What Controls Partitioning of the Nucleic Acid Bases between Chloroform and Water?

Giesen, David J.; Chambers, Clarke A.; Cramer, Christopher J.; Truhlar, Donald G.

doi:10.1021/jp971229c

Cited by 33 publications

(38 citation statements)

References 43 publications

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“…The contributions to the free energy of transfer from water to olive oil by F, and Cl in enflurane are −0.49 kcal/mol and −1.16 kcal/mol respectively, and in halothane the contributions of F and Br are −0.48 kcal/mol and −1.13 kcal/mol, respectively. These results agree with prior observations106 that group free energies of transfer are highly transferable for substituted nucleic acids partitioning between water and chloroform. The difference in the effect of F upon the transfer free energy compared to the effect of chlorine is quite large, ~0.7 kcal/mol, while the difference between the energetically more favorable Cl and Br is very small.…”

Section: Resultssupporting

confidence: 92%

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Modeling Free Energies of Solvation in Olive Oil

et al. 2008

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Olive oil partition coefficients are useful for modeling the bioavailability of drug-like compounds. Here we describe an extension of SM8T to predict air-olive oil and water-olive oil partitioning for druglike solutes as functions of temperature. We also describe the database of experimental partition coefficients used to parameterize the model; this database includes 371 entries for 304 compounds spanning the 291-310 K temperature range.

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Section: Resultssupporting

confidence: 92%

“…(Tables 11 and 12). The method for partitioning SM x solvation free energies into group contributions has been explained elsewhere 106. One salient example in the current data set is the positive contribution fluorine atoms make to the total free energy of solvation of fluorinated compounds in olive oil (Fig.…”

Section: Resultsmentioning

confidence: 99%

Modeling Free Energies of Solvation in Olive Oil

et al. 2008

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“…The H bonding properties of ClU and T are probably not substantially different, because the 5-Cl and 5-CH 3 substituents have a similar hydrophobic effect (π, Table 2), and previous studies have shown that the hydrophobicity of uracil was increased to the same extent by halogen (5-Br) and methyl (5-CH 3 ) substituents. 65,66 Moreover, the enthalpy of base pairing for the isolated A·T and A·ClU pairs was calculated to be 12.1 and 12.8 kcal/mol at the MP2(full)/6-311+G(2d,2p)//B3LYP/6-31G* level of theory. 43,67 Thus, the 572-fold greater activity of hTDG against ClU over T can be most readily explained by the superior leaving ability of ClU compared to T (ΔpK a N1 = −2.05), and is consistent with the higher intrinsic reactivity (k non ) of CldU over dT (Table 1).…”

Section: Htdg Activity Against 5-substituted Uracilsmentioning

confidence: 99%

Specificity of Human Thymine DNA Glycosylase Depends on N-Glycosidic Bond Stability

et al. 2006

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Initiating the DNA base excision repair pathway, DNA glycosylases find and hydrolytically excise damaged bases from DNA. While some DNA glycosylases exhibit narrow specificity, others remove multiple forms of damage. Human thymine DNA glycosylase (hTDG) cleaves thymine from mutagenic G·T mispairs and recognizes many additional lesions, and has a strong preference for nucleobases paired with guanine rather than adenine. Yet, hTDG avoids cytosine, despite the millionfold excess of normal G·C pairs over G·T mispairs. The mechanism of this remarkable and essential specificity has remained obscure. Here, we examine the possibility that hTDG specificity depends on the stability of the scissile base-sugar bond by determining the maximal activity (k max ) against a series of nucleobases with varying leaving group ability. We find that hTDG removes 5-fluorouracil 78-fold faster than uracil and 5-chlorouracil 572-fold faster than thymine, differences that can be attributed predominantly to leaving group ability. Moreover, hTDG readily excises cytosine analogues with improved leaving ability, including 5-fluorocytosine, 5-bromocytosine, and 5-hydroxycytosine, indicating that cytosine has access to the active site. A plot of log(k max ) versus leaving group pK a reveals a Brønsted-type linear free energy relationship with a large negative slope of β lg = −1.6 ± 0.2, consistent with a highly dissociative reaction mechanism. Further, we find that the hydrophobic active site of hTDG contributes to its specificity by enhancing the inherent differences in substrate reactivity. Thus, hTDG specificity depends on N-glycosidic bond stability, and the discrimination against cytosine is due largely to its very poor leaving ability rather than its exclusion from the active site.

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“…The optimized dielectric constant was used for the computation of electrostatics at the SM5. A point that merits emphasis is that application of the SMx models to predict solvation or partitioning behavior can certainly be useful as a predictive exercise, but a potentially still more important feature of the models is that the free energy associated with the particular phase transfer can be decomposed into atomic or group contributions, and thus interpreted in a fragment basis [163,164] For instance, Figure 3 illustrates the correlation between experimental and predicted logK OC values for polychlorinated biphenyls (PCBs). There is a systematic error of about 1 log unit in the absolute accuracy of the predictions, but otherwise a fairly good correlation (R 2 = 0.86).…”

Section: Smx Models For Other Condensed Phasesmentioning

confidence: 99%

SMx Continuum Models for Condensed Phases

Cramer

Truhlar

2006

Trends and Perspectives in Modern Computational Science

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Abstract:The SMx continuum models are designed to include condensed-phase effects in classical and quantum mechanical electronic structure calculations and can also be used for calculating geometries and vibrational frequencies in condensed phases. Originally developed for homogeneous liquid solutions, the SMx models have seen substantial application to more complicated condensed phases as well, e.g., the airwater interface, soil, phospholipid membranes, and vapor pressures of crystals as well as liquids. Bulk electrostatics are accounted for via a generalized Born formalism, and other physical contributions to free energies of interaction between a solute and the surrounding condensed phase are modeled by environmentally sensitive atomic surface tensions associated with solute atoms having surface area exposed to the surrounding medium. The underlying framework of the models, including the charge models used for the electrostatics, and some of the models' most recent extensions are summarized in this report. In addition, selected applications to environmental chemistry problems are presented.

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What Controls Partitioning of the Nucleic Acid Bases between Chloroform and Water?

Cited by 33 publications

References 43 publications

Modeling Free Energies of Solvation in Olive Oil

Modeling Free Energies of Solvation in Olive Oil

Specificity of Human Thymine DNA Glycosylase Depends on N-Glycosidic Bond Stability

SMx Continuum Models for Condensed Phases

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