An interesting possibility of forming special hole stepping stones with high-stacking aromatic rings in proteins: three-π five-electron and four-π seven-electron resonance bindings.

Long-range hole transfer of proteins plays an important role in many biological processes of living organisms. Therefore, it is highly useful to examine the possible hole stepping stones, which can facilitate hole transfer in proteins. However, the structures of stepping stones are diverse because of the complexity of the protein structures. In the present work, we proposed a series of special stepping stones, which are instantaneously formed by three and four packing aromatic side chains of amino acids to capture a hole, corresponding to three-π five-electron (π:π∴π↔π∴π:π) and four-π seven-electron (π:π∴π:π↔π:π:π∴π) resonance bindings with appropriate binding energies. The aromatic amino acids include histidine (His), phenylalanine (Phe), tyrosine (Tyr) and tryptophan (Trp). The formations of these special stepping stones can effectively reduce the local ionization potential of the high π-stacking region to efficiently capture the migration hole. The quick formations and separations of them promote the efficient hole transfer in proteins. More interestingly, we revealed that a hole cannot delocalize over infinite aromatic rings along the high π-π packing structure at the same time and the micro-surroundings of proteins can modulate the formations of π:π∴π↔π∴π:π and π:π∴π:π↔π:π:π∴π bindings. These results may contribute a new avenue to better understand the potential hole transfer pathway in proteins.