1H NMR Monitoring of Reactions Between a Thiohydantoin Derivative and Various Palladium(II) Complexes

Abstract

As cancer persists as one of the biggest threats to human health globally, the need for more potent, less toxic and harmful anticancer agents rises. The design and testing of such new potential agents has been a colaborative effort of chemists, biologist and pharmacologists for decades. Thiohydantoins are a large family of drug-based heterocyles with many biological activities and applications, including anticancer activity. This pharmacologically interesting moiety has been under the radar for anticancer research for quite some time now. Ever since the advent of cisplatin, platinum has been the number one metal in anticancer research. A number of platinum complexes are now used clinically for anticancer treatment. For investigation of chemical interactions, palladuim is often used as a model instead of platinum, because it is cheaper and reacts identically. This is a trait that is employed in this study. Reactions of 3-[(phenylethilene)amino]-2-thioxo-4-imadazolidinone with PdCl2, Pd(DMSO)2Cl2 and K2PdCl4 were monitored using time-dependent 1H NMR spectroscopy. All reactions were performed at ambient temperature in DMSO-d6 as solvent by mixing equimolar amounts of reactants. Under the given experimental conditions, there was no reaction with K2PdCl4. In both other cases, concerning PdCl2 and Pd(DMSO)2Cl2, the signal of the NH proton of the starting thiohydantoin has vanished, which indicates coordination in that position. Also, in both cases, the benzylidene double bond proton has doubly shifted from 8.30 ppm to 9.19 and 10.08 ppm, indicating that two different complexes were formed. This is also backed up by the two shifts of the CH2 proton signals from the thiohydantoin ring, shifting from 3.95 ppm to 4.08 and 4.15 ppm. The first one is shifted as a consequence of the NH deprotonation and coordination to the N1 thiohydantoin nitrogen, while the other signal is shifted most likely due to coordination to the imine nitrogen. These results are promising and the exact structure of these complexes will be obtained after their preparative synthesis and X-ray crystallografic analysis. The results obtained in this study could contribute to a better understanding of hydantoin chemistry, as well as palladium and/or platinum chemistry and mechanisms through which they interact. The results might also lead to the synthesis of novel palladium/platinum complexes with potential anticancer activities.