Quantum Chemical Modeling Research Articles

Quantum Chemical Model Calculations of Adhesion and Dissociation between Epoxy Resin and Si-Containing Molecules

There is no doubt that when solid surfaces are modified, the functional groups and atoms directly bonded to solid atoms play a major role in adsorption interactions with molecules or resins. In this study, the adhesion and dissociation between epoxy resin and molecules containing Si atoms were analyzed. The analysis, conducted in contact with the solid surface of silicon, utilized quantum chemical calculations based on a molecular model. We compared some Si-containing molecular models to test quantum chemical calculations that contribute to the study of adhesion and dissociation between epoxy resins and solid surfaces somehow other than simple potential energy curve calculations. The AFIR (artificial force induced reaction) method, implemented in the GRRM (global reaction route mapping) program, was employed to separate an epoxy resin model molecule and three types of silicon compounds (Si(CH3)2(OH)2, Si(CH3)4, and (CH3)2SiF2) in three directions, determining their minimum dissociation energy when changing the applied energy by 2.5 kJ/mol. In systems with weak hydrogen bonds, such as Si(CH3)4 or (CH3)2SiF2, the energy required for dissociation was not large; however, in systems with strong hydrogen bonds, such as Si(CH3)2(OH)2, dissociation was more difficult in the vertical direction. Although anisotropy due to hydroxyl groups was calculated in the horizontal direction, dissociation remained relatively easy.

Syn vs. Anti? What Controls Addition Stereochemistry in Chlorolactonization.

The stereochemistry of the uncatalyzed chlorolactonization of 4-phenylpent-4-enoic acid at room temperature was examined to probe the reaction's intrinsic diastereoselectivities as a function of chlorenium ion donor, solvent polarity, and reactant concentration ranges. Kinetic studies using Variable Time Normalization Analysis (VTNA) revealed differing reaction orders for the syn and anti alkene addition processes. Aided and illustrated by quantum chemical modeling, this detailed mechanistic analysis of the substrate's intrinsic chlorolactonization reactions points to concerted AdE3-type paths for both syn and anti additions. By illuminating the factors selecting for syn- vs anti-addition paths, the results provide key reference points for future studies of stereocontrol in halofunctionalization reactions.

Self-aggregation and microhydration mechanisms of monoethanolamine: Far-infrared identification of large-amplitude hydrogen bond libration.

The strong tendency for self-aggregation together with an intriguing mechanism for the microhydration of monoethanolamine (MEA) have been explored by low-temperature far-infrared cluster spectroscopy in doped neon "quantum" matrices at 4K complemented by high-level quantum chemical modeling. In addition to the assignment of new mid-infrared perturbed intramolecular transitions, a distinct far-infrared transition is unambiguously assigned to the concerted large-amplitude hydrogen bond librational motion of the MEA homodimer. This observation confirms a global "head-to-head" intermolecular potential energy minimum associated with the formation of a compact doubly intermolecular OH⋯N hydrogen-bonded cyclic structure, where both monomeric intramolecular OH⋯N hydrogen bonds are broken upon complexation. By means of relative mixing ratio dependencies, dedicated annealing procedures, and selective complexation between MEA and isotopic H216O and H218O samples, distinct far-infrared transitions associated with large-amplitude intra-molecular hindered OH torsional motion and inter-molecular H2O librational (hindered c-type overall rotational) motion of the MEA monohydrate are furthermore assigned unambiguously for the first time. These spectroscopic observations reveal an intriguing metastable conformation, where H2O acts as a OH⋯O hydrogen bond donor to the hydroxy group instead of the amino group of MEA upon microhydration in the cryogenic neon environment, where the microhydration strengthens the intramolecular OH⋯N hydrogen bond of MEA due to hydrogen bond cooperativity.

