On the reactions of methyl radicals with nitrilotris(methylenephosphonic-acid) complexes in aqueous solutions

Abstract

The reactions of methyl radicals with M^II-(ntp)(H₂O)₂ complexes were studied. The formation of an unstable intermediate (ntp)(H₂O)M^III-CH₃ is observed. This reaction is an equilibrium process, i.e. the M^III-C bond decomposes via homolysis. The (ntp)(H₂O)M^III-CH₃ complexes isomerize to a more stable form. The results compared to those obtained in analogous reactions of the M^II-(nta)(H₂O)₂ complexes were shown to be similar with one exception – for the nta complexes no isomerization process is observed.     

Synthesis and Biological Evaluation of Novobiocin Core Analogues as Hsp90 Inhibitors

Development of heat shock protein 90 (Hsp90) C‐terminal inhibitors has emerged as an exciting strategy for the treatment of cancer. Previous efforts have focused on modifications to the natural products novobiocin and coumermycin. Moreover, variations in both the sugar and amide moieties have been extensively studied, whereas replacements for the coumarin core have received less attention. Herein, 24 cores were synthesized with varying distances and angles between the sugar and amide moieties. Compounds that exhibited good anti‐proliferative activity against multiple cancer cell lines and Hsp90 inhibitory activity, were those that placed the sugar and amide moieties between 7.7 and 12.1 Å apart along with angles of 180°.     

Tuning Chemical and Physical Properties of Phosphorus Corroles for Advanced Applications

Although the affinity of metallocorroles to axial ligands is quite low, this is not the case when the chelated element is phosphorus. This work is hence focused on the mechanism of ligand exchange of six-coordinate phosphorus corroles as a tool for affecting their chemical and physical properties. These fundamental investigations allowed for the development of facile methodologies for the synthesis of a large series of complexes and the establishment of several new structure/activity profiles that may be used to understand and predict spectroscopic features and for tailor-made modification of photophysical and electrochemical properties. This is exemplified by the facile access to complexes with terminal groups that are of large potential for practical applications based on click chemistry, optical imaging, and surface science.     

CLT for Random Walks of Commuting Endomorphisms on Compact Abelian Groups

Let \(\mathcal S\) be an abelian group of automorphisms of a probability space \((X, {\mathcal A}, \mu )\) with a finite system of generators \((A_1, \ldots , A_d).\) Let \(A^{{\underline{\ell }}}\) denote \(A_1^{\ell _1} \ldots A_d^{\ell _d}\), for \({{\underline{\ell }}}= (\ell _1, \ldots , \ell _d).\) If \((Z_k)\) is a random walk on \({\mathbb {Z}}^d\), one can study the asymptotic distribution of the sums \(\sum _{k=0}^{n-1} \, f \circ A^{\,{Z_k(\omega )}}\) and \(\sum _{{\underline{\ell }}\in {\mathbb {Z}}^d} {\mathbb {P}}(Z_n= {\underline{\ell }}) \, A^{\underline{\ell }}f\), for a function f on X. In particular, given a random walk on commuting matrices in \(SL(\rho , {\mathbb {Z}})\) or in \({\mathcal M}^*(\rho , {\mathbb {Z}})\) acting on the torus \({\mathbb {T}}^\rho \), \(\rho \ge 1\), what is the asymptotic distribution of the associated ergodic sums along the random walk for a smooth function on \({\mathbb {T}}^\rho \) after normalization? In this paper, we prove a central limit theorem when X is a compact abelian connected group G endowed with its Haar measure (e.g., a torus or a connected extension of a torus), \(\mathcal S\) a totally ergodic d-dimensional group of commuting algebraic automorphisms of G and f a regular function on G. The proof is based on the cumulant method and on preliminary results on random walks.     

