Optimal transport in a ratchet coupled to a modulated environment: The role of Levy walks

We consider a Brownian particle in a ratchet potential coupled to a modulated environment and subjected to an external oscillating force. The modulated environment is modelled by a finite number N of uncoupled harmonic oscillators. Superdiffusive motion and Levy walks (anomalous random walks) are observed for any N and for low values of the external amplitude F. The coexistence of left and right running states enhances the power α from the time dependence of the mean square displacement (MSD). It is shown that α is twice the average of the power of the separated left and right MSDs. Normal random walks are obtained by increasing F. We show that the maximal mobility of particles along the periodic structure occurs just before superdiffusive motion disappears and Levy walks are transformed into normal random walks.     

Structure of 6-methyl-3,20-dioxo-4,6-pregnadien-17α-yl acetate,C24H32O4

The X-ray structure of 6-methyl-3,20-dioxo-4,6-pregnadien-17-yl acetate is reported. The crystals are monoclinic, space groupP2₁,Z=4,a=28.955(7),b=6.597(2),c=11.064(3) Å,/gb=90.80(2) °. The two crystallographically independent molecules have very similar overall geometries. The A rings have intermediate sofa-half-chair conformations and are bent relative to the steroid skeleton. The conformation of the 17-progesterone side chain is stabilized by the 17-ester substituent; the C(16)-C(17)-C(20)-O(20) torsion angle is –19.4(6) and –20.6(7)°.     

Structure‐Based Design of a Macrocyclic PROTAC

Constraining a molecule in its bioactive conformation via macrocyclization represents an attractive strategy to rationally design functional chemical probes. While this approach has been applied to enzyme inhibitors or receptor antagonists, to date it remains unprecedented for bifunctional molecules that bring proteins together, such as PROTAC degraders. Herein, we report the design and synthesis of a macrocyclic PROTAC by adding a cyclizing linker to the BET degrader MZ1. A co‐crystal structure of macroPROTAC‐1 bound in a ternary complex with VHL and the second bromodomain of Brd4 validated the rational design. Biophysical studies revealed enhanced discrimination between the second and the first bromodomains of BET proteins. Despite a 12‐fold loss of binary binding affinity for Brd4, macroPROTAC‐1 exhibited cellular activity comparable to MZ1. Our findings support macrocyclization as an advantageous strategy to enhance PROTAC degradation potency and selectivity between homologous targets.     

A definitive example of a geometric "entatic state" effect: electron-transfer kinetics for a copper(II/I) complex involving A quinquedentate macrocyclic trithiaether-bipyridine ligand

The quinquedentate macrocyclic ligand cyclo-6,6'-[1,9-(2,5,8-trithianonane)]-2,2'-bipyridine ([15]aneS3bpy = L), containing two pyridyl nitrogens and three thiaether sulfurs as donor atoms, has been synthesized and complexed with copper. The CuII/IL redox potential, the stabilities of the oxidized and reduced complex, and the oxidation and reduction electron-transfer kinetics of the complex reacting with a series of six counter reagents have been studied in acetonitrile at 25 degrees C, mu = 0.10 M (NaClO4). The Marcus cross relationship has been applied to the rate constants obtained for the reactions with each of the six counter reagents to permit the evaluation of the electron self-exchange rate constant, k11. The latter value has also been determined independently from NMR line-broadening experiments. The cumulative data are consistent with a value of k11 = 1 x 10(5) M(-1) s(-1), ranking this among the fastest-reacting CuII/I systems, on a par with the blue copper proteins known as cupredoxins. The resolved crystal structures show that the geometry of the CuIIL and CuIL complexes are nearly identical, both exhibiting a five-coordinate square pyramidal geometry with the central sulfur donor atom occupying the apical site. The most notable geometric difference is a puckering of an ethylene bridge between two sulfur donor atoms in the CuIL complex. Theoretical calculations suggest that the reorganizational energy is relatively small, with the transition-state geometry more closely approximating the geometry of the CuIIL ground state. The combination of a nearly constant geometry and a large self-exchange rate constant implies that this CuII/I redox system represents a true geometric "entatic state."     

The single-crystal, basal face of ice I(h) investigated with sum frequency generation

Sum frequency generation spectroscopy has been used to investigate the hydrogen-bonded region of single-crystal, hexagonal ice in the temperature range of 113-178 K. The temperature and polarization dependences of the signal are used in conjunction with a recent theoretical model to suggest an interpretation of the bluest and reddest of the hydrogen-bonded peaks. The reddest feature is associated with strong hydrogen bonding; the dynamic polarizability of this feature is primarily parallel to the surface. It is assigned to a cooperative motion among the companion to the free-OH and four-coordinate oscillators hydrogen bonded to dangling lone-pair molecules on the surface. The bluest hydrogen-bonded feature is similarly assigned to a cooperative motion of the OH stretch of dangling lone-pair molecules and of four-coordinate molecules in the lower half bilayer that are hydrogen bonded to free-OH molecules. Reconstruction induced strain is present at as low as 113 K. These results provide a richer picture of the ice surface than has heretofore been possible.     

