Acyloxybutadiene tricarbonyl iron complexes as enzyme-triggered CO-releasing molecules (ET-CORMs): a structure–activity relationship study

Abstract

A series of η⁴-acyloxycyclohexadiene–Fe(CO)₃ complexes was prepared and fully characterized by spectroscopic methods including single crystal X-ray diffraction. For this purpose a new synthetic access to differently acylated 1,3- and 1,5-dienol–Fe(CO)₃ complexes was developed. The enzymatically triggered CO release from these compounds was monitored (detection of CO through GC and/or by means of a myoglobin assay) and the anti-inflammatory effect of the compounds was assessed by a cellular assay based on the inhibition of NO-production by inducible NO synthase (iNOS). It was demonstrated that the properties (rate of esterase-triggered CO release, iNOS inhibition, cytotoxicity) of the complexes strongly depend on the substitution pattern of the π-ligand and the nature of the acyloxy substituent.