An organocatalytic ionic liquid

The carbene concentration in 1-ethyl-3-methylimidazolium-acetate ionic liquid is sufficiently high to act as a catalyst in benzoin condensation, hydroacylation and also in oxidation of an alcohol by using CO(2) and air. This observation reveals the potential of ionic liquid organocatalysts, uniting the beneficial properties of these two families of compounds.     

Exploring and characterizing the folding processes of Lys- and Arg-containing Ala-based peptides: a molecular dynamics study

In this study, molecular dynamics simulations were carried out on Lys- and Arg-containing Ala-based peptides (i.e. Ace-(AAAAK)(n)A-NH(2) and Ace-(AAAAR)(n)A-NH(2), where n=1-4), in order to explore and characterize their folding processes. For the oligopeptides, the evolution of α-helical structure with regard to the whole conformation, as well as to each residue was investigated, and the helix-forming propensities were characterized. On the basis of the helicity curves, representing the alteration of average helicity as a function of time, the typical time values describing the folding processes and subprocesses were identified. In the case of each peptide, the evolution and role of helix-stabilizing, non-local and side-chain-to-backbone H-bonds were examined. The appearing i←i+4 H-bonds pointed out the role of these interactions in the stabilization of α-helical conformations, while the occurring i←i+3 H-bonds indicated the presence of β-turn or 3(10)-helical structures. Studying the formation and role of non-local and side-chain-to-backbone H-bonds led to the observation that these types of interactions produced an effect on the evolution of helical conformations, as well as on the folding processes.     

Binding of alkaloids into the S1 specificity pocket of α-chymotrypsin: evidence from induced circular dichroism spectra

Non-covalent binding of planar aromatic molecules into the S1 specificity pocket of the serine protease α-chymotrypsin (αCHT) can be detected by measuring induced circular dichroism (CD) spectroscopic signals. Utilizing this phenomenon, αCHT association of proflavine (PRF), the well known serine protease inhibitor has been investigated together with plant-derived compounds including isoquinoline, pyridocarbazole and indoloquinoline alkaloids, of which αCHT binding has never been reported. Non-degenerate exciton coupling between π-π* transitions of the ligand molecules and two tryptophan residues (Trp172 and Trp215) near to the binding site is proposed to be responsible for the induced CD activity. The association constants calculated from CD titration data indicated strong αCHT association of sanguninarine, ellipticine, desmethyl-isocryptolepine and isoneocryptolepine (K(a) ≈ 10(5) M(-1)) while berberine, coptisine and chelerythrine bind to the enzyme with lower, PRF-like affinity (K(a) ≈ 10(4) M(-1)). PRF-trypsin and ellipticine-trypsin binding interactions have also been demonstrated. The binding of the alkaloids into the S1 pocket of αCHT has been confirmed by CD competition experiments. Molecular docking calculations showed the inclusion of PRF as well as the alkaloid molecules in the S1 cavity where they are stabilized by hydrophobic and H-bonding interactions. These novel nonpeptidic scaffolds can be used for developing selective inhibitors of serine proteases having chymotrypsin-like folds. Furthermore, the results provide a novel, CD spectroscopic based approach for probing the ligand binding of αCHT and related proteases.     

Promising anticancer mono- and dinuclear ruthenium(III) dithiocarbamato complexes: systematic solution studies