Thermal stability of HfO2 nanotube arrays

Thermal stability of highly ordered hafnium oxide (HfO₂) nanotube arrays prepared through an electrochemical anodization method in the presence of ammonium fluoride is investigated in a temperature range of room temperature to 900 °C in flowing argon atmosphere. The formation of the HfO₂ nanotube arrays was monitored by current density transient characteristics during anodization of hafnium metal foil. Morphologies of the as-grown and post-annealed HfO₂ nanotube arrays were analyzed by powder X-ray diffraction (XRD), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Although monoclinic HfO₂ is thermally stable up to 2000 K in bulk, the morphology of HfO₂ nanotube arrays degraded at 900 °C. A detailed X-ray photoelectron spectroscopy (XPS) study revealed that the thermal treatment significantly impacted the composition and the chemical environment of the core elements (Hf and O), as well as F content coming from the electrolyte. Possible reasons for the degradation of the nanotube at high temperature were discussed based on XPS study and possible future improvements have also been suggested. Moreover, dielectric measurements were carried out on both the as-grown amorphous film and 500 °C post-annealed crystalline film. This study will help us to understand the temperature impact on the morphology of nanotube arrays, which is important to its further applications at elevated temperatures.     

Characterization of cyclofructan-based chiral stationary phases by linear free energy relationship

Cyclofructans (CFs), a new class of chiral selectors, have been recently introduced for application in liquid chromatography and capillary electrophoresis. So far, derivatized CFs have performed interesting separation possibilities for a variety of compounds. The current work is focused on characterization of three different CF-based chiral stationary phases (CF-based CSPs), i.e. isopropyl carbamate cyclofructan 6 (IP-CF6), R-naphthylethyl carbamate cyclofructan 6 (RN-CF6) and dimethylphenyl carbamate cyclofructan 7 (DMP-CF7). The linear free energy relationship (LFER) model was used to reveal the dominant interactions participating in the complex retention mechanism. A set of 44 different test solutes, with known solvation parameters, was used to determine the regression coefficients of the LFER equation under two mobile-phase compositions in normal separation mode. The LFER results showed that hydrogen bond acidity, hydrophobicity and dipolarity/polarizibility mostly affect the retention and separation process on the CF-based columns in the studied separation systems.     

Degradation product emission from historic and modern books by headspace SPME/GC-MS: evaluation of lipid oxidation and cellulose hydrolysis

Volatile organic compounds emitted from a several decade series of bound periodicals (1859–1939) printed on ground wood paper, as well as historical books dating from the 1500s to early 1800s made from cotton/linen rag, were studied using an improved headspace SPME/GC–MS method. The headspace over the naturally aging books, stored upright in glass chambers, was monitored over a 24-h period, enabling the identification of a wide range of organic compounds emanating from the whole of the book. The detection of particular straight chain aldehydes, as well as characteristic alcohols, alkenes and ketones is correlated with oxidative degradation of the C₁₈ fatty acid constituency of paper. The relative importance of hydrolytic and oxidative chemistry involved in paper aging in books published between 1560 and 1939 was examined by comparing the relative abundances of furfural (FUR) a known cellulose hydrolysis product, and straight chain aldehydes (SCA) produced from the oxidation of fatty acids in paper. The relative abundance of furfural is shown to increase across the 379-year publication time span. A comparison of relative SCA peak areas across the series of books examined reveals that SCA emission is more important in the cotton/linen rag books than in the ground wood books.     

Schiff bases of indoline-2,3-dione: potential novel inhibitors of Mycobacterium tuberculosis (Mtb) DNA gyrase

In the present study a series of Schiff bases of indoline-2,3-dione were synthesized and investigated for their Mtb gyrase inhibitory activity. Promising inhibitory activity was demonstrated with some of these derivatives, which exhibited IC(50) values ranging from 50-157 mM. The orientation and the ligand-receptor interactions of such molecules within the Mtb DNA gyrase A subunit active site were investigated applying a multi-step docking protocol using Molecular Operating Environment (MOE) and Autodock4 docking software. The results revealed the importance of the isatin moiety and the connecting side chain for strong interactions with the enzyme active site. Among the tested compounds the terminal aromatic ring benzofuran showed the best activity. Promising new leads for developing a novel class of Mtb gyrase inhibitors were obtained from Schiff bases of indoline-2,3-dione.