@article{ph17040445,
title = {Butterfly Effect in Cytarabine: Combined NMR-NQR Experiment, Solid-State Computational Modeling, Quantitative Structure-Property Relationships and Molecular Docking Study},
author = {Jolanta Natalia Latosińska and Magdalena Latosińska and Janez Seliger and Veselko Žagar and Tomaž Apih},
url = {https://www.mdpi.com/1424-8247/17/4/445},
doi = {10.3390/ph17040445},
issn = {1424-8247},
year = {2024},
date = {2024-01-01},
journal = {Pharmaceuticals},
volume = {17},
number = {4},
abstract = {Cytarabine (Ara-C) is a synthetic isomer of cytidine that differs from cytidine and deoxycytidine only in the sugar. The use of arabinose instead of deoxyribose hinders the formation of phosphodiester linkages between pentoses, preventing the DNA chain from elongation and interrupting the DNA synthesis. The minor structural alteration (the inversion of hydroxyl at the 2′ positions of the sugar) leads to change of the biological activity from anti-depressant and DNA/RNA block builder to powerful anti-cancer. Our study aimed to determine the molecular nature of this phenomenon. Three 1H-14N NMR-NQR experimental techniques, followed by solid-state computational modelling (Quantum Theory of Atoms in Molecules, Reduced Density Gradient and 3D Hirshfeld surfaces), Quantitative Structure–Property Relationships, Spackman’s Hirshfeld surfaces and Molecular Docking were used. Multifaceted analysis—combining experiments, computational modeling and molecular docking—provides deep insight into three-dimensional packing at the atomic and molecular levels, but is challenging. A spectrum with nine lines indicating the existence of three chemically inequivalent nitrogen sites in the Ara-C molecule was recorded, and the lines were assigned to them. The influence of the structural alteration on the NQR parameters was modeled in the solid (GGA/RPBE). For the comprehensive description of the nature of these interactions several factors were considered, including relative reactivity and the involvement of heavy atoms in various non-covalent interactions. The binding modes in the solid state and complex with dCK were investigated using the novel approaches: radial plots, heatmaps and root-mean-square deviation of the binding mode. We identified the intramolecular OH···O hydrogen bond as the key factor responsible for forcing the glycone conformation and strengthening NH···O bonds with Gln97, Asp133 and Ara128, and stacking with Phe137. The titular butterfly effect is associated with both the inversion and the presence of this intramolecular hydrogen bond. Our study elucidates the differences in the binding modes of Ara-C and cytidine, which should guide the design of more potent anti-cancer and anti-viral analogues.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

@article{Latosiska2024,
title = {Favipiravir Analogues as Inhibitors of SARS-CoV-2 RNA-Dependent RNA Polymerase, Combined Quantum Chemical Modeling, Quantitative Structure–Property Relationship, and Molecular Docking Study},
author = {Magdalena Latosińska and Jolanta Natalia Latosińska},
url = {http://dx.doi.org/10.3390/molecules29020441},
doi = {10.3390/molecules29020441},
issn = {1420-3049},
year = {2024},
date = {2024-01-01},
journal = {Molecules},
volume = {29},
number = {2},
pages = {441},
publisher = {MDPI AG},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

@article{Hevorkian2024b,
title = {Foamy ceramic filters and new possibilities of their applications},
author = {E S Hevorkian and V P Nerubatskyi and R V Vovk and T Szumiata and Jolanta Natalia Latosińska},
url = {http://dx.doi.org/10.1016/j.ceramint.2023.12.046},
doi = {10.1016/j.ceramint.2023.12.046},
issn = {0272-8842},
year = {2024},
date = {2024-01-01},
journal = {Ceramics International},
volume = {50},
number = {4},
pages = {6961–6968},
publisher = {Elsevier BV},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

