Synthesis of methotrexate-betulonic acid hybrids and evaluation of their effect on artificial and Caco-2 cell membranes.

An efficient protocol for the synthesis of novel methotrexate-betulonic acid hybrids with a (tert-butoxycarbonylamino)-3,6-dioxa-8-octanamine (Boc-DOOA) linkage has been developed. Reaction of N-(2-(2-(2-aminoethoxy)ethoxy)ethyl)-betulonamide with methotrexate resulted in a mixture of isomeric conjugates which were separated by column chromatography. Their structures and composition have been fully established by 1H NMR, 13C spectra, FAB mass spectrometry and elemental analysis. The identity of conjugates was confirmed by LC-MS data. Membranotropic properties of the new hybrids were assessed on the basis of their interactions with artificial lipid membranes by differential scanning calorimetry (DSC) method. The ability of the conjugates to penetrate Caco-2 cells is inferior to methotrexate. Probably, this is due to the increasing lipophilicity, the affinity of these hybrid molecules for the lipid bilayer increases, which is confirmed by experiments with artificial membranes.

Portable Device for Multipurpose Research on Dendritic Yanson Point Contacts and Quantum Sensing.

Quantum structures are ideal objects by which to discover and study new sensor mechanisms and implement advanced approaches in sensor analysis to develop innovative sensor devices. Among them, one of the most interesting representatives is the Yanson point contact. It allows the implementation of a simple technological chain to activate the quantum mechanisms of selective detection in gaseous and liquid media. In this work, a portable device for multipurpose research on dendritic Yanson point contacts and quantum sensing was developed and manufactured. The device allows one to create dendritic Yanson point contacts and study their quantum properties, which are clearly manifested in the process of the electrochemical cyclic switchover effect. The device tests demonstrated that it was possible to gather data on the compositions and characteristics of the synthesized substances, and on the electrochemical processes that influence the production of dendritic Yanson point contacts, as well as on the electrophysical processes that provide information on the quantum nature of the electrical conductance of dendritic Yanson point contacts. The small size of the device makes it simple to integrate into a micro-Raman spectrometer setup. The developed device may be used as a prototype for designing a quantum sensor that will serve as the foundation for cutting-edge sensor technologies, as well as be applied to research into atomic-scale junctions, single-atom transistors, and any relative subjects.

Selective detection of complex gas mixtures using point contacts: concept, method and tools.

Of all modern nanosensors using the principle of measuring variations in electric conductance, point-contact sensors stand out in having a number of original sensor properties not manifested by their analogues. The nontrivial nature of point-contact sensors is based on the unique properties of Yanson point contacts used as the sensing elements. The quantum properties of Yanson point contacts enable the solution of some of the problems that could not be solved using conventional sensors measuring conductance. In the present paper, we demonstrate this by showing the potential of quantum point-contact sensors to selectively detect components of a gas mixture in real time. To demonstrate the high efficiency of the proposed approach, we analyze the human breath, which is the most complex of the currently known natural gas mixtures with extremely low concentrations of its components. Point-contact sensors allow us to obtain a spectroscopic profile of the mixture. This profile contains information about the complete set of energy interactions occurring in the point contact/breath system when the breath constituents adsorb to and desorb from the surface of the point-contact conduction channel. With this information we can unambiguously characterize the analyzed system, since knowing the energy parameters is key to successfully identifying and modeling the physicochemical properties of various quantum objects. Using the point-contact spectroscopic profile of a complex gas mixture it is possible to get a functional dependence of the concentration of particular breath components on the amplitude of the sensor output signal. To demonstrate the feasibility of the proposed approach, we analyze the point-contact profiles from the breath of several patients and compare them with the concentrations of serotonin and cortisol in the body of each patient. The obtained results demonstrate that the proposed methodology allows one to get an effective calibration function for a non-invasive analysis of the level of serotonin and cortisol in the human body using the point-contact breath test. The present study indicates some necessary prerequisites for the design of fast detection methods using differential sensor analysis in real time, which can be implemented in various areas of science and technology, among which medicine is one of the most important.