Cycloaromatization Reaction of 4‐Alkoxy‐1,1,1‐trifluoroalk‐3‐en‐2‐ones with 2,6‐Diaminotoluene: The Unexpected Regioselective Synthesis of 2,4,7,8‐Tetrasubstituted Quinolines

This article reports a convenient and general method for the regioselective synthesis of a new series of 2‐alkyl(aryl)‐8‐methyl‐4‐trifluoromethyl‐7‐aminoquinolines in 86–93% yields, from cycloaromatization reactions of N‐(oxotrifluoroalkenyl)‐2,6‐diaminotoluenes in a strongly acidic medium polyphosphoric acid and absence of solvent. The enaminoketone intermediates were easily isolated from the reaction of 4‐alkoxy‐4‐alkyl(aryl)‐1,1,1‐trifluoroalk‐3‐en‐2‐ones [CF₃C(O)CH═C(R)OR¹, where R = H, Me, Ph, 4‐FPh, 4‐BrPh, 4‐MePh, and R¹ = Me, Et] with 2,6‐diaminotoluene (2,6‐DAT) in methanol under mild conditions, in 46–70% yields. Another synthetic route also allowed the regioselective synthesis of 2‐aryl(heteroaryl)‐4‐methyl‐4‐trifluoromethyl‐7‐aminoquinolines from direct cyclocondensation reactions of 4‐alkoxy‐4‐aryl(heteroaryl)‐1,1,1‐trifluoroalk‐3‐en‐2‐ones with 2,6‐diaminotoluene in methanol under mild conditions, in 21–36% yields.     

The influence of Hofmeister series ions on hyaluronan swelling and viscosity

The dissolution of hyaluronan in water leads to its degradation, and as a result its molecular weight decreases. The degradation of hyaluronan is mainly influenced by temperature, solution composition, and also its pH. This study describes the influence of Hofmeister series ions on hyaluronan behaviour and hyaluronan film swelling by solutions of these ions. It was found that Hofmeister ions show lyotropic effects influencing the entanglement of hyaluronan coils and their expansion from solid polymer films into swollen gel state. The hydrophobic and hydrophilic interactions in the structure of hyaluronan macromolecules are represented by the mutual diffusion coefficient D(c), the mean mutual diffusion coefficient D(s), the expansion work of coil swelling RA(delta,s), the activation enthalpy of diffusion connected with swelling H(D,s) and kinematic viscosity of hyaluronan-ions solutions nu.     

Glycoform Heterogeneity of Human Serum α1-Acid Glycoprotein Determined by CZE in Malignant Diseases

A novel capillary zone electrophoresis method was developed to investigate the glycoform heterogeneity of human serum α1-acid glycoprotein (AGP). The simultaneous application of a dimethyl polysiloxane coated capillary and oligoamine additives, particularly spermidine resulted in a more detailed separation of AGP glycoforms than reported previously. The relative distribution of AGP glycoforms in CZE was determined by baseline integration of peak areas and verified by peak-fitting analysis. Providing high purity of AGP samples suitable for CZE a schedule of isolation and purification steps including sample preparation and an improved technique of ion exchange chromatography was applied. Based on data obtained by CZE and on the serum AGP levels measured the serum concentrations of AGP glycoforms were calculated in cancer patients with Hodgkin and non-Hodgkin lymphoma, ovary carcinoma and melanoma compared to healthy donors. Results presented here demonstrated a significant increase in the serum concentration of the more acidic AGP fractions also indicating the overproduction of these glycoforms in cancer. In conclusion, our observations may raise the clinical diagnostic relevance of changes in the molecular heterogeneity of AGP detected by CZE in the various forms of malignant diseases.     

