Tryptophan radical cations

The reduction potential of the tryptophan radical cation is estimated to be 1.13 eV, while the energy of Trp in its excited singlet state is 3.9 eV. The reduction potential of the protein-bound metal ion corresponds to the reduction potential (-1.05 V for Yb /Yb ) plus a correction of -0.18 eV to account for the larger binding constant for Ln° ions to parvalbumin ( 100 times that of Ln ions). These values yield a driving force for Yb of AG = -1.54 eV... 

Tryptophan is readily oxidised by various oxidising free radicals (Fletcher and Rosenfeld 1983, 1985, 1988). Except for HO radical which predominantly adds to the indole ring of tryprophan (OuDERKiRK et al. 1983), free-radical oxidants such as S04 (Fletcher and Rosenfeld 1983), Br (Fletcher and Rosenfeld 1985), (SCN)2 (Fletcher and Rosenfeld 1985), and Nj " (Fletcher and Rosenfeld 1988) react by one-electron transfer. The result is the tryptophan radical cation, which is in equilibrium with the neutral tryptophan radical. The reactivity of the tryptophan radical cation was found to be 1-2 orders of magnitude higher than that of the neutral radical (Jovanovic et al. 1991). 

Beilina B, Compagnon I, Flouver S, Maitre P, Allouche AR, Antoine R, Dugourd P (2011) Spectroscopic signatures of peptides containing tryptophan radical cations. Angew Chem Int Ed 50 11430-11432... 

El-Agamey, A., M. Burke, R. Edge et al. 2005. Photolysis of carotenoids in chloroform Enhanced yields of carotenoid radical cations in the presence of a tryptophan ester. Rad. Phys. Chem. 72 341-345. 

When the binding energy of a hydrogen to a heteroatom is weak, heteroatom-centered radicals are readily produced by H-abstraction or one-electron oxidation followed by H+ loss. Typical examples are phenols (e.g vitamin E in non-aqueous media), tryptophan and related compounds and thiols. Deprotonation of radical cations is indeed often a source of heteroatom-centered radicals even if a deprotonation at carbon or OH addition upon reaction with water would be thermodynamically favored. The reason for this is the ready deprotonation at a heteroatom (Chap. 6.2). 

Tryptophan and its derivatives such as the Hoechst compounds (Adhikary et al. 2000) have reduction potentials below that of G (tryptophan E7 = 1.0 V Jovanovic and Simic 1985) and thus are capable of repairing some of the DNA damage (for a review on indol free-radical chemistry see Candeias 1998 for the thermochemistry of N-centered radicals see Armstrong 1998). In these reactions, radical cations and N-centered radicals are formed. Similar to phenoxyl radicals, these radical react with 02- mainly by addition despite the large difference in the redox potential which would allow an ET as well (Fang et al. 1998). 

Deeble DJ, Schuchmann MN, Steenken S, von Sonntag C (1990) Direct evidence for the formation of thymine radical cations from the reaction of SO/" with thymine derivatives a pulse radiolysis study with optical and conductance detection. J Phys Chem 94 8186-8192 DeFelippis MR, Murthy CP, Faraggi M, Klapper MH (1989) Pulse radiolytic measurement of redox potentials the tyrosine and tryptophan radicals. Biochemistry 28 4847-4853 Delatour T, Douki T, D Ham C, Cadet J (1998) Photosensitization of thymine nucleobase by benzo-phenone through energy transfer, hydrogen abstraction and one-electron oxidation. J Photo-chem Photobiol 44 191-198... 

All of these compounds are expected to have ferryl iron with no porphyrin cation radical. As with optical spectroscopy the presence of the distant tryptophan radical in cytochrome c peroxidase compound I appears to have no effect on the MCD spectra. This was confirmed by a direct comparison of cytochrome c peroxidase compounds I and II [172] in the visible region. Tryptophan has a distinct MCD spectrum at 280 nm [173]. However, none of the changes in the UV MCD spectrum that occurred upon compound I formation could be attributed to the formation of the tryptophan radical [174]. 

A theoretical determination of vibrational absorption and Raman spectra of 3-methylindole radicals has been carried out in comparison to experimentally measured spectra for 3-methylindole (Table 28) to provide specific spectroscopic markers for the detection of neutral or cationic tryptophan radicals in biological systems <2001CPH(265)13>. Among isatin derivatives, substitution at C-5 has relatively greater influence on the electron density and the force constant of the amide than of the ketone carbonyl group (Table 29) <2001SAA469>. 

Tryptophan (Trp), tyrosine (Tyr), cystine (Cys), and phenylalanine (Phe) moieties play a determinant role regarding UV light-induced chemical alterations in many proteins. After the absorption of light by these moieties, in most cases mainly by Trp and Tyr, they undergo photoionization and participate in energy-and electron-transfer processes. This not only holds for structural proteins such as keratin and fibroin [11], but also for enzymes in aqueous media such as lysozyme, trypsin, papain, ribonuclease A, and insulin [7]. The photoionization of Trp and/or Tyr residues is the major initial photochemical event, which results in inactivation in the case of enzymes. A typical mechanism pertaining to Trp residues (see Scheme 8.3) commences with the absorption of a photon and the subsequent release of an electron. In aqueous media, the latter is rapidly solvated. By the release of a proton, the tryptophan cation radical Trp is converted to the tryptophan radical Trp. ... 

As shown in Scheme 8.4, the resulting disulfide anion radical dissociates into a thiolate ion R-S and a thiyl radical R-S. Proton transfer from the tryptophan cation radical to the thiolate ion leads to the tryptophan radical Trp and the thiol RSH. The final stage of the process is governed by radical coupling, which may result in sulfenylation of the Trp moiety yielding Trp-S-R, or in inter-molecular cross-linking, i.e. in the formation of enzyme dimers or trimers. 

The linewidth of the Wp species is - 17G and its g-value is 2.0036, as indicated. Model compound studies of tryptophan radicals produced in vitro by uv irradiation have shown that these radicals have g-values in the range g 2.004 (14). The linewidths of these models show an interesting dependence on the protonation state of the tryptophan indole nitrogen. In the cation radical the nitrogen remains protonated and the observed linewidth is - 25 G. If the nitrogen deprotonates upon radical formation to produce the neutral species, the observed linewidth is - 13 G. These model... 

I, which is generated in the light in these cells (1). Thus, the g value and line width of radical shown in lb are in reasonable agreement with the reported values for the neutral, unprotonated tryptophan radical in frozen powders, which had a linewidth of 13-14G and a g value of 2.004 (9). The pK of the radical has been measured to be 4.7 in vitro (10) the cation radical, which was also observed in ref. 9, had a line width of 21-25G, with a reported value of 2.004. 

CCI3O2 reacts with ascorbic and uric acid [71], as well as bilirubin [72] and glutathione [73] via electron transfer. However, with tryptophan and carotenoids another reaction also occurs, suggested to be radical addition [74, 75]. For the carotenoids the proposed adduct decays to yield more radical cation and for the carotenoid, astaxanthin, the radical cation is not formed initially but is formed solely through the proposed addition radical [75]. The one electron reduction potential of astaxanthin radical cation has been shown to be higher than several other carotenoids [76], so it may be that it is very close to that of CCI3O2 so that electron transfer is very slow. 

---