Ni/ZnO is used as a catalytic sorption material together with structural substrate for the S Zorb desulfurization process. At industrial scale, the use of Al₂O₃/SiO₂ materials as such structural substrate results in long-term deactivation via the formation of Zn₂SiO₄ under hydrothermal conditions. This work aims for the investigation of the origin of such solid-state reaction by applying multiple characterization techniques, e.g. in-situ XRD, solid-state NMR and FT-IR. Two different common Al₂O₃/SiO₂ materials, i.e. perlite and Al-montmorillonite, are studied comparatively in this work. As a result, Al-montmorillonite shows superior hydrothermal stability than perlite. It is observed that the density and reactivity of the Si-OH group is directly correlated to the formation rate of Zn₂SiO₄. Moreover, it has been further shown that the hydrogen-bonded Si-OH and bound molecular water are the major active species which lead to the formation of Zn₂SiO₄, as compared to the isolated silanol group. At last, both substrates are used for the preparation of the catalytic sorption materials in the S Zorb process. The desulfurization results show that the sorbent that has been prepared by using Al-MMT as structural substrate has maintained the sulfur-removal activity for much longer time than the one prepared from perlite.