Electronic structure, ionization potential, and electron affinity of the enzyme cofactor (6R)-5,6,7,8-tetrahydrobiopterin in the gas phase, solution, and protein environments.

(6R)-5,6,7,8-Tetrahydrobiopterin (BH(4)) is a key cofactor involved in the electron transfer to the P(450) heme of nitric oxide synthase. We calculated the electronic structure of the neutral, cationic, and anionic forms of BH(4) in the gas phase, in solution (both dielectric and explicit water), and in the protein environment using density functional theory (B3LYP/6-31+G(d,p)). Subsequently, we derived the ionization potential (IP) and electron affinity (EA) of the cofactor in these chemical environments. We found that the electronic structure of BH(4) is susceptible to the presence of an external electric field and that conformational changes in the structure of BH(4) alone do not affect its electronic structure significantly. In the gas phase, water, and protein environments neutral BH(4) is the most stable species, while in the dielectric environment the anion becomes the most stable species. The IP of BH(4) in the protein environment is about half of that in the gas phase, and its EA is about 5 times smaller than that in the gas phase. Our results indicate that changes in the external electric field created by moving charged amino acid residues around BH(4) may lead to configurations that have the BH(4) ion as stable as or more stable than the neutral form, thus facilitating the electron transfer.