Abstract
The acetic acid-catalyzed reaction between 5-chloro-isatin and 4-methyl-thio-semicarbazide yields the title compound, C10H9ClN4OS (I) (common name: 5-chloro-isatin-4-methyl-thio-semicarbazone). The mol-ecule is nearly planar (r.m.s. deviation = 0.047 Å for all non-H atoms), with a maximum deviation of 0.089 (1) Å for the O atom. An S(6) ring motif formed by an intra-molecular N-H⋯O hydrogen bond is observed. In the crystal, mol-ecules are linked by N-H⋯O hydrogen bonds, forming chains propagating along the a-axis direction. The chains are linked by N-H⋯S hydrogen bonds, forming a three-dimensional supra-molecular structure. The three-dimensional framework is reinforced by C-H⋯π inter-actions. The absolute structure of the mol-ecule in the crystal was determined by resonant scattering [Flack parameter = 0.006 (9)]. The crystal structure of the same compound, measured at 100 K, has been reported on previously [Qasem Ali et al. (2012 ▸). Acta Cryst. E68, o964-o965]. The Hirshfeld surface analysis indicates that the most important contributions for the crystal packing are the H⋯H (23.1%), H⋯C (18.4%), H⋯Cl (13.7%), H⋯S (12.0%) and H⋯O (11.3%) inter-actions. A mol-ecular docking evaluation of the title compound with the ribonucleoside diphosphate reductase (RDR) enzyme was carried out. The title compound (I) and the active site of the selected enzyme show Cl⋯H-C(LYS140), Cg(aromatic ring)⋯H-C(SER71), H⋯O-C(GLU200) and FeIII⋯O⋯FeIII inter-molecular inter-actions, which suggests a solid theoretical structure-activity relationship.
Highlights
Jecika Maciel Velasques,a‡ Vanessa Carratu Gervini,a* Lisliane Kickofel,a Renan Lira de Fariasb and Adriano Bof de Oliveirac
An S(6) ring motif formed by an intramolecular N—HÁ Á ÁO hydrogen bond is observed
Molecules are linked by N—HÁ Á ÁO hydrogen bonds, forming chains propagating along the a-axis direction
Summary
Methods for the synthesis of isatin derivatives were first reported in the first half of the 19th century (Erdmann, 1841a,b; Laurent, 1841), while for thiosemicarbazone derivatives one of the first reports can be traced back to the early 1900’s (Freund & Schander, 1902). Thiosemicarbazone chemistry was not related to the pharmacological sciences. This has changed since the discovery that in vitro assays of sulfur-containing compounds showed that they are effective for Mycobacterium tuberculosis growth inhibition (Domagk et al, 1946). In the 1950’s, the synthesis of isatin– thiosemicarbazone derivatives was reported (Campaigne & Archer, 1952) and in vitro assays indicated such compounds to be active against Cruzain, Falcipain-2 and Rhodesian (Chiyanzu et al, 2003). The title compound (I), 5-chloroisatin-4-methylthiosemicarbazone, is an intermediate in the synthetic pathway of HIV-1 (human immunodeficiency virus type 1) RT (reverse transcriptase) inhibitor synthesis (Meleddu et al, 2017); a new crystal structure determination is reported here, the original work having been published by Qasem Ali et al (2012). The torsion angle for the N4—C9— N3—N2 unit is À0.8 (2)
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