Selenium nanoparticles stabilized with chitosan for fortifying dairy products

Relevance. One solution to the problem of selenium deficiency is the enrichment of socially important food products, in particular dairy products, with bioavailable forms of selenium. Such forms include selenium nanoparticles. The aim of the work is to develop a dairy product enriched with selenium nanoparticles stabilized with chitosan.Methods. According to dynamic light scattering spectroscopy, a sample of selenium nanoparticles stabilized with chitosan has a monomodal size distribution with an average hydrodynamic particle radius of 25 nm.Results. Quantum chemical modeling of selenium nanoparticles stabilized by chitosan has revealed that the most energetically favorable interaction is the interaction of the surface of selenium nanoparticles with the hydroxo group attached to the C3 glucosamine residue of chitosan. A study was conducted of the influence of technological parameters on the stability of selenium nanoparticles stabilized with chitosan. It was found that increasing the exposure time leads to an increase in the average hydrodynamic radius of selenium nanoparticles stabilized by chitosan. In the case of pH, an inverse relationship is observed: particles with the largest average hydrodynamic radius are found in samples with an acidic environment (pH ˂ 5). As part of a study of the influence of technological parameters on the stability of selenium nanoparticles stabilized by chitosan, it was found that selenium nanoparticles stabilized by chitosan can be used as a source of selenium for food products that have a neutral pH, but can be subjected to heat treatment at temperatures above 70 °C in for 5–15 minutes, in particular pasteurized milk. A study of pasteurized milk fortified with selenium nanoparticles stabilized by chitosan showed that there were no significant changes in titratable acidity, surface tension and pH of milk, as well as the average hydrodynamic radius of casein micelles after milk fortification. The value of antioxidant activity increases by 0.88% — from 6.50 to 7.38%.

Accurate Geometries of Large Molecules at DFT Cost by Semiexperimental and Coupled Cluster Templating Fragments.

Accurate geometries of small semirigid molecules in the gas phase are available thanks to high-resolution spectroscopy and accurate quantum chemical approaches. These results can be employed for validating cheaper low-level quantum chemical models or correcting the corresponding structures of large molecules. On these grounds, in this work, a large panel of semiexperimental equilibrium structures already available in the literature is used to confirm the average error (1 mÅ for bond lengths and 2 mrad for valence angles) of a version of the Pisa composite schemes (PCS2), which is applicable to molecules containing up to about 20 atoms. Then, the geometries of 30 additional medium-sized systems were optimized at the PCS2 level to cover a more balanced chemical space containing moieties poorly represented in SE compilations. The final database is available on a public domain Web site (https://www.skies-village.it/databases/) and can be employed for correcting structures of larger molecules obtained by hybrid or double-hybrid density functionals in the framework of the templating molecule approach. Several examples show that corrections based on the structures of building blocks taken from this database reduce the error of the B3LYP geometrical parameters of large molecules by nearly an order of magnitude without increasing the computational cost. Furthermore, the results of different density functional theory (DFT) or wave function (e.g., MP2) models can be improved in the same way by simply computing both the whole molecule and suitable building blocks at the chosen level. Then, whenever reference structures of some building blocks containing up to about 20 atoms are not available, they can be purposely optimized at the PCS2 level by employing reasonable computer resources. Therefore, a new DFT-cost tool is now available for the accurate characterization of large molecules by experiment-oriented scientists.

A paradigm for natural eutectic solvents based on fatty acids: Molecular interactions and toxicological considerations

In this work, we present experimental and molecular modeling results on archetypal hydrophobic natural deep eutectic solvents (NADES) based on fatty acids (octanoic and dodecanoic acid) and menthol, a representative monoterpenoid. Our goal is to provide a multiscale characterization to enhance the understanding of this field by studying these selected archetypical mixtures. We examine their liquid state properties, intermolecular forces, nanoscopic arrangements, toxicity, and environmental impact.The computational study integrates quantum chemistry, molecular dynamics (both all-atom and coarse-grained approaches), and thermodynamic modeling (COSMO-RS approach) to analyze the fluids and their interactions with biological entities, such as proteins and plasma membranes. The experimental characterization focuses on elucidating intermolecular interactions and liquid phase dynamics using NMR spectroscopy, visible and UV Resonance Raman spectroscopy (UVRR). Notably, this is the first report of UVRR data on NADES.Additionally, we simulate the effect of the molecular moieties forming the solvents on biological targets—specifically, protein and cell membrane models –. This in silico analysis aims to rationalize and predict their potential toxicity.Overall, our experimental findings and in silico simulations contribute to a deeper understanding of these novel solvents in terms of their network of interactions. Additionally, they highlight the potential impact on biological targets, providing new data to accurately define the eco-friendliness of type V DES and their suitability as sustainable alternatives to traditional molecular solvents.

Impact of Protonation Sites on Collision-Induced Dissociation-MS/MS Using CIDMD Quantum Chemistry Modeling.

