The retention properties of nucleobases in alkyl C₈-/C₁₈- and IAM-chromatographic systems in relation to log P_ow

In order to evaluate the differences in the partition properties of 35 structurally congeneric nucleobases of biological interests in octanol-water biphasic, alkyl C₈/C₁₈, and IAM systems, a comparative chromatographic study was performed. Comparing with the reversed-phase C₈/C₁₈ retention data, most of the purines possessed weaker IAM retention except for those with specific H-bond and/or electrostatic interactions. Quantitative correlations between the experimental log P_ow literature values and the IAM, C₈, and C₁₈ log k were evaluated (R² = 0.943, 0.794, and 0.767, respectively). Although IAM retention correlated significantly better (larger R² value) with the log P_ow values statistically, the latter was revealed apparently behaving more like (slope approaching unity) alkyl C₈/C₁₈ retention and hence also has the same shortcoming in under-representing analytes capable of forming short-term H-bond/electrostatic interactions with polar head-groups of phospholipids. A chemically meaningful structure-retention model (q² = 0.824 and R² = 0.968) was derived, in which the hydrophobic interaction is identified as the underlying factor for the retention of purines in IAM system modulated non-trivially by H-bond/electrostatic interactions.