Ruthenium(III) polyaminocarboxylate complexes: efficient and effective nitric oxide scavengers

Inorg Chem. 2003 Mar 24;42(6):1868-76. doi: 10.1021/ic020219+.

Abstract

The preparation of two Ru(III) polyaminocarboxylate complexes, AMD6245 and AMD6221, and their nitrosyl analogues, AMD6204, AMD6263, and AMD3689, is described. The compounds are characterized by IR, ES-MS, and (13)C and (15)N NMR spectroscopy where appropriate and cyclic voltammetry. The crystal structures for AMD6245, AMD6263, and AMD3689 are presented. AMD6245 (C(10)H(14)N(2)O(9)Ru) crystallized in the P2(1)/c space group with a = 8.4382(2) A, b = 8.8304(2) A, c = 17.6321(4) A, beta = 99.603(o), V = 1295.3(2) A(3), and Z = 4. AMD6263 (C(10)H(14)N(3)O(10)Ru) crystallized in the P2(1)/c space group with a = 9.9043(4) A, b = 13.1144(3) A, c = 12.0914(4) A, beta = 100.191(o), V = 1545.8(5) A(3), and Z = 4. AMD3689 (C(14)H(24.56)N(4)O(13.28)Ru) crystallized in the P1 space group with a = 8.838(2) A, b = 9.452(3) A, c = 13.419(4) A, alpha = 78.413(6)(o), beta = 75.804(6)(o), gamma = 73.562(6)(o), V = 1031.8(5) A(3), and Z = 2. The reaction of AMD6245 and AMD6221 with nitric oxide is investigated using EPR spectroscopy and stopped flow kinetics. Upon reaction with NO, a linear, diamagnetic [RuNO](6) complex is formed. The substitution reaction of AMD6245 with NO proceeds with a second-order rate constant of 2.24 x 10(7) M(-1) s(-1) at 7.3 degrees C (pH = 7.4; 50 mM phosphate buffer). The substitution reaction of AMD6221 with NO proceeds with a second-order rate constant of 3 x 10(5) M(-1) s(-1) at 20 degrees C (pH = 7.4; 50 mM phosphate buffered saline). The NO scavenging ability was assessed using a RAW264 murine macrophage assay by measuring the difference in nitrite produced between untreated control cells and treated cells. At 100 microM AMD6245 has [NO(2-)] = 12.5 microM less than the untreated cells and AMD6221 has [NO(2-)] = 37.6 microM less than the untreated cells. There is an insignificant difference in the amount of nitrite produced between AMD6263 or AMD3689 treated cells and untreated cells.

MeSH terms

  • Animals
  • Crystallography, X-Ray
  • Dose-Response Relationship, Drug
  • Electrochemistry
  • Electron Spin Resonance Spectroscopy
  • Kinetics
  • Macrophages / drug effects
  • Mice
  • Molecular Structure
  • Nitric Oxide / metabolism*
  • Organometallic Compounds / chemical synthesis*
  • Organometallic Compounds / chemistry
  • Organometallic Compounds / pharmacology
  • Pentetic Acid / analogs & derivatives*
  • Pentetic Acid / chemical synthesis*
  • Pentetic Acid / chemistry
  • Pentetic Acid / pharmacology
  • Ruthenium / chemistry*

Substances

  • AMD 6221
  • Organometallic Compounds
  • Nitric Oxide
  • Pentetic Acid
  • Ruthenium