Factors Influencing the Course of the Macrocyclization of α,ω‐Diamines with Esters of α,ω‐Dicarboxylic Acids

The efficient synthesis of eight new macrocyclic amides (lactams) via reaction of diesters with diamines under normal dilution conditions is described. The role of intermolecular H‐bond formation and steric hindrance is discussed based on ¹H‐ and ¹⁵N‐NMR studies of appropriate model compounds. Principles for the optimal choice of esters that can be efficiently transformed into diamides have been developed.     

Homotopy of the classical configuration space for the two-magnon sector of a magnetic Heisenberg ring

A finite Heisenberg magnetic ring with an arbitrary single-node spin and two spin deviations from the ferromagnetic saturation is considered as the system of two Bethe pseudoparticles. The set of all relevant magnetic configurations spans a surface which can be recognised as a Mőbius strip. The dynamics of the system imposes the double twist of all regular orbits of the translation symmetry group.     

Flow-through solid-phase based optical sensor for the multisyringe flow injection trace determination of orthophosphate in waters with chemiluminescence detection

In this work, a novel flow-through solid-phase based chemiluminescence (CL) optical sensor is described for the trace determination of orthophosphate in waters exploiting the multisyringe flow injection analysis (MSFIA) concept with multicommutation. The proposed time-based injection flow system relies upon the in-line derivatisation of the analyte with ammonium molybdate in the presence of vanadate, and the transient immobilisation of the resulting heteropolyacid in a N-vinylpyrrolidone/divinylbenzene copolymer packed spiral shape flow-through cell located in front of the window of a photomultiplier tube. The simultaneous injection of well-defined slugs of luminol in alkaline medium and methanol solution towards the packed reactor is afterwards performed by proper switching of the solenoid valves. Then, the light emission from the luminol oxidation by the oxidant species retained onto the sorbent material is readily detected. At the same time, the generated molybdenum-blue compound is eluted by the minute amount of injected methanol, rendering the system prepared for a new measuring cycle. Therefore, the devised sensor enables the integration of the solid-phase CL reaction with elution and detection of the emitted light without the typical drawbacks of the molybdenum-blue based spectrophotometric procedures regarding the excess of molybdate anion, which causes high background signals due to its self-reduction. The noteworthy features of the developed CL-MSFIA system are the feasibility to accommodate reactions with different pH requirements and the ability to determine trace levels of orthophosphate in high silicate content samples (Si/P ratios up to 500). Under the optimised conditions, a dynamic linear range from 5 to 50 μg P l⁻¹ for a 1.8 ml sample, repeatability better than 3.0% and a quantification limit of 4 μg P l⁻¹ were attained. The flowing stream system handles 11 analysis h⁻¹ and has been successfully applied to the determination of trace levels of orthophosphate in environmental samples such as mineral, ground, tap and pond waters as well as samples from a water-steam cycle of an incineration plant. The t-test comparison of the means for the developed optical sensor and the molybdenum-blue spectrophotometric APHA/AWWA/WPCF reference method revealed that there is no evidence of significant differences between the obtained results at the 95% confidence level.     

Preparation of peptide-functionalized gold nanoparticles using one pot EDC/sulfo-NHS coupling

Although carbodiimides and succinimides are broadly employed for the formation of amide bonds (i.e., in amino acid coupling), their use in the coupling of peptides to water-soluble carboxylic-terminated colloidal gold nanoparticles remains challenging. In this article, we present an optimization study for the successful coupling of the KPQPRPLS peptide to spherical and rodlike colloidal gold nanoparticles. We show that the concentration, reaction time, and chemical environment are all critical to achieving the formation of robust, peptide-coated colloidal nanoparticles. Agarose gel electrophoresis was used for the characterization of conjugates.     

