PM3 Method Research Articles

The Effect of Acyl Chain Position on the 2D Monolayer Formation of Monoacyl-sn-Glycerol at the Air/Water Interface: Quantum Chemical Modeling

This paper deals with the results of quantum chemical modeling of the monoacyl-sn-glycerol 2D cluster formation at the air/water interface using a semi-empirical PM3 method. The impact of the 2 or 3 positions of the acyl substituent on the thermodynamics of the monolayer formation is assessed for surfactants with an acyl substituent CnH2n+1COO chain length of n = 6–17 carbon atoms. The calculation shows a significant change in the spontaneous clusterization threshold for isomeric compounds, which differs only in the position of the acyl substituent with respect to the glycerol backbone. This change is almost equal to substituent shortening by approximately two methylene fragments. At the same time, the geometric parameters of the unit cell for resulting monolayers are not affected so drastically. The 2D films in question possess an oblique or orthorhombic unit cell with parameters for 2 and 3-monoacyl-sn-glycerol monolayers, as follows: a = 4.91 Å and 4.82 Å and b = 5.00 Å and 4.92 Å, with hydrocarbon chains tilted at t = 23.0° and 23.5°. The calculated results are in accordance with existing experimental data obtained using grazing incidence X-ray diffraction measurements and the π-A isotherm technique.

High-throughput screening of spin states for transition metal complexes with spin-polarized extended tight-binding methods.

The semiempirical GFNn-xTB ( ) tight-binding methods are extended with a spin-dependent energy term (spin-polarization), enabling the fast and efficient screening of different spin states for transition metal complexes. While GFNn-xTB methods inherently can not differentiate properly between high-spin (HS) and low-spin (LS) states, this shortcoming is corrected with the presented methods termed spGFNn-xTB. The performance of spGFNn-xTB methods for spin state energy splittings is evaluated on a newly compiled benchmark set of 90 complexes (27 HS and 63 LS complexes) containing 3d, 4d, and 5d transition metals (termed TM90S) employing DFT references at the TPSSh-D4/def2-QZVPP level of theory. The challenging TM90S set contains complexes with charges between 4 and +3, spin multiplicities between 1 and 6, and spin-splitting energies that range from 47.8 to 146.6kcal/mol with a mean average of 32.2kcal/mol. On this set the (sp)GFNn-xTB methods, the PM6-D3H4 method, and the PM7 method are evaluated with spGFN1-xTB yielding the lowest MAD of 19.6kcal/mol followed by spGFN2-xTB with 24.8kcal/mol. While for the 4d and 5d subsets small or no improvements are observed with spin-polarization, large improvements are obtained for the 3d subset with spGFN1-xTB yielding the smallest MAD of 14.2kcal/mol followed by spGFN2-xTB with 17.9kcal/mol and PM6-D3H4 with 28.4kcal/mol. The correct sign of the spin state splittings is obtained with spGFN2-xTB in 89% of all cases closely followed by spGFN1-xTB with 88%. On the full set, a pure semiempirical vertical spGFN2-xTB//GFN2-xTB-based workflow for screening purposes yields a slightly better MAD of 22.2kcal/mol due to error compensation, while being qualitative correct for one additional case. In combination with their low computational cost (scanning spin states in seconds), the spGFNn-xTB methods represent robust tools for pre-screening steps of spin state calculations and high-throughput workflows.

STUDY OF THE EFFECT OF MODIFICATION OF THE STRUCTURE OF A NEW DERIVATIVE OF QUINAZOLINE–4(3H)–ONE ON FATTY ACID SYNTHASE (FAS) MYCOBACTERIUM

