Water nucleic acid bases

Neutral Water-Soluble Polymers Containing Nucleic Acid Bases. . . . 143... 

Neutral Water-Soluble Polymers Containing Nucleic Acid Bases... 

Santoro F, Barone V, Gustavsson T, Improta R (2006) Solvent effect on the singlet excited-state lifetimes of nucleic acid bases a computational study of 5-fluorouracil and uracil in acetonitrile and water. J Am Chem Soc 128 16312-16322... 

Our method has evolved during many studies over the last two decades. These include studies on the effect of strong internal electric fields in crystals on optical transition dipole directions of nucleic acid bases [2, 3], QM-MM predictions of time-dependent solvatochromism on 3-methylindole (3MI) in water [4], and on tryptophan in several proteins [5-8]. More recently, the same techniques have been... 

Orozco, M. Colominas, C. Luque, F. J., Theoretical determination of the solvation free energy in water and chloroform of the nucleic acid bases, Chem. Phys. 1996, 9, 209-678. 

Cieplak, P., Caldwell, J. W., Kollman, P. A., Molecular mechanical models for organic and biological systems going beyond the atom centered two body additive approximation aqueous solution free energies of methanol and IV-methyl acetamide, nucleic acid base, and amide hydrogen bonding and chloroform/water partition coefficients of the nucleic acid bases, J. Comput. Chem. 2001, 22, 1048-1057... 

The N-3 position of uracil also can be modified with carbodiimide reagents. In particular, the water-soluble carbodiimide CMC [l-cyclohexyl-3-(2-morpholinoethyl) carbodiimide, as the metho p-toluene sulfonate salt] can react with the N-3 nitrogen at pH 8 to give an unstable, charged adduct. The derivative is reversible at pH 10.5, regenerating the original nucleic acid base (Figure 1.47). Cytosine is unreactive in this process. 

The reaction of the p-nitrophenyl esters with the polymer (4) was studied in dimethyl sulfoxide ( DMSO ) solution in the presence of triethylamine at 25°C. The poly-L-lysine derivatives obtained have different IR absorption spectra from those of the starting compounds, and have absorptions assigned to the nucleic acid bases. Poly( e,N-Ade-L-lysine )(5) was soluble in DMSO and ethylene glycol, and also in water below pH 3, where it was present as a protonated form. In dimethylformamide (... 

The latter, ester-type derivatives (21) were prepared by the reaction of L-glutamic acid with hydroxyethyl derivatives of nucleic acid bases. The reaction was studied in the presence of p-toluenesulfonic acid at 100-110°C in dioxane, and water formed was removed by azeotropic distillation with dioxane ( ). 

Addition of P F]F2 (or CH3C02f F]F) at the double bond of substituted 2,4-dioxypyrimidines (Scheme 16) allows the preparation of the fluorine-18-labelled nucleic acid base 5-[ F]fluorouracil [91-94] and the nucleoside 2 -deoxy-5-[ F]fluorouridine [95-97]. The reaction, usually carried out in acetic acid, demonstrates an excellent regioselectivity, with only the 5-[ F]fluoro derivatives obtained because the C-5 position is the unique activated position for reaction with an electrophile in these systems. The mechanism of this reaction has been studied and the intermediate 5,6-fluoro-acetoxy adduct (or the 5,6-fluoro-hydroxy adduct if the solvent is water) has been isolated and characterised [92]. 

Table 11.3 Absolute free energies of solvation (kcal mol ) and chloroform/water partition coefficients (logio units) for nucleic acid bases at the SM5.4/AM1 Icvcf ...

The similar accuracies of different well-parameterized continuum models implies that they will also perform similarly for the computation of partition coefficients, and that has proven to be the case in most studies to date (see, for example, Bordner, Cavasotto, and Abagyan 2002 and Curutchet et al. 2003b). In Table 11.4 the previously presented SMx results for the chloroform/water partitioning of die methylated canonical nucleic acid bases are compared to results from die MST-ST/HF/6-31G method, and also to purely electrostatic results obtained using a multipole expansion SCRF method. As the latter does not include any accounting for non-electrostatic effects, its performance is significantly degraded compared to the other two. 

