Supported vanadium oxides have been the subject of much research for the oxidation of alcohols to aldehydes. Recent studies have shown that the specific activity of vanadium in such catalysts is a strong function of the support composition. For example isolated vanadate groups on titania exhibit nearly 10^3 times the activity of vandate species on silica. The aim of the present study was to examine the structure and performance of catalyst comprised of a high surface area, mesoporous silica support containing a fractional monolayer of titania and isolated vanadate groups. Several supports with varying titanium loadings, up to one monolayer, and low vanadium loading (0.5 V/nm2) were characterized with BET, x-ray diffraction (XRD), x-ray absorption spectroscopy (XAS), infrared (IR), Raman spectroscopy, and electron paramagnetic resonance (EPR) to determine the structure of the active site. Temperature programmed desorption (TPD) and temperature programmed reaction (TPRx) were performed on the catalyst to determine the kinetic data for the reaction. The experimental results were compared with theoretical models simulating the effect of the support on the reaction data using density functional theory calculations (DFT) for a combined study on the effect of the support on vanadium reactivity for oxidation of methanol to formaldehyde. The results of the experimental studies show a systematic change in the activity of the supported vanadate groups for methanol synthesis. The origins of this change can be traced to subtle changes in the local composition and structure of the vanadate groups. The interpretation deduced from catalyst characterization studies is supported by theoretical analysis, both of which will be discussed in detail.