Synthesis, structural characterisation and theoretical studies of a novel pyridazine derivative: Investigations of anti-inflammatory activity and inhibition of α-glucosidase
X-ray crystallography on pyridazine 1 (ethyl 2-(3-methyl-4-(4-methylbenzyl)-6-oxopyridazin1(6H)-yl)acetate) shows the planar pyridazinyl ring to exhibit significant delocalisation of πelectron density over the constituent atoms and to be substituted with oxo, methyl, (4- methylphenyl)methyl and N-b...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2021
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| Online Access: | http://eprints.sunway.edu.my/1652/ http://eprints.sunway.edu.my/1652/1/Tiekink%20Synthesis%20structural_accepted.pdf |
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| author | Zaoui, Younes Ramli, Youssef Tan, Sang Loon * Tiekink, Edward R. T. * Chemlal, L. Mague, Joel T. Taoufik, Jamal Faouzi, M. E. A. Ansar, M'hammed |
| author_facet | Zaoui, Younes Ramli, Youssef Tan, Sang Loon * Tiekink, Edward R. T. * Chemlal, L. Mague, Joel T. Taoufik, Jamal Faouzi, M. E. A. Ansar, M'hammed |
| author_sort | Zaoui, Younes |
| building | SU Institutional Repository |
| collection | Online Access |
| description | X-ray crystallography on pyridazine 1 (ethyl 2-(3-methyl-4-(4-methylbenzyl)-6-oxopyridazin1(6H)-yl)acetate) shows the planar pyridazinyl ring to exhibit significant delocalisation of πelectron density over the constituent atoms and to be substituted with oxo, methyl, (4-
methylphenyl)methyl and N-bound ethylacetate groups. While three of the ring-bound atoms are close to co-planar with the ring, the ethylacetate group is not; the latter exhibits a definitive kink in its conformation. In the molecular packing of 1, helical supramolecular
chains along the b-axis are formed through O- and N-methylene-C–H…O(carbonyl) and Omethylene-C–H…π(pyridazinyl) interactions. The chains are connected into a supramolecular layer by π(pyridazinyl)…π(phenyl) interactions. The flat layers stacks along the c-axis
2 without directional interactions between them. The geometry-optimisation of 1 resulted in the straightening of terminal ethylacetate group but no other substantial changes. Computational chemistry shows the most stabilising interactions in the crystal are due to the
π(pyridazinyl)…π(phenyl) (-10.7 kcal/mol) followed by O- and N-methylene-C–H…O(carbonyl) (-9.5 and -9.0 kcal/mol, respectively). The most prominent identified interlayer interaction is a weak methylene-C–H···N(pyridazinyl) contact. Throughout, comparisons are made with the phenyl analogue of 1, namely 2. Most notably, the lattice
energy of 1 is approximately 4.1 kcal/mol more stable than that of 2, an observation related to the influence upon the molecular packing exerted by the methyl substituent of 1. Compound 1 exhibits moderate inhibition against α-glucosidase, compared to Acarbose, and weak heatinduced haemolysis inhibition. |
| first_indexed | 2025-11-14T21:18:05Z |
| format | Article |
| id | sunway-1652 |
| institution | Sunway University |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-14T21:18:05Z |
| publishDate | 2021 |
| publisher | Elsevier |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | sunway-16522021-03-26T06:19:47Z http://eprints.sunway.edu.my/1652/ Synthesis, structural characterisation and theoretical studies of a novel pyridazine derivative: Investigations of anti-inflammatory activity and inhibition of α-glucosidase Zaoui, Younes Ramli, Youssef Tan, Sang Loon * Tiekink, Edward R. T. * Chemlal, L. Mague, Joel T. Taoufik, Jamal Faouzi, M. E. A. Ansar, M'hammed QD Chemistry X-ray crystallography on pyridazine 1 (ethyl 2-(3-methyl-4-(4-methylbenzyl)-6-oxopyridazin1(6H)-yl)acetate) shows the planar pyridazinyl ring to exhibit significant delocalisation of πelectron density over the constituent atoms and