Kharkiv University Bulletin. Chemical Series

In silico Investigations of Triazole-Tromethoxyphenyl Derivatives as Anti-Proliferative Agents against Adenocarcinomic Human Alveolar Basal Epithelial Cells (A549): DFT, QSAR and Molecular Docking Approaches.

2025-08-31T15:38:56+00:00

Twenty-eight sets of synthesized triazole-trimethoxyphenyl derivatives (TPDs) were considered as anti-proliferative drugs against human alveolar basal epithelial (A549) cancer cell lines using DFT, QSAR, ADMET profile and molecular docking methods. The considered compounds were used to develop a robust QSAR model, which was used to design new TPD compounds that could serve as anti-proliferative drug candidate against human alveolar basal epithelial (A549) cancer. The parameters obtained from DFT calculations such as the HOMO, LUMO, Dipole moment, chemical hardness and softness favoured TPD-11 and TPD-25 over etopoxide as strong inhibitors against human alveolar basal epithelialcancer cell (A549), which agreed with the experimental data. The QSAR modeling and validation indicated the major influence of Moran autocorrelation – lag 4/weighted by polarizabilities (MATS4p), Centered Broto-Moreau autocorrelation - lag 7/weighted by charges (ATSC7c), Minimum E-State descriptors of strength for potential Hydrogen Bonds of path length 3 (minHBint3) and Count of atom-type E-State: C (naasC) descriptors on the reported anticancer activity of the drugs in the A549- MLR-GFA QSAR (R² = 0.8146, adjusted R² = 0.7874, Q²_Loo= 0.6015 and R² - Q²_Loo= 0.2582). Using the model data, four new TPDs (NTPD-3, NTPD-4, NTPD-6 and NTPD-9) were proposed. The DFT and molecular docking analysis showed that these four compounds could be good inhibitors against A549 than etopoxide. However, the ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties revealed NTPD-6 showed excellent pharmacokinetic and toxicological profiles and might serve as a road map for new and more effective anticancer agents.

Extraction of radionuclides 137Cs, 90Sr, 90Y and UO22+ from aqueous solutions using solid-Phase extractants impregnated with calix[4]arene phosphine oxides.

2025-08-31T15:39:00+00:00

The extraction of radionuclides ¹³⁷Cs,⁹⁰Sr, ⁹⁰Y, and UO₂²⁺ was studied using solid-phase extractants SPE-TBP, SPE-C45 and SPE-CIP67 depending on the acidity of the aqueous solution. SPE-C45 and SPE-CIP67 are porous styrene-divinylbenzene copolymer pellets impregnated with calix[4]arene tetraphosphine oxide C45 (5,11,17,23-tetrakis-diethylphosphinoylmethyl-25,26,27,28-tetrapropoxycalix[4]arene) and CIP67 (5,11,17,23-tetrakis-dipropylphosphinoylmethyl-25,26,27,28-tetrapropoxycalix[4]arene). Commercial solid-phase extractant SPE-TBP based on tributylphosphate was used for comparison. The influence of the radionuclides contact time with extractant on the establishment of extraction equilibrium was analyzed. It was shown that the equilibria in the systems using SPE are established in 3-4 hours.

A significant influence of the acidity of the aqueous solution on the extraction efficiency of the radionuclides was found: an increase in acidity leads to an increase in the distribution coefficients.

The influence of the nature of cations on the extraction efficiency is shown. The extraction of the radionuclides increases in the following series: UO₂²⁺> ⁹⁰Y > ⁹⁰Sr > ¹³⁷Cs.

It was revealed that the extraction of the radionuclides depends on the length of the alkyl radical at the phosphorus atom of the macrocyclic skeleton of calix[4]arene phosphine oxide. Cations are extracted more efficiently with calix[4]arene of shorter alkyl radical length at phosphorus atom. The ability of SPE-calixarenes towards the studied radionuclides exceeds the extraction ability of SPE-TBP and varies in the following order: SPE-TBP< SPE-CIP67< SPE-C45.

The conducted studies have shown the possibility of using the studied solid-phase-liquid extraction systems in the organization of radiation control of natural waters. In this case, the method of solid-phase extraction is convenient for radionuclide extraction, as it is simple and allows minimizing waste.

Colloidal Behavior of Oxidized and Lysozyme-Coated Single-Walled Carbon Nanotubes. Analysis via Dynamic and Electrophoretic Light Scattering

2025-08-31T15:39:03+00:00

The concept of surface oxidation or noncovalent coating of carbon nanotubes for successful application in aqueous fluids has a cost in terms of pollution, fate, and toxicity. Co-existing components in vitro or in vivo can influence the nanotube colloidal behavior and affect their transport. In this work, the interaction of oxidized single-walled carbon nanotubes with CsI and Sr(NO₃)₂ and the effect of lysozyme on the colloidal behavior of these nanotubes in aqueous systems are examined using dynamic and electrophoretic light scattering.