Protonation is the most frequent adduct found in positive electrospray ionization collision-induced mass spectra (CID-MS/MS). In a parallel report Lee, J. J. Chem. Inf. Model. 2024, 10.1021/acs.jcim.4c00760, we developed a quantum chemistry framework to predict mass spectra by collision-induced dissociation molecular dynamics (CIDMD). As different protonation sites affect fragmentation pathways of a given molecule, the accuracy of predicting tandem mass spectra by CIDMD ultimately depends on the choice of its protomers. To investigate the impact of molecular protonation sites on MS/MS spectra, we compared CIDMD-predicted spectra to all available experimental MS/MS spectra by similarity matching. We probed 10 molecules with a total of 43 protomers, the largest study to date, including organic acids (sorbic acid, citramalic acid, itaconic acid, mesaconic acid, citraconic acid, and taurine) as well as aromatic amines including uracil, aniline, bufotenine, and psilocin. We demonstrated how different protomers can converge different fragmentation pathways to the same fragment ions but also may explain the presence of different fragment ions in experimental MS/MS spectra. For the first time, we used in silico MS/MS predictions to test the impact of solvents on proton affinities, comparing the gas phase and a mixture of acetonitrile/water (1:1). We also extended applications of in silico MS/MS predictions to investigate the impact of protonation sites on the energy barriers of isomerization between protomers via proton transfer. Despite our initial hypothesis that the thermodynamically most stable protomer should give the best match to the experiment, we found only weak inverse relationships between the calculated proton affinities and corresponding entropy similarities of experimental and CIDMD-predicted MS/MS spectra. CIDMD-predicted mechanistic details of fragmentation reaction pathways revealed a clear preference for specific protomer forms for several molecules. Overall, however, proton affinity was not a good predictor corresponding to the predicted CIDMD spectra. For example, for uracil, only one protomer predicted all experimental MS/MS fragment ions, but this protomer had neither the highest proton affinity nor the best MS/MS match score. Instead of proton affinity, the transfer of protons during the electrospray process from the initial protonation site (i.e., mobile proton model) better explains the differences between the thermodynamic rationale and experimental data. Protomers that undergo fragmentation with lower energy barriers have greater contributions to experimental MS/MS spectra than their thermodynamic Boltzmann populations would suggest. Hence, in silico predictions still need to calculate MS/MS spectra for multiple protomers, as the extent of distributions cannot be readily predicted.

Atmospheric Degradation Mechanism of Isoamyl Acetate Initiated by OH Radicals and Cl Atoms Revealed by Quantum Chemical Calculations and Kinetic Modeling.

Isoamyl acetate is one of the volatile organic compound class molecules relevant to agricultural and industrial applications. With the growing interest in isoamyl acetate applications in industry, the atmospheric fate of isoamyl acetate must be considered. Reaction mechanisms, potential energy profiles, and rate constants of isoamyl acetate reaction with atmospheric relevant oxidant OH radicals and Cl atoms have been obtained from the quantum chemical calculations and kinetic modeling. The geometry optimizations were conducted using M06-2X/6-311++G(3df,3pd) followed by single point-energy calculations at the DLPNO-CCSD(T) method with an extrapolated complete basis set. The rate constants were calculated by solving the master equation. A hydrogen-abstraction reaction dominates the first step of isoamyl acetate degradation, while the addition-substitution reaction plays a small role in the degradation products. The kinetic study was conducted to evaluate the rate constants within a temperature range of 200-400 K. The total rate constants for the isoamyl acetate degradation reactions initiated by the OH radical and Cl atom were determined to be 6.96 × 10-12 and 1.27 × 10-10 cm3 molecule-1 s-1, respectively, under standard temperature and pressure conditions. The product degradation mechanism, ozone formation potential, and atmospheric impacts were discussed.

Enhanced furfural extraction using neoteric hydrophobic solvents for sustainable biomass recovery and bioenergy applications

The recovery of furfural from hemicellulosic biowastes is important for developing sustainable and renewable energy alternatives to fossil fuels. However, current methods are inefficient and environmentally questionable. To address this issue, this study introduces neoteric hydrophobic solvents, specifically deep eutectic solvents (DESs) and ionic liquids (ILs). Of the 32 solvents tested, thymol:decanoic acid 1:1 (Thy:DecA) DES and trihexyltetradecyl phosphonium bis(trifluoro methylsulfonyl) imide [P14,6,6,6][NTf2] IL were the most effective, with extraction efficiencies of 94.1% and 97.1%, respectively. These solvents outperformed the reference solvent toluene, with an efficiency of 81.2%, while also showing favorable characteristics in multiple investigated criterions. For the first time, excellent performance stability was demonstrated under various operational conditions and reusability over multiple extraction and regeneration cycles. Furthermore, to provide insights into the molecular mechanisms of extraction, computational quantum chemistry modeling was employed, which showed a strong agreement with the experimental results. The development of these new neoteric solvents for furfural recovery from biowaste offers a highly effective, sustainable, and eco-friendly alternative to traditional solvents, representing a significant breakthrough in the field of renewable bioenergy production and sustainable materials recovery.