Cannabis-Derived Compounds Cannabichromene and Δ9-Tetrahydrocannabinol Interact and Exhibit Cytotoxic Activity against Urothelial Cell Carcinoma Correlated with Inhibition of Cell Migration and Cytoskeleton Organization

Cannabis sativa contains more than 500 constituents, yet the anticancer properties of the vast majority of cannabis compounds remains unknown. We aimed to identify cannabis compounds and their combinations presenting cytotoxicity against bladder urothelial carcinoma (UC), the most common urinary system cancer. An XTT assay was used to determine cytotoxic activity of C. sativa extracts on T24 and HBT-9 cell lines. Extract chemical content was identified by high-performance liquid chromatography (HPLC). Fluorescence-activated cell sorting (FACS) was used to determine apoptosis and cell cycle, using stained F-actin and nuclei. Scratch and transwell assays were used to determine cell migration and invasion, respectively. Gene expression was determined by quantitative Polymerase chain reaction (PCR). The most active decarboxylated extract fraction (F7) of high-cannabidiol (CBD) C. sativa was found to contain cannabichromene (CBC) and Δ9-tetrahydrocannabinol (THC). Synergistic interaction was demonstrated between CBC + THC whereas cannabinoid receptor (CB) type 1 and type 2 inverse agonists reduced cytotoxic activity. Treatments with CBC + THC or CBD led to cell cycle arrest and cell apoptosis. CBC + THC or CBD treatments inhibited cell migration and affected F-actin integrity. Identification of active plant ingredients (API) from cannabis that induce apoptosis and affect cell migration in UC cell lines forms a basis for pre-clinical trials for UC treatment.     

Aggregation Mode,Host-Guest Chemistry in Water,and Extraction Capability of an Uncharged,Water-Soluble,Liquid Pillar[5]arene Derivative

An uncharged, water-soluble per-ethylene-glycol pillar[5]arene derivative ( 1 ) was synthesized and its aggregation mode, host-guest chemistry in water and extraction ability was explored. Compound 1 is a liquid at room temperature; in water, limited self-aggregation occurred at high concentrations as deduced from diffusion NMR and dynamic light scattering. Compound 1 forms pseudo-rotaxane-like 1 : 1 host-guest complexes with 1,ω-di-substituted alkanes with association constants on the order of 10³–10⁴ m ⁻¹. Interestingly, NMR experiments showed that the guest location relative to the host ring system differs among the different complexes. In proof-of-concept experiments, compound 1 was shown to extract structurally related organic compounds from benzene into water with significant selectivity. Compound 1 , which is a liquid at room temperature and has only limited interactions with its side arms, can, in principle, be regarded as a complement to or as a kind of type I porous liquid.     

The influence of finite rates of temperature change in the creepT-jump experiment

Summary General equations for nonisothermal creep of a linear viscoelastic solid are presented. Both the time dependent strain and strain rate are predicted for an arbitrary temperature history. The creepT-jump experiment (imposition of a sudden temperature change on a creeping specimen) is analyzed using these equations in order to understand the influence of non-instantaneous temperature changes on the experimental observations. It is shown that an increase in the time required to impose the temperature change causes an increase in the activation energy,H _exp, determined via creepT-jump. This effect is most pronounced for materials with large activation energies. Appropriate extrapolation techniques can be used to obtain the result expected for an instantaneous temperature change. Verification of the theoretical prediction was obtained from isothermal and nonisothermal creep experiments on polymethylmethacrylate in the linear viscoelastic region. The activation energy for a nearly instantaneous temperature change was 43 ± 2 kcal/mol. As the rise time of the temperature change was increased to 600 seconds,H _exp increased to 70 ± 2 kcal/mol. The effects of the rate of temperature change on other aspects of the creepT-jump experiment were also found to be in keeping with the predictions of the nonisothermal linear theory.

