Synthesis, potent anti-TB activity against M. tuberculosis ATTC 27294, crystal structures and complex formation of selected 2-arylidenehydrazinylbenzothiazole derivatives

Abstract

The synthesis, anti-TB activity, crystal structures and ligand ability of a number of 2-arylidene-benzylidenehydrazinylbenzothiazole derivatives, 1, have been investigated. The compounds 1 were obtained from 2-hydrazinobenzothiazole and substituted benzaldehydes in refluxing methanol in yields, after recrystallisation, of 55–75%. The crystal structure determination of compounds, 1e (aryl = 4-MeOC6H4), 1h (aryl = pyridin-2-yl), 1f (aryl = 2-HO-5-MeC6H3) revealed amino forms, whereas an imino form was found for 1f (aryl = 2-HO-4-MeOC6H3). Despite the different tautomeric forms of 1e and 1h, the two compounds have similar cell dimensions and furthermore their intermolecular interactions combine to form similar sub-structures. Pairs of N–H⋯N hydrogen bonds and π···dπ stacking interactions produce dimers in all compound. The compounds with the best anti-mycobacterial activity were found to be 1c (aryl = 2-O2NC6H4), 1d, (aryl = 2-HOC6H4), 1e and 1h, all having superior activities to that of the standard drug, ethambutol. Moreover two of these compounds have the capacity to act as tridentate ligands, namely 1d [a potential ONN chelator] and 1h [a potential NNN chelator]. Compound 1d (HL) acts as a tridentate O,N,N-donor to Cu(II) in forming the dimeric octahedral complex{[(L) (H2O)Cu][O3SCF3]}2, 3, from Cu(II) (O3SCF3)2 in moist MeOH. The monomeric square-pyramidal [(L) (H2O)Cu][O3SCF3], with an axial OS(O2)CF3 ligand and equatorial H2O ligand, dimerizes through extensive π···π interactions involving two complete planar L-Cu fragments. The dimers are linked into a three dimensional array by O–H⋯O and N–H⋯O hydrogen bonds and by further π···π interactions. Complex 3, while still very active, has only about 40% of the activity of its ligand against M. tuberculosis ATTC 27294.