Kharkiv University Bulletin. Chemical Series

Towards the discovery of molecules with anti-COVID-19 activity: Relationships between screening and docking results

Dmytro Anokhin — 2024-06-21

The study presents the results of a combined approach to the theoretical description of potential antiviral activity against COVID-19. We found that pharmacophore screening based on limited experimental data on "protein-ligand" binding complexes might have low predictive ability. Therefore, in this study, we build a model based on the statistical description of QSAR for data obtained from docking which serves as a basis for adequate prediction of ligand activity. We use the logistic regression to construct the predictive model for the main protease M^pro inhibitors.

C=O group versus C=C(CN)2 moiety from the viewpoint of electronic absorption and fluorescence spectroscopy

Andrey Doroshenko — 2024-06-21

The effect of changing carbonyl group to methylidenepropanedinitrile moiety onto electronic absorption and fluorescence spectra was analyzed theoretically within DFT / TD-DFT scheme. Chalcone (1,3-diphenylpropeneone) was chosen as a model molecular system of this investigation. Methylidenepropanedinitrile moiety was characterized as more suitable for obtaining bright fluorescent products, however, its electron accepting ability was lower compared to carbonyl group, contrary to widespread insights.

Microstructure and transport properties of lithium hexafluorophosphate solutions in binary mixture of dimethyl carbonate with ethylene carbonate from molecular dynamics simulation

Dmytro Dudariev — 2024-06-21

Solutions of Li⁺ salts in many non-aqueous solvents used in Li-ion batteries have a maximum conductivity curve depending on the electrolyte concentration. For the microscopic interpretation of this phenomenon for one of the most popular electrolytes, LiPF₆ solutions in a binary mixture of dimethyl carbonate (DMC) / ethylene carbonate (EC) (1:1), molecular dynamics simulations of the corresponding systems with a salt content of 0.1, 0.5, 1.0, 1.5 and 2.0 M were performed. The potential models for DMC and EC molecules were developed as the combination of two different force fields: OPLS-AA and GAFF in order to properly reproduce the diffusion coefficients of pure solvents. The structure has been analyzed in terms of radial distribution functions (RDFs) and running co-ordination numbers (RCNs). The results show that Li⁺ cation can form contact ion pairs (CIPs) and solvent shared ion pairs (SSIPs) in the solutions. The total coordination number of the cation remains the same at around 5.5-6.0 for all concentrations. Also, EC molecules and PF₆^- anions are competing for the position in the first coordination shell of the cation. The aggregate analysis with two different distance criteria was performed: minima on the RDFs and the minima on the second derivative of the RCNs. The diffusion coefficients for all components of the solutions and viscosity of simulated systems were also obtained. The diffusion coefficients for all components are decreasing and viscosity values are non-linearly increasing with the salt concentration increase. The conductivity values were obtained with the diffusion coefficient values of ions via Nernst-Einstein relation. These findings and the drastic viscosity increase at 1.0 M and at higher concentrations of LiPF₆ are in agreement with the calculated experimental conductivity values.

Electronic structure of mesoionic compounds. The classification problem

Mariia Kyrpa — 2024-06-21

Mesoionic compounds are conventionally categorized into two types based on the primary origin of electrons within the conjugated system, specifically determined by the arrangement of heteroatoms in the five-membered ring. An examination of diverse mesoionic compounds has been undertaken to address the pivotal query surrounding their classification: does the primary origin of electrons hold significance, and does this criterion demarcate a definitive boundary between the two types of compounds? To comprehensively address this issue, the DFT calculations were performed for a set of mesoionic molecules. The electronic properties of the molecules were studied within the frameworks of quantum theory of atoms in molecules (QTAIM) and the Nuclear Independent Chemical Shift (NICS).

To comprehend the topological distinctions among representatives of the two types, we describe a set of indices designed to characterize the spatial distribution of electronic parameters within the molecular frameworks. The results obtained show that the existing classification is to a certain extent justified, with the main distinguishing factor between the two types being the nature of the distribution of the resulting ellipticities of bonds in five-membered ring and the structure of the molecular orbitals. At the same time, based on NICS calculations we concluded that both classes are not characterized by pronounced aromaticity of the mesoionic ring for the selected set of molecules.

Computing ionization free energies of indicator dyes in micelles with fast growth alchemical transformation

Volodymyr Farafonov — 2024-06-21

The problem of calculating free energy change in a process using molecular dynamic simulation has wide practical application, but is non-trivial. The developed methods are classified into equilibrium and non-equilibrium ones. In general, equilibrium methods have lower systematic error but require longer simulation time. This contributes to the interest in non-equilibrium methods, in particular the fast growth method. Here, this method is applied to the process of ionization of acid-base indicators bound by micelles of ionic surfactants. The alchemical transformation approach was utilized, where the interactions of the indicator's acidic proton with the rest of the system are coupled to coupling parameter λ ranged from 0 in the acidic form to 1 in the basic form. The values of deprotonation free energy of the typical indicator dye 4-n-dodecyl-2,6-dinitrophenol in water and micellar solutions of two common cationic and anionic surfactants were estimated and compared with the results of the equilibrium method. A simulation procedure allowing minimize the effect of non-equivalent sampling between the two methods was employed. It is noted that for the studied systems the method can provide the discrepancy within 2% while requiring significantly shorter total simulation time. Specifically, the duration of simulating non-physical intermediate states drastically reduces. The optimal duration of the fast growth runs is 20 ps in this case, while both shortening and prolonging the runs increase the error. The optimal number of fast growth runs can be found as one per each 100 ps of simulation of acidic or basic form. Reducing the number of runs also increases the discrepancy with the equilibrium method. The obtained results show the promise of the fast growth method for calculating shifts of the dissociation constants of acid-base indicators in micellar solutions with the perspective of further estimating the surface electrostatic potential of micelles.

