Gram‐Scale Synthesis of Chiral Cyclopropane‐Containing Drugs and Drug Precursors with Engineered Myoglobin Catalysts Featuring Complementary Stereoselectivity

Engineered hemoproteins have recently emerged as promising systems for promoting asymmetric cyclopropanations, but variants featuring predictable, complementary stereoselectivity in these reactions have remained elusive. In this study, a rationally driven strategy was implemented and applied to engineer myoglobin variants capable of providing access to 1‐carboxy‐2‐aryl‐cyclopropanes with high trans‐(1R,2R) selectivity and catalytic activity. The stereoselectivity of these cyclopropanation biocatalysts complements that of trans‐(1S,2S)‐selective variants developed here and previously. In combination with whole‐cell biotransformations, these stereocomplementary biocatalysts enabled the multigram synthesis of the chiral cyclopropane core of four drugs (Tranylcypromine, Tasimelteon, Ticagrelor, and a TRPV1 inhibitor) in high yield and with excellent diastereo‐ and enantioselectivity (98–99.9% de; 96–99.9% ee). These biocatalytic strategies outperform currently available methods to produce these drugs.     

Correlation of global electrophilicity with the activation energy in single-step concerted reactions

The experimental energy of activation (Ea) of the single-step concerted oxidation process of aliphatic primary alcohols by quinolinium bromochromate (QBC) are correlated with the theoretically evaluated global electrophilicity values (w) [as proposed by Parr et al. (J. Am. Chem. Soc. 1999, 121, 1922)]. Conceptual justification in favor of correlating w of the substrate with Ea involved in a single-step concerted reaction is also discussed. The evaluated w values at HF/cc-pVTZ and MP2/6-31G(d,p) methods are found to be as expected (when we consider structural aspects), although there are some inconsistencies in other methods [e.g., HF/6-31G(d,p), B3LYP/cc-pVTZ, BLYP/dnp, PW91/dnp, PWC/dnp, VWN/dnp]. The reasons for the inconsistencies, even with a superior B3LYP/cc-pVTZ method, are discussed thoroughly. It is observed that the higher the value of w, the more the value of Ea involved in the process of oxidation of primary alcohols by QBC. The present study also reveals that the apparent success of insignificant (i.e., much smaller) local electrophilicity values (S+O(OH)), evaluated using Hirshfeld population analysis (HPA), in explaining observed trend of experimental Ea values turns out to be ambiguous when more significant (i.e., much larger) local nucleophilicity values (S-O(OH)) are also compared. This is evident from the corresponding correlation coefficient values.     

Quantitative analysis of complex peptide mixtures using FTMS and differential mass spectrometry

Label-free LC-MS profiling is a powerful quantitative proteomic method to study relative peptide abundances between two or more biological samples. Here we demonstrate the use of a previously described comparative LC-MS method, differential mass spectrometry (dMS), to analyze high-resolution Fourier transform mass spectrometry (FTMS) data for detection and quantification of known peptide differences between two sets of complex mixtures. Six standard peptides were spiked into a processed plasma background at fixed ratios from 1.25:1 to 4:1 to make two sets of samples. The resulting mixtures were analyzed by microcapillary LC-FTMS and dMS. dMS successfully identified five out of the six peptides as statistically significant differences (p 相似文献   

[Cu2(en)2(N3)4]n – A new member in the family of copper(II)-azido assemblies: structural and magnetic studies

