We present a systematic density functional study of central- and surface-doped aluminum cluster anions Al12X- (X = Mg, B, Ga, Si, P, Sc-Zn), their interactions and reactivity with water. Adsorption of water molecules on central-doped clusters is governed by the cluster electron affinity. Doping introduces a dramatic change in the cluster electronic structure by virtue of different ordering and occupation of super-atomic shells, which leads to the creation of complementary active sites controlling the reactivity with water. Surface doping creates unequal charge distribution on the cluster surface, resulting in the adsorption and reactivity of surface-doped clusters being dominated by electrostatic effects. These results demonstrate the strong influence of the doping position on the nature of the interaction and reactivity of the cluster, and contribute to a better understanding of doping effects.