Multi PCET in symmetrically substituted benzimidazoles

Abstract

Proton-coupled electron transfer (PCET) reactions depend on the hydrogen-bond connectivity between sites of proton donors and acceptors. The 2-(2'-hydroxyphenyl) benzimidazole (BIP) based systems, which mimic the natural Tyr_Z-His190 pair of Photosystem II, have been useful for understanding the associated PCET process triggered by one-electron oxidation of the phenol. Substitution of the benzimidazole by an appropriate terminal proton acceptor (TPA) group allows for two-proton translocations. However, the prototropic properties of substituted benzimidazole rings and rotation around the bond linking the phenol and the benzimidazole can lead to isomers that interrupt the intramolecular hydrogen-bonded network and thereby prevent a second proton translocation. Herein, a strategic symmetrization of a benzimidazole based system with two identical TPAs yields an uninterrupted network of intramolecular hydrogen bonds regardless of the isomeric form. NMR data confirms the presence of a single isomeric form in the disubstituted system but not in the monosubstituted system in certain solvents. Infrared spectroelectrochemistry demonstrates a two-proton transfer process associated with the oxidation of the phenol occurring at a lower redox potential in the disubstituted system relative to its monosubstituted analogue. Computational studies support these findings and show that the disubstituted system stabilizes the oxidized two-proton transfer product through the formation of a bifurcated hydrogen bond. Considering the prototropic properties of the benzimidazole heterocycle in the context of multiple PCET will improve the next generation of novel, bioinspired constructs built by concatenated units of benzimidazoles, thus allowing proton translocations at nanoscale length.

Fig. 1. (A) Molecular structures of compounds 1–3. (B) 1,3-Annular tautomerization/rotation process in BIP monosubstituted at 7-position (top) with a terminal proton acceptor (TPA) and disubstituted at 4,7 positions (bottom) with an identical TPA.

Scheme 1. Synthetic strategy detailing reaction conditions, yields, and intermediate molecules for preparation of 3.

Fig. 2. Crystal structures of 2 (top) and 3 (bottom). Carbon atoms are shown in gray, oxygen atoms in red, nitrogen atoms in light violet, and hydrogen atoms in white. Thermal ellipsoids are drawn at the 50% probability level. The crystal structure of 2 is adapted from ref. .

Fig. 3. ¹H NMR spectra of 2 (purple) and 3 (red) in acetone-d₆ displaying resonances in the downfield (top), aromatic (middle), and aliphatic (bottom) regions. The resonances of both OCH₃ groups (δOCH₃) in 3 appear at different ppm. Signals of the minor isomer of 2 are highlighted (*).

Fig. 4. (A) NOESY of 3 in CDCl₃ showing the downfield/aromatic regions of the spectrum. (B) Expansion of the selected area (dotted rectangle) in A. The arrows shown in the molecular structure describe the interactions through the space of the azomethine protons (H_a and H_b) of both TPA branches (color coded).

Fig. 5. Rotamers, tautomers, and protonation states of 2 (A) and 3 (B). There are 11 and 15 possible arrangements of 2 and 3, respectively. The blue markers indicate possible positions of the proton initially on the phenol (before oxidation) within the hydrogen-bonded network. The orange markers indicate possible positions of the proton initially on benzimidazole (before oxidation) within the hydrogen-bonded network.

Fig. 6. CVs of G (blue), unsubstituted BIP 1 (black), 2 (purple) and 3 (red). Concentration: 1 mM of the indicated BIPs, 0.1 M TBAPF₆ supporting electrolyte in dry CH₂Cl₂. WE: glassy carbon. Pseudo RE: Ag wire (ferrocene as internal reference). CE: Pt wire. Scan rate, 100 mV s⁻¹.

Fig. 7. (A) Oxidized E2PT product of 2 lacking a stabilizing, bifurcated hydrogen bond. (B) Oxidized E2PT product of 3 containing a stabilizing, bifurcated hydrogen bond.

Fig. 8. IRSEC spectra of 3 recorded under electro-oxidative conditions in (A) the middle (1700–1450 cm⁻¹) and (B) the high (3500–3200 cm⁻¹) frequency regions. Solvent: dry CH₂Cl₂, 0.1 M TBAPF₆. Characteristic bands displaying changes under polarization are indicated with upward and downward grey arrows.