Re and (99m)Tc organometallic complexes containing pendant l-arginine derivatives as potential probes of inducible nitric oxide synthase

Dalton Trans. 2009 Jan 7:(1):152-62. doi: 10.1039/b805986a. Epub 2008 Oct 23.

Abstract

Aiming to design radioactive compounds based on the core "(99m)Tc(CO)(3)" for probing inducible nitric oxide synthase (iNOS) levels in vivo, we have synthesized conjugates containing a pyrazolyl-diamine chelating unit and pendant l-arginine analogues (substrates and inhibitors of NOS). Reaction of the conjugates with fac-[M(CO)(3)](+) (M = Re, (99m)Tc) gave bioorganometallic complexes of the type fac-[M(CO)(3)(k(3)-L)] in good yield. After in vitro testing using the oxyhemoglobin NO capture assay, we concluded that the affinity of the inhibitor-containing conjugates to iNOS seems to be less affected upon metallation with rhenium than the substrate-containing conjugates. The complexes bearing guanidino substituted analogues of l-arginine still present considerable inhibitory action (N(omega)-monomethyl-l-arginine, K(i) = 36 microM; N(omega)-nitro-l-arginine, K(i) = 84 microM), being the first examples of organometallic complexes able to inhibit the iNOS. These results seem to indicate that (99m)Tc(CO)(3)-labeled L-argininine analogues, namely NOS inhibitors, may hold potential for monitoring increased levels of iNOS in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arginine / chemistry*
  • Chromatography, High Pressure Liquid
  • Humans
  • Kinetics
  • Magnetic Resonance Spectroscopy
  • Molecular Probes*
  • Nitric Oxide Synthase Type II / chemistry*
  • Organometallic Compounds / chemistry*
  • Organotechnetium Compounds / chemistry*
  • Rhenium / chemistry*
  • Spectrometry, Mass, Electrospray Ionization
  • Spectrophotometry, Ultraviolet

Substances

  • Molecular Probes
  • Organometallic Compounds
  • Organotechnetium Compounds
  • Rhenium
  • Arginine
  • Nitric Oxide Synthase Type II