During the last decade, our research group has prepared a number of metal dithiocarbamato derivatives of Pt, Pd and Au that were expected to resemble the main features of cisplatin together with higher activity, improved selectivity and bioavailability, and lower side-effects. Furthermore, we have already published the synthesis, characterization and in vitro cytotoxicity studies of novel ruthenium(III) dithiocarbamato complexes such as [RuL(3)] monomers (11) and α-[Ru(2)L(5)]Cl dimers (12) with five different dithiocarbamate ligands. As both the monomer and the dinuclear complexes have shown significant antitumor activity in different human tumor cell lines, we decided to widen the characterization studies and to analyse thoroughly their behavior in physiological-like medium by UV-visible and CD spectroscopy. In the present paper we report on the crystal structure of [Ru(DMDT)(3)], [Ru(PDT)(3)] and [Ru(ESDT)(3)] complexes and we determine the spin state of the paramagnetic Ru(III) by means of Evans' method. Then, we discuss in detail the UV-visible spectral data of the complexes in different medium. All the studied complexes are stable in dimethyl sulfoxide, and show low solubility in phosphate buffered saline solution, particularly the monomer species, even at low concentration, while increased solubility for both types of complexes have been found in the presence of bovine serum albumin (BSA). Moreover, no changes on the coordination sphere of the metal, as well as no direct interaction between the BSA protein and the complex have been identified by UV-visible spectroscopy. However, some conformational changes on the BSA structure, induced by the ruthenium(III) complexes have been confirmed by CD spectroscopy, indicating a probable secondary electrostatic interaction between the metal complex and the peptide. In addition, no significant interaction has been demonstrated with the components of Dulbecco's Modified Eagle's Medium, used for the in vitro assays.     

? 1-Summability of d-Dimensional Fourier Transforms

A general summability method of more-dimensional Fourier transforms is given with the help of a continuous function θ. Under some weak conditions on θ we show that the maximal operator of the ℓ ₁–θ-means of a tempered distribution is bounded from H _p (ℝ ^d ) to L _p (ℝ ^d ) for all d/(d+α)<p≤∞ and, consequently, is of weak type (1,1), where 0<α≤1 depends only on θ. As a consequence we obtain a generalization of the one-dimensional summability result due to Lebesgue, more exactly, the ℓ ₁–θ-means of a function f∈L ₁(ℝ ^d ) converge a.e. to f. Moreover, we prove that the ℓ ₁–θ-means are uniformly bounded on the spaces H _p (ℝ ^d ), and so they converge in norm (d/(d+α)<p<∞). Similar results are shown for conjugate functions. Some special cases of the ℓ ₁–θ-summation are considered, such as the Weierstrass, Picar, Bessel, Fejér, de La Vallée-Poussin, Rogosinski, and Riesz summations.     

Absolute convergence of double Walsh?CFourier series and related results

We consider the double Walsh orthonormal system $$\{w_m(x)w_n(y):\, m,n \in \mathbb{N}\}$$ on the unit square $\mathbb{I}^{2}$ , where {w _m (x)} is the ordinary Walsh system on the unit interval $\mathbb{I}:=[0,1)$ in the Paley enumeration. Our aim is to give sufficient conditions for the absolute convergence of the double Walsh?CFourier series of a function $f \in L^{p}(\mathbb{I}^{2})$ for some 1<p?Q2. More generally, we give best possible sufficient conditions for the finiteness of the double series $$\sum_{m=1}^{\infty}\ \sum_{n=1}^{\infty} a_{mn} {|\hat{f}(m,n)|}^r,$$ where {a _mn } is a given double sequence of nonnegative real numbers satisfying a mild assumption and 0<r<2. These sufficient conditions are formulated in terms of (either global or local) dyadic moduli of continuity of?f.     

Triangular Ces??ro summability of two dimensional Fourier series

It is proved that the maximal operator of the triangular Ces??ro means of a two-dimensional Fourier series is bounded from the periodic Hardy space $H_{p}(\mathbb{T}^{2})$ to $L_{p}(\mathbb{T}^{2})$ for all 2/(2+??)<p?Q?? and, consequently, is of weak type (1,1). As a consequence we obtain that the triangular Ces??ro means of a function $f \in L_{1}(\mathbb{T}^{2})$ converge a.e. to?f.     

