First-principles electronic structure calculations have been performed to predict chromogenic properties of various candidate structures, including pyrrole monomers and dimers and their derivatives, of the chromophores formed from the reactions of 2,5-hexanedione (2,5-HD), a prototype of neurotoxic aliphatic gamma-diketones, with NH3, amino acids, and proteins. The calculated results indicate that the pyrrole monomer structures and a previously proposed dimer structure do not have an absorption in the visible region (lambda > similar to400 nm and < &SIM;700 nm), whereas a novel type of pyrrole dimer structure has absorptions (λ = &SIM;400 to 420 nm) in the visible region if the methyl (CH3) groups on the pyrrole rings are oxidized to CHO groups. The calculated results for the oxidized pyrrole dimer models for cross-linked proteins are consistent with all of the available experimental data for the chromogenic and neurotoxic effects of 2,5-HD. Our results strongly support the conclusion that the chromogenic effects of aliphatic γ-diketones are closely related to their neurotoxic effects and further predict that both the chromogenic and neurotoxic effects are associated with the same chemical reaction process. Such a reaction process most likely starts from the formation of the pyrrole-protein adducts followed by dimerization and further oxidization.