@article{molecules29133199,
title = {Serine/Threonine Protein Kinases as Attractive Targets for Anti-Cancer Drugs—An Innovative Approach to Ligand Tuning Using Combined Quantum Chemical Calculations, Molecular Docking, Molecular Dynamic Simulations, and Network-like Similarity Graphs},
author = {Magdalena Latosińska and Jolanta Natalia Latosińska},
url = {https://www.mdpi.com/1420-3049/29/13/3199},
doi = {10.3390/molecules29133199},
issn = {1420-3049},
year = {2024},
date = {2024-01-01},
journal = {Molecules},
volume = {29},
number = {13},
abstract = {Serine/threonine protein kinases (CK2, PIM-1, RIO1) are constitutively active, highly conserved, pleiotropic, and multifunctional kinases, which control several signaling pathways and regulate many cellular functions, such as cell activity, survival, proliferation, and apoptosis. Over the past decades, they have gained increasing attention as potential therapeutic targets, ranging from various cancers and neurological, inflammation, and autoimmune disorders to viral diseases, including COVID-19. Despite the accumulation of a vast amount of experimental data, there is still no “recipe” that would facilitate the search for new effective kinase inhibitors. The aim of our study was to develop an effective screening method that would be useful for this purpose. A combination of Density Functional Theory calculations and molecular docking, supplemented with newly developed quantitative methods for the comparison of the binding modes, provided deep insight into the set of desirable properties responsible for their inhibition. The mathematical metrics helped assess the distance between the binding modes, while heatmaps revealed the locations in the ligand that should be modified according to binding site requirements. The Structure-Binding Affinity Index and Structural-Binding Affinity Landscape proposed in this paper helped to measure the extent to which binding affinity is gained or lost in response to a relatively small change in the ligand’s structure. The combination of the physico-chemical profile with the aforementioned factors enabled the identification of both “dead” and “promising” search directions. Tests carried out on experimental data have validated and demonstrated the high efficiency of the proposed innovative approach. Our method for quantifying differences between the ligands and their binding capabilities holds promise for guiding future research on new anti-cancer agents.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

@article{HEVORKIAN202435226,
title = {Effect of the sintering parameters on the structure and mechanical properties of zirconia-based ceramics},
author = {Edvin Hevorkian and Remigiusz Michalczewski and Miroslaw Rucki and Dmitry Sofronov and Edyta Osuch-Słomka and Volodymyr Nerubatskyi and Zbigniew Krzysiak and Jolanta Natalia Latosińska},
url = {https://www.sciencedirect.com/science/article/pii/S0272884224027688},
doi = {https://doi.org/10.1016/j.ceramint.2024.06.331},
issn = {0272-8842},
year = {2024},
date = {2024-01-01},
journal = {Ceramics International},
volume = {50},
number = {19, Part A},
pages = {35226-35235},
abstract = {The paper presents the results of an investigations of the sintered zirconia ceramics that have been stabilized with Y2O3 and CeO2. The initial powders were synthesized via decomposition of the fluoride salts, which determined morphological features and dimensions of the particles. The specific electroconsolidation process, performed using the modified spark plasma sintering device, allowed for the retention of the nanoscale grain sizes and related properties of the sintered ceramic composites. It was found that the as-obtained materials with cerium oxide exhibited high bending strength of 609 MPa, by ca. 33 % higher than that of yttria-stabilized ones (410 MPa). In turn, the best combination of hardness and fracture toughness, K1С = 5.8 МPа·m1/2 аnd Нv = 14.8 GPа, respectively, exhibited ZrO2+3 wt% Y2O3. This result can be attributed to the chemical composition and morphology of the powders, which in turn is influenced by the synthesis conditions and calcination time and temperatures, as well as to the sintering parameters. In particular, yttria-stabilized zirconia showed higher sensitivity to the variations of the sintering temperatures and holding times.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

