To understand how oxide structures react at the molecular scale, rates of steady oxygen-isotope exchanges were followed in three isostructural molecules of similar to 40 atoms as a function of solution composition. These molecules were chosen because the structures in solution are known with complete confidence, yet isotope-exchange reactions can be followed spectroscopically at individual oxygens. The series of molecules differ only in a single Ti(IV) double right arrow Nb(V) substitution in one of the three metal sites, making a series of structures having the stoichiometries: [H(x)Nb(10)O(28)]((6-x)-), [H(x)TiNb(9)O(28)]((7-x)-), and [H(x)Ti(2)Nb(8)O(28)]((8-x)-). As in our previous study of the [H(x)Nb(10)O(28)]((6-x)-) ion, we find that isotope-ex hange reactions at particular oxygens cannot be understood without considering dynamics of the entire nanometer-size structure, and the interaction of the entire structure with solution. The rates for all reactive oxygens vary similarly with pH within a single molecule, but the relative importance of the proton- or hydroxide-enhanced pathways for isotopic exchange vary systematically across the series, along with Bronsted acid-base properties, and scale like the charge of the unprotonated structure in solution. The local effect on site reactivities of the Ti(IV) substitution is surprisingly small and is of the same order as that due to changes in the counterions. The extents to which the functional-group reactivities reflect global properties of the molecules is striking and emphasizes the importance of having accurate structural information in simulating geochemical reactions. The broad amphoteric chemistry of the rates resembles other classes of oxide reactions, such as ester hydrolysis and mineral dissolution kinetics.