Ru III Complexes of Edta and Dtpa Polyaminocarboxylate Analogues and Their Use as Nitric Oxide Scavengers

Autor: Gary Bridger, Jon Zubieta, Tim Storr, Renato T. Skerlj, Michael T. Wilson, Kevin P. Maresca, Beth R. Cameron, Nathan Davies, Robert A. Gossage, Simon P. Fricker, Marilyn C. Darkes, Helen Yee
Rok vydání: 2005
Předmět:
Zdroj: European Journal of Inorganic Chemistry. 2005:2685-2697
ISSN: 1099-0682
1434-1948
DOI: 10.1002/ejic.200500018
Popis: In this study a series of Ru I I I complexes, chelated by analogues of ethylenediaminetetraacetic acid (edta) and diethylenetriaminepentaacetic acid (dtpa), were produced and tested for NO scavenging ability. Modifications to the edta and dtpa ligand frameworks were made in an effort to alter the reactivity, aqueous stability and pharmacokinetics of the resulting Ru I I I complexes. The X-ray structure of the nitrosyl complex 38 confirms that the Ru I I I complex 27 reacts with NO to form a linear {Ru-NO} [ 6 ] complex. The nitrosyl complex [C 1 5 H 1 5 N 4 O 1 1 Ru] crystallized in the P2 1 /c space group with a = 12.731(3) A, b = 10.894(2) A, c = 14.241 (3) A, β = 107.320(4)°, V = 1885.6(7)A 3 , and Z = 4. Kinetic studies on the reactions of 14 (k = 2.38×10 6 M - 1 s - 1 ) and 27 (k = 2.30x 10 5 M - 1 s - 1 ) with NO exemplify the difference in chemical properties obtained by ligand framework manipulation. Binding constants of 14 (K B = 5×10 6 M - 1 ) and 27 (K B = 2 × 10 5 M - 1 ) with NO were also measured, indicating the tight binding of NO by the Ru I I I complexes. The activity of the Ru I I I complexes to scavenge nitric oxide was evaluated using RAW264 murine macrophage cells. Ligand analogues of edta that have a pyridine donor as part of the N,N chelate such as 20 and 24 exhibit similar scavenging activity to the parent compound. Ligand analogues of dtpa that have R groups at the central amine in place of the carboxylic acid such as 31, 34, and 37 are also efficient NO scavengers.
Databáze: OpenAIRE
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