium,rhodium and iridium complexes

Transition Metal Chemistry - Metal complexes 1–9 have been synthesized by reacting the benzothiazole–pyrazole derivative ligands (L1, L2 and L3) with the metal precursors of ruthenium...