Aström Hans, Limén Ethel, Strömberg Roger
Division of Organic and Bioorganic Chemistry, MBB, Scheele Laboratory, Karolinska Institutet, S-171 77 Stockholm, Sweden.
J Am Chem Soc. 2004 Nov 17;126(45):14710-1. doi: 10.1021/ja0477468.
As sugar-modified nucleosides, nucleotides, and oligonucleotides are much used in pharmacology and enzymatic studies, knowledge on the relative pKa values of the secondary hydroxyls can be of great help in design and interpretations. To obtain this, we have determined the acidity constants for ATP, dATP, 2'-F-dATP, 2'-NH2-ATP, and 2'-O-methyl ATP in aqueous solution. The influence of the relative acidities seem to be mainly from inductive effects since a good correlation between pKa values and group electronegativity is found. There is no clear energetic contribution from a much suggested H-bond between the 2'-OH and 3'-oxyanion in adenosine. To clarify if this kind of H-bond would make a more-prominent energetic contribution in less-polar solvents, we also determined the acidity of secondary hydroxyls in adenosine, 2'-O-methyladenosine, and 3'-O-methyladenosine in water, methanol, and DMSO. The relative differences in pKa values were, however, quite similar in all solvents, suggesting that no major energetic contribution is made by an intramolecular H-bond in adenosine.
由于糖修饰的核苷、核苷酸和寡核苷酸在药理学和酶学研究中被广泛应用，了解仲羟基的相对pKa值对于设计和解释具有很大帮助。为了获得这些信息，我们测定了ATP、dATP、2'-F-dATP、2'-NH2-ATP和2'-O-甲基ATP在水溶液中的酸度常数。相对酸度的影响似乎主要来自诱导效应，因为发现pKa值与基团电负性之间存在良好的相关性。腺苷中2'-OH与3'-氧阴离子之间备受关注的氢键并没有明显的能量贡献。为了阐明这种氢键在极性较小的溶剂中是否会产生更显著的能量贡献，我们还测定了腺苷、2'-O-甲基腺苷和3'-O-甲基腺苷在水、甲醇和二甲基亚砜中的仲羟基酸度。然而，在所有溶剂中pKa值的相对差异非常相似，这表明腺苷中的分子内氢键没有产生主要的能量贡献。
