A Route to Bis(benzimidazole) Ligands with Built-In Asymmetry:  Potential Models of Protein Binding Sites Having Histidines of Different Basicity

Abstract

A synthetic strategy has been developed for bis(benzimidazole) ligands in which the two halves are different (4−11), and consequently of different basicity, which could be important for biomimicry and metal ion transport. Their coordination chemistry toward copper(II) has been studied in the solid state via X-ray crystallography. The ligands were complexed with copper(II) bromide and perchlorate salts to yield complexes of a 1:1 stoichiometry. Crystal structures have been determined and compared for [Cu(4)(NCCH3)(OH2)](ClO4)2 (complex A, [C20H23CuN5O2](ClO4)2, monoclinic, space group P21/c, a = 10.2168(7) Å, b = 30.740(2) Å, c = 8.3403(6) Å, β = 105.960(2)°, V = 2518.4(3) Å3, Z = 4), [Cu(6)Br2]·DMF (complex B, [C17H16Br2CuN4O]·C3H7NO, monoclinic, space group P21/c, a = 8.3348(11) Å, b = 18.165(2) Å, c = 14.140(2) Å, β = 91.646(3)°, V = 2140.0(5) Å3, Z = 4), [Cu(8)Br2]·DMF·H2O (complex C, [C16H13Br2CuN5O3]·C3H7NO·H2O, monoclinic, space group P21/c, a = 8.7241(10) Å, b = 18.172(2) Å, c = 14.506(2) Å, β = 97.376(2)°, V = 2280.7(4) Å3, Z = 4), [Cu(3)Br2]·MeOH (complex D, [C16H14Br2CuN4O]·CH4O, orthorhombic, space group Pbca, a = 14.325(2) Å, b = 13.919(2) Å, c = 18.837(2) Å, V = 3756.0(9) Å3, Z = 8), [Cu(4)Br2]·MeOH (complex E, [C18H18Br2CuN4O]·CH4O, triclinic, space group P1̄, a = 7.3120(11) Å, b = 9.9460(15) Å, c = 15.189(2) Å, α = 87.476(4)°, β = 89.093(4)°, γ = 68.673(3)°, V = 1028.0(3) Å3, Z = 2), and Cu(10)Br2 (complex F, C16H13Br2CuN3OS, monoclinic, space group P21/c, a = 7.3130(9) Å, b = 15.861(2) Å, c = 14.846(2) Å, β = 98.318(2)°, V = 1704.0(4) Å3, Z = 4). The Cu(II) complexes were found to be five coordinate, lying between perfect square-based-pyramidal (SBP) and trigonal-bipyramidal (TBP) extremes; in each case the ligands act as tridentate donors coordinating through the pyridine-like nitrogens of the benzimidazole moieties and the ether donor atom of the linking bridge. Use of the structural index parameter (τ) for five-coordinate metal complexes indicated that all the copper(II) complexes exhibit a greater tendency toward square-based-pyramidal geometry (i.e. τ < 0.5). Comparison of the symmetrical bis(benzimidazole) complex with the other, asymmetric, complexes revealed no significant change in the geometrical parameters around the copper(II) ion consequent on introduction of asymmetry and a change of pKa within the bis(benzimidazole) fragment. The degree of hydrogen bonding, solvent of crystallization, and the nature of the anion have a greater impact on the geometrical parameters and coordination environment of the copper(II) ion. The import for biological metal coordination is considered.

FT-Raman, FT-IR and NMR spectra, vibrational assignments and density functional studies of 1,3-bis(benzimidazol-2-yl)-2-thiapropane ligand and its Zn(II) halide complexes

“…Depending on donor or ligand types, distorted tetrahedral, square planar, five-coordinate geometries and octahedral are frequently observed geometries. The coordinating environment provided by the thioether-bridging ligand (L) and its several species with various transition metal ions, including Zn 2+ have been previously examined crystallographically [11,12]. In the solid state, thioether ligand provided the expected N 2 donor set from the tertiary imine nitrogen atoms forming preferred four-co-ordinate tetrahedral environment, and the remaining coordination sites were filled by halide anions [12].…”

An efficient and versatile synthesis of 2, 2'-(alkanediyl)-bis-1H-benzimidazoles employing aqueous fluoroboric acid as catalyst: density functional theory calculations and fluorescence studies

“…A detailed analysis for the formation of the unsymmetrical bis-benzimidazoles 4i has been shown here in Figure 4. Although, statistically, the formation of all the three bis-benzimidazoles, 4i, 4j and 4g are possible, in real practice, only 4i and 4j are formed in a ratio of 5:1 from the integration ratios of the aromatic protons in the crude 1 H NMR spectra.. That compound 4g was absent was proved conclusively since 4g is insoluble in DMSO-d 6 and no product was present as a residue during the preparation of this crude mixture for NMR sampling. Theoretically, there should be formation of compound 4g along with compound 4j as shown above in Figure 4, but 4g was not formed in this reaction.…”

An Update on the Synthesis of Benzoxazoles

“…of 2-aminobenzoxazole with aroyl isothiocyanates gives N-aroyl-N'-(benzoxazolo-2yl) thioureas (10) [2]. The product (11) The reaction o-aminobenzoxazoles with benzonitriles gives N-(benzoxazol-2-yl) benzamidines in high yields.…”