@article{v16071073,
title = {The Chameleon Strategy—A Recipe for Effective Ligand Screening for Viral Targets Based on Four Novel Structure–Binding Strength Indices},
author = {Magdalena Latosińska and Jolanta Natalia Latosińska},
url = {https://www.mdpi.com/1999-4915/16/7/1073},
doi = {10.3390/v16071073},
issn = {1999-4915},
year = {2024},
date = {2024-01-01},
journal = {Viruses},
volume = {16},
number = {7},
abstract = {The RNA viruses SARS-CoV, SARS-CoV-2 and MERS-CoV encode the non-structural Nsp16 (2′-O-methyltransferase) that catalyzes the transfer of a methyl group from S-adenosylmethionine (SAM) to the first ribonucleotide in mRNA. Recently, it has been found that breaking the bond between Nsp16 and SAM substrate results in the cessation of mRNA virus replication. To date, only a limited number of such inhibitors have been identified, which can be attributed to a lack of an effective “recipe”. The aim of our study was to propose and verify a rapid and effective screening protocol dedicated to such purposes. We proposed four new indices describing structure-binding strength (structure–binding affinity, structure–hydrogen bonding, structure–steric and structure–protein–ligand indices) were then applied and shown to be extremely helpful in determining the degree of increase or decrease in binding affinity in response to a relatively small change in the ligand structure. After initial pre-selection, based on similarity to SAM, we limited the study to 967 compounds, so-called molecular chameleons. They were then docked in the Nsp16 protein pocket, and 10 candidate ligands were selected using the novel structure-binding affinity index. Subsequently the selected 10 candidate ligands and 8 known inhibitors and were docked to Nsp16 pockets from SARS-CoV-2, MERS-CoV and SARS-CoV. Based on the four new indices, the best ligands were selected and a new one was designed by tuning them. Finally, ADMET profiling and molecular dynamics simulations were performed for the best ligands. The new structure-binding strength indices can be successfully applied not only to screen and tune ligands, but also to determine the effectiveness of the ligand in response to changes in the target viral entity, which is particularly useful for assessing drug effectiveness in the case of alterations in viral proteins. The developed approach, the so-called chameleon strategy, has the capacity to introduce a novel universal paradigm to the field of drugs design, including RNA antivirals.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

@article{pr11092740,
title = {Exploring Partial Structural Disorder in Anhydrous Paraxanthine through Combined Experiment, Solid-State Computational Modelling, and Molecular Docking},
author = {Jolanta Natalia Latosińska and Magdalena Latosińska and Janez Seliger and Veselko Žagar},
url = {https://www.mdpi.com/2227-9717/11/9/2740},
doi = {10.3390/pr11092740},
issn = {2227-9717},
year = {2023},
date = {2023-09-14},
journal = {Processes},
volume = {11},
number = {9},
abstract = {Paraxanthine (PX), a major metabolite of caffeine, a protective agent against Alzheimer’s and Parkinson’s disease, and a promising drug for the treatment of post-COVID 2019 anosmia and ageusia, has been studied in the solid state and protein–ligand complex. Partial disorder in PX, caused by the methyl group at the N(7) position, has been modelled and discussed. The relationship between the unusual structural disorder and the propensity to form a specific system of non-covalent bonds was analyzed. Three 1H-14N NMR-NQR (nuclear magnetic resonance–nuclear quadrupole resonance) experimental techniques were used, namely multiple frequency sweeps, Larmor frequency scanning, and the two-frequency irradiation, followed by solid-state computational modelling (density functional theory, supplemented by quantum theory of atoms in molecules, 3D Hirshfeld surfaces, and reduced density gradient), and molecular docking approaches. New quantitative methods for estimating changes in the global pattern of interactions under the influence of rotation of the methyl group in N(7) based on the Pompeiu–Hausdorff and Bhattacharayya metrics and the Wasserstein distance have been proposed and applied. A spectrum consisting of 12 lines, indicating the presence of 4 chemically inequivalent nitrogen sites in the PX molecule, was recorded, and the lines’ assignment to particular sites was made. The influence of the methyl rotation on the eigenvalues and eigenvectors of the electric field gradient tensor, NQR parameters, and resonance line positions was modelled in the solid (GGA/RPBE, m-GGA/RSCAN) and cluster (Minnesota M062X hybrid). Three factors have been found to determine structural disorder in PX: larger crystal voids near the methyl at N(7) than at N(1) (opening the path for the disorder), hyperconjugation strongly affecting the density distribution in the five-membered ring, and the involvement of the methyl group at N(7) in many non-covalent bonds that intercept (capture) subsequent jumping protons. The Pompeiu–Hausdorff and Bhattacharayya metrics and the Wasserstein distance confirmed the changes in the distribution and strength of non-covalent interactions throughout the molecule as a result of methyl rotation. This effect is clearly visible regardless of the type of metric, and its order of magnitude is consistent with the modulation effect of the NQR spectra (experimental and calculated). Through molecular docking, it was discovered that the PX moiety in protein–ligand complexes adopt the same methyl group conformation at N(7) as in the solid state. It was found that the cooperation–competition between the C-H⋯O hydrogen bonds and C-H⋯H-C dispersion interactions is the crucial factor that impedes methyl rotation and induces structural disorder, as well as being an important factor in the formation of the protein–ligand complexes.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

