Hirshfeld analysis and mol-ecular docking with the RDR enzyme of 2-(5-chloro-2-oxoindolin-3-yl-idene)- N-methyl-hydrazinecarbo-thio-amide

Jecika Maciel Velasques; Vanessa Carratu Gervini; Lisliane Kickofel; Renan Lira de Farias; Adriano Bof de Oliveira

doi:10.1107/S2056989017005461

Hirshfeld analysis and mol-ecular docking with the RDR enzyme of 2-(5-chloro-2-oxoindolin-3-yl-idene)- N-methyl-hydrazinecarbo-thio-amide

Acta Crystallogr E Crystallogr Commun. 2017 Apr 13;73(Pt 5):702-707. doi: 10.1107/S2056989017005461. eCollection 2017 May 1.

Authors

Jecika Maciel Velasques¹, Vanessa Carratu Gervini¹, Lisliane Kickofel¹, Renan Lira de Farias², Adriano Bof de Oliveira³

Affiliations

¹ Universidade Federal do Rio Grande (FURG), Escola de Química e Alimentos, Rio Grande, Brazil.
² Universidade Estadual Paulista (UNESP), Instituto de Química, Araraquara, Brazil.
³ Universidade Federal de Sergipe (UFS), Departamento de Química, São Cristóvão, Brazil.

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 Fe^III⋯O⋯Fe^III inter-molecular inter-actions, which suggests a solid theoretical structure-activity relationship.

Keywords: Hirshfeld surface analysis; RDR-thiosemicarbazone in silico evaluation; crystal structure; hydrogen bonding; isatin thiosemicarbazone derivative.