The proton/electron transfer reactions between cysteine residue (Cys) and tyrosinyl radical (Tyr(•)) are an important step for many enzyme-catalyzed processes. On the basis of the statistical analysis of protein data bank, we designed three representative models to explore the possible proton/electron transfer mechanisms from Cys to Tyr(•) in proteins. Our ab initio calculations on simplified models and quantum mechanical/molecular mechanical (QM/MM) calculations on real protein environment reveal that the direct electron transfer between Cys and Tyr(•) is difficult to occur, but an inserted water molecule can greatly promote the proton/electron transfer reactions by a double-proton-coupled electron transfer (dPCET) mechanism. The inserted H2O plays two assistant roles in these reactions. The first one is to bridge the side chains of Tyr(•) and Cys via two hydrogen bonds, which act as the proton pathway, and the other one is to enhance the electron overlap between the lone-pair orbital of sulfur atom and the π-orbital of phenol moiety and to function as electron transfer pathway. This water-mediated dPCET mechanism may offer great help to understand the detailed electron transfer processes between Tyr and Cys residues in proteins, such as the electron transfer from Cys439 to Tyr730(•) in the class I ribonucleotide reductase.

The ab initio calculations predict that the side chains of four aromatic amino acids (Phe, His, Tyr, and Trp residues) may promote methionine and cystine residues to participate in the protein electron hole transport by the formation of special multicenter, three-electron bonds (S∴π) between the Satoms and the aromatic rings. The formations of S∴π bonds can efficiently lower the local ionization energies, which drive the electron hole moving to the close side chains of S-containing and aromatic residues in proteins. Additionally, the proper binding energies for the S∴π bonds imply that the self-movement of proteins can dissociate these three-electron bonds and promote electron hole relay.

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The paper is of relevance to weak interactions between two parallel rings of close aromatic amino acids, which may participate in electron hole transport in proteins. The ab initio calculations reveal the possibility for the formation of the π∴π three-electron bond between two parallel aromatic rings, facilitating electron hole transport in proteins as the effective relay stations. The relay functionality of these special structures comes from their lower local ionization energies and proper binding energies, which vary with the different aromatic amino acids and the arrangements of the same aromatic rings according to the local microsurroundings in proteins.

Density functional calculations were performed to investigate the interaction of the side chains of histidine, phenylalanine, tryptophan, and tyrosine with the outer surface of different charged graphene sheet (GS)/(7,7) single-walled carbon nanotube (CNT) at the M06-2X-6-31+g(d,p)//M06-2X-6-31G(d) level of theory, which can get insights into the π−π interactions in enzyme-modified CNT electrodes. The aromatic rings of the amino acids prefer to orient in parallel with the plane of the CNT at the different charge states, which bears the signature of π−π interactions. The π−π interactions mainly include the dispersion forces, the electrostatic forces, and the H−π bonds. The dispersion force nearly keeps constant for the same aromatic ring interaction with the GS/CNT at the different charge states. However, the electrostatic forces and the strength of H···π bonds are significantly affected by the different charge states. These factors cause the change of the binding order for the four aromatic rings with the GS and CNT. More importantly, the highest doubly occupied molecular orbitals (HDMOs), the singly occupied molecular orbitals (SOMOs), and the lowest unoccupied molecular orbital (LUMO) mostly reside on the CNT moieties for all charged systems, indicating that the negative and positive charges are ready to accumulate on the CNT moiety when the CNT interacts with the aromatic amino acids. These results support that the CNTs can be used to assemble the enzyme-modified CNT electrodes.