Relevance. Tuberculosis remains one of the main causes of disability and mortality from infectious diseases worldwide. The discovery of phenotypi-cally tolerant subpopulations of pathogen persisters has called into question the possibilities of known anti-tuberculosis drugs. In this connection, the search and development of new effective anti-tuberculosis drugs is an important direction in the development of modern pharmacology. Currently, it is relevant to consider substances of the quinazoline nature as antimicrobial agents that exhibit antitubercular activity. The aim of the work is computer modeling of the interaction of new derivatives of quinazoline–4(3H)–oh with NAD(H) in order to predict the possibility of influencing the fatty acid synthase (FAS) Mycobacterium. Material and methods. Modeling of intermolecular complexes in the interaction system of new derivatives of quinazoline-4(3H)–on – VMA–17–04 and VMA–13–05 with the oxidized form of NAD+ was carried out using the quantum chemical semi-empirical PM7 method implemented in the MOPAC 2016 program. Conclusions. The VMA–13–05 derivative, being in stable conformation I, forms an adduct with NAD+ having optimal energy characteristics. This inter-action can be considered as one of the stages of the biochemical pathway of suppressing the activity of FAS synthase, which takes part in the synthe-sis of mycolic acids and leads to the death of Mycobacterium cells.

Molecular modeling study of natural products as potential bioactive compounds against SARS-CoV-2.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the COVID-19 infection and responsible for millions of victims worldwide, remains a significant threat to public health. Even after the development of vaccines, research interest in the emergence of new variants is still prominent. Currently, the focus is on the search for effective and safe drugs, given the limitations and side effects observed for the synthetic drugs administered so far. In this sense, bioactive natural products that are widely used in the pharmaceutical industry due to their effectiveness and low toxicity have emerged as potential options in the search for safe drugs against COVID-19. Following this line, we screened 10 bioactive compounds derived from cholesterol for molecules capable of interacting with the receptor-binding domain (RBD) of the spike protein from SARS-CoV-2 (SC2Spike), responsible for the virus's invasion of human cells. Rounds of docking followed by molecular dynamics simulations and binding energy calculations enabled the selection of three compounds worth being experimentally evaluated against SARS-CoV-2. The 3D structures of the cholesterol derivatives were prepared and optimized using the Spartan 08 software with the semi-empirical method PM3. They were then exported to the Molegro Virtual Docking (MVD®) software, where they were docked onto the RBD of a 3D structure of the SC2Spike protein that was imported from the Protein Data Bank (PDB). The best poses obtained from MVD® were subjected to rounds of molecular dynamics simulations using the GROMACS software, with the OPLS/AA force field. Frames from the MD simulation trajectories were used to calculate the ligand's free binding energies using the molecular mechanics - Poisson-Boltzmann surface area (MM-PBSA) method. All results were analyzed using the xmgrace and Visual Molecular Dynamics (VMD)software.

Interaction of biopolymers with graphene for bio-electronic applications

Molecular modelling concepts always prove to be an efficient technique for studying the interaction between various substances prior to experimental work. They were utilized for investigating the interaction of chitosan (Cs) and carboxymethyl cellulose (CMC) biopolymers with a modified graphene structure (G). Geometry optimization calculations were carried out using PM6 method. Results illustrate that the proposed interactions are all stable; however, the interaction site has no role in the resulting energy values. The calculated energies for the G-CMC interactions are quite lower than those for the G-Cs ones indicating quite higher stability for the former group. On contrary to energy, the proposed interaction active site has a significant part in determining total dipole moment (TDM) and hence reactivity of the structures. The calculated quantitative structure-activity relationship (QSAR) parameters show that the interaction of graphene with these biopolymers lowers its hydrophobicity. Modification of Cs and CMC with graphene has a significant positive impact on enhancing their electrical features. The resulting bandgap of the proposed structures is lower than half of their original values. Bandgap values of the G-CMC proposed structures are quite lower than those of the G-Cs ones. An experimental trial was carried out by printing a sixty-layer simple electrode of both biocomposite inks via InkJet printing technique. Then, Sheet resistance and charge mobility measurements were conducted. Results demonstrate that the sheet resistance of the G-Cs printed electrode is about five times higher than that of the G-CMC one. Such result was confirmed by the measured Hall Effect measurement which showed that the charge mobility in the G-CMC electrode is much greater than that in the G-Cs one. Both theoretical and experimental parts agree that the G-CMC biocomposite has much more electrical conductivity than the G-Cs, proposing it as a potential candidate for bio-electronic applications.

