Substituent Effects on the Patterns of Intermolecular Interactions of 3-Alkyl and 3-Cycloalkyl Derivatives of Phenytoin: A Crystallographic and Quantum-Chemical Study
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2019
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A series of five derivatives of the anticonvulsant drug phenytoin was synthesized, and their crystal structures were determined. The relationship between the molecular and crystal structure of the investigated compounds was rationalized in the context of contribution of intermolecular interactions and supramolecular structural motifs. The conformational preferences were analyzed by comparing the rotational freedom of the phenyl groups in the investigated compounds with 5,5-diphenylhydantoins from the Cambridge Structural Database. With the exception of compound 3 bearing the cyclopropyl group, the crystal packing of the investigated compounds contains centrosymmetric dimers linked by paired N-H center dot center dot center dot O hydrogen bonds, which further self-organize through pairs of C-H center dot center dot center dot O interactions and a parallel interaction of two phenyl rings at a large offset into chains running along the c-axis. The principal feature of the crystal structur...e of compound 3 is formation of the chains by N-H center dot center dot center dot O hydrogen bonds and C-H center dot center dot center dot O and C-H center dot center dot center dot pi interactions. The coordination of phenytoin enables more rotational freedom for the phenyl groups. An emphasis was placed on docking of the investigated compounds into the voltage-gated ion channel in the open and closed state. The obtained results indicate that hydrogen bonding and hydrophobic interactions are dominant in stabilizing energetically favored orientations of the investigated compounds bound to the protein.
Izvor:
Crystal Growth & Design, 2019, 19, 4, 2163-2174Izdavač:
- American Chemical Society (ACS)
Finansiranje / projekti:
- Proučavanje sinteze, strukture i aktivnosti organskih jedinjenja prirodnog i sintetskog porekla (RS-MESTD-Basic Research (BR or ON)-172013)
- 0-3D nanostrukture za primenu u elektronici i obnovljivim izvorima energije: sinteza, karakterizacija i procesiranje (RS-MESTD-Integrated and Interdisciplinary Research (IIR or III)-45007)
- Istraživanja interakcija enzima sa toksičnim i farmakološki aktivnim molekulima (RS-MESTD-Basic Research (BR or ON)-172023)
DOI: 10.1021/acs.cgd.8b01776
ISSN: 1528-7483
WoS: 000463843600019
Scopus: 2-s2.0-85063380000
Kolekcije
Institucija/grupa
Tehnološko-metalurški fakultetTY - JOUR AU - Trišović, Nemanja AU - Radovanović, Lidija AU - Janjić, Goran V. AU - Jelić, Stefan T. AU - Rogan, Jelena PY - 2019 UR - http://TechnoRep.tmf.bg.ac.rs/handle/123456789/4244 AB - A series of five derivatives of the anticonvulsant drug phenytoin was synthesized, and their crystal structures were determined. The relationship between the molecular and crystal structure of the investigated compounds was rationalized in the context of contribution of intermolecular interactions and supramolecular structural motifs. The conformational preferences were analyzed by comparing the rotational freedom of the phenyl groups in the investigated compounds with 5,5-diphenylhydantoins from the Cambridge Structural Database. With the exception of compound 3 bearing the cyclopropyl group, the crystal packing of the investigated compounds contains centrosymmetric dimers linked by paired N-H center dot center dot center dot O hydrogen bonds, which further self-organize through pairs of C-H center dot center dot center dot O interactions and a parallel interaction of two phenyl rings at a large offset into chains running along the c-axis. The principal feature of the crystal structure of compound 3 is formation of the chains by N-H center dot center dot center dot O hydrogen bonds and C-H center dot center dot center dot O and C-H center dot center dot center dot pi interactions. The coordination of phenytoin enables more rotational freedom for the phenyl groups. An emphasis was placed on docking of the investigated compounds into the voltage-gated ion channel in the open and closed state. The obtained results indicate that hydrogen bonding and hydrophobic interactions are dominant in stabilizing energetically favored orientations of the investigated compounds bound to the protein. PB - American Chemical Society (ACS) T2 - Crystal Growth & Design T1 - Substituent Effects on the Patterns of Intermolecular Interactions of 3-Alkyl and 3-Cycloalkyl Derivatives of Phenytoin: A Crystallographic and Quantum-Chemical Study EP - 2174 IS - 4 SP - 2163 VL - 19 DO - 10.1021/acs.cgd.8b01776 ER -
@article{ author = "Trišović, Nemanja and Radovanović, Lidija and Janjić, Goran V. and Jelić, Stefan T. and Rogan, Jelena", year = "2019", abstract = "A series of five derivatives of the anticonvulsant drug phenytoin was synthesized, and their crystal structures were determined. The relationship between the molecular and crystal structure of the investigated compounds was rationalized in the context of contribution of intermolecular interactions and supramolecular structural motifs. The conformational preferences were analyzed by comparing the rotational freedom of the phenyl groups in the investigated compounds with 5,5-diphenylhydantoins from the Cambridge Structural Database. With the exception of compound 3 bearing the cyclopropyl group, the crystal packing of the investigated compounds contains centrosymmetric dimers linked by paired N-H center dot center dot center dot O hydrogen bonds, which further self-organize through pairs of C-H center dot center dot center dot O interactions and a parallel interaction of two phenyl rings at a large offset into chains running along the c-axis. The principal feature of the crystal structure of compound 3 is formation of the chains by N-H center dot center dot center dot O hydrogen bonds and C-H center dot center dot center dot O and C-H center dot center dot center dot pi interactions. The coordination of phenytoin enables more rotational freedom for the phenyl groups. An emphasis was placed on docking of the investigated compounds into the voltage-gated ion channel in the open and closed state. The obtained results indicate that hydrogen bonding and hydrophobic interactions are dominant in stabilizing energetically favored orientations of the investigated compounds bound to the protein.", publisher = "American Chemical Society (ACS)", journal = "Crystal Growth & Design", title = "Substituent Effects on the Patterns of Intermolecular Interactions of 3-Alkyl and 3-Cycloalkyl Derivatives of Phenytoin: A Crystallographic and Quantum-Chemical Study", pages = "2174-2163", number = "4", volume = "19", doi = "10.1021/acs.cgd.8b01776" }
Trišović, N., Radovanović, L., Janjić, G. V., Jelić, S. T.,& Rogan, J.. (2019). Substituent Effects on the Patterns of Intermolecular Interactions of 3-Alkyl and 3-Cycloalkyl Derivatives of Phenytoin: A Crystallographic and Quantum-Chemical Study. in Crystal Growth & Design American Chemical Society (ACS)., 19(4), 2163-2174. https://doi.org/10.1021/acs.cgd.8b01776
Trišović N, Radovanović L, Janjić GV, Jelić ST, Rogan J. Substituent Effects on the Patterns of Intermolecular Interactions of 3-Alkyl and 3-Cycloalkyl Derivatives of Phenytoin: A Crystallographic and Quantum-Chemical Study. in Crystal Growth & Design. 2019;19(4):2163-2174. doi:10.1021/acs.cgd.8b01776 .
Trišović, Nemanja, Radovanović, Lidija, Janjić, Goran V., Jelić, Stefan T., Rogan, Jelena, "Substituent Effects on the Patterns of Intermolecular Interactions of 3-Alkyl and 3-Cycloalkyl Derivatives of Phenytoin: A Crystallographic and Quantum-Chemical Study" in Crystal Growth & Design, 19, no. 4 (2019):2163-2174, https://doi.org/10.1021/acs.cgd.8b01776 . .