A series of complexes (FeII, CuII and NiII) of the N,O bidentate ligand 6,7-dichloroquinoline-5,8-dione in water was investigated by using Raman spectroscopy, and the experimental peaks were assigned with the help of computed spectra by density functional theory (DFT) calculations. A strong shift to lower wavenumbers was observed for the vibration of the CO group involved in chelation, depending on the type of metal ion. When each complex was used in the substitution reaction by the nucleophilic reagent piperidine, two products having the same molecular composition but showing the substituent in different regions of the molecule were obtained, and moreover their regioselective formation was in agreement with the size of the Raman shifts previously observed for the complexes. This example confirms the potential of the approach involving Raman spectroscopy combined with DFT calculations in the characterization of metal complexes as key intermediates in organic reactions, with the possibility of predicting the metal system capable to achieve the highest selectivity. Copyright © 2010 John Wiley & Sons, Ltd.