A DFT study of the chemical reactivity of cimetidine A, C and D in the gas phase and in H₂O, MeOH and EtOH solvents

In the present work, the chemical reactivity of cimetidine A, C and D in different solvents was analyzed through the evaluation of global and local DFT reactivity descriptors. In the gas, MeOH and EtOH phases, cimetidine A, C and D exhibit energy differences of 3-11 kcal∗∗ mol^-1. However, in the aqueous phase, cimetidine A and D are approximately isoenergetic. The values of the hardness indicate that cimetidine A, C and D are more reactive in the presence of a solvent than in the gas phase. In addition, the results suggested that CimC and CimD are better nucleophiles that CimA. The values of the Fukui function suggest that the more reactive sites of CimA are not modified in the different solvents. In the case of CimC, the more reactive sites to electrophilic and free radical attack are located on the thioether sulfur. For CimD, the number and place of the electrophilic and free radical sites are independent of the solvent.