Acid-base and metal-ion-coordinating properties of benzimidazole and derivatives (=1,3-dideazapurines) in aqueous solution: Interrelation between complex stability and ligand basicity

The stability constants of the 1:1 complexes formed between Mg2+-Ca2+. Sr2+, Ba2+, Mn2+, Co2+, Ni2+, Cu2+, Zn2+, or Cd2+ (= Mn2+) and benzimidazole-type ligands sterically unhindered at the N3 position (= L), namely, benzimidazole, 1-methylbenzimidazole. 5(6)-chlorobenzimidazole, 6-chloro-5-fluorobenzimidazole, 5(6)-nitrobenzimidazole, 5.6-dichloro-1(beta-D-ribofuranosyl)benzimidazole, and 5,6-dinitrobenzimidazole (DNBI), were determined by UV/VIS spectrophotometry for DNBI and for all the other ligands by potentiometric pH titration in aqueous solutions (25 degrees C. I = 0.5 M, NaNO3). The acidity constants for the monoprotonated ligands HL+ were also measured. For the HL+ species which are symmetric with respect to the H(N1) and H(N3) sites, the corresponding micro acidity constants are also given. Plots of log K-ML(M), versus pK(HL)(H), (taking into account the micro acidity constants where appropriate) give straight lines. The equations for these least-squares lines allow calculation of the expected stability constant for a complex of any benzimidazole-type ligand, provided its pk(HL)(H) value (in the PK, range 2-6) is known. For the stabilities of Fe2+ complexes with benzimidazole-type ligands an estimation procedure is described. The effect of steric inhibition resulting from annelation (the fusion of a benzene ring to C4 and C5 of imidazole), is quantified and compared to that of a methyl group in the ortho position to the N atom binding the metal ion. The effect of annelation is considerable for the complexes of the divalent 3d metal ions (-0.3 to -0.7 log units) but practically nonexistent for those of the alkaline earth ions, which indicates outer-sphere complex formation for the latter. This interpretation agrees with the observation that the stability of the ML2+ complexes of Ca2+, Sr2+, and Ba2+ is practically independent of the basicity of the benzimidazole derivative. The regression lines obtained for the complexes of the benzimidazole-type ligands now permit the determination of the extent of the steric inhibition of the (C6)NH2 group on metal-ion binding at N7 of the adenine residue.