Adamantyl ferrocene derivatives: Antioxidant abilities and effects on model lipid membranes

A series of homoannularly and heteroannularly substituted adamantyl ferrocene derivatives has been synthesized and their effects on membrane fluidity were investigated using liposomes as the membrane models. The liposome formulations of adamantyl ferrocene derivatives were characterized by using dynamic light scattering, differential scanning calorimetry and fluorescence anisotropy measurements. It was demonstrated that adamantyl ferrocene derivatives incorporated into the liposome significantly affect the structure of the lipid bilayer. The results of the study have revealed that adamantyl ferrocene derivatives, compounds 9 – 12, partition into the hydrophobic/hydrophilic interface of the membrane, causing a significant decrease in membrane fluidity. The antioxidant potential of synthesized compounds was assessed with DPPH method and it was shown that the examined compounds possess certain antioxidant activity.     

1′-Acetylferrocene amino acid esters and amides. A simple model for parallel β-helical peptides

In this study we present a synthesis and conformational analysis of 1′-acetylferrocene amino acid derivatives of type Ac–Fn–CO–AA–Y (Fn=ferrocene-1,1-diyl; AA=Gly, Ala or Val; Y=OMe or NHMe) as a simple model for parallel β-helical peptides. Derivatives with only one amino acid adopt a reduced number of total conformations and allow a more exact analysis of intramolecular hydrogen bonds (IHB) close to the ferrocene unit. Conformational analysis of these bioconjugates was performed by a combination of spectroscopic techniques (IR, NMR and CD) and corroborated by solution-phase DFT calculations. The investigation of ester conjugates 1–3 indicates the coexistence of non-bonded (an open forms) and hydrogen bonded NH_a group forming a 7-membered ring (γ-turn). The amide derivatives 4–6 with an additional NH_b hydrogen bond donor are mostly constituted of conformers with a 10-membered ring (β-turn) as a single IHB pattern or the β-turn accompanied by a 7-membered ring (γ-turn) containing NH_a group. The exchange of the amino acid side-chain does not significantly affect the conformational properties and IHB pattern of the studied conjugates 1–6.     

Synthesis and biological evaluations of mono‐ and bis‐ferrocene uracil derivatives

Mono‐ ( 3a – 3e and 4a – 4e ) and bis‐ferrocene ( 5a – 5e and 6a – 6e ) conjugated 5‐substituted uracil derivatives that are bridged by 1,2,3‐triazole linker were synthesized. The impact of ferrocene unit and spacer between ferrocene and triazole on radical scavenging potency was observed. Bis‐ferrocenyl uracil derivatives exhibited better antiproliferative activities than their mono‐ferrocenyl analogs. Bis‐ferrocenyl methyl‐ ( 5b ) and halogen‐substituted ( 5e , 6c , and 6d ) uracil derivatives showed pronounced and selective cytostatic activities on colon adenocarcinoma (CaCo‐2) and Burkitt lymphoma (Raji) cells, with higher potency and selectivity than the reference drug 5‐fluorouracil. Generation of reactive oxygen species (ROS) in CaCo‐2 and Raji cells when treated with compounds 5b , 5e , and 6d was observed. Bis‐ferrocenyl 5‐chlorouracil 6c induced significant disruption in mitochondrial membrane potential that is accompanied by activation of apoptosis in CaCo‐2, Raji, and acute lymphoblastic leukemia (CCRF‐CEM) cells, while 6d caused mitochondrial dysfunction and apoptosis induction in CaCo‐2 and Raji cells. Potent antiproliferative activity of 6c and 6d could be associated with mitochondrial membrane potential disruption accompanied by apoptosis induction. Our findings highlighted 6c and 6d with potent and selective antiproliferative activity on CaCo‐2, Raji, and CCRF‐CEM cells that may be associated with targeting cancer cell mitochondria, as a molecular target.     

