Elucidation of chiral recognition processes of macrocyclic antibiotic vancomycin

A theoretical investigation was carried out on the retention and separation of enantiomeric molecules including nonsteroidal anti-inflammatory drugs, anti-neoplastic compounds and N-derivatized amino acids by capillary electrophoresis using macrocyclic antibiotics, a new class of chiral selectors, as stationary phase. Firstly docking methods were used to study the enantiorecognition in chiral electrophoresis. The molecular dynamics simulations of the two diastereoisomer complexes were then performed in order to understand how these antibiotics recognize the enantiomers. Another approach was applied in this study to establish a quantitative structure-enantioselectivity relationship (QSER) model, able to describe the resolution of a series of chiral compounds in capillary electrophoresis using vancomycin as the resolving agent.     

Flow injection analysis simulations and diffusion coefficient determination by stochastic and deterministic optimization methods

Stochastic and deterministic simulations of dispersion in cylindrical channels on the Poiseuille flow have been presented. The random walk (stochastic) and the uniform dispersion (deterministic) models have been used for computations of flow injection analysis responses. These methods coupled with the genetic algorithm and the Levenberg–Marquardt optimization methods, respectively, have been applied for determination of diffusion coefficients. The diffusion coefficients of fluorescein sodium, potassium hexacyanoferrate and potassium dichromate have been determined by means of the presented methods and FIA responses that are available in literature. The best-fit results agree with each other and with experimental data thus validating both presented approaches.     

Model-based equipment-design for plant-based extraction processes – considering botanic and thermodynamic aspects

The growing demand for plant-based products in the food, cosmetics and pharmaceutical industry leads to the need for a systematic process and equipment-design for the potentially applicable extraction techniques. Therefore, in this article, the classification of plant-based raw materials according to their characteristics is discussed. Furthermore, physicochemical modelling via distributed plug flow approach is applied and its possible fields of application are examined. Here, especially the extraction of water from the plant-based raw material as well as the entailed effects on the equilibrium and the mass transport kinetics are concerned. In addition to that, an evaluation method for the examined and generally available equipment through spider diagram is proposed. The relation to the initially argued botanic systems is discussed in particular. The extraction of vanillin from vanilla beans serves as exemplary system for this.     

Modeling of the Simultaneous Hydrogen Evolution and Cobalt Electrodeposition

A mathematical model of simultaneous cobalt deposition and hydrogen evolution was developed and applied to the electroreduction process of 5 mM Co²⁺ ions investigated by cyclic voltammetry (CV) technique at different hydrogen ion concentrations (pH=2, 3, 4). The kinetic parameters of such a complex process were determined, and the validity of the model and its sensitivity to changes in individual parameters were verified. The relative value of the approximate standard deviation (ASD_%) was used to determine the degree of fit of the model to the experimental data. The catalytic effect of cobalt on the hydrogen evolution process was comprehensively confirmed.     

Elucidating the Binding Mode between Heparin and Inflammatory Cytokines by Molecular Modeling

Heparan sulfate (HS) interacts with a broad spectrum of inflammatory cytokines, thereby modulating their biological activities. It is believed that there is a structural-functional correlation between each protein and sugar sequences in the HS polysaccharides, however, the information in this regard is limited. In this study, we compared the binding of four inflammatory cytokines (CCL8, IL-1beta, IL-2 and IL-6) to immobilized heparin by an SPR analysis. To define the molecular base of the binding, we used a heparin pentasaccharide as representative structure to dock into the 3D-molecular structure of the cytokines. The results show a discrepancy in K_D values obtained by SPR analysis and theoretical calculation, pointing to the importance to apply more than one method when describing affinity between proteins and HS. By cluster analysis of the complex formed between the pentasaccharide and cytokines, we have identified several groups in heparin forming strong hydrogen bonds with all four cytokines, which is a significant finding. This molecular and conformational information should be valuable for rational design of HS/heparin-mimetics to interfere cytokine-HS interactions.     

Dual-Metal Electrolytes for Hybrid-Ion Batteries: Synergism or Antagonism?

