Kinetics of wetting of a compacted powder by aqueous solutions of surface active agents

Summary The capillary rise of aqueous solutions of anionic wetting agents into a compacted powder of an organic chromium complex is discussed on the basis of the Washburn-Rideal equation expanded to account for the porous structure parameters.At the porosity 1 —/6, corresponding to the loosest packing of monodisperse spheres the penetration rate is found to be mostly governed by the effective tensions operative at the moving three phase line of contact in case no deflocculation intervenes.

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Zusammenfassung Der Kapillaraufstieg wässeriger Lösungen anionischer Netzmittel in gepreßtem Pulver eines organischen Chrom-Komplexes wird durch die erweiterte Gleichung vonWashburn-Rideal wiedergegeben, in der die Parameter der porösen Struktur mit einbezogen werden.Bei der Porosität 1 —/6, die der lockersten Anordnung gleichförmiger Kugeln entspricht, wird die Eindringgeschwindigkeit meistens durch die an der sich bewegenden Dreiphasengrenze wirkenden Grenzflächenspannungen bestimmt, wenn keine Peptisation eintritt.

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Paper presented at the XII Intern. Congr. Fat Research, Milan, September 1974.     

Targeting oncogenic protein-protein interactions by diversity oriented synthesis and combinatorial chemistry approaches

We are currently witnessing a decline in the development of efficient new anticancer drugs, despite the salient efforts made on all fronts of cancer drug discovery. This trend presumably relates to the substantial heterogeneity and the inherent biological complexity of cancer, which hinder drug development success. Protein-protein interactions (PPIs) are key players in numerous cellular processes and aberrant interruption of this complex network provides a basis for various disease states, including cancer. Thus, it is now believed that cancer drug discovery, in addition to the design of single-targeted bioactive compounds, should also incorporate diversity-oriented synthesis (DOS) and other combinatorial strategies in order to exploit the ability of multi-functional scaffolds to modulate multiple protein-protein interactions (biological hubs). Throughout the review, we highlight the chemistry driven approaches to access diversity space for the discovery of small molecules that disrupt oncogenic PPIs, namely the p53-Mdm2, Bcl-2/Bcl-xL-BH3, Myc-Max, and p53-Mdmx/Mdm2 interactions.     

Anti-Ageing Potential of S. euboea Heldr. Phenolics

In recent years, the use of Sideritis species as bioactive agents is increasing exponentially. The present study aimed to investigate the chemical constituents, as well as the anti-ageing potential of the cultivated Sideritis euboea Heldr. The chemical fingerprinting of the ethyl acetate residue of this plant was studied using 1D and 2D-NMR spectra. Isomeric compounds belonging to acylated flavone derivatives and phenylethanoid glycosides were detected in the early stage of the experimental process through 2D-NMR techniques. Overall, thirty-three known compounds were isolated and identified. Some of them are reported for the first time not only in S. euboea, but also in genus Sideritis L. The anti-ageing effect of the ethyl acetate residue and the isolated specialized products was assessed as anti-hyaluronidase activity. In silico docking simulation revealed the interactions of the isolated compounds with hyaluronidase. Furthermore, the in vitro study on the inhibition of hyaluronidase unveiled the potent inhibitory properties of ethyl acetate residue and apigenin 7-O-β-d-glucopyranoside. Though, the isomers of apigenin 7-O-p-coumaroyl-glucosides and also the 4′-methyl-hypolaetin 7-O-[6′′′-O-acetyl-β-d-allopyranosyl]-(1→2)-β-d-glucopyranoside exerted moderate hyaluronidase inhibition. This research represents the first study to report on the anti-hyaluronidase activity of Sideritis species, confirming its anti-inflammatory, cytotoxic and anti-ageing effects and its importance as an agent for cosmetic formulations as also anticancer potential.     

Predicting the solubility of xenon in n-hexane and n-perfluorohexane: a simulation and theoretical study

The solubility of xenon in n-hexane and n-perfluorohexane has been studied using both molecular simulation and a version of the SAFT approach (SAFT-VR). The calculations were performed close to the saturation line of each solvent, between 200 K and 450 K, which exceeds the smaller temperature range where experimental data are available in the literature. Molecular dynamics simulations, associated with Widom's test particle insertion method, were used to calculate the residual chemical potential of xenon in n-hexane and n-perfluorohexane and the corresponding Henry's law coefficients. The simulation results overestimate the solubility of xenon in both solvents when simple geometric combining rules are used, but are in good agreement if a binary interaction parameter is included. With the SAFT-VR approach we are able to reproduce the experimental solubility for xenon in n-hexane, using simple Lorentz-Berthelot rules to describe the unlike interaction. In the case of n-perfluorohexane as a solvent, a binary interaction parameter was introduced, taken from previous work on (xe + C₂F₆) mixtures. Overall, good agreement is obtained between the simulation, theoretical and experimental data.     