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Zusammenfassung Es werden allgemeine Gleichungen für das nichtisotherme Kriechen eines linear-viskoelastischen Festkörpers abgeleitet. Sowohl die zeitabhängige Dehnung als auch die Dehngeschwindigkeit werden für eine beliebige Temperaturvorgeschichte vorausgesagt. Das Kriech-T-Sprung-Experiment, d.h. die Aufbringung einer plötzlichen Temperaturänderung bei einer Kriechprobe, wird mit diesen Gleichungen analysiert, um den Einfluß von kontinuierlichen Temperaturänderungen bei experimentellen Beobachtungen verständlich zu machen. Es wird gezeigt, daß eine Verlängerung der Zeitdauer zur Erzeugung der Temperaturänderung ein Anwachsen der AktivierungsenergieH _exp, verglichen mit derjenigen beim Kriech-T-Sprung, zur Folge hat. Dieser Effekt tritt am ausgeprägtesten bei Stoffen mit großen Aktivierungsenergien auf. Angepaßte Extrapolationsmethoden lassen sich anwenden, um das für eine plötzliche Temperaturänderung erwartete Ergebnis zu erhalten. Die theoretischen Voraussagen wurden mit Hilfe isothermer und nicht-isothermer Kriechexperimente an Polymethylmethacrylat im linearviskoelastischen Bereich verifiziert. Die Aktivierungsenergie für eine nahezu plötzliche Temperaturänderung ergab sich zu 43 ± 2 kcal/mol. Wenn das Zeitintervall für die Temperaturänderung auf 600 Sekunden erhöht wurde, stiegH _exp auf 70 ± 2 kcal/mol. Die Auswirkungen der Temperaturänderungsgeschwindigkeit bezüglich anderer Gesichtspunkte beim Kriech-T-Sprung-Experiment ergeben sich ebenso in Übereinstimmung mit den Voraussagen der nicht-isothermen linearen Theorie.

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With 15 figures     

A terminally anchored polymer chain in shear flow: Self-consistent velocity and segment density profiles

The behavior of a terminally anchored freely-jointed bead-rod chain, subjected to solvent shear flow, was investigated via Brownian dynamics simulations. Previous calculations have been improved by computing the segment density and fluid velocity profiles self-consistently. The segment density distributions, components of the radius of gyration, and chain attachment shear and normal stresses were found to be sensitive to low values of shear rate. Additionally, it was found that the thickness of a model polymer layer was a strong function of the shear rate, and that the functional dependence on shear rate changed dramatically as the chain length increased. For the longest chains studied, the thickness of the model polymer layer first increased as the shear rate increased, passed through a maximum, and then decreased at high shear rates, in accordance with experimental results in theta solvents. These results suggest that a dilute or semi-dilute layer model may explain hydrodynamic behavior previously thought to be due to the entanglements that occur in dense surface bound polymer layers.Nomenclature a _i acceleration of bead i - b radius of the beads - d length of the rods connecting the chain beads - d _i vector from bead i to bead i + 1 - F _i external force applied to bead i - F _i ^b external force on bead i due to Brownian motion of surrounding fluid - F _i ^h external force on bead i due to viscous drag - F _i ^s external force on bead i due to surface interactions - f Stokes drag coefficient - Boltzmann's constant - L _h effective hydrodynamic thickness - m _i mass of bead i - N number of beads on a model chain - n number of chains anchored to the surface per unit surface area - P segment density distribution P pressure - Q flow in a tube with no surface bound polymer layer - Q _a flow in a tube with a surface bound polymer layer - R _g vector representation of the radius of gyration - R tube radius - r radial coordinate in the tube geometry - S _ij pair hydrodynamic interaction tensor for beads i and j - T _i internal chain force in rod i connecting beads i and i + 1 - T _X component of the surface attachment force in the direction of the fluid flow - T _y component of the surface attachment force perpendicular to the surface - T temperature - v _i velocity of the center of mass of bead i - V _if average fluid velocity at the location of bead i - v _if ⁰ fluid velocity in the absence of a polymer chain - v _if perturbation to the fluid velocity due to hydrodynamic interactions - V _b bead volume = 4 b ³/3 - scalar fluid speed in the axial direction down the tube - x axial coordinate in the tube geometry Greek symbols _w apparent shear rate - fluid viscosity - polymer layer permeability - volume fraction of space occupied by chain beads - (_w)_a chain attachment stress perpendicular to the surface - (_w)_a chain attachment stress in the plane of the surface and in the direction of fluid flow     

Homogeneous monotropic elastic rods: Normal uniform configurations and universal solutions

A number of simple solutions are obtained which are universal for an homogeneous monotropic elastic rod whose theory is based on a Cosserat-type model.

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Sommario Si ottengono alcune soluzioni semplici che sono universali per una trave omogenea monotropica la cui teoria è basata su un modello alla Cosserat.