The concentration regimes of CsI and Sr(NO₃)₂ that determine the colloidal stability and instability of oxidized single-walled carbon nanotubes were identified. Oxidizing of the nanotube surface enhances colloidal stability to CsI and adsorption of Sr²⁺ cations by decorating the surface with COOH groups. Selective binding of metal cations and large specific surface area favor the removal of heavy and radioactive metals in cationic form from the bulk phase.

Biological and medical applications contribute to the fact that the interactions of carbon nanotubes with lysozyme are the object of several works. Covalent and noncovalent decoration by the enzyme creates a combination of electrical, mechanical, thermal, and optical properties of carbon nanotubes with inherent antibacterial activity of lysozyme. For example, Horn et al. reported antimicrobial fibers with four times the toughness of spider silk. However, to the best of our knowledge, little is known about colloidal stability and interaction with ions of protein-coated carbon nanotubes.

Estimation of the binding free energy of doubly charged cations to amino acid functional groups by means of modern force fields.

2025-08-31T15:39:07+00:00

Purification of water from heavy metal ions is an urgent environmental problem. An actively studied method for this is the binding of metal ions by means of proteins that can be isolated from easily accessible plant materials. Carboxyl, thiolate groups of amino acid residues are capable of complexing with metal cations, which leads to the removal of pollutants from water. Methods of computational chemistry are actively used for research, in particular classical molecular dynamics modeling. The work evaluates the correctness of reproducing binding free energies of a number of doubly charged metal cations with functional groups of amino acids. A set of modern potential models of cations is used, which correctly reproduces the characteristics of cations in aqueous solution. Comparisons are made with experimentally measured stability constants of modeled complexes or their structural analogues. Calculations of free energies are performed by the method of alchemical transformation. It is shown that despite the validity of the potential models used, the binding free energies to functional groups of amino acids are generally poorly reproduced: moderately underestimated for the thiolate and amino groups, extremely overestimated for the carboxylate group, and incorrect for imidazole. Thus, it is shown that the classical molecular dynamics modeling method should be used with caution for calculation of the energy characteristics of metal binding by amino acids and proteins.

Magnetic properties of modified diamond spin chain

2025-08-31T15:39:08+00:00

The work is devoted to the theoretical study of the energy spectrum and magnetic properties of the modified antiferromagnetic spin (1/2, s) diamond chain. This is a frustrated mixed spin system with the unit cells formed by two spin ½ and one spin s>1/2. On the base of extended Lieb theorem we proved the possibility of the appearance of quantum phase transitions mediated by ratio of coupling parameters at arbitrary nonzero value of the spin s for the above model. The results of our exact diagonalization study for some finite chain clusters with s=1 supports this conclusion. We also studied analytically and numerically magnetic properties of Heisenberg –Ising diamond mixed spin chain. The exact energy spectrum of this model is found in analytical form at arbitrary values of model parameters. On the base of this spectrum we studied the field dependence of two-particle correlators for neighbor Ising spins. It was found that at special relation between coupling parameters there is a critical value of external magnetic field for which the above correlator takes zero value (the absence of the correlation between Ising spins). For infinite spin chain model we studied field dependence of specific magnetization by means of classical transfer- matrix method and found intermediate plateau in the low-temperature magnetization profile. According to our calculations, the size of this plateau depends strongly on the relations between coupling parameters of the model. We hope this feature of our model gives new possibilities for the design of new magnetic chemo-sensors.

Studying Ligand-Protein Interactions in the Era of Artificial Intelligence: Benchmarking Boltz-1 for 3D-Structure Prediction of Biomolecular Complexes

2025-08-31T15:39:11+00:00

Modeling ligand-protein interactions is essential in various scientific and industrial applications, especially in drug discovery and structural biology. In the past year, several AI-driven computational tools, such as AlphaFold 3 and Chai-1r, have revolutionized the field of biomolecular structure prediction. Most recently, an open-source deep learning model called Boltz-1 has also been introduced, marking a significant advancement in biomolecular interaction modeling. To assess the performance of Boltz-1 in comparison to other computational tools, we benchmarked its capability to accurately reproduce the 3D structures of various biomolecular complexes. These complexes included essential enzymes and ligands of varying complexities, such as low-molecular organic ligands, sterols, and peptidomimetics. We found that Boltz-1 demonstrated strong performance in reproducing protein folding, achieving a root mean square deviation (RMSD) of less than 1 Å. When compared to other computational tools, such as Glide by Schrödinger and AutoDock Vina, Boltz-1's ability to predict the 3D structures of biomolecular complexes was well balanced. It successfully re-docked a diverse set of ligands with varying complexities, achieving binding poses that were comparable to those of the commercial software Glide. In terms of a RMSD and ligand-binding ranking, Boltz-1 outperformed the widely used docking tool AutoDock Vina for all evaluated ligands, creating opportunities to enhance computational screening of ligand-protein interactions.

