Application of thin-layer chromatographic data in quantitative structure-activity relationship assay of thiazole and benzothiazole derivatives with H1-antihistamine activity. II

Quantitative structure-activity relationship (QSAR) analysis of H1-antihistamine activity was carried out and chromatographic data of 2-[2-(phenylamino)thiazol-4-yl]ethanamine, 2-(2-benzyl-4-thiazolyl)ethanamine, 2-(2-benzhydrylthiazol-4-yl)ethylamine derivative, and 2-(1-piperazinyl- and 2-(hexahydro-1H-1,4-diazepin-1-yl)benzothiazole derivatives were obtained. Normal-phase (NP) TLC plates (silica gel 60F254), impregnated with solutions of selected amino acid mixtures (L-Asp, L-Asn, L-Thr and L-Lys) were used in two developing solvents as human histamine H1-receptor (hH1R) antagonistic interaction models. The lipophilicity data of the examined compounds were obtained and used in the QSAR assay. Using regression analysis, relationships between chromatographic and biological activity data were found. The correlations obtained in the present experiment with NP-TLC are more significant that those obtained in the experiment with RP2 TLC, because of the optimal fitting of the chromatographic system conditions to the lipophilicity of solutes. All proposed chromatographic models should facilitate pre-selection of the new drug candidates. The correlations of calculated pA2(H1) values of the tested compounds predicted by the use of the best equations versus their pA2(H1) obtained from the biological tests were significant (R2 = 0.91-0.94).     

Solution and solid state 13C NMR and X-ray studies of genistein complexes with amines. Potential biological function of the C-7, C-5, and C4'-OH groups

Parent genistein and its new amine complexes with morpholine and piperazine were studied comparatively in the solid and liquid states by X-ray crystallography and 13C and 15N NMR spectroscopy. Biochanine A and its complexes were used as reference. Secondary deuterium isotope effects on 13C chemical shifts in solution were studied in parent isoflavones and their morpholine and piperazine complexes to aid in evaluation of the electronic distribution in both systems. In addition, to quantify the extent of proton transfer as well as to establish strong hydrogen bonding of the 7-OH group in a morpholine complex, proton transfer from the 7-OH group to the piperazine nitrogen atom was also confirmed by 13C NMR in the solid state and by X-ray studies. The effect of 7-OH deprotonation yields a high frequency shift of 7-8 ppm on the C-7 carbon atom of the piperazine complex whereas it is as large as 12 ppm in the morpholine complex in the solid. The former trend is confirmed from solution state concentration studies which also show that the isoflavones have a strong tendency to form complexes with bases. Depending on the pKa difference between the isoflavones and the base this leads either to proton transfer and ion-pair formation or, in the case of a larger pKa difference, to a hydrogen bonded ion pair. The concentration studies show formation of a 1:1 genistein-piperazine complex in DMSO. Addition of water leads to formation of solvent separated ions. The C-5 OH group is involved in strong intramolecular hydrogen bonding leading to a pseudo aromatic ring extending the aromatic part of the drug pharmacophore. The analysis also suggests the way that both the C-7 and C-4' hydroxyl group of genistein may participate in stabilising the ternary inhibitor complexes of tyrosine-specific kinases or DNA topoisomerase II.     

Guest induced reversible on–off switching of elastic frustration in a 3D spin crossover coordination polymer with room temperature hysteretic behaviour

