Synthesis and imaging of blood-brain-barrier permeable nitroxyl-probes for free radical reactions in brain of living mice.

Three different lipophilic nitroxyl-probes having capability to pass the blood-brain barrier were, for the first time, synthesized to estimate free radical reactions in brain of living animals. Two of the three were designed to be hydrolyzed by esterase and remain in cell. All 3 probes had high n-octanol/buffer partition coefficients and gave 2 signal components in in vivo ESR spectra at head of living mice after intravenous injection. The ESR parameters of 2 components agreed with those of probes dissolved in water and lipidic phases. ESR-CT imaging on the nitroxyl-proves after intravenous injection revealed that all probes presented in both encephalon and extracranial region of head. Tissue distribution of the nitroxyl-probes demonstrated that the newly synthesized lipophilic nitroxyl-probes had capability to pass the blood-brain barrier and accumulated in brain than that of hydrophilic probe.