The mechanism by which Zr-substituted and [GRAPHIC] other transition metal-substituted polyoxometalates (POMs) form covalently linked dimers has been analyzed by means of static density functional theory (DFT) calculations with a continuous solvent model as well as Car-Parrinello molecular dynamics (CPMD) simulations with explicit solvent molecules. The study includes different stages of the process: the formation of the active species by alkalination of the solution and formation of intercluster linkages. CPMD simulations show that the Zr-triaqua precursor, [W5O18Zr(H2O)(3)](2-), under basic conditions, reacts with hydroxide anions to form Zr-aqua-hydroxo active species, [W5O18Zr(OH)(H2O)](3-). We computed the DFT potential energy profile for dimerization of [W5O18TM(OH)](n-) [TM = Zr-IV(H2O), Zr-IV, Ti-IV, and W-VI] anions. The resulting overall energy barrier is low for Zr-IV, moderate for Ti-IV, and high for Wi(IV). The computed thermodynamic balance favors the dibridged (mu OH)(2) linkages for Zr-IV, the monobridged (mu OH) linkage for Ti-IV, and the monomeric forms for W-VI, in agreement with experimentally observed trends. The lowest energy barrier and largest coordination number of Zrsubstituted POMs are both a consequence of the flexible coordination environment and larger radius of Zr.