Ruthenium(III) complexes with monodentate 5-methyl-1,2,4-triazolo[1,5-a]pyrimidin-7(4H)-one: Structural characterization, interaction with DNA and proteins

•Formation of Ru(III) complexes with 5-methyl-1,2,4-triazolo[1,5-a]pyrimidin-7(4H)-one of a “Keppler-type”.•Used of X-ray and EPR to determinate a structure of ruthenium(III) complex.•Apotransferrin and albumin as a good binding partner for Ru(III) complex.

X-ray structures of two Ru(III) complexes of the “Keppler-type”, [(CH3)2NH2]trans-[RuCl4(HmtpO)2] (1a) and [H2mtpO]trans-[RuCl4(HmtpO)2]·3H2O (1b), have been determined. The structures of both compounds established two monodentate heterocycle ligands (HmtpO) via N3 in axial positions and four equatorial chloride ions. The complexes differ only in the counter ion, which is a protonated dimethylamine [(CH3)2NH2]+ for (1a) and a protonated [H2mtpO]+ for (1b). Additionally, (1a) was characterized by EPR spectroscopy, and the effective magnetic moment measurement supports the paramagnetic character, corresponding to the expected 4d5 (S = 1/2) electron configuration for a Ru(III) core. CD studies on hydrophilic (1a) (logP = −1.28) suggested Ru(III) mechanisms of biological action that involve activation by reduction (with Ered = −0.053 V versus NHE) and selective delivery by apotransferrin. Furthermore, it is suggested that the described (1a)-BSA adducts might form in vivo and might be relevant for the biological properties of this complex, and thus adducts may be tested as specific carriers of the ruthenium complex to cancer cells.

Graphical abstractX-ray structures of two Ru(III) complexes of the “Keppler-type”, [(CH3)2NH2]trans-[RuCl4(HmtpO)2] (1a) and [H2mtpO]trans-[RuCl4(HmtpO)2]·3H2O (1b), have been determined. The structures of both compounds established two monodentate heterocycle ligands (HmtpO) via N3 in axial positions and four equatorial chloride ions. The complexes differ only in the counter ion, which is a protonated dimethylamine [(CH3)2NH2]+ for (1a) and a protonated [H2mtpO]+ for (1b). Additionally, (1a) was characterized by EPR spectroscopy, and the effective magnetic moment measurement supports the paramagnetic character, corresponding to the expected 4d5 (S = 1/2) electron configuration for a Ru(III) core. CD studies on hydrophilic (1a) (log P = −1.28) suggested Ru(III) mechanisms of biological action that involve activation by reduction (with Ered = −0.053 V versus NHE) and selective delivery by apotransferrin. Furthermore, it is suggested that the described (1a)-BSA adducts might form in vivo and might be relevant for the biological properties of this complex, and thus adducts may be tested as specific carriers of the ruthenium complex to cancer cells.Figure optionsDownload full-size imageDownload as PowerPoint slide