Semi-empirical calculations and potentiometric studies on complexation equilibria of 2,2’-Bipyridyl in SDS and TBAB micellar media

Chemical speciation of Cu(II) complexes of 2,2-Bipyridyl in the of the presence of different- surfactant media (TBAB and SDS) has been studied pH metrically. The models containing different kinds of species were refined using the computer program, MINIQUAD75 and formation constants were determined. The predominant species detected were Cu(bipyH) and Cu(bipy)2 in both surfactant media. It was found that the formation constant is more in SDS compared to TBAB and aqueous media because the proton association is more in the anionic micellar medium. Binding energies and HOMO-LUMO energy gaps were calculated from semi-empirical studies based on PM6 method. It was found that Cu(bipy)2 is more stable than Cu(bipy) and Cu(bipyH+).

Host–Guest Inclusion Systems of Vanillic Acid into α-Cyclodextrin: Structures, Electronic Properties, QTAIM, NCI and IGM Analyses with Dispersion Corrected Calculations

In this work, a theoretical study of the host–guest inclusion process involving the vanillic acid (VA) into α-cyclodextrin (α-CD) was investigated by the semi empirical methods PM6 and its modern variant PM6-D3H4 and density functional theory with the BP86-D3/6-31G+(d,p) functional to elucidate the relationship between host, guest and their molecular structures. According to the results from theoretical calculation, the model in which the VA molecule points it’s the carboxylic acid group toward the wider rim of α–CD is energetically preferred. The global reactivity descriptors were calculated and analyzed. The electronic transitions of the two complexes computed with the TD-DFT approach on the optimized geometries at BP86-D3/6-31G+ (d, p) level of theory including the CPCM model were investigated. Finally, quantum theory of atoms in molecules (QTAIM) analysis, the non-covalent interactions analysis (NCI) and the independent gradient model (IGM) results confirms that the van der Waals interactions and hydrogen bonds play a major role in the stabilization of the complexes.

2D-monolayer formation of 3-monoacyl-sn-glycerols at the air/water interface. A comprehensive quantum chemical approach

Thermodynamic and structural aspects of the monolayer film formation of 3-monoacyl-sn-glycerol homologous series with the alkyl chain length n = 7–18 at the air/water interface are considered. The calculations are carried out within the framework of the semiempirical quantum chemical method PM3 and supported experimentally using surface pressure-area per molecule (π–A) isotherms, Brewster angle microscopy (BAM), as well as grazing incidence X-ray diffraction analysis (GIXD). A conformational analysis of 3-monoacyl-sn-glycerol monomers reveals three stable conformations of monomers with Monomer 1 as the possible basis for the construction of the most energetically advantageous structures of small clusters, which subsequently can form a 2D monolayer. Optimized tetramer structure of 3-monoacyl-sn-glycerol is considered as a unit cell of the 2D film with geometric parameters: a= 4.82 Å, b= 4.92 Å, and the angle between them θ = 91°. The molecular tilt angle of surfactant molecules with respect to the normal to the interface is 23.5°. These structural parameters are in good agreement with existing experimental data. The spontaneous clusterization threshold of 3-monoacyl-sn-glycerol at the air/water interface is 16 carbon atoms in the alkyl chain at standard temperature. The temperature dependences of the Ac area per film molecule at the beginning of the liquid-expanded–liquid-condensed (LE–LC) phase transition are analyzed. The values of the Ac change per 1 °C for 3-monoacyl-sn-glycerol are commensurable with corresponding values of other surfactant classes confirming the dominating role of intermolecular CH···HC interactions in the clusterization energy of surfactants.

Functional group corrections to the GFN2-xTB and PM6 semiempirical methods for noncovalent interactions in alkanes and alkenes.

Analytical corrections were developed to improve the accuracy of the PM6 and GFN2-xTB semiempirical quantum mechanical methods for the evaluation of noncovalent interaction energies in alkanes and alkenes. We followed the approach of functional group corrections, wherein the atom-atom pair corrections depend on the nature of the interacting functional groups. The training set includes 21 alkane and 13 alkene complexes taken from the Donchev et al.'s database [Sci. Data 8, 55 (2021)], with interaction energies calculated at the CCSD(T)/CBS level, and our own data obtained for medium-size complexes (of 100 and 112 atoms). In general, for the systems included in the training and validation sets, the errors obtained with the PM6-FGC and xTB-FGC methods are within the chemical accuracy.