Simultaneous Determination of Sulfonamides, Fluoroquinolones, Macrolides and Trimethoprim in Wastewater and River Water by LC-Tandem-MS

A sensitive and highly selective method for the simultaneous determination of sulfonamides, macrolides, fluoroquinolones and trimethoprim in wastewater and river water has been developed. Samples were enriched by solid-phase extraction and analysed by reversed-phase liquid chromatography coupled to electrospray ionisation tandem mass spectrometry. Several surrogate standards were used for quantification purposes. Absolute recoveries of individual antimicrobials were between 49 and 133% with RSD between 1 and 18% in all investigated matrices. Detection limits in low ng L^?1 range were achieved. The method was successfully applied to the analysis of raw municipal wastewater, wastewater effluents and river waters.     

Quinoline and ferrocene conjugates: Synthesis,computational study and biological evaluations

Novel O‐alkylated quinoline and N‐alkylated 4‐quinolone derivatives attached to the ferrocene moiety through 4,1‐ ( 7a–d , 8a–d and 12a–d ) and 1,4‐disubstituted ( 9a , 9b , 10a and 10b ) 1,2,3‐triazole moiety were synthesized. The observed regioselectivity of O‐ vs. N‐alkylation was explored by the use of NMR and computational techniques. Among the N‐alkylated derivatives, the quinolone‐ferrocene conjugate 9a displayed marked activities against chronic myeloid leukemia in blast crisis (K562) and Burkitt lymphoma (Raji). The 6‐chloroquinolone‐ferrocene conjugate 12c , with selective inhibitory activity on Raji cells and no cytostatic effect on normal MDCK1 cells was highlighted as the most promising anticancer organometallic complex in a group of O‐alkylated quinolines.     

Screening of degradation products,impurities and precursors of chemical warfare agents in water and wet or dry organic liquid samples by in-sorbent tube silylation followed by thermal desorption–gas chromatography–mass spectrometry

A standard method used by inspection teams of the Organisation for the Prohibition of Chemical Weapons (OPCW) for preparation of aqueous samples requires several extraction and derivatization steps. This results in tedious and time consuming on-site analysis. A simple thermal desorption–gas chromatography–mass spectrometry (TD–GC–MS) method was developed to analyse for a broad range of degradation products, impurities and precursors of chemical warfare agents (CWA) in water solutions and wet or dry organic liquid samples. The method is fast, sensitive, requires only microliter volumes of sample and enables the simultaneous determination of a wide range of compounds with widely differing polarity, volatility and reactivity. The applicability of the method was demonstrated by successful analysis of five OPCW Official Proficiency Test samples.     

Intramolecular hydrogen bonding in disubstituted ethanes. A comparison of NH...O- and OH...O- Hydrogen bonding through conformational analysis of 4-amino-4-oxobutanoate (succinamate) and monohydrogen 1,4-butanoate (monohydrogen succinate) anions

Relative strengths of amide NH...O- and carboxyl OH...O- hydrogen bonds were investigated via conformational analysis of succinamate and monohydrogen succinate anions with the aid of vicinal proton-proton NMR couplings and B3LYP DFT quantum mechanical calculations for a variety of solvents. New experimental results for succinamate are compared with those obtained from previous studies of monohydrogen succinate. While some computational results for monohydrogen succinate were published previously, the results contained herein are the product of a more powerful methodology than that used earlier. The experimental results clearly show that intramolecular hydrogen-bond formation is more favored in aprotic solvents than in protic solvents for both molecules. Furthermore, the preference of the succinate monoanion for the gauche conformation is much stronger in aprotic solvents than that of succinamate, indicating that the OH...O- hydrogen bond is substantially stronger than its NH...O- counterpart, despite the approximately 5 kcal cost for formation of the E configuration of the carboxyl group needed to make an intramolecular hydrogen bond. The actual energy differences between formation of internal hydrogen bonds for monohydrogen succinate and succinamate anion were estimated by comparison of the relative values of K1 of the respective acids in water and DMSO by a procedure first developed by Westheimer. Recent theoretical work with succinamate highlights the necessity of considering substituent orientational degrees of freedom to understand the conformational equilibria of the central CH2-CH2 torsions in disubstituted ethanes. Similar methodology is applied here to succinic acid monoanion, by mapping potential-energy surfaces with respect to the CH2-CH2 torsional, carboxyl-substituent rotational, and carboxyl-proton E/Z isomeric degrees of freedom. Boltzmann populations were compared with gauche populations estimated from the experimentally determined coupling constants. The quantum mechanical results for succinamate show a much weaker tendency toward hydrogen bonding than for the succinic acid monoanion. However, the theoretical methods employed appear to substantially overestimate contributions from intramolecularly hydrogen-bonded structures for the succinic acid monoanion when compared with experimental results. Natural bond orbital analysis, applied to the quantum mechanical wave functions of fully optimized gauche and trans structures, showed a strong correlation between the population of amide sigma*(N-H) and carboxyl sigma*(O-H) antibonding orbitals and apparent hydrogen-bonding behavior.     