A copper(II) complex with ethylene diamine and azide, viz., [Cu₂(en)₂(N₃)₄]_n has been isolated under self-assembling conditions and characterized both structurally and magnetically in order to probe the role of reactant molar ratios in generating supramolecular assemblies with strong magnetic interactions toward achieving molecule-based magnets as a long-term objective. The title structure with ferromagnetic interactions is an intermediate member in the family of copper-azido assemblies involving ethylene diamine, obtained by systematic modifications in the reactant molar ratios, highlighting the inherent difficulty in controlling the final solid formation and potential of the delicate equilibrium conditions in directing supramolecular structures, which may display interesting structure-correlated properties. The structure is a chain of μ-1,1 bridged dimers of Cu2, connected to Cu1 through μ-1,3 azide bridges, leading to a rail-road arrangement of polymeric chains. Two such parallel chains are further linked to each other through Cu3, which is connected to Cu2′ of the dimer, through asymmetric end-on μ-1,1 azide bridges, resulting in a 2-D network in the unit cell. The magnetic behavior revealed ferromagnetic interactions in Cu(II) pairs and is dominated by overall antiferromagnetic interactions within the network.     

Aptamer based voltammetric biosensor for the detection of <Emphasis Type="Italic">Mycobacterium tuberculosis</Emphasis> antigen MPT64

The authors report an aptaelectrode based on graphene modified iron-oxide chitosan hybrid (CHIT-IO-GR) nanocomposite film deposited on fluorine tin oxide (FTO) for the detection of the Mycobacterium tuberculosis specific antigen MPT64. The biotinylated DNA aptamer sequence specific to the MPT64 was immobilized onto the CHIT-IO-GR/FTO electrode by using streptavidin-biotin interactions. XRD, FT-IR, FE-SEM and electrochemical studies were applied to monitor the steps of the fabrication. The aptaelectrode, operated best at typical voltage of 0.44 V, exhibited a limit of detection (LOD) of 0.9 fg?mL^?1 within 20 min. The biosensor retained about 80% of its initial activity after 10 uses. The potential application of the aptasensor was established by spike-in studies to obtain recoveries between 83 and 95%.

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Graphical abstract An electrochemical aptaelectrode based on nanocomposite consisting of chitosan (CHIT), iron-oxide nanoparticles (IO) and functionalized graphene (GR) has been fabricated to detect M. tb antigen MPT64 with an LOD of 0.9 fg?mL^?1 within 20 min.

     

Effects of yttrium substitution on structural and electrical properties of barium zirconate titanate ferroelectric ceramics

In the present study, structural, dielectric and ferroelectric properties of Ba_1?3x/2Y_x Zr_0.025Ti_0.975O₃ ferroelectric ceramics have been investigated. The compound was synthesized using solid state reaction technique. The effect of yttrium substitution on structural, dielectric and ferroelectric properties was studied using X-ray diffractometer, scanning electron microscopy (SEM), LCR meter and P–E loops. Phase analysis shows the formation of secondary phase YTi₂O₆ for Y ≥ 2.5 mol% substitution. The microstructural investigation shows that Y substitution significantly reduces the grain size. An increase in Y content up to 2.5 mol% increases the Curie temperature (T_c) initially but decreases subsequently. The maximum dielectric constant at T_c has been observed for 2 mol% Y substitution and with further increase in Y content the dielectric constant decreases considerably. The solubility limit is found to be 2.5 mol% of Y and after that some of the yttrium atoms enter B-sites and leading to the formation of the secondary phase. The P–E loop studies show that there is an increase in the coercive field with increasing Y content.     

Synthesis and antibacterial activity of novel series of 2‐(p‐tolyloxy)‐3‐(5‐(pyridin‐4‐yl)‐1,3,4‐oxadiazol‐2‐yl)quinoline

A new series of 2‐(p‐tolyloxy)‐3‐(5‐(pyridin‐4‐yl)‐1,3,4‐oxadiazol‐2‐yl)quinoline were synthesized from oxidative cyclization of N′‐((2‐(p‐tolyloxy)quinoline‐3‐yl)methylene)isonicotinohydrazide in DMSO/I₂ at reflux condition for 3–4 h. The structures of the new compounds were confirmed by elemental analyses as well as IR, ¹H‐NMR, and mass spectral data. All the synthesized compounds were screened for their antibacterial activities against various bacterial strains. Several of these compounds showed potential antibacterial activity. J. Heterocyclic Chem., (2011).     

