Study of Organic Radicals Generated by Naphthoquinone-Hydantoins Interaction in Basic Aqueous Solution

Thiohydantoin’s characteristic thiourea core provides important biologic activity to the molecule that has been explored for pharmaceutic industry in nervous system treatment. Quinones are a family of compounds with a series of interesting properties characterized by a strong redox character due to the presence of an α,β-unsaturated system in the highly conjugated system of the ring, these properties give quinones affinity to such biological process that involves polar elements.

In the present work we study the synthesis of thiohydantoins from L-amino acids and isothiocyanates with a high purity method based on Edman cycle, these molecules where completely characterized for the next synthesis steps. Reactivity of naphthoquinones through Michael addition was studied to obtain the thiohydantoin-naphthoquinone hybrid with potential biological properties. Preliminary studies with thiohydantoin analogs like commercial hydantoin and thiohydantoin with 1,4-naphthoquinone and 2,3-dichloro-1,4-naphthoquinone were made in different conditions, including microwave assisted synthesis. Interesting results were obtained in all cases, color change was observed without structural changes. The impossibility to obtain the NMR spectra properly joined to the presence of redox properties give the clues to the presence of radicals in the final molecules. EPR spectroscopy analysis give positive results to all the hydantoin-naphthoquinone hybrids. Radicals obtained showed stability in different conditions despite de absence of transition metals in their structure like common radical molecules.