Structure and Microbiological Activity of 1 H-benzo[ d]imidazole Derivatives

Abstract

Three new crystal structures of 1H-benzo[d]imidazole derivatives were determined. In the structures of these compounds, an identical system of hydrogen bonds, C(4), was observed. Solid-state NMR was applied for testing the quality of the obtained samples. All of these compounds were tested for in vitro antibacterial activity against Gram-positive bacteria and Gram-negative bacteria, as well as antifungal activity, by checking their selectivity. ADME calculations indicate that the compounds can be tested as potential drugs.

Keywords: 1H-benzo[d]imidazole derivatives; ADME; X-ray; antimicrobial activity; crossing the blood–brain barrier; structure–activity relationship.

Figure 1

Structural formulas of the tested compounds.

Figure 2

Synthesis of desired compounds.

Figure 3

Molecular structures of all compounds showing atom-labeling schemes. Displacement ellipsoids are drawn at the 50% probability level. Drawings were prepared with Mercury software 2022.3.0 [18]. Light gray color (EJMCh-6 and EJMCh-9) shows alternative conformations of disordered rings.

Figure 4

(a) Intermolecular hydrogen bonds in EJMCh-6. (b) Intermolecular hydrogen bonds in EJMCh-9 (c) Intermolecular hydrogen bonds in EJMCh-13. The colors indicate three different molecules in the asymmetric unit and their crystallographic symmetry equivalents.

Figure 5

Superimposition of the studied molecules and HIQXIR (HIQXIR—red, pink, magenta and violet; EJMCh-9—green; EJMCh-6—orange; EJMCh-13—light blue, blue and cyan).

Figure 6

¹³C CP MAS spectra of EJMCh-6 (a), EJMCh-9 (b) and EJMCh-13 (c) recorded at a spinning rate of 8 kHz. The recycle delay was 3 s. Asterisks indicate spinning sidebands.

Figure 7

Bioavailability radars of all compounds.

Figure 8

BOILED-Egg diagram for all compounds (lipophilicity (WLOGP) and polarity (tPSA)). Human intestinal absorption—white area; blood–brain barrier permeation—yellow area.