In order to study or/and inhibit ribonucleotide reductase, thio derivatives of uridine and cytidine which can interact with the reducing cysteines at the active site have been prepared. The first nucleosidic thionitrites 12 and 15 have been synthesized from 2â ²-thiouridine 4 and 2â ²-thiocytidine 11, respectively and their ability to generate spontaneously nitric oxide, a potent inhibitor of Escherichia coli ribonucleotide reductase (RDPR), has been evidenced. The 2â ²-thiol function in 2â ²-thiouridine is protected as a mixed disulfide to obtain the stable and useful precursor 18 of 2â ²-thiouridine 5â ²-diphosphate 19 which has been found strongly to inhibit RDPR.The same protection has been successfully used during the conversion of 2â ²-thiouridine into 2â ²-thiocytidine.