Intact skin analysis by desorption electrospray ionization mass spectrometry

In vivo skin analysis by Desorption Electrospray Ionization was characterized on healthy human volunteers by directing pneumatically assisted electrospray directly onto their fingertips. In order to eliminate the risk of electric shock, a high ohmic resistor was built into the system. Positive ion DESI-MS analysis yields low intensity spectra, while negative ion spectra feature a number of various biogenic carboxylic acids. Compounds of external origin and excreted molecules were found to have different analysis kinetics, with the exception of highly hydrophobic species. The difference was demonstrated in the case of nicotine and cotinine. Pharmacokinetic studies were performed using a rat animal model. The kinetics of the anesthetic ketamine was followed by DESI, and results were in agreement with off-line HPLC-MS blood analysis. Using a similar approach for N,N'-dimethylthiourea (DMTU), a novel method was developed for the real-time quantification of oxidative stress. DMTU was administered to the animals, and the ratio of the molecule and its oxidized form was monitored from the skin surface. The ratio was found to be highly sensitive to experimentally induced diabetes mellitus type I and angiotensin-induced chronic oxidative stress. It was concluded that the method has a number of potential applications in the fields of forensics, pharmacology and clinical chemistry.     

Complexation of phenols by calix[4]arene Diethers in a low-permittivity solvent. Self-switched complexation by 25,27-Dibenzyloxycalix[4]arene

To improve the selectivity of sensing, the thermodynamics of the complex formation of some calix[4]arene hosts with neutral phenol guests was studied in carbon tetrachloride as nonpolar solvent. The molecular shape of calixarenes was varied by the selective functionalization with tBu and O-CH2-Ph (O-benzyl) or OPr groups at the upper and lower rim, respectively. To vary the electron density on the guest's aromatic rings, the parent phenol was functionalized in the para position with electron-withdrawing Cl, as well as H, and electron-releasing CH3 and tBu groups. To study the interaction between calixarene and the guests, PL and quantum-chemical methods were applied. The results revealed an overall 1:1 complex stoichiometry except for the parent dibenzyloxycalix[4]arene, where 1:2 host-guest stoichiometries were observed irrespective of the quality of phenol. In the latter case, the complex formation shows a self-switched character: the first phenol molecule is included in the calixarene cavity, and only afterward, a second guest molecule is bound by the two benzyloxy aromatics. Although the enthalpy change predicts strong interaction between the host and the guest, the Gibbs free energy change of the complex formation is small, resulting in a relatively low complex stability. The solvent-relaxation measurements support that the unexpected entropy change could be the consequence of the reorientation of solvent molecules around the calixarene building block. The reorientation is assisted by dispersive forces between solute and solvent molecules. IR and RAMAN analysis of the complexes exclude a considerable participation of the phenolic OH group in the stabilization of the complex. This result is in agreement with earlier findings where deterministic role of pi-pi interaction in the complex stability was assumed.     

1H and 13C NMR spectral data of new saponins from Cordia piauhiensis

Two new bidesmoside triterpenoid saponins were isolated from stems of Cordia piauhiensis. Their structures, characterized as 3-O-alpha-L-rhamnopyranosyl-(1 --> 2)-beta-D-glucopyranosyl pomolic acid 28-O-beta-D-glucopyranosyl ester (1) and 3-O-alpha-L-rhamnopyranosyl-(1 --> 2)-beta-D-glucopyranosyl oleanolic acid 28-O-beta-D-glucopyranosyl-(1 --> 6)-beta-D-glucopyranosyl ester (2), were unequivocally established after extensive NMR (1H, 13C, DEPT 135 degrees, COSY, HSQC, HMBC, TOCSY, and NOESY) studies.     

Host–guest system of 4-nerolidylcatechol in 2-hydroxypropyl-β-cyclodextrin: preparation, characterization and molecular modeling

The interaction of 4-nerolidylcatechol (4-NRC), a potent antioxidant agent, and 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) was investigated by the solubility method using Fourier transform infrared (FTIR) methods in addition to UV–Vis, ¹H-nuclear magnetic resonance (NMR) spectroscopy and molecular modeling. The inclusion complexes were prepared using grinding, kneading and freeze-drying methods. According to phase solubility studies in water a B_S-type diagram was found, displaying a stoichiometry complexation of 2:1 (drug:host) and stability constant of 6494 ± 837 M^?1. Stoichiometry was established by the UV spectrophotometer using Job’s plot method and, also confirmed by molecular modeling. Data from ¹H-NMR, and FTIR, experiments also provided formation evidence of an inclusion complex between 4-NRC and HP-β-CD. 4-NRC complexation indeed led to higher drug solubility and stability which could probably be useful to improve its biological properties and make it available to oral administration and topical formulations.     