A binary reversible switch between low-temperature multi-step spin crossover (SCO), through the evolution of the population γ_HS(T) with high-spin (HS)-low-spin (LS) sequence: HS₁LS₀ (state 1) ↔ HS_2/3LS_1/3 (state 2) ↔ HS_1/2LS_1/2 (state 3) ↔ HS_1/3LS_2/3 (state 4) ↔ HS₀LS₁ (state 5), and complete one step hysteretic spin transition featuring 20 K wide thermal hysteresis centred at 290 K occurs in the three-dimensional (3D) Hofmann-type porous coordination polymer {Fe^II(3,8phen)[Au(CN)₂]₂}·xPhNO₂ (3,8phen = 3,8-phenanthroline, PhNO₂ = nitrobenzene), made up of two identical interpenetrated pcu-type frameworks. The included PhNO₂ guest (x = 1, 1·PhNO₂) acts as a molecular wedge between the interpenetrated 3D frameworks via PhNO₂-3,8phen intermolecular recognition and is the source of the strong elastic frustration responsible for the multi-step regime. Detailed X-ray single crystal analysis reflects competition between spatial periodicities of structurally inequivalent HS and LS SCO centres featuring: (i) symmetry breaking (state 3) with ⋯HS–LS⋯ ordering with γ_HS = 1/2; and (ii) occurrence of spatial modulation of the structure providing evidence for stabilization of local or aperiodic ordered mixed spin states for states 2 and 4 (with γ_HS ≈ 2/3) and 4 (with γ_HS ≈ 1/3), respectively. Below c.a. 20 K, structural and magnetic analyses show the photogeneration of a metastable HS*, state 6. The room-temperature single-step hysteretic regime appears with release of the guest (x = 0, 1) and the elastic frustration, and reversibly switches back to the original four-step behaviour upon guest re-adsorption. Both uncommon relevant SCO events meeting in the same material represent a rare opportunity to compare them in the frame of antiferro- and ferro-elastic transitions.

Reversible switch between a robust bistable two-state room temperature spin crossover (SCO) and its transformation in a four-stepped elastically frustrated SCO due to guest inclusion in a metal–organic Hofmann framework.     

Speciation of chromium in mineral waters and salinas by solid-phase extraction and graphite furnace atomic absorption spectrometry

A simple GF-AAS method for speciation analysis of chromium in mineral waters and salinas was developed. Cr(VI) species were separated from Cr(III) by solid-phase extraction with APDC (ammonium pyrrolidinedithiocarbamate). The APDC complexes were formed in the sample solution under proper conditions, adsorbed on Diaion HP-2MG resin and the resin was separated from the sample. After elution with concentrated nitric acid Cr(VI) was determined by GF-AAS. Total chromium was determined by GF-AAS directly in the sample and Cr(III) concentration was calculated as the difference between those results.

The detection limit of the method defined as 3 s of background variation was 0.03 μg l⁻¹ for Cr(VI) and 0.3 μg l⁻¹ for total chromium. RSD for Cr(VI) determination at the concentration of 0.14 μg l⁻¹ was 9%, and for total chromium at the concentration of 5.6 μg l⁻¹ was 5%. The recovery of Cr(VI) was in the range of 94–100%, dependently on type of the sample.

The investigation of recovery of the spiked Cr(VI) showed that at concentration levels near 1 μg l⁻¹ and lower recovery may be reduced significantly even by pure reagents that seem to be free from any reductants.     

FT-IR spectroscopic, AM1 and PM3 computational studies of conformation of natural products: cytisine

Infrared spectra were recorded for cytisine (1) and its model compounds: N-methyl-2-pyridone (2) and piperidine (3) in solution. Eight solvents of different polarity, polarizability and acid-base properties: CCl(4), CS(2), CHCl(3), CDCl(3) (for comparison with the NMR spectra), CH(2)Cl(2), MeOH, Et(2)O and Et(3)N were chosen. Experimental FT-IR spectra were analysed with the help of those calculated for isolated derivatives at the AM1 and PM3 levels. Influence of environment on the conformational preferences in solvated cytisine was discussed and compared with those in the solid state (X-ray measurements) and in the gas phase (quantum-mechanical calculations).     

Nanoscale organization of adsorbed collagen: influence of substrate hydrophobicity and adsorption time

The adsorption of collagen on polystyrene (PS) and polystyrene oxidized by oxygen plasma discharge (PSox) was studied as a function of time using radiolabeling, X-ray photoelectron spectroscopy (XPS), and atomic force microscopy (AFM). Radiolabeling and XPS indicated that the initial step of adsorption was faster on PS than on PSox. AFM imaging under water revealed very different supramolecular organization of the adsorbed films depending on time and on the nature of the substrate: PS showed patterns of collagen aggregates at all adsorption times (from 1 min to 24 h); PSox was covered with a smooth layer except at long adsorption times (24 h), for which a mesh of collagen structures was observed. After fast drying, the collagen layer remained continuous and showed a morphology which recalled that observed under water. The mechanical stability of the adsorbed films was assessed under water by scraping with the AFM probe at different loading forces: no perturbations were created on PSox; in contrast, the layer adsorbed on PS was sensitive to scraping, the minimum force required to alter the collagen layer morphology increasing with time. These differences in the film properties were correlated with force measurements upon retraction: multiple adhesion forces were observed with collagen adsorbed on PS samples, whereas such an effect was never observed on PSox. The results show that the amount adsorbed and the organization of the adsorbed film respond differently to the adsorption time and that this is influenced by surface hydrophobicity. The quick initial adsorption on PS, compared to PSox, is thought to leave dangling collagen segments that are responsible for the observed morphology, for adhesion forces, and for lower mechanical resistance of the adsorbed layer.     

