A [1H, 15N] Heteronuclear Single Quantum Coherence NMR Study of the Solution Reactivity of the Ruthenium‐Based Mitochondrial Calcium Uniporter Inhibitor Ru265. Issue 6 (21st January 2022)

• Record Type: Journal Article
• Authors: Woods, Joshua J.; Spivey, Jesse A.; Wilson, Justin J.
• Is Part Of: European journal of inorganic chemistry. Volume 2022:Issue 6(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-01-21
• Subjects: Bioinorganic chemistry -- Heteronuclear single quantum coherence -- NMR spectroscopy -- Peptides -- Ruthenium; Chemistry, Inorganic -- Periodicals; Organometallic chemistry -- Periodicals; Bioinorganic chemistry -- Periodicals; Solid state chemistry -- Periodicals; 546
• DOI: 10.1002/ejic.202100995
• Languages: English
• ISSNs: 1434-1948

Abstract

Abstract: The synthesis and characterization of the 15 N‐labeled analogue of the mitochondrial calcium uptake inhibitor [Cl(NH3 )4 Ru(μ‐N)Ru(NH3 )4 Cl] 3+ (Ru265) bearing [ 15 N]NH3 ligands is reported. Using [ 1 H, 15 N] HSQC NMR spectroscopy, the rate constants for the axial chlorido ligand aquation of [ 15 N]Ru265 in pH 7.4 buffer at 25 °C were found to be k 1 =(3.43±0.03)×10 −4 s −1 and k 2 =(4.03±0.09)×10 −3 s −1 . The reactivity of [ 15 N]Ru265 towards biologically relevant small molecules was also assessed via this method, revealing that this complex can form coordination bonds to anionic oxygen and sulfur donors. Time‐based studies on these ligand‐binding reactions reveal this process to be slow relative to the time required for the complex to inhibit mitochondrial calcium uptake, suggesting that hydrogen‐bonding interactions, rather than the formation of coordination bonds, may play a more significant role in mediating the inhibitory properties of this complex. Abstract : An analogue of the mitochondrial calcium uptake inhibitor Ru265 with 15 N‐labeled ammine ligands is reported. This isotopically enriched compound was used to study the solution speciation and reactivity of Ru265 with different biological nucleophiles.