Exploring Partial Structural Disorder in Anhydrous Paraxanthine through Combined Experiment, Solid-State Computational Modelling, and Molecular Docking DOI Open Access
Jolanta Natalia Latosińska, Magdalena Latosińska, J. Seliger

et al.

Processes, Journal Year: 2023, Volume and Issue: 11(9), P. 2740 - 2740

Published: Sept. 14, 2023

Paraxanthine (PX), a major metabolite of caffeine, protective agent against Alzheimer’s and Parkinson’s disease, promising drug for the treatment post-COVID 2019 anosmia ageusia, has been studied in solid state protein–ligand complex. Partial disorder PX, caused by methyl group at N(7) position, modelled discussed. The relationship between unusual structural propensity to form specific system 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 scanning, two-frequency irradiation, followed solid-state computational modelling (density functional theory, supplemented quantum theory atoms molecules, 3D Hirshfeld surfaces, reduced density gradient), molecular docking approaches. New quantitative methods estimating changes global pattern interactions under influence rotation based on Pompeiu–Hausdorff Bhattacharayya metrics Wasserstein distance have proposed applied. A spectrum consisting 12 lines, indicating presence 4 chemically inequivalent nitrogen sites PX molecule, recorded, lines’ assignment particular made. eigenvalues eigenvectors electric field gradient tensor, NQR parameters, resonance line positions (GGA/RPBE, m-GGA/RSCAN) cluster (Minnesota M062X hybrid). factors found determine PX: larger crystal voids near than N(1) (opening path disorder), hyperconjugation strongly affecting distribution five-membered ring, involvement many that intercept (capture) subsequent jumping protons. confirmed strength throughout molecule as result rotation. This effect is clearly visible regardless type metric, its order magnitude consistent with modulation spectra (experimental calculated). Through docking, it discovered moiety complexes adopt same conformation state. It cooperation–competition C-H⋯O hydrogen C-H⋯H-C dispersion crucial factor impedes induces disorder, well being an important formation complexes.

Language: Английский

Favipiravir Analogues as Inhibitors of SARS-CoV-2 RNA-Dependent RNA Polymerase, Combined Quantum Chemical Modeling, Quantitative Structure–Property Relationship, and Molecular Docking Study DOI Creative Commons
Magdalena Latosińska, Jolanta Natalia Latosińska

Molecules, Journal Year: 2024, Volume and Issue: 29(2), P. 441 - 441

Published: Jan. 16, 2024

Our study was motivated by the urgent need to develop or improve antivirals for effective therapy targeting RNA viruses. We hypothesized that analogues of favipiravir (FVP), an inhibitor RNA-dependent polymerase (RdRp), could provide more nucleic acid recognition and binding processes while reducing side effects such as cardiotoxicity, hepatotoxicity, teratogenicity, embryotoxicity. proposed a set FVP together with their forms triphosphate new SARS-CoV-2 RdRp inhibitors. The main aim our investigate changes in mechanism capacity resulting from these modifications. Using three different approaches, QTAIM, QSPR, MD, differences reactivity, toxicity, efficiency, ability be incorporated were assessed. Two quantum chemical reactivity descriptors, relative electro-donating electro-accepting power, defined successfully applied. Moreover, quantitative method comparing modes developed based on mathematical metrics atypical radar plot. These methods deep insight into desirable properties responsible inhibiting RdRp, allowing ligands conveniently screened. modification structure seems its enhance productive mode binding. In particular, two (the trifluoro- cyano-) bind very strongly template, primer, cofactors, thus may constitute good alternative FVP.

Language: Английский

Citations

7
Chalcogenides encapsulated Pt-doped carbon quantum dot (Pt@CQD) as a carrier for the controlled release of lapachone: Outlook from theoretical calculations DOI

Gideon A. Okon,

Daniel G. Malu,

Hewa Y. Abdullah

et al.

Diamond and Related Materials, Journal Year: 2024, Volume and Issue: unknown, P. 111628 - 111628

Published: Sept. 1, 2024

Language: Английский

Citations

5
Butterfly Effect in Cytarabine: Combined NMR-NQR Experiment, Solid-State Computational Modeling, Quantitative Structure-Property Relationships and Molecular Docking Study DOI Creative Commons
Jolanta Natalia Latosińska, Magdalena Latosińska, J. Seliger

et al.

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(4), P. 445 - 445

Published: March 29, 2024

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

Language: Английский

Citations

3
Quantification of hydrogen bond energy based on equations using spectroscopic, structural, QTAIM-based, and NBO-based descriptors which calibrated by the molecular tailoring approach DOI Creative Commons
А. В. Афонин, Danuta Rusińska‐Roszak

Journal of Molecular Modeling, Journal Year: 2023, Volume and Issue: 30(1)

Published: Dec. 30, 2023

Abstract Context Hydrogen bonds critically influence the structure and properties of both organic molecules biomolecules, as well supramolecular assemblies. For this reason, development elaboration methods for quantitative assessment hydrogen bond energy is an urgent challenge. In study, using a large series hydroxycarbonyl aliphatic compounds with O‒H···O = C intramolecular bond, bank descriptors was created, including spectroscopic, structural, QTAIM-based, NBO-based parameters. It shown that O‒H vibration frequency, OH chemical shift spectroscopic descriptors, O···H length, O···O distance, covalent length structural electron density its Laplacian, potential in critical point, at ring point QTAIM-based change correlated manner. The same correlation found charge transfer through occupancy antibonding orbital, Wiberg indices polarization which are descriptors. also recognized specified from categories functionally related to values energy, quantified via molecular tailoring approach. This allowed one obtain system equations estimation based on QTAIM, NBO makes such quantification more dependable reliable. Methods To vibrational spectra shielding constants were calculated GIAO method. Structural obtained equilibrium geometry molecules, MP2(FC)/6–311 + (2d,2p) level Gaussian 09 program. AIMAll program within framework quantum theory “Atoms Molecules.” 3.1 implemented into 09. quantify bonds, fragmentation used

