The 2′-deoxyribofuranoside of 3-phenyltetrahydropyrimido[4,5-c]pyridazin-7-one: a bicyclic nucleoside with sugar residues in N and S conformations, and its molecular recognition

Abstract

The title compound 3-phenyltetrahydropyrimido[4,5-c]pyridazine 2′-deoxyribonucleoside [systematic name: 6-(2-deoxy-β-D-erythro-pentofuranosyl)-5,6,7,8-tetrahydro-3-phenylpyrimido[4,5-c]pyridazin-7-one monohydrate, C17H18N4O4·H2O, 1] shows two conformations in the crystalline state and the two conformers (1a and 1b) adopt different sugar puckers. The sugar residue of 1a shows a C2′-endo S-type conformation, while 1b displays a C3′-endo N-type sugar pucker. Both conformers adopt similar anti conformations around the N-glycosylic bonds, with χ = −97.5 (3)° for conformer 1a and χ = −103.8 (3)° for conformer 1b. The extended crystalline network is stabilized by several intermolecular hydrogen bonds involving nucleoside and water molecules. The nucleobases and phenyl substituents of the two conformers (1a and 1b) are stacked and display a reverse alignment. A Hirshfeld surface analysis supports the hydrogen-bonding pattern, while curvedness surfaces visualize the stacking interactions of neighbouring molecules. The recognition face of nucleoside 1 for base-pair formation mimics that of 2′-deoxythymidine. Nucleoside 1 shows two pK a values: 1.8 for protonation and 11.2 for deprotonation. DNA oligonucleotides containing nucleoside 1 were synthesized and hybridized with complementary DNA strands. Nucleoside 1 forms a stable base pair with dA which is as stable as the canonical dA–dT pair. The bidentate 1–dA base pair is strengthened by a third hydrogen bond provided by the dA analogue 3-bromopyrazolo[3,4-d]pyrimidine-4,6-diamine 2′-deoxyribofuranoside (4). By this, duplex stability is increased and the suggested base-pairing patterns are supported.