Intermolecular interactions of ten 2-acylamino and 2,4-bis(acylamino)pyrimidines (7 of which are previously unknown) have been investigated by X-ray structural, quantum chemical (DFT), and NMR spectral methods. Especially the concentration dependencies of the (1)H NMR chemical shifts and titrations with other molecules capable of multiple hydrogen bonding provided useful information regarding their association via triple or quadruple hydrogen bonding, which is controlled by the conformational preferences of 2-acylamino- and 2,4-bis(acylamino)pyrimidines. On comparison of the properties of 2-acylamino- and 2,4-bis(acylamino)pyrimidines with the corresponding pyridines, an additional nitrogen in the heterocyclic ring is the crucial factor in explaining the stability of various conformers and dimers of pyrimidines. Computational modeling of their dimerization (self-association) and heteroassociation supports the experimental findings. The substituent effects in 2-acylamino- and 2,4-bis(acylamino)pyrimidines are discussed via inter- and intramolecular terms. The subtle balance between several structural factors and their influence on the aggregation of studied pyrimidines was confirmed also by variable-temperature NMR and NOE experiments. X-ray structures of 2-methyl- and 2-adamantyl-CONH-pyrimidines revealed very different intermolecular interactions, showing the importance of the substituent size on the self-assembly process. As a whole NMR spectral, X-ray structural, and computational data of 2-acylamino- and 2,4-bis(acylamino)pyrimidines can be interpreted in terms of multiple intra-/intermolecular interactions.

Aqueous Sonogashira cross-coupling reactions of 5-iodopyrimidine or 7-iodo-7-deazaadenine nucleosides with bile acid-derived terminal acetylenes linked via an ester or amide tether gave the corresponding bile acid-nucleoside conjugates. Analogous reactions of halogenated nucleoside triphosphates gave directly bile acid-modified dNTPs. Enzymatic incorporation of these modified nucleotides to DNA was successfully performed using Phusion polymerase for primer extension. One of the dNTPs (dCTP bearing cholic acid) was also efficient for PCR amplification.

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