The Antioxidant,Cytotoxic and Antimicrobial Potential of Phenolic Acids-Enriched Extract of Elicited Hairy Roots of Salvia bulleyana

Hairy root cultures are valuable sources of a range of phytochemicals. Among them, Salvia bulleyana root culture is a promising source of polyphenols, especially rosmarinic acid (RA), a phenolic acid depside with pleiotropic activity and a wide application in medicine and cosmetology. The aim of the study was to enhance the culture productivity by finding suitable elicitation protocol and to determine its biological potential in terms of antioxidant, anticancer and antimicrobial properties. The total content of phenols and the levels of particular constituents in root extracts were analyzed using HPLC-PDA. Among four elicitors tested (yeast extract; methyl jasmonate, MJA; trans-anethol; and cadmium chloride), MJA was found to be the most effective. The greatest boost in phenolic production (up to 124.4 mg/g dry weight) was observed after three-day treatment with MJA at 100 µM, with an almost 100% improvement compared to the controls (non-treated root culture). The hydromethanolic extract from the elicited culture exhibited strong antioxidant activity with IC₅₀ values of 11.1 µg/mL, 6.5 µg/mL and 69.5 µg/mL for DPPH (2,2-diphenyl-1-picrylhydrazyl), ABTS (2,2-azinobis-(3-ethylbenzthiazoline-6-sulfonic acid)) and superoxide anion radical, respectively. Moreover, in concentrations of 0.5–5 mg/mL the extract inhibited the growth of LoVo, AGS and HeLa cell lines, but was safe for the L929 cells up to the concentration of 5 mg/mL. The extract also exhibited moderate antimicrobial activity. Thus, the results confirmed that elicitation can be a beneficial strategy for increase the phenolic acid biosynthesis in hairy roots of S. bulleyana, and that such a highly productive culture can show significant biological potential.     

Studying Ice with Environmental Scanning Electron Microscopy

Scanning electron microscopy (SEM) is a powerful imaging technique able to obtain astonishing images of the micro- and the nano-world. Unfortunately, the technique has been limited to vacuum conditions for many years. In the last decades, the ability to introduce water vapor into the SEM chamber and still collect the electrons by the detector, combined with the temperature control of the sample, has enabled the study of ice at nanoscale. Astounding images of hexagonal ice crystals suddenly became real. Since these first images were produced, several studies have been focusing their interest on using SEM to study ice nucleation, morphology, thaw, etc. In this paper, we want to review the different investigations devoted to this goal that have been conducted in recent years in the literature and the kind of information, beyond images, that was obtained. We focus our attention on studies trying to clarify the mechanisms of ice nucleation and those devoted to the study of ice dynamics. We also discuss these findings to elucidate the present and future of SEM applied to this field.     

Quadrupole relaxation enhancement and polarisation transfer in DMSO solution of [Bi(NO3)3(H2O)3]*18-crown-6 in solid state

ABSTRACT

¹H spin-lattice relaxation studies have been performed for pure [Bi(NO₃)₃(H₂O)₃]*18-crown-6 in powder and its solution in dimethyl sulfoxide (DMSO). The experiments have been carried out in the frequency range of 10?kHz–30?MHz and the temperature range of 240–277?K; at 277?K the solution is already frozen. The ¹H relaxation of pure [Bi(NO₃)₃(H₂O)₃]*18-crown-6 has been interpreted in terms of three dynamical processes. Quadrupole Relaxation Enhancement effects have been observed in the frozen DMSO solution of [Bi(NO₃)₃(H₂O)₃]*18-crown-6. The specific mechanisms of the ¹H spin-lattice relaxation enhancement have been discussed distinguishing between effects caused by time independent (residual) and fluctuating ¹H-²⁰⁹Bi dipole-dipole interactions.