In Silico Analysis of the Antidepressant Fluoxetine and Related Drugs at SARS-CoV-2 Main Protease (Mpro) and Papain-like Protease (PLpro).

SARS-CoV-2 main protease (Mpro or 3CLpro) and papain-like protease (PLpro) are common viral targets for repurposed drugs to combat COVID-19 disease. Recently, several antidepressants (such as fluoxetine, venlafaxine and citalopram) belonging to the Selective Serotonin Reuptake Inhibitors (SSRIs) and the Serotonin-Norepinephrine Reuptake Inhibitors (SNRI) classes have been shown to in vitro inhibit viral replication. Investigate a possible action of fluoxetine and derivatives on SARS-CoV-2 protease sites. Molecular docking was performed using AutoDock Vina. Both protease structures and different drug conformations were used to explore the possibility of SARS-CoV-2 inhibition on a Mpro or PLpro related pathway. Drug structures were obtained by optimization with the Avogadro software and MOPAC using the PM6 method. Results were analysed on Discovery Studio Visualizer. The results indicated that Mpro interacted in a thermodynamically favorable way with fluoxetine, venlafaxine, citalopram, atomoxetine, nisoxetine and norfluoxetine in the region of the active site, whether PLpro conformers did not come close to the active site. In an in silico perspective, it is likely that the SSRIs and other anti-depressants could interact with Mpro and cause the enzyme to malfunction. Unfortunately, the same drugs did not present similar results on PLpro crystal, therefore, no inhibition is expected in an in vitro trial. Anyway, in vitro tests are necessary for a better understanding of the links between SARS-CoV-2 proteases and antidepressants.

In Ukrainian

The peculiarities of the interaction in the supramolecular system: the natural hydrophobic polyphenol curcumin - the antiseptic cationic surface-active substance decamethoxin - highly dispersed silica was revealed by the spectrophotometric method. It was established that significant changes in the spectral characteristics of curcumin in aqueous solutions and on the surface of the sorbent depend on the concentration of this cationic surfactant, which can exist in the solution in the form of monomers, associates, and micelles. The PM7 method and the COSMO solvation model, implemented in the MOPAC2016 software package were used to determine the mechanism of adsorption of the supramolecular complex of curcumin (in ketone or enol form) with decamethoxine on the silica surface. The distribution of electrostatic and hydrophobic potentials of the studied molecules, calculated by the FieldView 2.0.2 method (Flare software package), indicates a significant contribution of hydrophobic interactions in the formation of supramolecular complexes of curcumin with decamethoxin in solution and on the surface of silica. The obtained results are of practical importance and can be used in the development of new more effective drugs containing bioactive curcumin, antiseptic decamethoxine and enterosorbent silicon dioxide.

Penambatan Molekuler Penghambatan Aktivitas Enzim α-Amilase dan α-Glukosidase oleh Senyawa Aktif Daun Kirinyuh (Chromolaena odorata L.)

An in silico study was conducted to inhibit the active compound in Kirinyuh leaves (Chromolaena odorata L.) against α-amylase and α-glucosidase enzymes using a molecular docking approach. The docking was carried out on 19 active compounds that had been identified in Kirinyuh leaves and were optimized using the PM3 method. The best results in inhibit on of the α-amylase enzyme were shown by compounds from the flavanone group, namely genkwanin and sakuranetin with binding affinities of -8.3 kcal/mol and -8.1 kcal/mol, respectively, while the best results in inhibiting on of the α-glucosidase enzyme were shown by two compounds from the hydroxybenzoic acid group, namely p-coumaric acid and p-hydroxybenzoic acid with bond affinities of -5.7 kcal.mol and -5.5 kcal.mol, respectively. The interaction between α-amylase with genkwanin and sakuranetin produces one conventional hydrogen bond GLU 233 and GLN 63 respectively. The interaction between α-glucosidase with p-coumaric acid and p-hydroxybenzoic acid produces three conventional hydrogen bonds, HIS 112; GLN 182; ASP 352 and GU 277; GLN 279; ASP 352.

