Hydrophobicities of the nucleic acid bases: distribution coefficients from water to cyclohexane.
To establish an experimental scale of hydrophobicities for the nucleic acid bases, comparable with a scale developed earlier for amino acid side-chains, these bases and their parent compounds (purine and pyrimidin-2-one) were converted to n-butylated and tetrahydrofurylated derivatives that are appreciably soluble in cyclohexane, a truly non-polar solvent that dissolves negligible water at saturation. Distribution measurements between neutral aqueous solution and cyclohexane, at varying solute concentrations, showed no evidence of self-association of the solute in either solvent, and the possibility of specific entrainment of water by solutes entering cyclohexane was ruled out by the results of experiments with tritiated water. In both the n-butyl and tetrahydrofuryl series, the bases span a range of approximately 5.3 kcal mol-1 in their free energies of transfer from water to cyclohexane, and are arranged in the following rank, in order of decreasing hydrophobicity: purine>thymine>adenine>uracil>pyrimidin-2-one>hypoxanthine>/=cytosine >/=guanine. In both series of pyrimidin-2-ones, hydrophobicity decreases with introduction of an amino substituent, but addition of an exocyclic keto group results in a modest enhancement of hydrophobicity; and free energies of transfer are relatively insensitive to the position of N-alkyl substitution. In both series of purines, hydrophobicity decreases with the introduction of exocyclic amino and keto groups, the keto group having the greater effect; and free energies of transfer vary substantially depending on the position of N-alkyl substitution. Several additional compounds were examined to test recent predictions based on SM5.4/A, a quantum mechanical self-consistent-field solvation model; and that model was found to yield values in reasonable agreement with the experimental results.
Shih
P
P
Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27599-7260, USA.
Pedersen
L G
LG
Gibbs
P R
PR
Wolfenden
R
R
D000225:Adenine / Q000737:chemistry*; D000478:Alkylation; D003510:Cyclohexanes / Q000737:chemistry; D003596:Cytosine / Q000737:chemistry*; D006147:Guanine / Q000737:chemistry*; D008956:Models, Chemical; D012997:Solvents / Q000737:chemistry; D013941:Thymine / Q000737:chemistry*; D014867:Water / Q000737:chemistry*
D003510:Cyclohexanes; D012997:Solvents; D014867:Water; D006147:Guanine; D003596:Cytosine; D000225:Adenine; D013941:Thymine