Unexpected enzyme-catalyzed regioselective acylation of flavonoid aglycones and rapid product screening

Unprecedented regioselective acylation of flavonoid aglycones was achieved using Candida antarctica lipase B (CALB). The rapid screening of product formation was performed by the use of the high resolution phenol-type OH (1)H NMR spectral region recorded after the addition of picric acid.     

Complementary segmental labeling of large RNAs: economic preparation and simplified NMR spectra for measurement of more RDCs

NMR structure determination of large RNAs is often restricted by limited RDC information caused by chemical shift degeneracy. We established a general, time- and cost-effective methodology for the preparation of 13C/15N complementary labeled RNAs from a single plasmid. Applying this method to the 25 kDa BC1-DTE RNA, we were able to resolve severe chemical shift degeneracy, thereby almost doubling the number of RDC restraints in comparison to the conventional 13C,15N uniform-labeled RNA.     

Fine-tuning of the diffusion dimension of –OH groups for high resolution DOSY NMR applications in crude enzymatic transformations and mixtures of organic compounds

A convenient DOSY methodology was developed that can be applied directly in crude reaction products or mixtures containing polyphenol organic compounds, for the rapid identification of their various components without any prior separation or isolation. The method is based on the resolution enhancement of the resonances of the –OH protons and the fine-tuning of their diffusion coefficients to the molecular diffusion coefficient; this can be achieved in DMSO-d₆ in combination with the addition of picric acid and the use of temperatures near the freezing point of the solution. This method, which does not modify the apparent molecular diffusion, allowed the recording of high resolution DOSY spectra, both in crude enzymatic reactions and mixtures of organic compounds based on the phenolic OH NMR spectral region which is much less crowded and, thus, much more informative compared to the aromatic region.     

Dynamic changes in composition of extracts of natural products as monitored by in situ NMR

The direct in situ NMR observation and quantification, based on the aldehyde –CH chemical shift region, of the inter‐conversion of secoiridoid derivatives due to temperature and solvent effects is demonstrated in complex extracts of natural products without prior isolation of the individual components. The equilibrium between the aldehyde hydrate form and the dialdehyde form of the oleuropein aglycon of an olive leaf aqueous extract in D₂O was shown to be temperature dependent. The resulting thermodynamic values of the Van't Hoff plot with ΔH^o = ?26.34 ± 1.00 kJ mol^?1 and TΔS° (298 K) = ?24.70 ± 1.00 kJ mol^?1 demonstrate a significant entropy term which nearly compensates the effect of enthalpy at room temperature. The equilibrium between the two diastereomeric hemiacetal forms and the dialdehyde form of the oleuropein 6‐O‐β‐d ‐glucopyranoside aglycon of an olive leaf aqueous extract in CD₃OD was also shown to be strongly temperature dependent again because of the significant entropy term (TΔS° (298 K) = ?26.50 ± 1.39 kJ mol^?1) compared with that of the enthalpy term (ΔH^o = ?36.64 ± 1.46 kJ mol^?1). This is the first demonstration of the significant role of the entropy parameter in determining the equilibrium of chemical transformations in complex mixtures of natural products due to solvent and temperature effects. Copyright © 2014 John Wiley & Sons, Ltd.     

Single Peptide Backbone Surrogate Mutations to Regulate Angiotensin GPCR Subtype Selectivity

Mutating the side-chains of amino acids in a peptide ligand, with unnatural amino acids, aiming to mitigate its short half-life is an established approach. However, it is hypothesized that mutating specific backbone peptide bonds with bioisosters can be exploited not only to enhance the proteolytic stability of parent peptides, but also to tune its receptor subtype selectivity. Towards this end, four [Y]⁶-Angiotensin II analogues are synthesized where amide bonds have been replaced by 1,4-disubstituted 1,2,3-triazole isosteres in four different backbone locations. All the analogues possessed enhanced stability in human plasma in comparison with the parent peptide, whereas only two of them achieved enhanced AT₂R/AT₁R subtype selectivity. This diversification has been studied through 2D NMR spectroscopy and unveiled a putative more structured microenvironment for the two selective ligands accompanied with increased number of NOE cross-peaks. The most potent analogue, compound 2 , has been explored regarding its neurotrophic potential and resulted in an enhanced neurite growth with respect to the established agent C21.