Oxamate and pyruvate are isoelectronic molecules. They both quench tryptophan fluorescence with Stern-Volmer constants of 16 and 20 M-1, respectively, which are comparable to that of arcrylamide, a commonly used probe for protein structure. On the other hand, it is well known that neither the carboxylate group of these molecules nor the amide group is a good quencher. To find the mechanism of the quenching by oxamate and pyruvate, density functional theory computations with a polarizable continuum model, solvation based on density, and explicit waters, were performed. Results indicate that both molecules can be an electron acceptor via photoinduced electron transfer. There are two requirements. First, the carboxylate and amide moieties must be in direct contact to bring about noticeable quenching. The conjugation between the amide (or the keto) group and the carboxylate group leads to a lower pi* orbital, which is the lowest unoccupied molecular orbital (LUMO), and can then accept an electron from the excited tryptophan. Second, since oxamate and pyruvate ions have high electron density, hydrogen bonds with waters, which can be simulated by an explicit water model, are essential. Their LUMO energies are strongly influenced by water in aqueous solution. The above findings demonstrate how tryptophan fluorescence gets quenched in aqueous solution. The findings may be important in dealing with those problems where frontier orbitals are considered, especially with molecules having high electron density.