A New MBH Adduct as an Efficient Ligand in the Synthesis of Metallodrugs: Characterization, Geometrical Optimization, XRD, Biological Activities, and Molecular Docking Studies.

This article reports the synthesis, characterization, geometrical optimization, and biological studies of new MBH-based organometallic compounds of medicinal significance. The ligand (MNHA) was prepared via the Morita-Baylis-Hillman (MBH) synthetic route, from aromatic aldehyde containing multiple functional groups. Metal complexes were prepared in an alkaline medium and under other suitable reaction conditions. Spectral and elemental analyses were used to identify the structural and molecular formulas of each compound. Optimized geometry was determined through density functional theory (DFT) B3LYP and 6-311++ G (d,p) basis set for the MBH adduct, whereas structures of novel complexes were optimized with the semi-empirical PM6 method. Powder XRD analysis furnished the crystal class of complexes, with Co3+, Cr3+, and Mn2+ being cubic, while Ni2+ was hexagonal, and Cu2+ was orthorhombic. Moreover, the ligand, along with Ni2+ and Co3+ complexes, showed profound antibacterial action against S. aureus, E. coli, B. pumilis, and S. typhi. Additionally, all of the complexes were shown to persist in the positive antioxidant potential of the ligand. Contrarily, not a single metal complex conserved the antifungal potentials of the ligand.

Prediction of the photofading of 1‐H or 1‐ethyl derivatives of 3‐cyano‐6‐hydroxy‐4‐methyl‐5‐(p‐X‐phenylazo)‐2‐pyridone dyes and their azo‐hydrazone tautomerism: A theoretical study

AbstractThe lightfastness calculations for photofading of monoazo pyridone dyes were performed. For this purpose, all‐valence molecular orbital method PM3 was applied. Frontier electron density distribution on the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) was examined. The obtained parameters seem to reflect the tendency for an electrophilic attack with a singlet oxygen (1O2) atom or a nucleophilic attack with superoxide anion (O2●─) on a particular atom in a molecule. Reactivity indicators for superdelocalisability () and electron density distribution in ground and excited state were calculated. Superdelocalisabilities enable the fastness values to be explained in different chemical molecules depending on tautomeric forms in which they may occur.

Structural and vibrational investigations and molecular docking studies of a vinca alkoloid, vinorelbine

Vinorelbine, a vinca alkaloid, is an antimitotic drug that inhibits polymerisation process of tubulins to microtubules, and is widely used in cancer chemotherapy. Due to the importance of the structure-activity relationship, in this work the conformational preferences of the vinorelbine molecule were surched by PM3 method. The obtained lowest energy conformer was then optimized at DFT/B3LYP/6-31G(d,p) level of theory and the structural characteristics were determined. Frontier orbital (HOMO, LUMO) and molecular electrostatic potential (MEP) analyses were performed for the optimized structure. The experimental FT-IR, Raman and UV-VIS spectral data of vinorelbine along with the theoretical DFT/B3LYP/6-31G(d,p) calculations were investigated in detail. The vibrational wavenumbers were assigned based on the calculated potential energy distribution (PED) of the vibrational modes. To shed light into the anticancer property of vinorelbine as microtubule destabilizer, the most favourable binding mode and the interaction details between vinorelbine and tubulin were revealed by molecular docking studies of vinorelbine into the α,β-tubulin (PDB IDs: 4O2B; 1SA0; 7CNN) and binding free energies were calculated by the combination of Molecular Mechanics/Generalized Born Surface Area (MMGBSA) and Molecular Mechanics/Poisson-Boltzmann Surface Area (MM-PBSA) methods {MM/PB(GB)SA}. The calculated vinorelbine-7CNN binding free energy, using by MM/PB(GB)SA approach, was found to be the best (-50.39 kcal/mol), and followed by vinorelbine-4O2B (-28.5 kcal/mol) and vinorelbine-1SA0 (-17.59 kcal/mol) systems. Moreover, the interaction of vinorelbine with the cytochrome P450 enzymes (CYP), which are known to help in the metabolism of many drugs in the body, was investigated by docking studies against CYP2D6 and CYP3A4 targets. Communicated by Ramaswamy H. Sarma

Reliable gas-phase tautomer equilibria of drug-like molecule scaffolds and the issue of continuum solvation.

