Cytosine proton transfer

The proton transfer in these clusters via the water bridge was found to be about three times as fast as a nonassisted transfer, underscoring the importance of the solvent for the reaction mechanism [98IJQ855]. In addition to the relative stabilities of the cytosine tautomers, the structures and properties of some cytosine derivatives have been investigated, mainly those of 5-hydroxycytosine 111 and 5,6-dihydroxycytosine 112 (Scheme 73) [99JST1, 99JST49]. 

It has been shown that photoexcitation of the guanine-cytosine (G-C) base pair leads to proton transfer [231], Watson-Crick (WC) base pairs have excited state lifetimes much shorter than other non-WC base pairs indicating once again that the natural occurring WC base pairs are more photostable than other alternative configurations [115, 118, 232-235], Much work has been done in the gas phase where many different base pair isomers exist. The ultrafast relaxation of the WC base pair has also been confirmed in solution using fluorescence up-conversion measurements [117]. 

Sobolewski AL, Domcke W, Hattig C (2005) Tautomeric selectivity of the excited-state lifetime of guanine/cytosine base pairs The role of electron-driven proton-transfer processes. Proc Natl Acad Sci USA 102 17903-17906... 

For oxidation of G in duplex DNA, Steenken concluded that the proton on N-1 of G shifts spontaneously to N-3 of the cytosine in the normal Watson-Crick base pair to generate [C+(H)/G ]. Consistent with this proposal, calculations indicate that charge transfer in oxidized DNA is coupled with proton transfer from G to Experiments carried out in D2O also reveal a kinetic isotope effect for G oxidation, implicating a concerted proton-coupled electron transfer mechanism. However, density functional theory (DFT) calculations in the gas phase predict that the structure with a proton on G N-1 [C/HG ] is more stable than [C (H)/G ] by 1.4kcal/mol. " ... 

Figure 1 Free radical structures, parent compounds, and stable end products for the various components of DNA (a) deoxyribose, (b) guanine, (c) adenine, (d) thymine, and (e) cytosine. Panel (f) shows trapping of the electron and hole by proton transfer in the GC base pair in duplex DNA.

The present level of theoretical work can be seen in a recent paper by Sevilla s group. They have employed DFT to study the details of proton transfer reactions in Gua Cyt base pairs [57]. Using the DFT functional B3LYP with the 6-31 + G(d) basis set on the entire Gua Cyt molecule (19 heavy atoms), the results are presented which show that it is energetically favorable for the N1 proton of guanine to transfer to the N3 of cytosine after reduction of cytosine or after oxidation of guanine. 

Bansal KM, Patterson LK, Schuler RH (1972) Production of halide ion in the radiolysis of aqueous solutions of the 5-halouracils. J Phys Chem 76 2386-2392 Barnes JP, Bernhard WA (1994) One-electron-reduced cytosine in acidic glasses conformational states before and after proton transfer. J Phys Chem 98 887-893 Barvian MR, Greenberg MM (1992) Independent generation of the major adduct of hydroxyl radical and thymidine. Examination of intramolecular hydrogen atom transfer in competition with thiol trapping.Tetrahedron Lett 33 6057-6060... 

As pointed out in the previous section, chemical modification of a nucleobase can lead to the situation that a cationic (protonated) nucleobase is involved in base pairing. Two cases are to be differentiated First, the modified base is cationic. This situation is realized in the base pair between 7,9-dimethylguani-nium (58a) or 7-methylguanosinium (58b) and the corresponding neutral betain (cf. Fig. 2). Second, the modified base forces the complementary base to become protonated in order to form hydrogen bond for increased base pair stability. This situation is realized in the pair formed between 06-alkylguanine and protonated cytosine (59b) or adenine (69), and also in the pair between 3-methylguanine and protonated cytosine (60) (cf. above). Of course, the above differentiation is in a way superficial in that simple proton transfer will interconvert the two cases. 

Since coiled chains of proteins are known to uncurl because of ionic repulsions when ionization occurs, Reid (1957) suggested that excited state dissociation acts as a trigger in rapid biological processes. The 7-azaindole dimer, which undergoes photo-induced double proton transfer (see Section 4), has similarities to the adenine-thymine and guanine-cytosine base pairs of DNA. Its excited state proton transfers have been proposed as possible mechanisms of mutagenesis (Ingram and El-Bayoumi, 1974). 

Figure 12.10. Potential-energy functions of the S0 state, the locally excited 1 hit states of guanine and cytosine, the lowest1 rnr state, and the tt-jt charge-transfer state of the WC conformer (a), the conformer B (b), and the conformer C (c) of the CG dimer. The PE functions have been calculated along the linear-synchronous-transit proton-transfer reaction path from the S0 minimum to the biradical minimum. Insets show the potential-energy function of the locally excited 1mr state of guanine calculated along the minimum-energy path for stretching of the NH bond...

Figure 17-12. Potential energy surfaces of the ground and excited states of the cytosine-guanine base pair versus proton transfer (Nt -H-N3) and skeletal bond deformation coordinates (adapted from Ref. [53])...

In the cytosine-guanine Watson-Crick base-pair, radiationless decay occurs instead via an intermolecular charge transfer state, and is triggered by proton transfer. The locally excited states that were studied in the isolated cytosine are rapidly displaced to higher energy along the proton transfer coordinate. Here the protein environment causes a part of the conical intersection seam to become accessible which cannot be reached in the gas phase. 

The anionic Watson-Crick guanine-cytosine base pair behaves in a different manner [75], Namely, out of several possible configurations, differing with the position of proton(s), the geometry with proton transferred from the N1 atom of guanine to the N3 atom of cytosine turned out to be the global minimum. This structure is more stable than the Watson-Crick anion by 2.9 (B3LYP) and... 

At the ambient temperature barrier of that size is easily overcome and, therefore, attachment of excess electron to the GC base pair (incorporated in DNA as the Watson-Crick configuration) should end up with the neutral radical of hydrogenated cytosine solvated by the anion of deprotonated guanine. Proton transfer induced by electron attachment has already been suggested in the past by the group of Sevilla within their computational [76] and experimental studies [77],... 

Storoniak P, Kobylecka M, D bkowska I, Rak J, Gutowski M (2007). Comparison of intermolecular proton transfer in the Watson-Crick anionic guanine-cytosine and 8-oxoguanine-cytosine pairs. To be submitted. 

Evidence for involvement of a cytosine nucleobase in proton transfer... 

Shih IH, Been MD. Involvement of a cytosine side chain in proton transfer in the rate-determining step of ribozyme self-cleavage. Proc. Natl. Acad. Sci. U.S.A. 2001 98 1489-1494. 

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