Biophysical Bulletin

Calculation of the relative permittivity of Rhodamine 6G using the quantum mechanical method

Iuliia Riabenko — 2023-12-19

Background: The article describes a method for calculating the permittivity of organic molecules in quantum mechanics using the well-studied Rhodamine 6G molecule as an example. The study of optical properties of large organic molecules requires not only experimental data but also the use of calculations obtained both analytically and numerically.

Objectives: Methods for calculating permittivity as phenomenological characteristics of a sample are to be tested on well-studied molecules to be further applied to more complex nonlinear structures. However, the integral changes need to be approximated in the wave functions of large molecules.

Material and methods: The numerical simulations in MATLAB were carried out to be compared with the data from Gaussian 09, which are accurate for such small molecules as Rhodamine 6G. MATLAB calculated permittivity values for the frequency domains corresponding to absorption and fluorescence based on the Fermi golden rule. Hence, any molecule can be represented as a composite quantum mechanical system. Meanwhile, Gaussian 09 used the DFT method to determine permittivity.

Results: The Fermi golden rule can be applied due to the representation of the molecule as a complex quantum mechanical system. The proposed numerical methods minimize error by using the Dirac delta function. According to our hypothesis, the sum of the wave function of a particle in a potential well and a particle in a ring equals the wave function of the entire system, thus making it possible to study large molecules. As a result of the calculation for two wavelengths of 337 and 573 nm, the permittivity results calculated using the proposed method in MATLAB are 2.98 and 6.27, respectively. Gaussian 09 calculated the same parameters at 2.85 and 6.23.

Conclusion: The resulting datasets show a high degree of correlation. Therefore, the research hypothesis has been confirmed. The selected method also proved efficient, hence the enhancement of luminescence can be achieved by changing the relaxation time of the excited state. Plasmonic nanostructures with predetermined properties will controllably enhance the resulting field by the square of the superposition modulus of their near-field. Consequently, conditions for highly coherent radiation with high intensity and polarization can be predicted and calculated before an experiment is carried out.

New promising agents against COPD and asthma among the amides of 1-oxo-3-phenyl-isochroman-6-carboxylic acid

Alex Nyporko — 2023-12-30

Background: Bronchodilators, which are compounds that can relax airway smooth muscle, are perhaps the most important component of combination therapy for chronic obstructive pulmonary disease, one of the most common non-communicable diseases in the world, which is the second most lethal disease after cardiovascular disease. Unfortunately, current clinical bronchodilators, whose activity is mediated by their interaction with muscarinic acetylcholine receptors, have side effects (up to myocardial infarction) due to their cross-affinity for different types of these receptors, including those prevalent in the heart muscle.

Objectives: The aim of this work is to search/develop compounds — effective bronchodilators capable of selectively inhibiting type 3 muscarinic acetylcholine receptors (M₃ receptors), predominantly present in smooth muscles and not characteristic of cardiomyocytes.

Materials and Methods: High-throughput virtual screening of a collection of 150,000 compounds was conducted on the spatial structure of the M₃ receptor, reconstructed in our previous studies. The effect of substances on contractile activity was investigated using tensometry in isometric mode on multicellular tracheal preparations. Antagonistic activity and type of inhibition were determined against the background of acetylcholine application (concentration range 10^-10–10^-3 M). To establish the affinity value of the compound-antagonist, the Schild regression equation was used.

Results: Based on virtual screening data, a series of compounds — amides of 1-oxo-3-phenyl-iso-chroman-6-carboxylic acid — were selected for biological testing. For two of these compounds (Compounds 1 and 7), the ability to selectively inhibit M₃ receptors was demonstrated. Specifically, the affinity value pK_B for Compound 1 was 7.28 ± 0.70, with an IC₅₀ of 5.25·10^-8 M. A critically important advantage of this compound is its ability, at equal concentrations, to more effectively inhibit signal transmission through M₃ receptors compared to ipratropium bromide — a clinical cholinergic receptor inhibitor.

Conclusions: The sufficient effectiveness of inhibition and significantly increased selectivity of the studied compounds specifically towards M₃ receptors provide strong grounds to consider these compounds as promising precursors of new generation cholinolytic drugs with targeted action on M₃-type cholinergic receptors.

