Integrated Structural, Functional, and ADMET Analysis of 2-Methoxy-4,6-diphenylnicotinonitrile: The Convergence of X-ray Diffraction, Molecular Docking, Dynamic Simulations, and Advanced Computational Insights
This study systematically investigates the molecular structure and electronic properties of 2-methoxy-4,6-diphenylnicotinonitrile, employing X-ray diffraction (XRD) and sophisticated computational methodologies. XRD findings validate the compound’s orthorhombic crystallization in the P21212 space gr...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-09-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/28/19/6859 |
| _version_ | 1797575436079726592 |
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| author | Ahmed H. Bakheit Hamad M. Alkahtani |
| author_facet | Ahmed H. Bakheit Hamad M. Alkahtani |
| author_sort | Ahmed H. Bakheit |
| collection | DOAJ |
| description | This study systematically investigates the molecular structure and electronic properties of 2-methoxy-4,6-diphenylnicotinonitrile, employing X-ray diffraction (XRD) and sophisticated computational methodologies. XRD findings validate the compound’s orthorhombic crystallization in the P21212 space group, composed of a pyridine core flanked by two phenyl rings. Utilizing the three-dimensional Hirshfeld surface, the research decodes the molecule’s spatial attributes, further supported by exhaustive statistical assessments. Key interactions, such as π–π stacking and H⋯X contacts, are spotlighted, underscoring their role in the crystal’s inherent stability and characteristics. Energy framework computations and density functional theory (DFT) analyses elucidate the prevailing forces in the crystal and reveal geometric optimization facets and molecular reactivity descriptors. Emphasis is given to the exploration of frontier molecular orbitals (FMOs), aromaticity, and π–π stacking capacities. The research culminates in distinguishing electron density distributions, aromatic nuances, and potential reactivity hotspots, providing a holistic view of the compound’s structural and electronic landscape. Concurrently, molecular docking investigates its interaction with the lipoprotein-associated phospholipase A2 protein. Notably, the compound showcases significant interactions with the protein’s active site. Molecular dynamics simulations reveal the compound’s influence on protein stability and flexibility. Although the molecule exhibits strong inhibitory potential against Lp-PLA2, its drug development prospects face challenges related to solubility and interactions with drug transport proteins. |
| first_indexed | 2024-03-10T21:39:36Z |
| format | Article |
| id | doaj.art-3dfa47d09edc46659a30d12db4392402 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T21:39:36Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-3dfa47d09edc46659a30d12db43924022023-11-19T14:46:32ZengMDPI AGMolecules1420-30492023-09-012819685910.3390/molecules28196859Integrated Structural, Functional, and ADMET Analysis of 2-Methoxy-4,6-diphenylnicotinonitrile: The Convergence of X-ray Diffraction, Molecular Docking, Dynamic Simulations, and Advanced Computational InsightsAhmed H. Bakheit0Hamad M. Alkahtani1Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi ArabiaDepartment of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi ArabiaThis study systematically investigates the molecular structure and electronic properties of 2-methoxy-4,6-diphenylnicotinonitrile, employing X-ray diffraction (XRD) and sophisticated computational methodologies. XRD findings validate the compound’s orthorhombic crystallization in the P21212 space group, composed of a pyridine core flanked by two phenyl rings. Utilizing the three-dimensional Hirshfeld surface, the research decodes the molecule’s spatial attributes, further supported by exhaustive statistical assessments. Key interactions, such as π–π stacking and H⋯X contacts, are spotlighted, underscoring their role in the crystal’s inherent stability and characteristics. Energy framework computations and density functional theory (DFT) analyses elucidate the prevailing forces in the crystal and reveal geometric optimization facets and molecular reactivity descriptors. Emphasis is given to the exploration of frontier molecular orbitals (FMOs), aromaticity, and π–π stacking capacities. The research culminates in distinguishing electron density distributions, aromatic nuances, and potential reactivity hotspots, providing a holistic view of the compound’s structural and electronic landscape. Concurrently, molecular docking investigates its interaction with the lipoprotein-associated phospholipase A2 protein. Notably, the compound showcases significant interactions with the protein’s active site. Molecular dynamics simulations reveal the compound’s influence on protein stability and flexibility. Although the molecule exhibits strong inhibitory potential against Lp-PLA2, its drug development prospects face challenges related to solubility and interactions with drug transport proteins.https://www.mdpi.com/1420-3049/28/19/68592-methoxy-4,6-diphenylnicotinonitrileX-ray diffractionorthorhombic crystal systemCH–π interactionHirshfeld surfaceπ–π stacking |
| spellingShingle | Ahmed H. Bakheit Hamad M. Alkahtani Integrated Structural, Functional, and ADMET Analysis of 2-Methoxy-4,6-diphenylnicotinonitrile: The Convergence of X-ray Diffraction, Molecular Docking, Dynamic Simulations, and Advanced Computational Insights Molecules 2-methoxy-4,6-diphenylnicotinonitrile X-ray diffraction orthorhombic crystal system CH–π interaction Hirshfeld surface π–π stacking |
| title | Integrated Structural, Functional, and ADMET Analysis of 2-Methoxy-4,6-diphenylnicotinonitrile: The Convergence of X-ray Diffraction, Molecular Docking, Dynamic Simulations, and Advanced Computational Insights |
| title_full | Integrated Structural, Functional, and ADMET Analysis of 2-Methoxy-4,6-diphenylnicotinonitrile: The Convergence of X-ray Diffraction, Molecular Docking, Dynamic Simulations, and Advanced Computational Insights |
| title_fullStr | Integrated Structural, Functional, and ADMET Analysis of 2-Methoxy-4,6-diphenylnicotinonitrile: The Convergence of X-ray Diffraction, Molecular Docking, Dynamic Simulations, and Advanced Computational Insights |
| title_full_unstemmed | Integrated Structural, Functional, and ADMET Analysis of 2-Methoxy-4,6-diphenylnicotinonitrile: The Convergence of X-ray Diffraction, Molecular Docking, Dynamic Simulations, and Advanced Computational Insights |
| title_short | Integrated Structural, Functional, and ADMET Analysis of 2-Methoxy-4,6-diphenylnicotinonitrile: The Convergence of X-ray Diffraction, Molecular Docking, Dynamic Simulations, and Advanced Computational Insights |
| title_sort | integrated structural functional and admet analysis of 2 methoxy 4 6 diphenylnicotinonitrile the convergence of x ray diffraction molecular docking dynamic simulations and advanced computational insights |
| topic | 2-methoxy-4,6-diphenylnicotinonitrile X-ray diffraction orthorhombic crystal system CH–π interaction Hirshfeld surface π–π stacking |
| url | https://www.mdpi.com/1420-3049/28/19/6859 |
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