A study of host-guest complexation between amodiaquine and native cyclodextrin. Characterization in solid state and its in-vitro anticancer activity

Amodiaquine (AQ) has been used widely as an antimalarial drug. Amodiaquine is a mannich base 4-amino quinolone with a mode of action similar to that of chloroquine. The inclusion complex of AQ with β-Cyclodextrin (β-CD) in solution phase is studied from the ground and excited state with UV-Visible and fluorescence spectroscopy, respectively. A binding constant and stoichiometric ratio between AQ and β-CD are calculated by BH equation. The solid complexes are prepared by physical method (PM), kneading method (KM) and co-precipitation method (CP). The solid complex is characterized by Fourier transform infrared spectroscopy, scanning electron microscopy and powder X-ray diffraction. The CP method gives the solid product with a better yield than that of physical mixture and KM products. The orientation and structure of the complex are proposed based on the analysis of Patch-Dock server. The anticancer activity also performed for pure AQ and their complex with β-CD. It is clearly shown that an improvement of anticancer activity of AQ while forming complex with β-CD. The solid inclusion complex behaves as the better anticancer ability than AQ alone.     

Photochemical Synthesis of the Bioactive Fragment of Salbutamol and Derivatives in a Self-Optimizing Flow Chemistry Platform

The implementation of self-optimizing flow reactors has been mostly limited to model reactions or known synthesis routes. In this work, a self-optimizing flow photochemistry platform is used to develop an original synthesis of the bioactive fragment of Salbutamol and derivatives. The key photochemical steps for the construction of the aryl vicinyl amino alcohol moiety consist of a C−C bond forming reaction followed by an unprecedented, high yielding (>80 %), benzylic oxidative cyclization.     

SpecInfo—A multidimensional spectroscopic interpretation system

Formerly developed inside the BASF company for inhouse use, Spec-Info is now available to the public due to a project of the German Federal Ministry of Research and Technology (BMFT). The system is meant as a supporting tool for interpreting spectroscopists elucidating the structure of chemical compounds. SpecInfo supports the synergistic use of NMR-, IR- and MS-spectra for the correlation between structure and spectral patterns, based on a large spectroscopic databank. Additionally, statistical evaluations on this database are used to link spectral patterns to (sub-) structures responsible for these patterns.     

Practical guide for selection of 1H qNMR acquisition and processing parameters confirmed by automated spectra evaluation

In our recent paper, a new technique for automated spectra integration and quality control of the acquired results in qNMR was developed and validated (Monakhova & Diehl, Magn. Res. Chem. 2017, doi: 10.1002/mrc.4591 ). The present study is focused on the influence of acquisition and postacquisition parameters on the developed automated routine in particular, and on the quantitative NMR (qNMR) results in general, which has not been undertaken previously in a systematic and automated manner. Results are presented for a number of model mixtures and authentic pharmaceutical products measured on 500‐ and 600‐MHz NMR spectrometers. The influence of the most important acquisition (spectral width, transmitter [frequency] offset, number of scans, and time domain) and processing (size of real spectrum, deconvolution, Gaussian window multiplication, and line broadening) parameters for qNMR was automatically investigated. Moderate modification of the majority of the investigated parameters from default instrument settings within evaluated ranges does not significantly affect the trueness and precision of the qNMR. Lite Gaussian window multiplication resulted in accuracy improvement of the qNMR output and is recommended for routine measurements. In general, given that the acquisition and processing parameters were selected based on the presented guidelines, automated qNMR analysis can be employed for reproducible high‐precision concentration measurements in practice.     

Rosin Derivatives as a Platform for the Antiviral Drug Design

The increased complexity due to the emergence and rapid spread of new viral infections prompts researchers to search for potential antiviral and protective agents for mucous membranes among various natural objects, for example, plant raw materials, their individual components, as well as the products of their chemical modification. Due to their structure, resin acids are valuable raw materials of natural origin to synthesize various bioactive substances. Therefore, the purpose of this study was to confirm the possibility of using resin acid derivatives for the drug design. As a result, we studied the cytotoxicity and biological activity of resin acid derivatives. It was shown that a slight decrease in the viral load in the supernatants was observed upon stimulation of cells (II) compared with the control. When using PASS-online modeling (Prediction of Activity Spectra for Substances), the prediction of the biological activity spectrum showed that compound (I) is capable of exhibiting antiviral activity against the influenza virus. The use of the SWISS-ADME webserver to reveal the drug-like properties of compounds did not directly indicate the presence of antiviral activity. These results indicate the potential of resin acid derivatives as a starting point for extensive research in the study of biological activity.     