Accurate calculation of relative tautomer energies in different environments is a prerequisite to many parameters of relevance in drug discovery. This work provides a thorough benchmark of the semiempirical methods AM1, PM3 and GFN2-xTB, the force-field OPLS4, Hartree-Fock and HF-3c, the density functionals PBEh-3c, B97-3c, r2SCAN-3c, PBE, PBE0, TPSS, r2SCAN, ω-B97X-V, M06-2X, B3LYP, B2PLYP, and second-order perturbation theory MP2 versus the gold-standard coupled-cluster DLPNO-CCSD(T) using the def2-QZVPP basis set. The outperforming method identified is M06-2X, whereas r2SCAN-3c is the best-perfoming one in the set of cost-optimized methods. Application of the two methods on a challenging subset from the SAMPL2 challenge provides evidence that deviations from experiment are caused by deficiencies of current continuum solvation methods.

Reliable prediction of crystal density of high nitrogen-containing organic compounds as powerful, less sensitive, eco-friendly energetic materials for dependable assessment of their performance

Many efforts have been done in recent years to seek more powerful, less sensitive, eco-friendly high nitrogen-containing organic compounds (HNCOCs). It is essential to have reliable methods for the prediction of crystal density of the new proposed HNCOCs because increasing density is associated with increased performance. This work uses structural parameters of HNCOCs and semiempirical quantum mechanical calculations using the PM6 method for reliable prediction of their densities at or near room temperature. A core correlation is introduced for the calculation of the density of HNCOCs based on the number of functional groups –NH2, >NH, –OH, and –N3 as well as the calculated density from the PM6 method. The reliability of the core correlation is improved by considering two non-additive correcting functions, which can increase or decrease the predicted values of core density. The reported densities of 137 HNCOCs as training (117 compounds) and test (20 chemicals) sets are used to establish the new model. High reliability of the core and improved models are compared with the computed results of the best available molecular surface electrostatic potential (MESP)-based method. The values of Root Mean Square Error (RMSE) for the improved model and comparative MESP-based method are 0.0472 and 0.0951 g/cm3, respectively. High reliability of the new method was also confirmed as compared to four MESP-based models for 32 compounds of external test data set where RMSE of the improved model (0.0674 g/cm3) is smaller than four MSPE-based methods, i.e. 0.126, 0.276, 0.0716, and 0.0703 g/cm3.

Molecular area dependences of monolayers at the air/water interface

The quantum chemical approach and a thermodynamic model for amphiphilic monolayers are used to find the temperature dependence of the area per amphiphile molecule in a monolayer at the onset of liquid-expanded – liquid-condensed phase transition (A c ). Quantum chemical calculations within the semiempiric PM3 method for clusterization thermodynamics and structure of surfactant dimers and trimers are used, as well as for assessment of their molecular area in an aggregate. Calculations are done for seven amphiphile classes: saturated and ethoxylated alcohols, saturated and unsaturated carboxylic acids, α-hydroxylic acids, N -acyl-substituted alanine and dialkyl-substituted melamine that are well experimentally explored. Calculations reflect the experimental data and show that a temperature increase leads to decrease of A c for an amphiphile with a given alkyl chain length, and vice versa with a chain length increase at a fixed temperature the A c value grows. It was shown that as the temperature increases the increment of A c per methylene unit of the hydrocarbon chain becomes less significant. The average values of the slope reflecting the change of A c per 1 ​°C for saturated and ethoxylated alcohols, saturated, cis - and trans -unsaturated carboxylic acids, α-hydroxylic acids, N -acyl-substituted alanine and dialkyl-substituted melamine are 0.57, 1.32, 1.14, 1.26, 1.15, 0.66, 1.07 and 0.67 ​Å 2 /°С, respectively. These data are quite similar to the experimental values of − d A c d T for tetradecanoic acid, dipalmitoyl-phosphatidylcholine and dipalmitoyl phosphatididic acid. The proposed approach can be used as a predictive tool for amphiphiles lacking experimental data.