Energetic Landscape and Terminal Emitters of Phycobilisome Cores from Quantum Chemical Modeling.

Phycobilisomes (PBs) are giant antenna supercomplexes of cyanobacteria that use phycobilin pigments to capture sunlight and transfer the collected energy to membrane-bound photosystems. In the PB core, phycobilins are bound to particular allophycocyanin (APC) proteins. Some phycobilins are thought to be terminal emitters (TEs) with red-shifted fluorescence. However, the precise identification of TEs is still under debate. In this work, we employ multiscale quantum-mechanical calculations to disentangle the excitation energy landscape of PB cores. Using the recent atomistic PB structures from Synechoccoccus PCC 7002 and Synechocystis PCC 6803, we compute the spectral properties of different APC trimers and assign the low-energy pigments. We show that the excitation energy of APC phycobilins is determined by geometric and electrostatic factors and is tuned by the specific protein-protein interactions within the core. Our findings challenge the simple picture of a few red-shifted bilins in the PB core and instead suggest that the red-shifts are established by the entire TE-containing APC trimers. Our work provides a theoretical microscopic basis for the interpretation of energy migration and time-resolved spectroscopy in phycobilisomes.

Chitosan-ricobendazole complex: Synthesis, characterization and anthelmintic activity

Synthesis, characterization and assessment of therapeutic efficacy of chitosan-ricobendazole complex were carried out for the first time in this work. Study of physico-chemical properties revealed the optimal ratio of chitosan: ricobendazole (30:4). Quantum chemical modeling set the optimal parameters for the formation of the chitosan-ricobendazole molecular system (E = −3765.26 kcal/mol, η = 0.127 eV), which was confirmed by Fourier-transform infrared spectroscopy. Scanning electron microscopy showed spherical particles of chitosan-ricobendazole complex ranging in size from 100 to 200 μm. Study of therapeutic efficiency was conducted on sheep with dicroceliosis. Notably, the therapeutic efficiency of the chitosan-ricobendazole complex (4 mg/kg of ricobendazole) reached 89 %, while the therapeutic efficiency of the commercial preparation ricazole (8 mg/kg of ricobendazole) was 92 %. Biochemical blood test indicated equivalent normalization of hematological parameters in sheep after treatment with ricazole and the chitosan-ricobendazole complex. Histological examination of infected sheep liver revealed that treatment with the chitosan-ricobendazole complex leads to a decrease in the number of helminth eggs with subsequent therapeutic effect on the severity of the disease. This proves the enhanced solubility of ricobendazole at a dosage of 4 mg/kg, active interaction of the components and relatively high bioavailability without increasing the release rate of ricobendazole.

Synergistic synthesis and computational analysis of novel indazole-2-Pyrone hybrids: Toxicity, Hirshfeld surface insights, and antiviral potential against HIV-1 and Coronaviruses

A novel category of hybrids, termed (Z)-6-methyl-3-(1-((1-(prop‑2-yn-1-yl)-1H-indazol-6-yl)amino)ethylidene)-2H-pyran-2,4(3H)‑dione, was synthesized by reductive coupling of N-alkyl-6-nitroindazoles and 2-pyrone using indium or stannous chloride in tetrahydrofuran (THF) with acetic acid. This process yielded (Z)-2H-pyran-2,4(3H)-diones in satisfactory yields. Each synthesized molecule underwent comprehensive characterization through NMR analysis and X-ray diffraction. Additionally, our investigation incorporates quantum chemical modeling via density functional theory (DFT) at the B3LYP/6–311G(d,p) level, along with molecular docking analysis. An analysis of the Hirshfeld molecular surface was undertaken to characterize the type of intermolecular connections. The percentage contributions, shown in the footprint plot, indicate that H…H interactions (33.0 %) are particularly significant in the constitution of the crystal. The favorable pharmacological properties of compounds 5a and 6a, such as good bioavailability, ability to penetrate the blood-brain barrier, and adherence to the Lipinski rule, make them excellent candidates for therapeutic development.

The origin of selectivity in the trimerization of 1,3-cyclopentadiene from an activation strain perspective.

