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

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

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Departamento de Química, ITN, Estrada Nacional 10, 2686-953, Sacavém, Portugal.


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.

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