METFORMIN-SENSITIVE ION-SELECTIVE ELECTRODE

Metformin in its protonated form as metformin hydrochloride is used worldwide as an advanced antidiabetic drug for type 2 diabetes. Hyperinsulinemia and insulin resistance of cells are the main causes of this disease. For patients with diabetes, metformin hydrochloride (MET) works by improving cell sensitivity to insulin.
 It has been shown that metformin with methyl orange (MO) forms an ionic associate that can be isolated in solid form and is suitable for the creation of plasticized membrane potentiometric metformin-sensitive sensors.
 The energy efficiency of IA formation is substantiated by the method of mathematical modeling. Molecular modeling of MO- + MET+ systems and related calculations were performed using the PM3 method for various initial variants of counter ion relative to each other (single point procedure). Geometric optimization of ions was performed by the method of molecular mechanics MM+. The standard enthalpy (ΔH0) of ion formation and the association “MET+ + MO-” was determined by the semi-empirical method PM3. The difference in the energy of formation of the ionic associate and the sum of the energies of formation of its components is 258 kJ/mol. Therefore, the process of IA formation is thermodynamically advantageous.
 Modeling and optimization of membrane composition is carried out. The results of the study of the influence of the nature of plasticizers on the electroanalytical properties of the developed sensors indicate that the best plasticizer for the system is TCP or DNF. For these solvents, the product of the dielectric constant and Rohrschneider polarity (ε × PR) is 123.5 and 175, respectively. For plasticizers that were less effective (DBF and DEF), these values are 235.6 and 326 respectively. For membranes with the same content of plasticizer of one homologous series (DEF, DBF, DOF, DNF), the slope of the Nernst function decreases with increasing dielectric constant of the plasticizer solvent. It is shown that the working pH range of the electrode is from 2 to 11. The drift potential does not exceed 1-3 mV/day. Stable values of electrode potentials are set for 5-15 s. The stability of the electroanalytical characteristics of the optimized membranes can be traced for at least three months. The developed sensors show satisfactory selectivity in relation to a number of substances and ions. The 300-1000 amount of glucose, starch, polyvinyl alcohol, Na+, K+, Mg2+, Ca2+, Ba2+ ions do not interfere with MET determination. This, in turn, allows the practical use of developed MET-sensitive sensors in a variety of objects.
 A method of potentiometric determination of metformin has been developed, which has been tested in its determination in dosage forms.

QUANTUM CHEMICAL STUDY OF THE PROCESS OF CLEANING BIOFUEL FROM FREE FATTY ACIDS USING IONIC LIQUIDS AT THE MOLECULAR LEVEL

Among alternative sources of energy, such as solar, wind, and hydrogen energy, biofuel occupies a special place because it has a few useful properties. Compared to the current price of gasoline,the price of biofuel is very low. During its use, biofuel releases less greenhouse gases into the environment and is less flammable. However, in order to support biofuel, it is necessary to purify its composition from unnecessary glycerol, methanol, and free fatty acids. Free fatty acids in biofuel are flammable and pollute car engines. Various ionic liquids have been developed for the purification of biofuel. One of them is 1-butyl-3-methylimidazolium dicyanamide. The purpose of this work is to study the state of purification of free fatty acids in biofuel by 1-butyl-3-methylimidazolium dicyanamide at the molecular level using chemical quantum calculations. Methodology. HyperChem PM3 method was used for quantum chemical calculations of chemical structures, molecular electrostatic potentials, molecular orbitals, bond distances, and energies. Results. During the study of bond energy, bond length, and structure of free fatty acids in biofuel using 1-butyl-3-methylimidazolium dicyanamide, it wasfound that there is a strong chemical bond between ionic liquid and free fatty acid. It is known that free fatty acids in biofuels chemically bond with hydrogen atoms close to nitrogen in ionic liquids. Conclusion. This research will contribute to the rational design of ionic liquids and will help advance research related to the purification of biofuels from free fatty acids.