Two novel potent perfluorophenylhydrazone derivatives, 1-((4-bromothiophen-2-yl)methylene)-2-(perfluorophenyl) hydrazine, and 1-((4-bromo-5-methylthiophen-2-yl)methylene)-2-(perfluorophenyl)hydrazine as multi-target compounds to combat Alzheimer disease and their crystal, molecular, and electronic properties

Abstract

Abstract Two potent novel perfluorophenylhydrazone derivatives are presented as multi-target compounds to combat Alzheimer disease C11H4BrF5N2S, 1-((4-bromothiophen-2-yl)methylene)-2-(perfluorophenyl) hydrazine, (I) and C12H6BrF5N2S, 1-((4-bromo-5-methylthiophen-2-yl)methylene)-2-(perfluorophenyl) hydrazine, (II), which can potentially be improved by further design. Their multi-target structures and features have been combined as potential AD therapeutics. Crystals (I), and (II), are molecules with two rings and a hydrazone part as a centre of the molecule. The compounds have been synthesised and characterised by elemental spectroscopic (1H-NMR) analysis. Crystal structures of the solid phase were determined by single crystal X-ray diffraction method. Both compounds crystallise in the monoclinic space group with Z = 4 and Z = 2 molecules per unit-cell. Compound (I) crystallises as a racemate in the centrosymmetric space group and compound (II) crystallises as a non-racemate in the non-centrosymmetric space group. Their “absolute configuration and conformation for bond values” were derived from the anomalous dispersion (rmad) for (II). Crystal structures revealed diverse non-covalent interactions such as intra- and inter-hydrogen bonding, π-ring…π-ring, C—H…π-ring. The expected stereochemistry of hydrazones atoms C7, N2 and N1 were confirmed for (I) and (II). Both molecules show “boat conformation” like a 6-membered ring. Results of single crystal studies were reproduced with the help of Hirshfeld surface study and Gaussian software.