The construction of hybrid metal-ion batteries faces a plethora of challenges. A critical one is to unveil the solvation/desolvation processes at the molecular level in electrolytes that ensure efficient transfer of several types of charge carriers. This study reports first results on simulations of mixed-ion electrolytes. All combinations of homo- and hetero-binuclear complexes of Li⁺, Na⁺ and Mg²⁺, solvated with varying number of ethylene carbonate (EC) molecules are modeled in non-polar and polar environment by means of first principles calculations and compared to the mononuclear analogues in terms of stability, spatial organization, charge distribution and solvation/desolvation behavior. The used PF₆⁻ counterion is shown to have minor impact on the geometry of the complexes. The desolvation energy penalty of binuclear complexes can be lowered by the fluoride ions, emerging upon the PF₆⁻ decay. These model investigations could be extended to rationalize the solvation structure and ionic mobility in dual-ion electrolytes.     

Discovery of Novel Sultone Fused Berberine Derivatives as Promising Tdp1 Inhibitors

A new type of berberine derivatives was obtained by the reaction of berberrubine with aliphatic sulfonyl chlorides. The new polycyclic compounds have a sultone ring condensed to C and D rings of a protoberberine core. The reaction conditions were developed to facilitate the formation of sultones with high yields without by-product formation. Thus, it was shown that the order of addition of reagents affects the composition of the reaction products: when sulfochlorides are added to berberrubine, their corresponding 9-O-sulfonates are predominantly formed; when berberrubine is added to pre-generated sulfenes, sultones are the only products. The reaction was shown to proceed stereo-selectively and the cycle configuration was confirmed by 2D NMR spectroscopy. The inhibitory activity of the synthesized sultones and their 12-brominated analogs against the DNA-repair enzyme tyrosyl-DNA phosphodiesterase 1 (Tdp1), an important target for a potential antitumor therapy, was studied. All derivatives were active in the micromolar and submicromolar range, in contrast to the acyclic analogs and 9-O-sulfonates, which were inactive. The significance of the sultone cycle and bromine substituent in binding with the enzyme was confirmed using molecular modeling. The active inhibitors are mostly non-toxic to the HeLa cancer cell line, and several ligands show synergy with topotecan, a topoisomerase 1 poison in clinical use. Thus, novel berberine derivatives can be considered as candidates for adjuvant therapy against cancer.     

Combined Experimental and Theoretical Insights into the Corrosion Inhibition Activity on Carbon Steel Iron of Phosphonic Acids

The inhibition effect of N,N′-phosphonomethylglycine (PMG) and vinyl phosphonic acid (VPA) on the 3% NaCl acidic solution corrosion of carbon steel iron was studied at different immersion times by potentiodynamic polarization, electrochemical impedance spectroscopy, attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy, and computational methods. It is found from the polarization studies that PMG and VPA behave as mixed-type inhibitors in NaCl. Values of charge transfer resistance (R_ct) and double layer capacitance (C_dl) in the absence and presence of inhibitors are determined. The PMG and VPA inhibitors were capable of inhibiting the corrosion process up to ≈91% and ≈85%, respectively. In the presence of PMG, the synergic effect of chlorine ions was observed. Density functional theory (DFT) was engaged to establish the adsorption site of PMG, VPA, and their deprotonated states. For studied compounds, the resulted values of E_LUMO, E_HOMO, energy gap (∆E), dipole moment (μ), electronic hardness (η), global softness (σ), electrophilic index (ω), and the electronic potential map are in concordance with the experimental data results regarding their corrosion inhibition behavior and adsorption on the metal surface.     

Towards a Computational Comparative Neuroprimatology: Framing the language-ready brain

We make the case for developing a Computational Comparative Neuroprimatology to inform the analysis of the function and evolution of the human brain.First, we update the mirror system hypothesis on the evolution of the language-ready brain by (i) modeling action and action recognition and opportunistic scheduling of macaque brains to hypothesize the nature of the last common ancestor of macaque and human (LCA-m); and then we (ii) introduce dynamic brain modeling to show how apes could acquire gesture through ontogenetic ritualization, hypothesizing the nature of evolution from LCA-m to the last common ancestor of chimpanzee and human (LCA-c). We then (iii) hypothesize the role of imitation, pantomime, protosign and protospeech in biological and cultural evolution from LCA-c to Homo sapiens with a language-ready brain.Second, we suggest how cultural evolution in Homo sapiens led from protolanguages to full languages with grammar and compositional semantics.Third, we assess the similarities and differences between the dorsal and ventral streams in audition and vision as the basis for presenting and comparing two models of language processing in the human brain: A model of (i) the auditory dorsal and ventral streams in sentence comprehension; and (ii) the visual dorsal and ventral streams in defining “what language is about” in both production and perception of utterances related to visual scenes provide the basis for (iii) a first step towards a synthesis and a look at challenges for further research.