On structural invariants of energy spectrum of S=1 Heisenberg antiferromagnets with single-ion anisotropy

Victor Tokariev — 2024-06-21

We study the relationship of the energy spectrum of finite S=1 Heisenberg antiferromagnets with their structure in the presence of single-ion anisotropy. We show that in the limit of strong easy-plane anisotropy magnets with the structure of adjacency cospectral graphs have equal ground state energies with magnetization M=0. We derive additional necessary condition for equality of lowest energy levels with M=±1. For strong easy-axis anisotropy we found that bipartite S=1 magnets with structures, for which S=1/2 Ising models have equal spectra for arbitrary longitudinal magnetic field, have close energy spectra of S=1 antiferromagnets for arbitrary parameter of single-ion anisotropy. For moderate easy-axis anisotropy bipartite S=1 antiferromagnets with equal energies of spin waves in linear approximation are also approximately isoenergetic. Overall, this explains the remarkable similarity of energy spectra in M=0 subspace for S=1 antiferromagnetic Heisenberg model on bipartite cospectral regular graphs.

Comparison of radical scavenging properties of gosypol and its derivatives in the reaction with DPPH

Oleksii Dykun — 2024-06-21

Radical scavenging activity of 7,7'-ditosyloxygossypol in reaction with 2,2'-diphenyl-1-piсrylhydrazyl (DPPH) in ethanol was evaluated by total stoichiometries and EC₅₀ values. The stoichiometric coefficient of the reaction of DPPH with 7,7'-ditosyloxygossypol is close to two. This indicates that in ethanol this compound exists mainly in the dilactol tautomeric form, and the lactol hydroxyl groups are not capable of reacting with DPPH. Such a result can be an indirect confirmation that no tautomeric transformation occurs during the reaction with DPPH due to the consumption of one of the tautomers. A comparative analysis of the radical scavenging properties of 7,7'-ditosyloxygossypol, gossypol, gossypol Schiff base with 4-methoxyaniline and gossypol hydrazone with phenylhydrazine in reactions with DPPH was carried out. The influence of tautomerism on the radical scavenging properties of the investigated compounds was determined. It was established that the presence of NH groups in the structure of gossypol Schiff base with 4-methoxyaniline and hydrazone with phenylhydrazine does not increase the radical scavenging properties in the reaction with DPPH. And the change of the tautomeric form and the appearance of additional phenolic hydroxyl groups (instead of NH groups) will lead to increased radical scavenging properties. It was shown that the most effective radical scavenging agent is the gossypol hydrazone in the diimine tautomeric form (6 phenolic hydroxyl groups). And the least effective is 7,7'-ditosyloxygossypol (2 phenolic hydroxyl groups).

Absorption spectra of Nitrazine Yellow indicator. Experimental data and quantum chemical evaluations

Inna Khristenko — 2024-06-21

This article presents an experimental investigation and theoretical analysis of the electronic absorption spectra of the indicator nitrazine yellow (NY) in aqueous solutions. Quantum chemical modeling of electronically excited states is performed within the framework of time-dependent density functional theory (TD-DFT). A variety of approaches and basis sets are explored, particularly focusing on the B3LYP and CAM-B3LYP functionals. The standard 6-31+G(d,p) basis set is employed, along with combinations using pseudopotential basis sets for Na and S atoms.

In the first variant of calculations, the LanL2DZ basis set (and corresponding pseudopotential) is used for all atoms within the molecules. In the second variant, the LanL2DZ basis set is applied exclusively to Na and S atoms, while the standard valence double-zeta split basis set 6-31+G(d,p) is utilized for the remaining elements (H, C, N, O). Solvent effects on the absorption spectra are incorporated using the polarizable continuum model, employing the linear response method.

Calculations are performed on three forms of NY. Two of these forms (A and B) correspond to azo-hydrazone tautomerism, while the third form (C) represents the deprotonated state. Ground state geometry calculations indicate that the π-conjugated part of form A is largely planar and stabilized by an intramolecular hydrogen bond O-H...N. The tautomeric form B is also characterized by a high degree of planarity in its conjugation system. In contrast, the deprotonated form C shows significant rotation of the 2,4-dinitrophenyl group and the nitro group in the ortho position of the benzene ring.

Analysis of excited-state calculations for the three forms of NY reveals that both variants (B3LYP/LanL2DZ and B3LYP/LanL2DZ/6-31+G(d,p)) require minimal computational resources while producing results that correspond well with the experimentally observed absorption bands.

Volodymyr Dmytrovich Kalugin

Editorial board — 2024-06-21