Phthalocyanines (Pcs) are established sensitive materials for chemical gas sensors due to their superb sensing characteristics and the achievable manifold in their analyte interaction properties. Their sorption properties are determined by the metal ion center and substituents attached to the periphery of the ring system. Similarly, vic-dioximes can be modified in their sorption properties and employed as sensitive materials. In this work, a nickel Pc and various vic-dioximes functionalized with the same hexafluoroisopropanol moiety are assessed and compared in their gas-sensing properties using the quartz crystal microbalance for the first time. This specific substituent is selected for its hydrogen bond acidity for strong interactions with analytes having corresponding sites. The synthesis and characterization of the new compounds are described. Sensor results are presented for ten selected organic compounds and the chemical warfare agent simulant dimethyl methylphosphonate (DMMP). Both compound classes exhibit good sensing performance but were found to exhibit very diverging analyte preferences, as preferential sorption of either amines or polar compounds was observed depending on the molecule type. Thus, by applying the same substituent to different base molecules, sensitive compounds with very distinct sensing properties can be realized.