Drug-dendrimer supramolecular complexation studied from molecular dynamics simulations and NMR spectroscopy

Fully atomistic molecular dynamics (MD) simulations and NMR spectroscopy were employed to get insights about the molecular details of drug-dendrimer supramolecular association phenomena, using piroxicam (PRX) and the third generation poly(amido amine) (PAMAM-G3) dendrimer as model systems. Theoretical results concerning the complex stoichiometry suggest that PRX forms drug-dendrimer complexes of the type 24:1 at pH 7.0. This result was validated with the experimental quantities obtained from aqueous solubility profiles, which led to an empiric stoichiometry of 23:1 for the PRX:PAMAM-G3 system. The predicted binding mode between PRX and PAMAM-G3 accounts for the preferred encapsulation of the drug inside dendrimer cavities, which is mainly driven by van der Waals and hydrogen bonding interactions, and to a lesser extent, for the external association of the guest through electrostatic contacts with the positively charged amino groups of PAMAM periphery. The binding mode obtained from MD simulations was confirmed with 2D-NOESY experiments, which evidence the preferred internal complexation of PRX with PAMAM-G3. The predominance of internal encapsulation over external contacts in the PRX:PAMAM-G3 system differs from the general behaviour expected for acidic anionic guests, for which external electrostatic interactions with the positively charged PAMAM surface have been postulated as the most relevant factor for drug association.     

Operator Formulation of Classical Mechanics

By making use of the Weyl–Wigner–Groenewold–Moyalassociation rules, acommutative product and a new quantum bracket are constructed in the spaceof operators F(H). In this way, an isomorphism between the Lie algebra ofclassical observables (with Poisson bracket) and the Lie algebra of quantumobservables with this new bracket is established. By these observations, aformulation of classical mechanics in F(H) is obtained and is shown to be the 0 limit of the Heisenberg-picture formulation of quantum mechanics.     

Discovering Higher-Order Interactions Through Neural Information Decomposition

If regularity in data takes the form of higher-order functions among groups of variables, models which are biased towards lower-order functions may easily mistake the data for noise. To distinguish whether this is the case, one must be able to quantify the contribution of different orders of dependence to the total information. Recent work in information theory attempts to do this through measures of multivariate mutual information (MMI) and information decomposition (ID). Despite substantial theoretical progress, practical issues related to tractability and learnability of higher-order functions are still largely unaddressed. In this work, we introduce a new approach to information decomposition—termed Neural Information Decomposition (NID)—which is both theoretically grounded, and can be efficiently estimated in practice using neural networks. We show on synthetic data that NID can learn to distinguish higher-order functions from noise, while many unsupervised probability models cannot. Additionally, we demonstrate the usefulness of this framework as a tool for exploring biological and artificial neural networks.     

Microemulsion electrokinetic chromatography as a suitable tool for lipophilicity determination of acidic,neutral, and basic compounds

In the present work, several MEEKC systems are studied to assess their suitability for lipophilicity determination of acidic, neutral, and basic compounds. Thus, several microemulsion compositions over a wide range of pH values (from 2.0 to 12.0), containing heptane, 1?butanol and different types and amounts of surfactant (SDS or sodium cholate: from 1.3 to 3.3%) are characterized using Abraham's solvation model. The addition of acetonitrile (up to 10%) is also studied, since it increases the resolution of the technique for the most lipophilic compounds. The system coefficients obtained are very similar to those of the 1?octanol/water, used as the reference lipophilicity index, allowing simple and linear correlations between the 1?octanol/water partition values (log P_o/w) and MEEKC mass distribution ratios (log k_MEEKC). Variations in the microemulsion composition (aqueous buffer, surfactant, concentration of ACN) did not significantly affect the similarity of the MEEKC systems to log P_o/w partition.     

