A ruthenium polypyridyl complex with the antihypertensive drug valsartan: Synthesis, theoretical calculations and interaction studies with human serum albumin

作者：de Oliveira Roger S; Boffo Elisangela F; Reis Felipe C C; Nikolaou Sofia; Andriani Karla F; Caramori Giovanni F; Doro Fabio G^*

来源：Polyhedron, 2016, 114: 232-241.

DOI：10.1016/j.poly.2015.12.029

• Ruthenium
• Valsartan
• Antihypertensive drug
• Human serum albumin
• Metallopharmaceutical

Coordination of widely used antihypertensive drug valsartan (val) to [Ru(bpy)(terpy)](2+) moiety resulted in the new complex [Ru(val)(bpy)(terpy)](+) which was characterized by electronic and vibrational spectroscopy, nuclear magnetic resonance, mass spectrometry, and electrochemistry. As probed by NMR, coordination of valsartan to Ru(II) occurred by tetrazol ring which is consistent with other spectroscopic and electrochemical data. Altogether, our data suggests that valsartan did not degrade upon coordination. Electronic-structure calculations performed at BP86/def2-TZVPP level of theory showed that the drug adopts the anti-configuration in [Ru(val)(bpy)(terpy)](+) due to hydrogen bonding interactions with terpy ligand and a Ru-N-tetrazole bond length of 2.050 angstrom. Fluorescence spectroscopy binding studies of valsartan complex with human serum albumin indicated spontaneous interaction with a significant contribution of static mechanism. The Stern-Volmer quenching constant K-sv, and corresponding thermodynamic parameters Delta N, Delta S and Delta G were calculated. These parameters suggest that albumin-complex interaction is mainly entropy-driven and hydrophobic interactions predominate.

• 出版日期2016-8-16