The ability of the vanadyl pyrophosphate (1 0 0) surface to selectively activate n-butane in the slow step of paraffin oxyfunctionalisation was investigated. Quantum chemical calculations were performed on small cluster models for orthophosphate and pyrophosphate surface terminations. Electrostatic potential surfaces for n-butane and the catalyst clusters show favourable electrostatic interaction, with the reactant oriented to maximise Coulombic attraction between terminal hydrogens and surface oxygens. Site-selectivity for covalent interaction at the reactant-surface interface, as measured by frontier molecular orbital (FMO) surfaces and Fukui functions, indicates that surface vanadium species can selectively cleave methylene C-H bonds for butane activation. Both surface terminations, orthophosphate and pyrophosphate, feature the same activation mechanism. The pyrophosphate model, however, has a higher concentration of surface P-O oxygen species which feature prominently in the high-lying occupied orbitals. Hence, the pyrophosphate-terminated surface may promote subsequent controlled oxidation of activated n-butane to maleic anhydride. The susceptibility of maleic anhydride to further reaction at the surface was also examined using the active site reactivity analyses. © 2002 Elsevier Science B.V. All rights reserved.