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Enzyme-Mediated Cross-Benzoin Reaction of Highly Enolizable Aldehydes and Aryl Aldehydes for Acess to Chiral Phosphonates
No full textEnzymatic catalysis has emerged as an attractive technology for organic synthesis but remains in its infancy for constructing biologically-relevant chiral phosphonates. Here, we disclose a highly chemo- and enantioselective reactions between highly enolizable 2-phosphonate aldehydes and aryl aldehydes for synthesis of chiral phosphonates. This reaction mediated by PfBAL or its mutant A28G features the first example of cross-benzoin reaction involving highly enolizable aldehydes, an elusive challenge previously. Unlike the small molecule NHC-mediated process that give complex mixture of multiple adducts, our enzymatic process selectively gives biologically active hydroxyl ketone-containing phosphonate products in excellent yields and enantioselectivities. The chiral phosphonate products can be obtained on gram scales and carry rich reactivities for further downstream transformation to afford diverse molecules, which will bring more opportunity to the development of novel C-P drugs. This work opened a new avenue in the development of novel cross-benzoin reaction and will stimulate the widespread application of cross-benzoin in organic synthesis
Photoswitchable arylazopyrazoles surfactants at the water-air interface: a microscopic perspective
No full textSurfactants play an important role in modifying the properties of water-air interfaces. However, information on the microscopic behavior of the mechanisms is scarce. Here, we combine information from molecular dynamics simulations, surface tensiometry, and vibrational sum frequency generation spectroscopy to study the behavior of arylazopyrazole (AAP) as a surfactant. This combination of the experimental techniques allows a direct relation between surface tension and surface excess rather than just bulk concentration. Specifically, we compare the case with (O-AAP) and without (H-AAP) the addition of an octyl carbon chain, as well as for two different isomers (E and Z). From the simulations of these four systems, we see that a stronger cluster formation is accompanied by a weaker reduction of the surface tension for intermediate surface excesses. In some cases, even a small but noticeable maximum in the surface tension isotherm is observed. This correlation is expected from the general properties of the Frumkin isotherm. Both the addition of the carbon chain and the consideration of the E isomer compared to the Z isomer increase this effect. Although the experimental data of the surface tension vs. surface excess do not show a maximum, the general features of the surface tension isotherm are consistent between experiment and simulation. Evidence is also provided that it is primarily the interaction of the aromatic benzene rings that determines the strength of the surfactant interactions
PCTpro: A Machine learning model for rapid prediction of Pressure-Composition-Temperature (PCT) isotherms
No full textWe present a machine-learning powered Pressure-Composition-Temperature isotherm Predictor (PCTpro) for metal compositions. To train the PCTpro, an experimental database of PCT isotherms (MH-PCT) is built from published literature. The database comprises over 14,000 data points extracted from 237 PCT isotherms, representing 138 distinct compositions. The dataset encom- passes more than 25 elements and spans a broad spectrum of absorption tem- peratures (263-653 K) and hydrogen pressures (0.001 to 40 MPa). The feature set includes weighted average of elemental properties, hydriding properties, and experimental parameters like absorption temperature and hydrogen pressure. The comprehensive feature set equips PCTpro to predict the PCT isotherms for a given composition. The model is validated on a wide range of alloy fam- ilies and its predictions are consistent with experimental results. The model also captures temperature-dependent variations in plateau pressure, enabling determination of enthalpy and entropy of hydride formation through Van’t Hoff plots. We also demonstrate that training PCTpro on a subset of relevant data provides improved PCT isotherm prediction. Hence, PCTpro can be used as an ML tool for guiding PCT experiments, offering PCT isotherm predictions and valuable thermodynamic insights into materials suitable for solid-state hydrogen storage
Chemical composition, antileishmanial, and antifungal activi-ties of essential oils from Cinnamomum cassia bark, Schinus molle dried leaves and their blends
No full textThis study reports on the chemical composition and antileishmanial and anticandidal activities of essential oils (EOs) distilled from Schinus molle dried leaves (SM-EO), Cinnamomum cassia branch bark (CC-EO) and their blends against promastigote forms of Leishmania (Leishmania) ama-zonensis and nine Candida strains. Major constituents of SM-EO were spathulenol (26.93%), β-caryophyllene (19.90%), and caryophyllene oxide (12.69%), whereas cinnamaldehyde (60.11%), cinnamyl acetate (20.90%) and (E)-cis-2-methoxycinnamic acid (10.37%) were predominant in CC-EO. SM-EO (IC50 = 21.45 µg/mL) and CC-EO (IC50 = 23.27 µg/mL) displayed good activity against L. amazonensis. SM-EO and CC-EO also proved to be good or moderate activity against nine Can-dida strains, with Minimum Inhibitory Concentration (MIC) values ranging from 31.25 to 250 µg/mL. While the three SM-EO and CC-EO blends were not more active than the EOs tested in-dividually, they exhibited remarkably high antileishmanial activity, with IC50 values ranging between 3.12 and 7.04 µg/mL, which is very similar to the IC50 of amphotericin B (positive con-trol). These results show that SM-EO, CC-EO, and their blends may be considered to participate in the formulation of drugs with antileishmanial and antifungal activities
Synthesis of Fluorinated Spiroindolenines by Transition Metal-Catalyzed Indole Dearomatizations
No full textA new strategy to access fluorinated spiroindolenines has been developed, involving a selective functionalization of indoles with fluorinated moieties and subsequent catalytic dearomatization. Trifluomethylthio (SCF3), diethyl phosphono(difluoromethyl)thio (SCF2P(O)(OEt)2) and (phenylsulfonyl)difluoromethyl (CF2SO2Ph) groups were successfully embedded at the C2 position of indole derivatives substituted with alkynes, allenes, and allyl carbonate moieties at the C3 position. A gold-catalyzed cycloisomerization gave access to six spiroindolenines, and an enantioselective palladium catalyzed cyclization provided 10 fluorinated spirocyclic products with up to 77% ee