@article{molecules28083308,
title = {Elucidating the Role of Noncovalent Interactions in Favipiravir, a Drug Active against Various Human RNA Viruses; a 1H-14N NQDR/Periodic DFT/QTAIM/RDS/3D Hirshfeld Surfaces Combined Study},
author = {Jolanta Natalia Latosińska and Magdalena Latosińska and Janez Seliger and Veselko Žagar and Tomaž Apih and Paweł Grieb},
url = {https://www.mdpi.com/1420-3049/28/8/3308},
doi = {10.3390/molecules28083308},
issn = {1420-3049},
year = {2023},
date = {2023-04-07},
journal = {Molecules},
volume = {28},
number = {8},
abstract = {Favipiravir (6-fluoro-3-hydroxypyrazine-2-carboxamide, FPV), an active pharmaceutical component of the drug discovered and registered in March 2014 in Japan under the name Avigan, with an indication for pandemic influenza, has been studied. The study of this compound was prompted by the idea that effective processes of recognition and binding of FPV to the nucleic acid are affected predominantly by the propensity to form intra- and intermolecular interactions. Three nuclear quadrupole resonance experimental techniques, namely 1H-14N cross-relaxation, multiple frequency sweeps, and two-frequency irradiation, followed by solid-state computational modelling (density functional theory supplemented by the quantum theory of atoms in molecules, 3D Hirshfeld Surfaces, and reduced density gradient) approaches were applied. The complete NQR spectrum consisting of nine lines indicating the presence of three chemically inequivalent nitrogen sites in the FPV molecule was detected, and the assignment of lines to particular sites was performed. The description of the nearest vicinity of all three nitrogen atoms was used to characterize the nature of the intermolecular interactions from the perspective of the local single atoms and to draw some conclusions on the nature of the interactions required for effective recognition and binding. The propensity to form the electrostatic N−H···O, N−H···N, and C−H···O intermolecular hydrogen bonds competitive with two intramolecular hydrogen bonds, strong O−H···O and very weak N−H···N, closing the 5-member ring and stiffening the structure, as well as π···π and F···F dispersive interactions, were analysed in detail. The hypothesis regarding the similarity of the interaction pattern in the solid and the RNA template was verified. It was discovered that the -NH2 group in the crystal participates in intermolecular hydrogen bonds N–H···N and N–H···O, in the precatalytic state only in N–H···O, while in the active state in N–H···N and N–H···O hydrogen bonds, which is of importance to link FVP to the RNA template. Our study elucidates the binding modes of FVP (in crystal, precatalytic, and active forms) in detail and should guide the design of more potent analogues targeting SARS-CoV-2. Strong direct binding of FVP-RTP to both the active site and cofactor discovered by us suggests a possible alternative, allosteric mechanism of FVP action, which may explain the scattering of the results of clinical trials or the synergistic effect observed in combined treatment against SARS-CoV-2.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

