The formation of canonical base pairs through Watson-Crick hydrogen bonding sits at the heart of the genetic apparatus. The specificity of the base pairing of adenine with thymine/uracil and guanine with cytosine preserves accurate information for the biochemical blueprint and replicates the instructions necessary for carrying out biological function. The chemical evolution question of how these five canonical nucleobases were selected over various other possibilities remains intriguing. Since these and alternative nucleobases would have been available for chemical evolution, the reasons for the emergence of this system appear to be primarily functional. While investigating the base-pairing properties of structural nucleic acid analogs, we encountered a relationship between the pK(a) of a series of nonstandard (and canonical) nucleobases and the pH of the aqueous medium. This relationship appeared to correspond with the propensity of these molecules to self-assemble via Watson-Crick-type base-pairing interactions. A simple correlation of the "magnitude of the difference between the pK(a) and pH" (pK(a)-pH correlation) enables a general prediction of which types of heterocyclic recognition elements form hydrogen-bonded base pairs in aqueous media. Using the pK(a)-pH relationship, we can rationalize why nature chose the canonical nucleobases in terms of hydrophobic and hydrophilic interactions, and further extrapolate its significance within the context of chemical evolution. The connection between the physicochemical properties of bioorganic compounds and the interactions with their aqueous environment directly affects structure and function, at both a molecular and a supramolecular level. A general structure-function pattern emerges in biomolecules and biopolymers in aqueous media near neutral pH. A pK(a) - pH < 2 generally prompts catalytic functions, central to metabolism, but a difference in pK(a) - pH > 2 seems to result in the emergence of structure, central to replication. While this general trend is observed throughout extant biology, it could have also been an important factor in chemical evolution.