In Vivo Nitric Oxide Synthase Inhibitors Can Be Deprived of This Activity: Unexpected Influence of the Tetrachloroplatinate(II) Counteranion. Crystal Structures of Bis(S-Methyl-Isothiouronium)-N,N′-Bis(3-Guanidinopropyl)Piperazinium and Hexamidinium Tetrachloroplatinates(II) Salts

摘要

The synthesis and crystal structures of bis(S-methylisothiouronium) (MSTUH)+, N,N′-bis((3-guanidinopropyl)piperazinium (PipeC3GuaH4)4+ and hexamidinium (HexaH2)2+ tetrachloro platinate(ll) salts ( called hereafter PtMSTU, PtPipeC3Gua and PtHexa respectively ) wereinvestigated. These compounds contain the “amidine” function ( - C(=NH)NH2 ) in which the Hatoms supplied by the acid have become attached to the imino group of each terminal amidinofunction. Moreover, in PtPipeC3Gua, the nitrogen atoms of the chair-piperazine moiety are alsoprotonated. The influence of tetrachloroplatinate(ll) counteranion ( versus sulfate, nitrate anddiisethionate ) in the in vivo nitrite inhibition by the (MSTUH)+, (PipeC3GuaH4)4+ and (HexaH2)2+ cations was investigated. The three tetrachloroplatinate(ll) salts, unexpectedly, do not inhibitsignificantly the in vivo nitrite production in comparison with the other salts (sulfate, nitrate anddiisethionate and their corresponding previous countercations) which exhibit NO synthaseinhibition, especially bis(S-methylisothiouronium) sulfate, a selective and potent inducible NOsynthase (iNOS) inhibitor commonly used as standard.