A Universal Cassette-Based System for the Dissolution of Solid Targets

Cyclotron-based radionuclides production by using solid targets has become important in the last years due to the growing demand of radiometals, e.g., ⁶⁸Ga, ⁸⁹Zr, ^43/47Sc, and ^52/54Mn. This shifted the focus on solid target management, where the first fundamental step of the radiochemical processing is the target dissolution. Currently, this step is generally performed with commercial or home-made modules separated from the following purification/radiolabelling modules. The aim of this work is the realization of a flexible solid target dissolution system to be easily installed on commercial cassette-based synthesis modules. This would offer a complete target processing and radiopharmaceutical synthesis performable in a single module continuously. The presented solid target dissolution system concept relies on an open-bottomed vial positioned upon a target coin. In particular, the idea is to use the movement mechanism of a syringe pump to position the vial up and down on the target, and to exploit the heater/cooler reactor of the module as a target holder. All the steps can be remotely controlled and are incorporated in the cassette manifold together with the purification and radiolabelling steps. The performance of the device was tested by processing three different irradiated targets under different dissolution conditions.     

Modern automated microextraction procedures for bioanalytical,environmental, and food analyses

Sample preparation frequently is considered the most critical stage of the analytical workflow. It affects the analytical throughput and costs; moreover, it is the primary source of error and possible sample contamination. To increase efficiency, productivity, and reliability, while minimizing costs and environmental impacts, miniaturization and automation of sample preparation are necessary. Nowadays, several types of liquid-phase and solid-phase microextractions are available, as well as different automatization strategies. Thus, this review summarizes recent developments in automated microextractions coupled with liquid chromatography, from 2016 to 2022. Therefore, outstanding technologies and their main outcomes, as well as miniaturization and automation of sample preparation, are critically analyzed. Focus is given to main microextraction automation strategies, such as flow techniques, robotic systems, and column-switching approaches, reviewing their applications to the determination of small organic molecules in biological, environmental, and food/beverage samples.     

Transient Analysis for State-Dependent Queues with Catastrophes

Abstract

Queueing systems with catastrophes and state-dependent arrival and service rates are considered. For two types of queueing systems namely, queues with discouraged arrivals and infinite server queue, explicit expressions for the transient probabilities of system size are obtained by using continued fractions technique. Some system performance measures and steady-state probabilities are studied. The effect of system parameters on system size probabilities are also illustrated numerically. It is observed that the steady-state probabilities differ when catastrophes are present, while they are identical in the absence of catastrophes.     

On the incomplete results for the heterogeneous server problem

In this article, we show that the arguments in Rykov [9] on the optimality of a threshold routing policy when there are more than two heterogeneous servers are incomplete. AMS Subject Classifications: 93E20, 60K25, 90B22     

Analysis of Alternating-Priority Queueing Models with (Cross) Correlated Switchover Times

This paper analyzes a single server queueing system in which service is alternated between two queues and the server requires a (finite) switchover time to switch from one queue to the other. The distinction from classical results is that the sequence of switchover times from each of the queues need not be i.i.d. nor independent from each other; each sequence is merely required to form a stationary ergodic sequence. With the help of stochastic recursive equations explicit expressions are derived for a number of performance measures, most notably for the average delay of a customer and the average queue lengths under different service disciplines. With these expressions a comparison is made between the service disciplines and the influence of correlation is studied. Finally, through a number of examples it is shown that the correlation can significantly increase the mean delay and the average queue lengths indicating that the correlation between switchover times should not be ignored. This has important implications for communication systems in which a common communication channel is shared amongst various users and where the time between consecutive data transfers is correlated (for example in ad-hoc networks). In addition to this a number of notational mistakes in well-known existing literature are pointed out. AMS subject classification: 68M20, 60J85 A shorter version of this work has been published in the proceedings of IEEE Infocom 2005. This work was partly sponsored by the EURONGI network of excellence.