title: Synthesis, Molecular Structure Optimization, and Cytotoxicity Assay of a Novel 2-Acetyl-3-amino-5-[(2-oxopropyl)sulfanyl]-4-cyanothiophene.
abstract: A novel thiophene-containing compound, 2-acetyl-3-amino-5-[(2-oxopropyl)sulfanyl]-4-cyanothiophene (4) was synthesized by reaction of malononitrile with CS₂ in the presence of K₂CO₃ under reflux in DMF and the subsequent reaction with chloroacetone followed by cyclization. This compound has been characterized by means of FT-IR, ¹H-NMR, (13)C-NMR, and mass spectrometry as well as elemental analysis. In addition, the molecular structures of compound 4 was determined by X-ray crystallography. The geometry of the molecule is stabilized by an intramolecular interaction between N1-H1···O1 to form S6 graf set ring motif. In the crystal, molecules are linked via N1-H2···O1 and C7-H7A···N2 interactions to form a three-dimensional network. Molecular structure and other spectroscopic properties of compound 4 were calculated using DFT B3LYP/6-31G (d,p) method. Results revealed a good agreement between the optimized geometric parameters and the observed X-ray structure. Furthermore, and by employing the natural bond orbital (NBO) method, the intramolecular charge transfer (ICT) interactions along with natural atomic charges at different sites, were calculated; results indicated strong n→π* ICT from LP(1)N5→BD*(2)C15-C16 (63.23 kcal/mol). In addition, the stabilization energy E(2) of the LP(2)O3→ BD*(1)N5-H6 ICT (6.63 kcal/mol) indicated the presence of intramolecular N-H···OH bonding. Similarly, calculations of the electronic spectra of compound 4 using, TD-DFT revealed a good agreement with the experimental data. Finally, compound 4 was evaluated for its in vitro cytotoxic effect against PC-3 and HeLa cell lines, as an anticancer agent, and found to be nontoxic.
authors.affiliation: Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia. yahia@ksu.edu.sa.
authors.forename: Yahia N
authors.initials: YN
authors.lastname: Mabkhot
authors.affiliation: Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia. fzsw2010@hotmail.com.|King Abdulaziz City for Science and Technology, P.O. Box 6086, Riyadh 11442, Saudi Arabia. fzsw2010@hotmail.com.
authors.forename: Fahad D
authors.initials: FD
authors.lastname: Aldawsari
authors.affiliation: Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia. showiman@ksu.edu.sa.
authors.forename: Salim S
authors.initials: SS
authors.lastname: Al-Showiman
authors.affiliation: Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia. ambarakat@ksu.edu.sa.|Department of Chemistry, Faculty of Science, Alexandria University, P.O. Box 426, Ibrahimia, 21321 Alexandria, Egypt. ambarakat@ksu.edu.sa.
authors.forename: Assem
authors.initials: A
authors.lastname: Barakat
authors.affiliation: Department of Chemistry, Faculty of Science, Alexandria University, P.O. Box 426, Ibrahimia, 21321 Alexandria, Egypt. saied1soliman@yahoo.com.|Department of Chemistry, Rabigh College of Science and Art, King Abdulaziz University, P.O. Box 344, Rabigh 21911, Saudi Arabia. saied1soliman@yahoo.com.
authors.forename: Saied M
authors.initials: SM
authors.lastname: Soliman
authors.affiliation: Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia. iqbal.choudhary@iccs.edu.|H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270, Pakistan. iqbal.choudhary@iccs.edu.
authors.forename: Muhammad I
authors.initials: MI
authors.lastname: Choudhary
authors.affiliation: H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270, Pakistan. dr.sammer.yousuf@gmail.com.
authors.forename: Sammer
authors.initials: S
authors.lastname: Yousuf
authors.affiliation: Lab of Chemical Material, Faculty of Sciences, University Mohammed Premier, Oujda 60000, Morocco. taibi.ben.hadda@gmail.com.
authors.forename: Taibi
authors.initials: T
authors.lastname: Ben Hadda
authors.affiliation: Department of Chemistry, The University of Jordan, Amman 11942, Jordan. mmubarak@ju.edu.jo.
authors.forename: Mohammad S
authors.initials: MS
authors.lastname: Mubarak
mesh_terms: D000096:Acetone / Q000031:analogs & derivatives* / Q000737:chemistry; D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D003500:Cyclization; D006367:HeLa Cells; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D013876:Thiophenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D013876:Thiophenes; D000096:Acetone; C006973:chloroacetone
keywords: 2-acetyl-3-amino-5-[(2-oxopropyl)sulfanyl]-4-cyanothiophene; DFT; X-ray diffraction; cytotoxicity; molecular structure