A Study on the Inhibition of DiHydroFolateReductase (DHFR) from Escherichia coli by Gold(I) Phosphane Compounds. Computational Studies and X-ray Crystal Structures of (4,5-dichloro-1H-imidazolate-1-yl)-triphenylphosphane-gold(I) and (4,5-dicyano-1H-imidazolate-1-yl)-triphenylphosphane-gold(I).

An unprecedented study on the inhibitory activities of a class of phosphane gold(I) complexes on E. coli dihydrofolate reductase (DHFR) is reported. The gold(I) complexes considered in this work consist of azolate or chloride ligands and phosphane as co-ligands. The ligands have been functionalized with polar groups (–COOH, –COO−, NO2, Cl, CN) to obtain better solubility in polar media. Neutral, anionic and cationic gold(I) complexes have been tested as DHFR inhibitors by means of a continuous direct spectrophotometric method. X-ray structural characterizations were performed on ((triphenylphosphine)-gold(I)-(4,5- dicyanoimidazolyl-1H-1yl) and the second on the analog (triphenylphosphine)-gold(I)-(4,5-dichloroimidazolyl- 1H-1yl). The inhibition constants obtained from the enzyme tests range from 20 μM to 63 nM (auranofin) and are conducive to promoting these compounds as potential DHFR inhibitors.