Interactions of doxorubicin with self-assembled monolayer-modified electrodes: electrochemical, surface plasmon resonance (SPR), and gravimetric studies

We present the results on the partitioning of doxorubicin (DOX), a potent anticancer drug, through the model membrane system, self-assembled monolayers (SAMs) on gold electrodes. The monolayers were formed from alkanethiols of comparable length with different ω-terminal groups facing the aqueous electrolyte: the hydrophobic -CH(3) groups for the case of dodecanethiol SAMs or hydrophilic -OH groups of mercaptoundecanol SAMs. The electrochemical experiments combined with the surface plasmon resonance (SPR) and gravimetric studies show that doxorubicin is likely adsorbed onto the surface of hydrophilic monolayer, while for the case of the hydrophobic one the drug mostly penetrates the monolayer moiety. The adsorption of the drug hinders further penetration of doxorubicin into the monolayer moiety.     

Determination of growth hormone releasing peptides (GHRP) and their major metabolites in human urine for doping controls by means of liquid chromatography mass spectrometry

A family of small peptides has reached the focus of doping controls representing a comparably new strategy for cheating sportsmen. These growth hormone releasing peptides (GHRP) are orally active and induce an increased production of endogenous growth hormone (GH). While the established test for exogenous GH fails, the misuse of these prohibited substances remains unrecognized. The present study provides data for the efficient extraction of a variety of known drug candidates (GHRP-1, GHRP-2, GHRP-4, GHRP-5, GHRP-6, alexamorelin, ipamorelin, and hexarelin) from human urine with subsequent mass spectrometric detection after liquid chromatographic separation. The used method potentially enables the retrospective evaluation of the acquired data for unknown metabolites by means of a non-targeted approach with high-resolution/high-accuracy full-scan mass spectrometry with additional higher collision energy dissociation experiments. This is of great importance due to the currently unknown metabolism of most of the targets and, thus, the method is focused on the intact peptidic drugs. Only the already characterised major metabolite of GHRP-2 (d-Ala-d-2-naphthylAla-l-Ala, as well as its stable isotope-labelled analogue) was synthesised and implemented in the detection assay. Method validation for qualitative purpose was performed with respect to specificity, precision (<20%), intermediate precision (<20%), recovery (47–95%), limit of detection (0.2–1 ng/mL), linearity, ion suppression and stability. Two stable isotope-labelled internal standards were used (deuterium-labelled GHRP-4 and GHRP-2 metabolite). The proof-of-principle was obtained by the analysis of excretion study urine samples obtained from a single oral administration of 10 mg of GHRP-2. Here, the known metabolite was detectable over 20 h after administration while the intact drug was not observed.     

LC�CMS�CMS Method for the Analysis of New Non-Imidazole Histamine H3 Receptor Antagonist 1-[3-(4-tert-Butylphenoxy)propyl]piperidine in Rat Serum��Application to Pharmacokinetic Studies

A sensitive and specific liquid chromatography electrospray ionisation-tandem mass spectrometry method for determination of new non-imidazole histamine H(3) receptor antagonist 1-[3-(4-tert-butylphenoxy)propyl]piperidine (DL76) in rat serum has been developed and validated. Chromatography was performed on a XBridge? C18 analytical column (2.1?×?30?mm, 3.5?μm, Waters, Ireland) with gradient elution using a mobile phase containing acetonitrile and water with an addition of 0.1% of formic acid. Detection was achieved by an Applied Biosystems MDS Sciex (Concord, Ontario, Canada) API 2000 triple quadrupole mass spectrometer. Electrospray ionization (ESI) was used for ion production. The limit of detection in the SRM mode was found to be 0.5?ng?mL(-1). The limit of quantification was 1?ng?mL(-1). The precision and accuracy for both intra- and inter-day determination of DL76 ranged from 1.65 to 15.09% and from 88.74 to 113.43%. The results of this analytical method validation allow to carry out pharmacokinetic studies in rats. The method was used for the pilot study of the pharmacokinetic behavior of DL76 in rats after intravenous administration.