Quantum chemical modeling (DFT-PBE0/cc-pVTZ) of the [4 + 2]-cycloaddition reaction of 1,3-cyclopentadiene (CPD) to (exo/endo)-dicyclopentadiene (DCPD) was carried out, resulting in 14 products-CPD trimers. According to calculations, exo-addition of CPD to the norbornene (NB) fragment of DCPD and trans-addition of CPD to the cyclopentene (CP) fragment of DCPD are kinetically preferred. Ring strain energies ERS were calculated for all trimers using the homodesmotic reaction approach. The least strained trimers are formed by exo-addition of CPD to the NB fragment of exo-DCPD, while the most strained ones are formed by endo-addition of CPD to the NB fragment of endo-DCPD. ERS values are in good agreement with thermodynamic stability of trimers. Analysis of activation energy using the activation strain model showed steric effects causing deformation of the DCPD molecule upon reaching the transition state to be the leading factor of the magnitude of the cycloaddition reaction activation barrier. Deformation of the DCPD molecule mostly occurs in two dihedral angles-the angle of escape of H atoms from the plane of the double bond involved in cycloaddition and the angle between the NB and CP fragments. The sum of deviations of these angles in the transition states (or products) structures is in good agreement with Gibbs activation energies of cycloaddition reactions of CPD to DCPD. Quantum chemical calculations were carried out using density functional theory in Gaussian 09 software. Hybrid exchange-correlation PBE0 functional was used with cc-pVTZ basis set.

Formation of active centers of polymer catalysts for radical-coordination polymerization

Chromatography–mass spectrometry of samples representing the interaction products of ferrocene, radical initiator and monomer taken in the molar ratio of 1:2:10 in toluene solution was used for experimental detection of products indicating the structure and mechanism of formation of metal complex active centers of radical-coordination polymerization. Structures similar to those proposed by the quantum-chemical modeling were demonstrated to be formed with the participation of secondary radicals.

Biosynthetic fuels: A marriage of renewable resources and chemical thermodynamics

Terpenes represent a highly diverse group of natural products with wide applications. Terpenoid structures can be derived from different renewable sources and utilized as fuels. Application as fuels requires hydrogenation of the double bonds in the respective molecules to ensure clean combustion. This hydrogenation can be performed either directly with elemental hydrogen or indirectly via transfer hydrogenation with a Liquid Organic Hydrogen Carrier. In this study, the thermochemical fundamentals of these reaction has been evaluated. For this task, for a first time a combination of experimental thermochemistry and quantum-chemical molecular modelling has been applied. The results show the hydrogenation of the respective structures is thermodynamically highly favourable. Correspondingly, dehydrogenation would be comparatively unfavorable. Yet, for a fuel no dehydrogenation is required. As an alternative to conventional hydrogenation, transfer hydrogenation, which is often subject to partial conversions due to limitations by the reaction equilibrium, can be realized with a high degree of conversion. While the entropy of reaction for hydrogen transfer from cyclohexyl-structures to terpene structures is close to zero, the enthalpy of reaction is highly negative. This leads to a Gibbs energy of reaction which is clearly negative and ensures a large thermodynamic driving force for the reaction. As a consequence, downstream processing, which is usually very demanding for transfer hydrogenations, is comparatively easy. These finding underline the great potential of these bio-derived substances for conversion into sustainable fuels.

The Magnetic Properties of Fluorenyl and tert-Butyl-nitroxyl Acene-Based Derivatives: A Quantum Chemical Insight

Acenes, as a class of polycyclic aromatic hydrocarbons, attract considerable attention due to their remarkable nonlinear optical and magnetic properties. The aim of this work was the elucidation of the capability of radical-substituted acene derivatives to undergo spin-state-switching rearrangements. For this purpose, a series of acene-based (anthracene, pentacene, heptacene) molecules bearing fluorenyl and tert-butyl-nitroxyl radicals were investigated through comprehensive quantum chemical modeling of their electronic structures, isomerization and magnetic properties. A possible mechanism of the transformation of the closed-shell folded isomer into the biradical twisted structure of the bis-fluorenyl anthracene has been ascertained by applying the procedure of searching for the Minimum Energy Crossing Point. The conditions favoring the occurrence of spin-state-switching in such classes of polycyclic aromatic hydrocarbon derivatives have been formulated. By varying the size of an acene core and the type of radical substituent, the compounds capable of changing their magnetic properties have been revealed. Considering the unique features of radical-bearing acene-based derivatives, the proposed molecules can be used as functional materials in photonics and electronics.