Kinetics and mechanism of hydrolysis of N-acyloxymethyl derivatives of azetidin-2-one

The pH-independent, acid-catalyzed and base-catalyzed hydrolyses of N-acyloxymethylazetidin-2-ones all occur at the ester function. The pH-independent hydrolysis involves rate-limiting alkyl C-O fission and formation of an exocyclic beta-lactam iminum ion. This iminium ion is then trapped by water at the exocyclic iminium carbon atom, rather than at the beta-lactam carbonyl carbon atom, to form the corresponding N-hydroxymethylazetidin-2-ones. Calculations carried out at the B3LYP/6-31+G(d) level of theory also support that nucleophilic attack by water takes place at the exocyclic carbon rather than at the beta-lactam carbonyl carbon of the iminium ion. The mechanism for the acid-catalyzed pathway involves a preequilibrium protonation, probably at the beta-lactam nitrogen, followed by rate-limiting alkyl C-O fission with formation of an exocyclic iminum ion. The base-catalyzed hydrolysis involves rate-limiting hydroxide attack at the ester carbonyl carbon. These results imply formation of a beta-lactam system containing a positively charged amide nitrogen atom that hydrolyzes via a pathway that preserves the beta-lactam structure in the product and provide further evidence that cleavage of the beta-lactam C-N bond is not as facile as is commonly imagined.     

Inclusion complexes of α-cyclodextrins with poly(d,l-lactic acid): structural,characterization, and glass transition dynamics

Poly (d,l-lactic acid) (PDLLA) was combined with α-CD to form inclusion complexes (ICs) with distinct PDLLA fractions. The structural changes resulting from this coalescence process were analyzed by Fourier transform infrared spectroscopy (FTIR), proton nuclear magnetic resonance (¹H NMR), and X-ray diffraction (XRD). The presence of both components in the ICs was confirmed by FTIR. The encapsulated PDLLA fraction was quantified by ¹H NMR. XRD data evidenced that it was possible to transform the amorphous PDLLA into a well-organized channel-type crystalline structure. DSC showed that the glass transition temperature of the PDLLA fraction in the ICs was higher than in the pure polymer, indicating that the ultra-confinement effect imposed by the ICs organization clearly limits PDLLA molecular dynamics. The confinement effect on the glass transition dynamics was investigated by unconventional dynamic mechanical analysis experiments, which confirmed that ICs segmental mobility is highly restricted when compared with the one of pure PDLLA. Bulk PDLLA presents a typical VFTH behavior while the ICs dynamics shows an Arrhenius trend.     

Thermal stability of metastable nano-composites in planar flow cast Ti–Zr–Ni alloys

The influence of the solidification rate, the thermal stability, and devitrification process of the rapidly solidified Ti₄₅Zr₃₈Ni₁₇ alloy have been examined on ribbons prepared by the planar flow casting method. Differential scanning calorimetry in the continuous heating mode, X-ray diffraction, and electron microscopy techniques were applied. Comparison of the so-obtained microstructures revealed the competition between icosahedral quasi-crystalline and β-Ti(Zr) phases, both dispersed in an amorphous matrix. It has been found that the decomposition process of rapidly quenched ribbons consists of the sequence of several independent exothermic and endothermic reactions involving the additional precipitation of quasi-crystalline nanoparticles and both irreversible and reversible changes between the unstable high-temperature β and stable low-temperature α phases. The formation of the intermetallics as well as the transformation of quasi-crystals into Laves phase has been observed at higher temperatures in all ribbons.