Structure-activity relationship study of splicing modulators on Hsh155/SF3B1 through chemical synthesis and yeast genetics
No full textMeayamycins are synthetic analogs of the natural product FR901464 and exhibit potent anticancer activity against human cancers. They bind SF3B1 and PHF5A, components of the human spliceosome, and alter pre-mRNA splicing. Detailed analysis of the active site led us to investigate a narrow pocket within the binding site which surrounds the ,-unsaturated amide portion of meayamycin. We describe the synthesis and biological activity of two new analogs bearing a methyl substituent on the or position of the amide. With these analogs, we investigated the discrete interactions within the narrow region of SF3B1 using a human/yeast chimeric SF3B1 protein and found the V1078 residue of SF3B1 affects compound binding at the amide moiety
Core-electron contributions to the magnetic response of molecules with heavy elements and their significance in aromaticity assessments
No full textThis study delves into the magnetic response of core electrons and their influence on the global magnetic response of systems planar and three-dimensional containing heavy elements, employing the removing valence electron (RVE) approximation. We also explore electronic aromaticity indices to understand the potential role of core electrons on electron delocalization in absence of an external perturbation. The study reveals that core electrons significantly contribute to the overall magnetic response, especially to the magnetic shielding, affecting the interpretation of aromaticity. In contrast, the calculation of the electronic aromaticity indices suggests a negligible participation of the core electrons to the electron delocalization. Despite its widespread use, the study emphasizes caution in labeling systems as strongly aromatic based solely on shielding function computations. It is noteworthy to emphasize the limitations associated with each aromaticity criterion, particularly in the context of magnetic shielding function calculations, the core-electron effect contamination is undeniable. Hence, the integration of various criteria becomes imperative for attaining a comprehensive understanding of magnetic responses within complex systems
CONDUCTOR, a fast, efficient and robust tool for continuum solvation computations for macromolecules
No full textThis introduces CONDUCTOR, an algorithm for computing solvation effects for large molecules using the continuum approximation. While we represent electrostatic polarization by the mechanism of induced surface charge, we avoid the explicit computation of a Green function as found with the Boundary Element Method (BEM). Instead, we assume as a starting point the conducting approximation for aqueous solvent, and adjust the induced polarization charge defined on the molecular surface, so as to force the electric potential to zero at field points positioned on the solvent side of the surface. The charge density for finite external dielectric constant can then be approximated using a simple perturbation approach. The reaction field arising from the induced charge distribution is used to compute the contribution of solvent to the electrostatic potential and forces for the molecular fixed charges. The method is robust, being relatively insensitive to small defects or singularities in the molecular surface, and can be extended to periodic structures such as membranes. Computations for proteins with nearly 300 residues can be carried out in about ten minutes on inexpensive server hardware. We compare the results of our new approach to the conventional Boundary Element Method, and find them equivalent, and by some measures superior, to the BEM, and achieved with much less computational expense
Binding Study of Berenil and d(CGCGAATTCGCG)2 and d(CGCAAATTTGCG)2 DNA Dodecamers by Isothermal Titration Calorimetry and Molecular Docking Simulations
No full textBerenil, an anti-trypanosomal agent, is a dicationic bis-benzamidine that has been classified as a minor groove binding ligand in AT-rich regions of DNA. However, previous studies have suggested that berenil can bind to various DNA double strands exhibiting both intercalative and minor groove binding modes. In this work we present a biophysical study analyzing the interaction between berenil and two synthetic DNAs that suggests that this molecule shows a mixed bind behaviour when binding to double stranded DNA. It is possible that more than one berenil molecule can bind to DNA dodecamers double strands. The second molecule may be interacting through intercalation. The data from isothermic calorimetric titrations at 298 K were analyzed by Wiseman Isotherm and classical thermodynamic equations. Thermodynamic parameters for complexation between the two DNAs were obtained by ITC experiments and Autodock calculations. The results show that the intercalative effect of the molecule is entropically driven
A Simple and Efficient Preparation of High-Purity and High-Yield Unsolvated Lithium Dodecaborate
No full textWe present a new and simple approach for the synthesis of lithium dodecaborate (Li2B12H12) in high purity and high yield, based on the reaction between borane dimethyl sulfide complex (DMS·BH3) and lithium borohydride (LiBH4) in glymes (monoglyme or diglyme). The reaction can conveniently be performed either in a Schlenk flask with or without reflux, or in an autoclave. This strategy exhibits various advantages over existing methods, including high product purity, high reaction yields (up to 96%), and operational simplicity. The enclosed system provided by an autoclave is shown to be more favorable for the synthesis of the B12H122– anion and enables obtaining the highest yields. The reaction mechanism has been investigated by 11B NMR spectroscopy, revealing a stepwise formation of B2H7−, B3H8−, B9H14−, B11H14− and B11H132− intermediates. This synthesis method is extended to the M2B12H12 (M = Li, Na, K) series, yielding metal dodecaboranes coordinated with glymes, characterized by single crystal X-ray diffraction. We show that glymes can be removed through simple exchange with weaker coordinating solvents like DMSO or H2O, followed by heating under vacuum