Analysis of therapeutic peptides in human urine by combination of capillary zone electrophoresis-electrospray mass spectrometry with preparative capillary isotachophoresis sample pretreatment

The presented study deals with the off-line coupling of preparative isotachophoresis (pITP) with on-line combination of capillary zone electrophoresis with electrospray mass spectrometric detection (CZE-ESI-MS) used for the analysis of therapeutic peptides (anserine, carnosine, and buserelin) in complex matrix (urine). Preparative capillary isotachophoresis, operating in a discontinuous fractionation mode in column-coupling configuration, served as a sample pretreatment technique to separation, and fractionation of mixture of therapeutic peptides present in urine at low concentration level. The fractions isolated by pITP procedure were subsequently analyzed by capillary zone electrophoresis with electrospray mass spectrometric detection. Acetic acid at 200 mmol L(-1) concentration served as background electrolyte in CZE stage and it is compatible with MS detection in positive ionization mode. In pITP fractionation procedure, sodium cation (10 mmol L(-1) concentration) as leading ion and beta-alanine as terminating ion (20 mmol L(-1) concentration) were used. While using CZE-ESI-MS, the limits of detection were 0.18 μg mL(-1) for carnosine, 0.17 μg mL(-1) for anserine and 0.64 μg mL(-1) for buserelin in water and 0.19 μg mL(-1) for carnosine, 0.50 μg mL(-1) for anserine and 0.74 μg mL(-1) for buserelin in 10 times diluted urine, respectively. The cleaning power of pITP sample pretreatment was proved as the peptides provided the higher MS signals at lower concentration levels resulting from the minimized matrix effects. The quality of obtained MS/MS spectra was very good so that they can provide information about the structure of analytes, and they were used for verification of the analytes identities. The pITP pretreatment improved the detection limits of the analyzed therapeutic peptides at least 25 times compared to the CZE-ESI-MS itself.     

First identification of dimethoxycinnamic acids in human plasma after coffee intake by liquid chromatography-mass spectrometry

There is a substantial amount of published literature on the bioavailability of various coffee components including the most abundant metabolites, caffeic and ferulic acids. Surprisingly, to date, the appearance of dimethoxycinnamic acid derivatives in humans has not been reported despite the fact that methylated form of catechol-type polyphenols could help maintain, modify or even improve their biological activities. This study reports an LC-MS method for the detection of dimethoxycinnamic acid in human plasma after treatment with an esterase. Liquid chromatography, including the combination of methanol and acetonitrile as organic eluent, was optimized to resolve all interferences and enable reliable detection and identification of 3,4-dimethoxycinnamic and 3,4-dimethoxy-dihydrocinnamic acids. In addition to the good mass accuracy achieved (better than 5 ppm), tandem mass spectrometric and co-chromatography experiments further confirmed the identity of the compounds. The optimized method was applied to analyze samples obtained immediately, 1 and 10 h after coffee ingestion. The results show that in particular 3,4-dimethoxycinnamic acid appears in high abundance (～380 nM at 60 min) in plasma upon coffee intake, indicating that it is important to consider these derivatives in future bioavailability and bioefficacy studies.     

Synthesis of (E)-2-(1-ferrocenylmethylidene)malonic acid derivatives by a cobalt-catalyzed domino reaction of ethyl diazoacetate, carbon monoxide and ferrocenylimines

The domino reaction of ethyl diazoacetate, carbon monoxide and ferrocenylimines was investigated in the presence of Co₂(CO)₈ as catalyst. In most cases the main products are 2-(1-ferrocenylmethylidene) malonates formed by an N(1)-C(4) cleavage of the primarily derived β-lactams. The latter compounds could only be isolated when the reaction was carried out at relatively low CO pressure, using an excess of ethyl diazoacetate. trans-N-(tert-Butyl)-3-ethoxycarbonyl-4-ferrocenyl-β-lactam proved to be the most stable one among these compounds and could be isolated in 55% yield. N-alkyl β-lactams were shown to undergo acidic cleavage leading to the E isomers of 2-(1-ferrocenylmethylidene) malonates as the main products. The structures of the two new compounds, (E)-2-ethoxycarbonyl-3-ferrocenyl-N-((R)-1-phenylethyl)-2-propenamide and trans-N-(tert-butyl)-3-ethoxycarbonyl-4-ferrocenyl-β-lactam were confirmed by X-ray crystallography. The relative thermodynamical stability of the products as well as the energetics of the acid-mediated cleavage of the β-lactam ring was elucidated with DFT calculations.