Developing iron nitrosyl complexes as NO donor prodrugs

A novel class of water-soluble iron nitrosyl complexes has been developed for use as NO donor prodrugs. To elaborate these NO prodrugs various water-soluble ligands were used such as P(CH2OH)3, 1,3,5-triaza-7-phosphatricyclo[3.3.1.1]decane (PTA), 1,2-bis[bis(hydroxymethyl)phosphino]ethane (HMPE), 1,2-bis[bis(hydroxymethyl)phosphino]benzene (TMBz), cysteamine, cysteamine hydrochloride, L-cysteine ethyl ester hydrochloride (LCEE) and pyrimidine-2-thiol (pyrim). The mononuclear complexes Fe(NO)2P(CH2OH)3Cl , Fe(NO)2(P(CH2OH)3)2, Fe(NO)2(PTA)2, Fe(NO)2HMPE , Fe(NO)2TMBz , [Fe(NO)2pyrimI] , [Fe(NO)3P(CH2OH)3][X] (X=PF6, SbF6, BF4) and the dinuclear species [Fe(NO)2S(CH2)2NH3Cl]2, [Fe(NO)2S(CH2)2NH3I2] , [Fe(NO)2LCEE]2 and [Fe(NO)2pyrim]2 were obtained. Complexes , , , , , , and are water-soluble. , and were identified as nitroxyl and , , , and as nitric oxide donors by applying an EPR NO-trap assay. To determine the amount of nitric oxide which was released from the nitric oxide donors, an additional electrochemical methodology was used. The equilibrium release or the trapping concentration of NO was also studied by a UV-vis method, which allowed the rate constant of NO release to be determined.