Dry Reforming of Methane on a Highly‐Active Ni‐CeO2 Catalyst: Effects of Metal‐Support Interactions on C−H Bond Breaking

Ni‐CeO₂ is a highly efficient, stable and non‐expensive catalyst for methane dry reforming at relative low temperatures (700 K). The active phase of the catalyst consists of small nanoparticles of nickel dispersed on partially reduced ceria. Experiments of ambient pressure XPS indicate that methane dissociates on Ni/CeO₂ at temperatures as low as 300 K, generating CH_x and CO_x species on the surface of the catalyst. Strong metal–support interactions activate Ni for the dissociation of methane. The results of density‐functional calculations show a drop in the effective barrier for methane activation from 0.9 eV on Ni(111) to only 0.15 eV on Ni/CeO_2?x(111). At 700 K, under methane dry reforming conditions, no signals for adsorbed CH_x or C species are detected in the C 1s XPS region. The reforming of methane proceeds in a clean and efficient way.     

Multiphoton reactive surfaces using ruthenium(II) photocleavable cages

Photoreactive surfaces derived from a new photocleavable surface modification agent and with photosensitivity in the Vis and IR region are described. A ruthenium(II) caged aminosilane, [Ru(bpy)(2)(PMe(3))(APTS)](PF(6))(2), was synthesized and attached to silica surfaces. Light irradiation removed the cage and generated surface patterns with reactive amine groups. The photosensitivity of this compound under single (460 nm) and two-photon (900) excitation is demonstrated. Functional patterns with site-selective attachment of other molecular species are described.     

A non-adiabatic quantum-classical dynamics study of the intramolecular excited state hydrogen transfer in ortho-nitrobenzaldehyde

Ab initio surface-hopping dynamics calculations have been performed to simulate the intramolecular excited state hydrogen transfer dynamics of ortho-nitrobenzaldehyde (o-NBA) in the gas phase from the electronic S(1) excited state. Upon UV excitation, the hydrogen is transferred from the aldehyde substituent to the nitro group, generating o-nitrosobenzoic acid through a ketene intermediate. The semiclassical propagations show that the deactivation from the S(1) is ultrafast, in agreement with the experimental measurements, which detect the ketene in less than 400 fs. The trajectories show that the deactivation mechanism involves two different conical intersections. The first one, a planar configuration with the hydrogen partially transferred, is responsible for the branching between the formation of a biradical intermediate and the regeneration of the starting material. The conversion of the biradical to the ketene corresponds to the passage through a second intersection region in which the ketene group is formed.     

Optimized high-performance thin-layer chromatography‒bioautography screening of Ecuadorian Chenopodium quinoa Willd. leaf extracts for inhibition of α-amylase

JPC – Journal of Planar Chromatography – Modern TLC -     

The Structure of a Non-Symmetric Disordered Tetramer: A Crystallographic and Solid State Multinuclear NMR Study of the Properties of 3(5)-Ethyl-5(3)-Phenyl-1H-Pyrazole

The X-ray structure and the solid-state NMR measurements, mainly ¹⁵N CPMAS of the labelled compound, allow to determine the static and dynamic properties of 3(5)-ethyl-5(3)-phenyl-1H-pyrazole. The compound is a tetramer formed by three 5-ethyl-3-phenyl-1H-pyrazole and one 3-ethyl-5-phenyl-1H-pyrazole tautomers in dynamic equilibrium with the complementary situation.     

Nature of the intermediates in gold(I)-catalyzed cyclizations of 1,5-enynes

The carbene or carbocationic nature of the intermediates in the gold-catalyzed cycloisomerization of 1,5-enynes can be revealed, depending on the ligands on the gold catalysts. Gold complexes with highly electron-donating ligands promote reactions that proceed via intermediates with carbene-like character, leading to products with a bicyclo[3.1.0]hexene skeleton. The intermediate cyclopropyl endo-gold carbenes formed in this cyclization have been trapped, for the first time, to give biscyclopropane derivatives in a reaction that proceeds in a concerted fashion, according to DFT calculations.