Nanostructured Molecular-Network Arsenoselenides from the Border of a Glass-Forming Region: A Disproportionality Analysis Using Complementary Characterization Probes.

Binary AsxSe100-x alloys from the border of a glass-forming region (65 < x < 70) subjected to nanomilling in dry and dry-wet modes are characterized by the XRPD, micro-Raman scattering (micro-RS) and revised positron annihilation lifetime (PAL) methods complemented by a disproportionality analysis using the quantum-chemical cluster modeling approach. These alloys are examined with respect to tetra-arsenic biselenide As4Se2 stoichiometry, realized in glassy g-As65Se35, glassy-crystalline g/c-As67Se33 and glassy-crystalline g/c-As70Se30. From the XRPD results, the number of rhombohedral As and cubic arsenolite As2O3 phases in As-Se alloys increases after nanomilling, especially in the wet mode realized in a PVP water solution. Nanomilling-driven amorphization and reamorphization transformations in these alloys are identified by an analysis of diffuse peak halos in their XRPD patterning, showing the interplay between the levels of a medium-range structure (disruption of the intermediate-range ordering at the cost of an extended-range one). From the micro-RS spectroscopy results, these alloys are stabilized by molecular thioarsenides As4Sen (n = 3, 4), regardless of their phase composition, remnants of thioarsenide molecules destructed under nanomilling being reincorporated into a glass network undergoing a polyamorphic transition. From the PAL spectroscopy results, volumetric changes in the wet-milled alloys with respect to the dry-milled ones are identified as resulting from a direct conversion of the bound positron-electron (Ps, positronium) states in the positron traps. Ps-hosting holes in the PVP medium appear instead of positron traps, with ~0.36-0.38 ns lifetimes ascribed to multivacancies in the As-Se matrix. The superposition of PAL spectrum peaks and tails for pelletized PVP, unmilled, dry-milled, and dry-wet-milled As-Se samples shows a spectacular smoothly decaying trend. The microstructure scenarios of the spontaneous (under quenching) and activated (under nanomilling) decomposition of principal network clusters in As4Se2-bearing arsenoselenides are recognized. Over-constrained As6·(2/3) ring-like network clusters acting as pre-cursors of the rhombohedral As phase are the main products of this decomposition. Two spontaneous processes for creating thioarsenides with crystalline counterparts explain the location of the glass-forming border in an As-Se system near the As4Se2 composition, while an activated decomposition process for creating layered As2Se3 structures is responsible for the nanomilling-driven molecular-to-network transition.

Unraveling the Interface Chemistry between HCN and Cosmic Silicates by the Interplay of Infrared Spectroscopy and Quantum Chemical Modeling

Unraveling the Interface Chemistry between HCN and Cosmic Silicates by the Interplay of Infrared Spectroscopy and Quantum Chemical Modeling

Quantum Chemical Modeling of the Full Catalytic Cycle for Selective Oxidation of Propane to Propene on the M1 Phase of Mo–Te–Nb–O Mixed-Metal Oxide Catalysts

Quantum Chemical Modeling of the Full Catalytic Cycle for Selective Oxidation of Propane to Propene on the M1 Phase of Mo–Te–Nb–O Mixed-Metal Oxide Catalysts

New Amphiphilic Terpolymers of N-Vinylpyrrolidone with Acrylic Acid and Triethylene Glycol Dimethacrylate as Promising Drug Delivery: Design, Synthesis and Biological Properties In Vitro.

The terpolymers of N-vinylpyrrolidone (VP) with acrylic acid and triethylene glycol methacrylate were synthesized with more than 90% yield by radical copolymerization in ethanol from monomeric mixtures of different molar composition (98:2:2, 95:5: 2 and 98:2:5) and their monomer composition, absolute molecular masses and hydrodynamic radii in aqueous media were determined. Using the MTT test, these terpolymers were established to be low toxic for non-tumor Vero cells and HeLa tumor cells. Polymer compositions of hydrophobic dye methyl pheophorbide a (MPP) based on studied terpolymers and linear polyvinylpyrrolidone (PVP) were obtained and characterized in water solution. Quantum-chemical modeling of the MPP-copolymer structures was conducted, and the possibility of hydrogen bond formation between terpolymer units and the MPP molecule was shown. Using fluorescence microscopy, the accumulation and distribution of polymer particles in non-tumor (FetMSC) and tumor (HeLa) cells was studied, and an increase in the accumulation of MPP with both types of particles was found.