Nsient flavosemiquinones, like those of most transient radicals, are not simple to determine; the values quoted here are the most widely HS-173 chemical information employed. Many reports of pH 7 midpoint one electron potentials for flavins have emerged, but perhaps the most widely accepted values were reported by Anderson.305 Those data were later used to fit E versus pH data for flavins and obtain 1H+/1e- potentials at pH 0.306 Using the known dissociation constants (Figure 7) we have calculated the standard 1e- (not proton-coupled) reduction potentials shown along the vertical arrows in Figure 7. The derived bond strengths are in excellent agreement with the average bond strength calculated from the pH 7 midpoint potential (-0.21 V,155 equivalent to +0.2 V at pH 0 upon extrapolation with the Nernstian 59 mV per pH). The free energy to lose 1H+/2e- (or H-) is also shown in Figure 7, as the long steep diagonal. As with BDFEs, hydride affinities can be determined from thermodynamic square schemes.5 In a given solvent, the hydride affinity is calculated from the sum of two free energies for reduction/oxidation (23.06E?, the free energy for protonation/deprotonation (1.37pKa), and 23.06E?H+/-) (= 23.06(E?H+/? + E?H?-)), see Table 19 and Section 5.8.3, below).5 By Hess’ law, it does not matter which two reduction potentials and pKa are used to calculate a hydride affinity so long as together they connect the two species differing by H-. The 2H+/2e- potentials for non-biological substituted flavins do not vary drastically with respect to substitution,155,307 ranging from E?= 0.30 V to E?= 0.19 V (the later for the biological flavins discussed above). This implies a range of average N BDFEs from 64.5 kcal mol-1 to 62 kcal mol-1. Unfortunately, there are no individual pKa/E?data for many of these compounds, precluding construction of complete GGTI298 side effects thermochemical cycles. As noted above, the thermochemistry of flavins allows them to mediate a wide range of redox reactions, including hydride transfers and single electron transfers. The ability of flavins to transfer H- is in contrast with hydroquinones, which do not normally react by hydride transfer presumably because the hydroquinone anion (HQ-) is a high energy species, and difficult to generate under typical conditions (see above). In contrast, the reduced flavin anion is much lower in energy. In this way flavins are also unique from the other nitrogen containing compounds discussed above. Inspection of Figure 7 shows that the thermochemical landscape for flavins is more “flat” than other compounds discussed here. Because the redox potentials of flavins are less sensitive to their acid/base chemistry (and vice versa), they are able to mediate a wider range of reactions, and are not limited to H?transfer like phenols or ascorbate. 5.6.3 Nucleosides–The redox chemistry of nucleotides, nucleosides, and nucleobases has been of great interest because of its relevance to the effects of free radicals, oxidants, and ionizing radiation on DNA, and to understand long-range change transport along DNA. 308 This section summarizes the PCET thermochemistry of individual nucleosides. These data are a foundation for understanding the redox chemistry of DNA, although the properties of the nucleosides can be different within the DNA helix. There is some evidence that charge transport along DNA can be a PCET process.308f,309 Guanine is the most easily oxidized nucleobase and therefore has received the most attention. At pH 7, one-electron o.Nsient flavosemiquinones, like those of most transient radicals, are not simple to determine; the values quoted here are the most widely employed. Many reports of pH 7 midpoint one electron potentials for flavins have emerged, but perhaps the most widely accepted values were reported by Anderson.305 Those data were later used to fit E versus pH data for flavins and obtain 1H+/1e- potentials at pH 0.306 Using the known dissociation constants (Figure 7) we have calculated the standard 1e- (not proton-coupled) reduction potentials shown along the vertical arrows in Figure 7. The derived bond strengths are in excellent agreement with the average bond strength calculated from the pH 7 midpoint potential (-0.21 V,155 equivalent to +0.2 V at pH 0 upon extrapolation with the Nernstian 59 mV per pH). The free energy to lose 1H+/2e- (or H-) is also shown in Figure 7, as the long steep diagonal. As with BDFEs, hydride affinities can be determined from thermodynamic square schemes.5 In a given solvent, the hydride affinity is calculated from the sum of two free energies for reduction/oxidation (23.06E?, the free energy for protonation/deprotonation (1.37pKa), and 23.06E?H+/-) (= 23.06(E?H+/? + E?H?-)), see Table 19 and Section 5.8.3, below).5 By Hess’ law, it does not matter which two reduction potentials and pKa are used to calculate a hydride affinity so long as together they connect the two species differing by H-. The 2H+/2e- potentials for non-biological substituted flavins do not vary drastically with respect to substitution,155,307 ranging from E?= 0.30 V to E?= 0.19 V (the later for the biological flavins discussed above). This implies a range of average N BDFEs from 64.5 kcal mol-1 to 62 kcal mol-1. Unfortunately, there are no individual pKa/E?data for many of these compounds, precluding construction of complete thermochemical cycles. As noted above, the thermochemistry of flavins allows them to mediate a wide range of redox reactions, including hydride transfers and single electron transfers. The ability of flavins to transfer H- is in contrast with hydroquinones, which do not normally react by hydride transfer presumably because the hydroquinone anion (HQ-) is a high energy species, and difficult to generate under typical conditions (see above). In contrast, the reduced flavin anion is much lower in energy. In this way flavins are also unique from the other nitrogen containing compounds discussed above. Inspection of Figure 7 shows that the thermochemical landscape for flavins is more “flat” than other compounds discussed here. Because the redox potentials of flavins are less sensitive to their acid/base chemistry (and vice versa), they are able to mediate a wider range of reactions, and are not limited to H?transfer like phenols or ascorbate. 5.6.3 Nucleosides–The redox chemistry of nucleotides, nucleosides, and nucleobases has been of great interest because of its relevance to the effects of free radicals, oxidants, and ionizing radiation on DNA, and to understand long-range change transport along DNA. 308 This section summarizes the PCET thermochemistry of individual nucleosides. These data are a foundation for understanding the redox chemistry of DNA, although the properties of the nucleosides can be different within the DNA helix. There is some evidence that charge transport along DNA can be a PCET process.308f,309 Guanine is the most easily oxidized nucleobase and therefore has received the most attention. At pH 7, one-electron o.