Regenerable Fe-Mn-ZnO/SiO2 sorbents for room temperature removal of H2S from fuel reformates: performance, active sites, Operando studies

Fe- and Mn-promoted H(2)S sorbents Fe(x)-Mn(y)-Zn(1-x-y)O/SiO(2) (x, y = 0, 0.025) for desulfurization of model fuel reformates at room temperature were prepared, tested and characterized. Sulfur uptake capacity at 25 °C significantly exceeds that of both commercial unsupported ZnO sorbents and un-promoted supported ZnO/SiO(2) sorbents. Sulfur capacity and breakthrough characteristics remain satisfactory after multiple (～10) cycles of adsorption/regeneration, with regeneration performed by a simple and robust heating in air. XRD shows that both "calcined" and "spent" sorbents contain nano-dispersed ZnO, and XPS confirms conversion of ZnO to ZnS. "Calcined" sorbent contains Fe(3+) and Mn(3+) that are reduced to Mn(2+) upon reaction with H(2)S, but not with H(2). Operando ESR is used for the first time to study dynamics of reduction of Mn(3+) promoter sites simultaneously with measuring sulfidation dynamics of the Fe(x)-Mn(y)-Zn(1-x-y)O/SiO(2) sorbent. Fe cations are believed to occupy the surface of supported ZnO nanocrystallites, while Mn cations are distributed within ZnO.     

Solution-phase synthesis of silver nanodiscs in HPMC-matrix and simulation of UV-vis extinction spectra using DDA based method

Present investigation demonstrates a very simple seed-mediated route, using hydroxypropyl methyl cellulose (HPMC) as stabilizing agent, for the synthesis of silver nanodiscs in aqueous solution. Central to the concept of seed-mediated growth of nanoparticles is that small nanoparticle seeds serve as nucleation centres to grow nanoparticles to a desired size and shape. It is found that the additional citrate ions in the growth solution play the pivotal role in controlling the size of silver nanodiscs. Similar to the polymers in the solution, citrate ions could be likewise dynamically adsorbed on the growing silver nanoparticles and promote the two-dimensional (2D) growth of nanoparticles. Morphological, structural, and spectral changes associated with the seed-mediated growth of the nanoparticles in the presence of HPMC are characterized using UV–vis and TEM spectroscopic studies. Metal nanoparticles have received increasing attention for their peculiar capability to control local surface plasmon resonance (LSPR) when interacting with incident light waves. Extensive simulation study of the UV–vis extinction spectra of our synthesized silver nanodiscs has been carried out using discrete dipole approximation (DDA) methodology.     

New Insights into Optoelectronic Features of Eu(III) Complexes with Heterocyclic Ligand for Advanced Optical Applications

Our present technological society needs the assistance of lanthanide luminescence in almost every field to meet the global energy demands. In present research work we have synthesized five (one binary and four ternary) 5-(4-methylphenyl)-2- furoic acid based Eu(III) complexes with ancillary ligands, namely, aqua (H₂O), neocuproine (neo), 2, 2’-bipyridyl (bipy), bathophenanthroline (batho) and 1, 10-phenanthroline (phen). The spectroscopic analysis and photophysical features are characterized by the use of different investigative techniques. All the findings obtained from EDAX, elemental (CHN) analysis, FT-IR, NMR, UV–visible spectroscopy declared the coordination of ligand binding sites with the europium ion. These Eu(III) complexes possess good thermal stability and excellent optoelectronic features as predicted with the help of TGA and PL analysis. Diffuse reflectance spectral studies confirm their applications in the wide band gap semiconductors. The Judd–Ofelt analysis and monoexponential behavior of lifetime reveals the existence of asymmetric and single local environment around europium ion. All the complexes show sharp red emission validated by CIE color coordinates, color purity, asymmetric ratio and CCT values. SEM analysis tells that the bulk of these complexes comprised of spherical shaped particles with uniform distribution.