to be substituted with oxo, methyl, (4- methylphenyl)methyl and N-bound ethylacetate groups. While three of the ring-bound atoms are close to co-planar with the ring, the ethylacetate group is not; the latter exhibits a definitive kink in its conformation. In the molecular packing of 1, helical supramolecular chains along the b-axis are formed through O- and N-methylene-C–H…O(carbonyl) and Omethylene-C–H…π(pyridazinyl) interactions. The chains are connected into a supramolecular layer by π(pyridazinyl)…π(phenyl) interactions. The flat layers stacks along the c-axis 2 without directional interactions between them. The geometry-optimisation of 1 resulted in the straightening of terminal ethylacetate group but no other substantial changes. Computational chemistry shows the most stabilising interactions in the crystal are due to the π(pyridazinyl)…π(phenyl) (-10.7 kcal/mol) followed by O- and N-methylene-C–H…O(carbonyl) (-9.5 and -9.0 kcal/mol, respectively). The most prominent identified interlayer interaction is a weak methylene-C–H···N(pyridazinyl) contact. Throughout, comparisons are made with the phenyl analogue of 1, namely 2. Most notably, the lattice energy of 1 is approximately 4.1 kcal/mol more stable than that of 2, an observation related to the influence upon the molecular packing exerted by the methyl substituent of 1. Compound 1 exhibits moderate inhibition against α-glucosidase, compared to Acarbose, and weak heatinduced haemolysis inhibition. Elsevier 2021-06 Article PeerReviewed text en cc_by_nc_4 http://eprints.sunway.edu.my/1652/1/Tiekink%20Synthesis%20structural_accepted.pdf Zaoui, Younes and Ramli, Youssef and Tan, Sang Loon * and Tiekink, Edward R. T. * and Chemlal, L. and Mague, Joel T. and Taoufik, Jamal and Faouzi, M. E. A. and Ansar, M'hammed (2021) Synthesis, structural characterisation and theoretical studies of a novel pyridazine derivative: Investigations of anti-inflammatory activity and inhibition of α-glucosidase. Journal of Molecular Structure, 1234. p. 130177. ISSN 00222860 http://doi.org/10.1016/j.molstruc.2021.130177 doi:10.1016/j.molstruc.2021.130177 |
| spellingShingle | QD Chemistry Zaoui, Younes Ramli, Youssef Tan, Sang Loon * Tiekink, Edward R. T. * Chemlal, L. Mague, Joel T. Taoufik, Jamal Faouzi, M. E. A. Ansar, M'hammed Synthesis, structural characterisation and theoretical studies of a novel pyridazine derivative: Investigations of anti-inflammatory activity and inhibition of α-glucosidase |
| title | Synthesis, structural characterisation and theoretical studies of a novel pyridazine derivative: Investigations of anti-inflammatory activity and inhibition of α-glucosidase |
| title_full | Synthesis, structural characterisation and theoretical studies of a novel pyridazine derivative: Investigations of anti-inflammatory activity and inhibition of α-glucosidase |
| title_fullStr | Synthesis, structural characterisation and theoretical studies of a novel pyridazine derivative: Investigations of anti-inflammatory activity and inhibition of α-glucosidase |
| title_full_unstemmed | Synthesis, structural characterisation and theoretical studies of a novel pyridazine derivative: Investigations of anti-inflammatory activity and inhibition of α-glucosidase |
| title_short | Synthesis, structural characterisation and theoretical studies of a novel pyridazine derivative: Investigations of anti-inflammatory activity and inhibition of α-glucosidase |
| title_sort | synthesis, structural characterisation and theoretical studies of a novel pyridazine derivative: investigations of anti-inflammatory activity and inhibition of α-glucosidase |
| topic | QD Chemistry |
| url | http://eprints.sunway.edu.my/1652/ http://eprints.sunway.edu.my/1652/ http://eprints.sunway.edu.my/1652/ http://eprints.sunway.edu.my/1652/1/Tiekink%20Synthesis%20structural_accepted.pdf |