Fast vs Accurate: Evaluating TD-DFTB for Large-Scale Screening of Organic Dyes

2025-08-31T15:39:14+00:00

The effectiveness of the semi-empirical TD-DFTB (Time-Dependent Density Functional Tight Binding) method in reproducing the spectral properties of organic dyes was investigated using the example of a library of isomers of the thiophene-containing donor-acceptor Effenberger dye, known for its pronounced solvatochromism. The aim of the work was to find out how suitable the accelerated TD-DFTB approach is for modern molecular design tasks, with a necessity to quickly and reliably identify compounds with intense electronic transitions in the long-wavelength region of the UV-Vis spectrum. The library contained 60 structures in which the positions of the donor (N,N-dimethylamine) and acceptor (NO₂) substituents, as well as the degree of planarity of the π-framework, were systematically varied. For each isomer, the geometry was first optimized at the DFTB level, after which the excitation energies were calculated using the TD-DFTB method. The obtained values were compared with TD-DFT calculations (B3LYP and CAM-B3LYP functionals) performed with geometries, obtained both at DFT and DFTB methods. Such a hybrid scheme significantly reduces the computational costs, allowing screening of large libraries without losing the accuracy. The correlation between excitation energies calculated by TD-DFTB and TD-DFT is given. As obtained, TD-DFTB tends to systematically underestimate the excitation energies, but largely reflects compounds with minimal excitation energies and large oscillator strengths, which makes it a reliable tool for initial screening. Several isomers with long-wavelength absorption and sufficient transition intensity were identified, which are promising for further modification. Thus, TD-DFTB in combination with TD-DFT on optimized DFTB geometries demonstrates an optimal balance between accuracy and speed for prescreening donor-acceptor dyes with given spectral parameters, which significantly enhances the capabilities of rational design of functional organic materials.

Quantum-Chemical and Experimental Study of Nitrazine Yellow on Silica Surface

2025-08-31T15:39:16+00:00

The article presents the results of a study on the spectral characteristics (UV-Vis region) of the indicator dye Nitrazine Yellow on the surface of organosilica materials. Experimental data are compared with the results of theoretical (quantum chemical) calculations. Several model scenarios were considered, in which the organosilica surface is represented by characteristic structural features, including isolated Si(OH) groups, vicinal Si(OH)–O–Si(OH) pairs, and geminal Si(OH)₂ groups.

Quantum-chemical calculations were carried out using ab initio Time-Dependent Density Functional Theory (TD-DFT), CAM-B3LYP functional and LANL2DZ basis set.

The results obtained indicate a satisfactory description of the influence of environmental effects on the absorption spectra of the three forms of nitrazine yellow over the silica surface.

Verification of the predictive ability of some probability distribution functions in test analysis

2025-08-31T15:39:18+00:00

The increased interest of analytical chemists in test methods of analysis is due to their expressivity and relative simplicity of implementation. There is no doubt about the need for test methods for the analysis of toxic substances in the environment, food products and general consumer goods. Test analyses can also be useful in medical diagnostics, drug and doping control. Along with the increase in the number of test systems on the market, theoretical methods for determining the metrological characteristics of test analysis methods are also developing rapidly. The selection of a probability distribution function and the estimation of their parameters in qualitative analysis procedures with a binary response and semi-quantitative determination methods is a well-studied problem. At the same time, relatively little attention has been paid to such an aspect as the assessment of the predictive ability of such models. Most often, it is necessary to estimate the value of the threshold concentration for the probability of detecting a component that goes beyond the studied area of unreliability of the test reaction. In this work, for this purpose, the cross-evaluation procedure was used - a method for studying the predictive ability of mathematical models.

A comprehensive method for assessing the predictive ability of probability distribution functions for analyte detection in qualitative chemical analysis methods is proposed. Based on the results of calculations, probability distribution functions characterized by maximum predictive ability are determined. The increased interest of analytical chemists in test methods of analysis is due to their expressivity and relative simplicity of implementation. There is no doubt about the need for test methods for the analysis of toxic substances in the environment, food products and general consumer goods. Test analyses can also be useful in medical diagnostics, drug and doping control. Along with the increase in the number of test systems on the market, theoretical methods for determining the metrological characteristics of test analysis methods are also developing rapidly. The selection of a probability distribution function and the estimation of their parameters in qualitative analysis procedures with a binary response and semi-quantitative determination methods is a well-studied problem. At the same time, relatively little attention has been paid to such an aspect as the assessment of the predictive ability of such models. Most often, it is necessary to estimate the value of the threshold concentration for the probability of detecting a component that goes beyond the studied area of unreliability of the test reaction. In this work, for this purpose, the cross-evaluation procedure was used - a method for studying the predictive ability of mathematical models.

A method for testing the predictive ability of exponential, logistic, and normal distribution functions for approximating the uncertainty region of binary response test methods is proposed. A cross-validation procedure was used to define a set of functions that can be used to assess the metrological characteristics of test analysis methods. Analysis of the set of statistical adequacy criteria showed the advantage of using normal and logistic distribution functions. The exponential distribution function is not characterized by acceptable predictive ability.

Anatolii Petrovych Shkumat (09.02.1951 – 31.03.2025)

2025-08-31T15:39:20+00:00

Olena Oleksandrivna Reshetniak (26.11.1954 – 24.04.2025)

2025-08-31T15:39:20+00:00