Structural study of bioisosteric derivatives of 5-(1 H -indol-3-yl)-benzotriazole and their ability to form chalcogen bonds.

Recently, inter-est in the isosteric replacement of a nitro-gen atom to selenium, sulfur or oxygen atoms has been highlighted in the design of potential inhibitors for cancer research. In this context, the structures of 5-(1 H -indol-3-yl)-2,1,3-benzotriazole derivatives [5-(1 H -indol-3-yl)-2,1,3-benzo-thia-diazole (bS, C 14 H 9 N 3 S) and 5-(1 H -indol-3-yl)-2,1,3-benzoxa-diazole (bO, C 14 H 9 N 3 O)], as well as a synthesis inter-mediate of the selenated bioisostere [5-[1-(benzensulfon-yl)-1 H -indol-3-yl]-2,1,3-benzoselena-diazole (p-bSe, C 20 H 13 N 3 O 2 SSe)] were determined using single-crystal X-ray diffraction (SCXRD) analyses. Despite being analogues, different crystal packing, torsion angles and supra-molecular features were observed, depending on the substitution of the central atoms of the benzotriazole. In particular, chalcogen inter-actions were described in the case of p-bSe and not in the bS and bO derivatives. An investigation by ab initio computational methods was therefore conducted to understand the effect of the substitution on the ability to form chalcogen bonds and the flexibility of the compounds.