Crystal packing and theoretical analysis of halogen- and hydrogen-bonded hydrazones from pharmaceuticals. Evidence of type I and II halogen bonds in extended chains of dichloromethane

The supramolecular assembly of halogenated and hydroxyl hydrazones derived from two well known pharmaceuticals, isoniazid (IsX, where X = I, Br, OH) and hydralazine (HyX, where X = I, Br, OH), was studied by X-ray crystallography and theoretical methods. Crystal packing of IsI and HyI shows weak I center dot center dot center dot N and I center dot center dot center dot pi halogen bonds, whereas the hydrogen bonds are dominant in the brominated scaffolds IsBr and HyBr. Although the calculated I center dot center dot center dot N interaction strength appears almost three times weaker than the O-H center dot center dot center dot N contacts in the isoniazid-based hydrazones, the higher directionality of the halogen bonds induces a linear and planar architecture of self-complementary tectons, observed only with the help of a bridging water molecule in the case of IsOH. Finally, the X-ray structure of HyOH is characterized by an unexpected linear arrangement of clathrated dichloromethane molecules bound through type I and II halogen bonds. This rare phenomenon, observed in less than ten structures, was studied by coupled cluster-based energy decomposition.