C60 fullerene nanoparticles permeability through the model lipid envelope of coronavirus and their anticoronavirus effect in the in ovo system

Vasyl Hurmach — 2023-12-30

Background: An urgent problem of modern biomedicine is the search for potential ways to reduce the spread of coronavirus infections in human and animal populations and eliminate the impact of coronavirus on their bodies.

Aim of the work was to determine the structural organization of C₆₀ fullerenes in a model cell medium, to assess their potential ability to penetrate the model lipid envelope of a coronavirus, thus destroying its integrity, as well as the effectiveness of the anticoronavirus action in the in ovo system.

Methods: The research was conducted using the Gromacs 2020 software package and the Charmm36 force field. The CHARMM-GUI web resource was used to construct the lipid envelope of a coronavirus. Virological and toxicological methods were used in the in ovo experiments.

Results: It is shown that at the initial stages of molecular dynamics C₆₀ fullerene forms small nanoclusters in the amount of 7–16 molecules, which is affected by the initial concentration of C₆₀ fullerene in a model cell medium. At the same time, the shape of nanostructures for the number of molecules over 16 may differ from the correct spherical shape. It was established that C₆₀fullerene and its nanoclusters are able to penetrate inside the lipid envelope of a coronavirus. In particular, a single C₆₀ molecule can migrate, completely embed itself in the lipid envelope, or move within it. It was found that C₆₀ fullerene aqueous solution, at the maximum permissible concentration (MPC) of 30 μg/embryo, reduces the infectious activity of the chicken infectious bronchitis (CIB) coronavirus when it is used 1, 2 and 4 h after the infection of a sensitive biological system with a coronavirus.

Conclusions: It is shown that aggregation of C₆₀ fullerene in a model cell medium can occur in different ways: either before penetration into the lipid envelope of a coronavirus, or inside it. C₆₀ fullerenes, both individually and as part of nanoclusters, are able to form pores in the envelope of a coronavirus, destroying its integrity, which possibly leads to disruption of the corresponding stages of its replication cycle and attachment to cell receptors. It was established that C₆₀ fullerene aqueous solution, when used in the MPC value, shows antiviral activity against the CIB coronavirus in its early stages of interaction with the cell (1–4 h).

Kinetic biopharmaceutical studies of a new paracetamol–glucosamine analgetic drug

O. V. Vashchenko — 2023-12-29

Background: Intercomponent drug interactions could play important role for drug release, membrane permeability and membranotropic action. Therefore, newly developed drugs need for checking their biopharmaceutical characteristics. A new analgetic drug based on paracetamol (Actimask® Acetaminoprofen) and a hepatoprotector N-acetyl-D-glucosamine has been developed, with increased safety and potentiation of the analgesic effect (Ruban O., 2022). Multibilayer lipid membranes were chosen as promising testing medium due to their proved appropriation and sensitivity for study multi-compound drug-membrane interactions. It is the basis for a kinetic approach allowing elucidation of biopharmaceutical interactions in model membrane medium.

Objectives: Revealing changes of paracetamol release and membrane penetration in the new paracetamol-glucosamine analgetic drug as well as estimation the rationale of the approach developed to trace biopharmaceutical interactions in model membrane medium.

Materials and Methods: L-a-dimyristoyl phosphatidylcholine (DMPC) multibilayer membrane was used as a model biomimetic testing medium. Differential scanning calorimetry (DSC) was applicated to trace kinetics of drug-membrane interactions.

Results: Gelatin as a part of Actimask® increased the characteristic time of paracetamol diffusion about threefold, but it had no pronounced effect on the equilibrium paracetamol penetration into the membrane. Sole glucosamine manifested no membranotropic effect under the experimental conditions, however, in combination with gelatin, it sufficiently reduced equilibrium paracetamol penetration while paracetamol diffusion remained within the experimental error. The full drug formulation increased membrantoropic effect by 34 % in compared with sole paracetamol.

Conclusions: Glucosamine and gelatin can affect both kinetic and equilibrium parameters of paracetamol-membrane interactions, while the full set of the drug components is able to increase the effect which correlates well with the previously established enhancement of analgetic effect of the drugs. The approach developed allows accurate tracing of drug release and membrane penetration depending on a set of drug components. Generally, the results obtained prove the rationale of applying the approach to pre-clinical drug examination.