Language: Английский

Citations

6
Prediction of Metastable Zone Widths: Optimizing the Nucleation Potential Model with Solid–Liquid Interfacial Energy DOI

Haijun Gao,

Yizhen Yan, Ting Gong

et al.

Industrial & Engineering Chemistry Research, Journal Year: 2024, Volume and Issue: 63(10), P. 4397 - 4407

Published: Feb. 28, 2024

The solid–liquid interfacial energy was optimized based on the nucleation potential model, aligning it more closely with actual crystallization process. solubility, induction time, and metastable zone width (MSZW) were determined using favipiravir-acetonitrile system. excellence of model (N-model) optimization (N(T)-model n(T)-model) evaluated by comparing model-predicted MSZWs experimental MSZWs. results indicated that accuracy enhanced 4–7% compared to (N-model). Additionally, three systems compared, including dicyandiamide in water (narrow MSZW), butyl paraben ethanol l-ascorbic acid (wide MSZW). 23–29, 51–52%, respectively. show N(T)-model n(T)-model have some prediction improvement for narrow MSZW In addition, wide system, has significant improvement.

Language: Английский

Citations

1
The Chameleon Strategy—A Recipe for Effective Ligand Screening for Viral Targets Based on Four Novel Structure–Binding Strength Indices DOI Creative Commons
Magdalena Latosińska, Jolanta Natalia Latosińska

Viruses, Journal Year: 2024, Volume and Issue: 16(7), P. 1073 - 1073

Published: July 3, 2024

The RNA viruses SARS-CoV, SARS-CoV-2 and MERS-CoV encode the non-structural Nsp16 (2'-O-methyltransferase) that catalyzes transfer of a methyl group from S-adenosylmethionine (SAM) to first ribonucleotide in mRNA. Recently, it has been found breaking bond between SAM substrate results cessation mRNA virus replication. To date, only limited number such inhibitors have identified, which can be attributed lack an effective "recipe". aim our study was propose verify rapid screening protocol dedicated purposes. We proposed four new indices describing structure-binding strength (structure-binding affinity, structure-hydrogen bonding, structure-steric structure-protein-ligand indices) were then applied shown extremely helpful determining degree increase or decrease binding affinity response relatively small change ligand structure. After initial pre-selection, based on similarity SAM, we 967 compounds, so-called molecular chameleons. They docked protein pocket, 10 candidate ligands selected using novel index. Subsequently 8 known pockets SARS-CoV-2, SARS-CoV. Based indices, best one designed by tuning them. Finally, ADMET profiling dynamics simulations performed for ligands. successfully not screen tune ligands, but also determine effectiveness changes target viral entity, is particularly useful assessing drug case alterations proteins. developed approach, chameleon strategy, capacity introduce universal paradigm field drugs design, including antivirals.

Language: Английский

Citations

1
Exploring Partial Structural Disorder in Anhydrous Paraxanthine through Combined Experiment, Solid-State Computational Modelling, and Molecular Docking DOI Open Access
Jolanta Natalia Latosińska, Magdalena Latosińska, J. Seliger

et al.

Processes, Journal Year: 2023, Volume and Issue: 11(9), P. 2740 - 2740

Published: Sept. 14, 2023

Paraxanthine (PX), a major metabolite of caffeine, protective agent against Alzheimer’s and Parkinson’s disease, promising drug for the treatment post-COVID 2019 anosmia ageusia, has been studied in solid state protein–ligand complex. Partial disorder PX, caused by methyl group at N(7) position, modelled discussed. The relationship between unusual structural propensity to form specific system 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 scanning, two-frequency irradiation, followed solid-state computational modelling (density functional theory, supplemented quantum theory atoms molecules, 3D Hirshfeld surfaces, reduced density gradient), molecular docking approaches. New quantitative methods estimating changes global pattern interactions under influence rotation based on Pompeiu–Hausdorff Bhattacharayya metrics Wasserstein distance have proposed applied. A spectrum consisting 12 lines, indicating presence 4 chemically inequivalent nitrogen sites PX molecule, recorded, lines’ assignment particular made. eigenvalues eigenvectors electric field gradient tensor, NQR parameters, resonance line positions (GGA/RPBE, m-GGA/RSCAN) cluster (Minnesota M062X hybrid). factors found determine PX: larger crystal voids near than N(1) (opening path disorder), hyperconjugation strongly affecting distribution five-membered ring, involvement many that intercept (capture) subsequent jumping protons. confirmed strength throughout molecule as result rotation. This effect is clearly visible regardless type metric, its order magnitude consistent with modulation spectra (experimental calculated). Through docking, it discovered moiety complexes adopt same conformation state. It cooperation–competition C-H⋯O hydrogen C-H⋯H-C dispersion crucial factor impedes induces disorder, well being an important formation complexes.

Language: Английский

Citations

2