Red clover (<Emphasis Type="Italic">Trifolium pratense</Emphasis> L.) honey: volatiles chemical-profiling and unlocking antioxidant and anticorrosion capacity

Headspace solid-phase micro-extraction (HS-SPME) and ultrasonic solvent extraction (USE) were used for red clover honey volatiles extraction. The extracts were analysed using gas chromatography and mass spectrometry (GC-MS). Lilac aldehyde isomers dominated in the headspace (individual range from 7.6 % to 21.4 %) followed by phenylacetaldehyde (10.1–31.2 %) and benzaldehyde (7.0–15.7 %). Higher aliphatic alcohols and hydrocarbons were the predominant constituents of the honey extracts. The honey and its extracts exhibited rather weak anti-radical activity (DPPH assay) and total antioxidant activity (FRAP assay). On the other hand, the honey’s inhibitive properties towards the corrosion of AA 2017A alloy in NaCl solution (potentiodynamic polarisation and potentiostatic pulse measurements) revealed the honey to be a very good anodic inhibitor (efficiency up to 76 %) while the honey extracts (USE) showed better inhibition efficacy.     

Tribalj dam-break and flood wave propagation

In this paper we present numerical simulations for the dam-break flood wave propagation from Tribalj accumulation to the town of Crikvenica (Croatia). The mathematical models we used were the one-dimensional open channel flow and the two-dimensional shallow water equations. They were solved with the well-balanced finite volume numerical schemes which additionally include special numerical treatment of the wetting/drying front boundary. These schemes were tested on CADAM test problems. The aim of this study was to assess potential damage in the village of Tribalj and the town of Crikvenica. Results of these simulations were used as the basis for urban planning and micro-zoning of the flood-risk areas. Several different dam-break scenarios were considered, ranging from sudden dam disappearance to partial and dynamic breach formation.      

Efficient implementation of WENO schemes to nonuniform meshes

Most of the standard papers about the WENO schemes consider their implementation to uniform meshes only. In that case the WENO reconstruction is performed efficiently by using the algebraic expressions for evaluating the reconstruction values and the smoothness indicators from cell averages. The coefficients appearing in these expressions are constant, dependent just on the scheme order, not on the mesh size or the reconstruction function values, and can be found, for example, in Jiang and Shu (J Comp Phys 126:202–228, 1996). In problems where the geometrical properties must be taken into account or the solution has localized fine scale structure that must be resolved, it is computationally efficient to do local grid refinement. Therefore, it is also desirable to have numerical schemes, which can be applied to nonuniform meshes. Finite volume WENO schemes extend naturally to nonuniform meshes although the reconstruction becomes quite complicated, depending on the complexity of the grid structure. In this paper we propose an efficient implementation of finite volume WENO schemes to nonuniform meshes. In order to save the computational cost in the nonuniform case, we suggest the way for precomputing the coefficients and linear weights for different orders of WENO schemes. Furthermore, for the smoothness indicators that are defined in an integral form we present the corresponding algebraic expressions in which the coefficients obtained as a linear combination of divided differences arise. In order to validate the new implementation, resulting schemes are applied in different test examples.