@article{Latosińska2023,
title = {Synthesis and Crystal Structure of Adamantylated 4,5,6,7-tetrahalogeno-1H-benzimidazoles Novel Multi-Target Ligands (Potential CK2, M2 and SARS-CoV-2 Inhibitors). X-ray/DFT/QTAIM/Hirshfeld Surfaces/Molecular Docking Study },
author = {Jolanta Natalia Latosińska and Magdalena Latosińska and Andrzei Orzeszko and Jan Krzysztof Maurin },
doi = {10.3390/molecules28010147},
year = {2023},
date = {2023-01-02},
journal = {Molecules},
volume = {28},
number = {1},
pages = {147},
abstract = {A series of new congeners, 1-[2-(1-adamantyl)ethyl]-1H-benzimidazole (AB) and 1-[2-(1-adamantyl)ethyl]-4,5,6,7-tetrahalogeno-1H-benzimidazole (Hal=Cl, Br, I; tClAB, tBrAB, tIAB), have been synthesized and studied. These novel multi-target ligands combine a benzimidazole ring known to show antitumor activity and an adamantyl moiety showing anti-influenza activity. Their crystal structures were determined by X-ray, while intermolecular interactions were studied using topological Bader’s Quantum Theory of Atoms in Molecules, Hirshfeld Surfaces, CLP and PIXEL approaches. The newly synthesized compounds crystallize within two different space groups, P-1 (AB and tIAB) and P21/c (tClAB and tBrAB). A number of intramolecular hydrogen bonds, C−H⋯Hal (Hal=Cl, Br, I), were found in all halogen-containing congeners studied, but the intermolecular C−H⋯N hydrogen bond was detected only in AB and tIAB, while C−Hal⋯π only in tClAB and tBrAB. The interplay between C−H⋯N and C−H⋯Hal hydrogen bonds and a shift from the strong (C−H⋯Cl) to the very weak (C−H⋯I) attractive interactions upon Hal exchange, supplemented with Hal⋯Hal overlapping, determines the differences in the symmetry of crystalline packing and is crucial from the biological point of view. The hypothesis about the potential dual inhibitor role of the newly synthesized congeners was verified using molecular docking and the congeners were found to be pharmaceutically attractive as Human Casein Kinase 2, CK2, inhibitors, Membrane Matrix 2 Protein, M2, blockers and Severe Acute Respiratory Syndrome Coronavirus 2, SARS-CoV-2, inhibitors. The addition of adamantyl moiety seems to broaden and modify the therapeutic indices of the 4,5,6,7-tetrahalogeno-1H-benzimidazoles.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

@article{latosinska2022,
title = {Features of synthesis of Y2Ti2O7 ceramics for the purpose of obtaining dispersion-strengthened steels},
author = {E.S. Gevorkyan and V.P. Nerubatskyi and R.V. Vovk and V.O. Chyshkala and S.V. Lytovchenko and O.M. Morozova and Jolanta Natalia Latosińska},
url = {http://przyrbwn.icm.edu.pl/APP/SPIS/a142-4.html},
doi = {10.12693/APhysPolA.142.529},
year = {2022},
date = {2022-10-17},
journal = {Acta Physica Polonica A},
volume = {142},
number = {4},
pages = {529},
abstract = {The method of electron beam heating of a mixture of yttrium and zirconium oxides for the synthesis of complex oxides has been implemented. It is established that the applied technology of melting the mixture of oxides leads to the formation of fluorite phases. It is determined that homogenization of the initial mixture of oxides should be carried out in a high-energy mill, which will reduce the temperature and duration of the synthesis of complex oxide compounds, including the desired structure of pyrochlorine. It is proposed to improve the technique of intensive thermal influence on the process of pyrochlorine synthesis by using an equiatomic alloy Y-Ti (65 wt. Y-35 wt Ti), which has been smelted using the arc melting method in an argon atmosphere. It was found that hydrogen saturation reduces the efficiency of pyrochlorine synthesis and increases the grain size, which may be associated with grain growth at the stage of hydrogen saturation.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

@article{Bogdanov2021,
title = {Electron Microscopic Study of Interdiffusion in Equiatomic Fe-Ni Composite},
author = {V.V. Bogdanov and R.V. Vovk and S.V. Dukarov and M.V. Klislitsa and S.I. Petrushenko and V.N. Sukhov and G.Ya. Khadzhai and Y.L. Goulatis and S.R. Vovk and E.S. Gevorkyan and A. Feher and P. Kollar and J. Fuzer and Jolanta Natalia Latosińska},
doi = {10.12693/APhysPolA.139.62},
year = {2021},
date = {2021-01-15},
journal = {Acta Physica Polonica A},
volume = {139},
number = {1},
pages = {62},
abstract = {The paper presents a study of interdiffusion processes in a binary Fe-Ni system (obtained by electroconsolidation of nickel and iron powders) by X-ray energy dispersive spectroscopy. Well-separated regions of almost pure iron and nickel have been discovered. The content of nickel, estimated from the concentration dependence of the interdiffusion coefficient, which determines the kinetics of the homogenization process of the electroconsolidated Fe-Ni composite sample, was ~70 at.%. The value of the interdiffusion coefficient of the electroconsolidated Fe-Ni composite is significantly higher than that of the alloy of similar composition which probably results from the effect of spark plasma sintering technology (pressure and current along the same direction during consolidation) but also from a significant contribution of diffusion with mass transfer along the particle boundaries in the composite.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}