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

Abstract

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 ) were investigated. These compounds contain the “amidine” function (- C(=NH)NH2 ) in which the H atoms supplied by the acid have become attached to the imino group of each terminal amidino function. Moreover, in PtPipeC3Gua, the nitrogen atoms of the chair-piperazine moiety are also protonated. The influence of tetrachloroplatinate(ll) counteranion ( versus sulfate, nitrate and diisethionate ) 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 inhibit significantly the in vivo nitrite production in comparison with the other salts (sulfate, nitrate and diisethionate and their corresponding previous countercations) which exhibit NO synthase inhibition, especially bis(S-methylisothiouronium) sulfate, a selective and potent inducible NO synthase (iNOS) inhibitor commonly used as standard.