The organic side chain of tin-substituted Dawson polyoxotungstates alpha(1)- and alpha(2)-[P2W17O61{SnCH2-CH2COOH}](7-) can be used to direct regioselective acylations of oxo ligands in the inorganic backbone, which was examined both experimentally and computationally. Acylation of the oxo ligand gave exalted electrophilicity to the acyl moiety, and the compounds that were obtained led to direct ligation of POMs to complex organic molecules.