The 2′-C-methylribonucleoside of 5-aza-7-deaza-7-iodoguanine: Hydrogen and halogen bonding in nucleoside crystals, synthesis and physical properties

Abstract

The single-crystal X-ray structure of the 5-aza-7-deaza-7-iodoguanine 2′-C-methylribonucleoside 1 is described. The nucleoside was synthesized by stereoselective nucleobase anion glycosylation, yielding the protected nucleoside (70%), which was then deprotected to 1. By the same route, the non-iodinated 2′-C-methylribonucleoside 2 was obtained. In solution, the CD-spectrum of the iodinated 2′-C-methylribonucleoside 1 displays an almost mirror-like Cotton effect compared to the non-halogenated 2, revealing the strong impact of the iodo substituent to the molecule. Suzuki-Miyaura cross-coupling of 1 with pyrene boronic acid yielded a dye conjugate. The pyrene conjugate shows solvent dependent exciplex fluorescence. From the single-crystal X-ray structure of 1, conformational parameter were determined in solid state. The molecule shows anti conformation, a C3’-endo (N) sugar pucker and an antiperiplanar orientation of the 5′‑hydroxyl group. Apart from classical hydrogen bonds, nucleoside 1 possesses a halogen bond from the iodo substituent to the sugar oxygen O3’. A Hirshfeld surface analysis supports this finding. Nucleoside 1 forms a regular, tightly packed structure with stacking interactions between nucleobases and among sugar residues. A comparison of crystal packing of the iodinated 2′-C-methylribonucleoside 1 with the corresponding ribo- and 2′-deoxyribonucleosides demonstrates that halogen bonding depends on the sugar structure and determines the connectivity in crystal layers.