Of course, the simplicity of the QM/MM operator does not imply diat it has only a small effect. Large atomic partial charges placed near the QM fragment would be expected to polarize the system strongly. Table 13.2 compares the dipole moments of the standard nucleic acid bases at the AMI level evaluated in the gas phase and in a QM/MM calculation carried out modeling aqueous solvation with a periodic box of TIP31 water molecules. Eor comparison, results from the AM1-SM2 aqueous continuum solvation model are also provided. 

The bases are numbered outward from the central C and G.) The small solid spheres are water molecules. Notice the water mediated interactions of the basic arginine and lysine side chains with the nucleic acid bases and also the interaction of R240 and R243 (in B) with a backbone phosphate. The overall structure of the protein is similar to that of another leucine zipper shown in Fig. 2-21. From Keller et al.419 Drawings courtesy of Timothy J. Richmond. 

Reuther A, Iglev FI, Laenen R, Lauberau A (2000) Femtosecond photo-ionization of nucleic acid bases electronic lifetimes and electron yields. Chem Phys Lett 325 360-368 Reynisson J, Steenken S (2002) DFT calculations on the electrophilic reaction with water of the guanine and adenine radical cations. A model for the situation in DNA. Phys Chem Chem Phys... 

When oxides of nitrogen come in contact with water, both nitrous and nitric acids are formed (18) (Table IV). Toxic reactions may result from pH decrease. Other toxic reactions may be a consequence of deamination reactions with amino acids and nucleic acid bases. Another consideration is the reactions of oxides of nitrogen with double bonds (Table IV). The cis-trans isomerization of oleic acid exposed to nitrous acid has been reported (19). Furthermore, the reaction of nitrogen dioxide with unsaturated compounds has resulted in the formation of both transient and stable free radical products (20, 21) (Table V). A further possibility has been raised in that nitrite can react with secondary amines to form nitrosamines which have carcinogenic properties (22). Thus, the possible modes of toxicity for oxides of nitrogen are numerous and are not exhausted by this short list. 

Our study of the photostability issue of nucleic acid bases began with isolated bases, and later extended to their water complexes [15, 32], Our observation has thus revealed not only intrinsic properties of the bases, but also the effect of the environment on the decay mechanism of the excited state. Most of our results have been obtained from 1,3-dimethyl uracil (DMU) due to the ease of vaporization. To generalize our conclusion, however, we have also investigated 1-methyl uracil (MT), thymine (T), and 1,3-dimethyl thymine (DMT). In particular, we believe that 1-methyl uracil is an excellent mimic of uradine because of the similar substitution position on uracil. 

We present experimental results on photophysical deactivation pathways of uracil and thymine bases in the gas phase and in solvent/solute complexes. After photoexcitation to the S2 state, a bare molecule is tunneled into and trapped in a dark state with a lifetime of tens to hundreds of nanoseconds. The nature of this dark state is most likely a low lying nn state. Solvent molecules affect the decay pathways by increasing IC from the S2 to the dark state and then further to the ground state, or directly from S2 to S0. The lifetimes of the S2 state and the dark state are both decreased with the addition of only one or two water molecules. When more than four water molecules are attached, the photophysics of these hydrated clusters rapidly approaches that in the condensed phase. This model is now confirmed from other gas phase and liquid phase experiments, as well as from theoretical calculations. This result offers a new interpretation on the origin of the photostability of nucleic acid bases. Although we believe photochemical stability is a major natural selective force, the reason that the nucleic acid bases have been chosen is not because of their intrinsic stability. Rather, it is the stability of the overall system, with a significant contribution from the environment, that has allowed the carriers of the genetic code to survive, accumulate, and eventually evolve into life s complicated form. 

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